Tolerability and efficacy of high-dose furosemide and small-volume hypertonic saline solution in refractory congestive heart failure

Thirty patients aged 65-85 years, with refractory New York Heart Association (NYHA) class IV congestive heart failure (CHF) were treated with an intravenous infusion of furosemide (250-2000 mg/d) and small-volume hypertonic saline solution (150 mL of 1.4-4.6% NaCl) twice a day for 6 to 12 days. A daily fluid oral intake of 1000 mL and previous cardiac therapy were maintained. Clinical signs and symptoms of CHF, such as dyspnea, edema and weakness, improved, as did severity of illness as defined by NYHA class. The infusion was well tolerated. After a 12-month follow-up, 24 patients (80%) were alive and in the NYHA class assigned on discharge from the hospital. This therapeutic combination is…

Heredity and obesity-associated hypertension: impact of hormonal characteristics and left ventricular mass.

Objectives : To investigate the influence of heredity on obesity-associated hypertension, we evaluated casual and 24-h blood pressure, left ventricular mass and some metabolic and hormonal measurements in normotensive obese subjects. Design : Healthy, normotensive obese subjects (n = 81) with positive or negative family history of hypertension were studied. Both groups were also subdivided according to a positive or a negative family history of obesity. Accordingly, 45 obese subjects had a positive family history of hypertension, 25 of these having a positive (subgroup A) and 20 having a negative family history of obesity (subgroup B). The other 36 obese subjects had a negative family histo…

Preoperative chemoradiotherapy for oesophageal cancer: a systematic review and meta-analysis

Background: The benefit of neoadjuvant chemoradiotherapy in oesophageal cancer has been extensively studied but data on survival are still equivocal. Objective: To assess the effectiveness of chemoradiotherapy followed by surgery in the reduction of mortality in patients with resectable oesophageal cancer. Methods: Computerised bibliographic searches of MEDLINE and CANCERLIT (1970–2002) were supplemented with hand searches of reference lists. Study selection: Studies were included if they were randomised controlled trials (RCTs) comparing preoperative chemoradiotherapy plus surgery with surgery alone, and if they included patients with resectable histologically proven oesophageal cancer wit…

Non invasive tools for the diagnosis of liver cirrhosis

Liver cirrhosis (LC), the end stage of many forms of chronic hepatitis of different etiologies is a diffuse process characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules surrounded by annular fibrosis. This chronic progressive clinical condition, leads to liver cell failure and portal hypertension, which can favour the onset of hepatocellular carcinoma. Defining the phase of the natural history is crucial for therapeutic choice and prognosis. Liver biopsy is currently considered the best available standard of reference but it has some limits, so alternative tools have been developed to substitute liver biopsy when assessing liver fibros…

A questionable diagnosis in a woman with drowsiness

A 60-year-old caucasian woman was admitted to our Division of Internal Medicine for a 10-day history of drowsiness, irritability, dysphasia, weakness and difficulties in the maintenance of an upright position with numerous falls, with a traumatic lumbar spine injury and on the left shoulder. Then, while general clinical conditions were getting worse with drowsiness and hyposthenia of the right side of the body, after neurological evaluation, she was recovered in hospital. Pathological history includes a 20-year epilepsy and depression with emotional lability, behavior’s disorders and attempted suicide. For such reason, she was followed in a mental health institute, treated with phenobarbita…

La malattia epatica da epatite C: una condizione guaribile?

Expansion of specific alphabeta+ T-cell subsets in the myocardium of patients with myocarditis and idiopathic dilated cardiomyopathy associated with Coxsackievirus B infection

Idiopathic dilated cardiomyopathy (IDC) is one of the major causes of death in humans and has been linked to Coxsackievirus B (CVB) infection. The aim of this study was to analyze phenotypes of heart-infiltrating immune cells in patients suffering from myocarditis and IDC associated with CVB infections. We found that the myocardium of these patients was infiltrated by CD4(+) and CD8(+) T lymphocytes as well as macrophages. Evidence of CVB3/4 infections was also found. In the majority of patients, the T-cell receptor repertoire (TCR) of the infiltrating lymphocytes was restricted, with a polyclonal expansion of the Vbeta7 gene family. We also found that human leukocyte antigen (HLA) class II…

Resistance test guided retreatment of HCV infected patients with a previous failure to a NS5A inhibitor-containing regimen: the Italian Vironet C real life experience

Previous article in issueNext article in issue Introduction: There is a limited documentation about the retreatment of patients failing a recommended NS5A-containing regimen in Italy. Materials & methods: Within the VIRONET-C network, 386 NS5A-failing patients infected with different HCV-genotypes (GT) (GT1a/1b/2a-c/3a-b-g-h/4a-d-n-o-v=93/124/19/112/38) were analyzed. Retreatment of 105 failures was investigated. HCV-resistance-test was performed by Sanger-sequencing. Results: Failures following seven different NS5A-containing regimens were studied: 3D/2D (paritaprevir/ombitasvir ± dasabuvir) ± ribavirin (N = 72/4), daclatasvir/ledipasvir/velpatasvir + sofosbuvir ± ribavirin (N = 105/13…

Small-volume hypertonic saline solution and high-dosage furosemide in the treatment of refractory congestive heart failure. A pilot study

Objective: To evaluate a new therapeutic approach to hospitalised patients with refractory congestive heart failure (CHF) based on published data on the efficacy of furosemide (frusemide) intravenous infusion in refractory CHF and of small volumes of hypertonic saline solution in the low-flow state. Design and Setting: Prospective, uncontrolled study of hospital inpatients. Study Participants and Interventions: Thirty patients (20 males and 10 females) aged 65 to 85 years with refractory New York Heart Association (NYHA) functional class IV CHF were given a twice-daily intravenous infusion of a small volume of hypertonic saline solution (150 ml of 1.4 to 4.6 NaCl) containing high-dosage fur…

Retreatment with pegylated interferon plus ribavirin of chronic hepatitis C non-responders to interferon plus ribavirin: A meta-analysis.

BACKGROUND/AIMS: Efficacy of retreatment with pegylated interferon (PEG-IFN) plus ribavirin of non-responders to standard or pegylated IFN plus ribavirin has been assessed in various studies, but sustained virologic response (SVR) rates are variable and factors influencing efficacy and tolerability still remain incompletely defined. We aimed to focus on SVR rates and to identify factors influencing them in this meta-analysis. METHODS: MEDLINE as well as a manual search were used. Studies were included if they were controlled or uncontrolled trials, if they had been published as full-length papers and if they included non-responders to standard or pegylated IFN and ribavirin therapy. Fourtee…

Transforming growth factor ß1 ed effetto nefroprotettivo dell’associazione ACE-inibitore/ AT1 antagonista in soggetti ipertesi con iniziale danno renale.

Drugs and Toxins Effects on the Liver

Drug induced hepatotoxicity can be defined as a liver injury caused by drug or herbal medicines leading to liver test abnormalities or to a liver dysfunction with a reasonable exclusion of the other competing aetiologies. The liver has a central function in the metabolism of the xenobiotics, and as a result it may be susceptible to its toxic or idiosyncratic effects. While the overall incidence of drug induced liver injury (DILI) is infrequent (1 in 10.000 to 100.000 persons exposed), the impact is significant in the general population, with broad implications for patients, physicians, pharmaceutical industries and governmental regulatory agencies. DILI is the principle reason for the termi…

Serology in adults with celiac disease: limited accuracy in patients with mild histological lesions.

Celiac disease (CD) is a gluten-triggered enteropathy, presenting with insidious clinical patterns. It can occasionally be diagnosed in asymptomatic subjects. Our aim was to define the relationship among symptoms at diagnosis, serological markers [tissue transglutaminase antibodies (tTGA), anti-endomysium antibodies (EMA) anti-actin antibodies (AAA)] and degree of mucosal damage. A total of 68 consecutive adult patients with CD were enrolled. Intestinal biopsies were scored according to the Marsh classification modified by Oberhuber: I–II minimal lesions or absent villous atrophy; IIIA partial villous atrophy; IIIB–C total villous atrophy (TVA). HLA-typing was done for all patients. No asso…

Drug Induced Liver Injury (Dili) and Non Alcoholic Fatty Liver Disease (Nafld)

This review article includes a review of the latest literature searched on PubMed in the field of hepatotoxicity caused by drugs that have a wide daily application. The concept of the review article consists of several parts dealing with the definition of drugs induced liver injury - DILI, diagnostic challenges related to it, and the clinical spectrum of liver disease, with an emphasis on the development of nonalcoholic fatty liver disease - NAFLD and review of drugs involved in formation of NAFLD.

Treatment of Congestive Heart Failure in the Elderly

Congestive heart failure (CHF) is a complex clinical syndrome which constitutes the epilogue of the natural history of virtually all heart diseases and in its advanced stages, has a poor prognosis. In the elderly, heart failure exhibits particular characteristics linked to the age-related alterations of cardiovascular system, to the association with other pathologies, to the atypical clinical presentation and to the increased iatrogenic risk. Heart failure now afflicts over 1% of the general population with nearly 1 in 10 elderly subjects affected, and the frequency of CHF is progressively increasing in most industrialized societies1,2. Further, CHF remains a significant cause of death and …

Comorbidities impact and de-prescribing in elderly with HCV-related liver disease: analysis of a prospective cohort.

AbstractManagement for HCV has undergone a notable change using direct-acting antiviral drugs (DAAs), which are safe and effective even in elderly. Here, we define impact of comorbidities, concomitant medication and drug–drug interactions in elder patients with HCV related disease before starting DAAs regimen. We analyzed data of 814 patients prospectively enrolled at our Unit within the web based model HCV Sicily Network. Out of 814, 590 were treated with DAAs and 414 of them were older than 65 years. We divided those 414 in two groups, one including 215 patients, aged between 65 and 74 years, and another with 199 patients, aged of 75 years and over. Charlson Comorbidity Index (CCI) was as…

The Changing Epidemiology of Hepatocellular Carcinoma :  Experience of a Single Center

Aims. To analyze the main etiological factors and some clinical features of patients with hepatocellular carcinoma (HCC) at diagnosis and to compare them with those we described ten years ago. Materials and Methods. We compared two groups of patients with HCC, Group 1 consisting of 132 patients (82 M, 50 F) diagnosed in the 2003–2008 period and Group 2 including 119 patients (82 M, 37 F) diagnosed in the 2013–2018 period. For all patients, age, sex, viral markers, alcohol consumption, serum alpha-fetoprotein (AFP) levels, and the main liver function parameters were recorded. The diagnosis of HCC was based on AASLD, EASL guidelines. The staging was classified according to the “Barcelona Clin…

AISF position paper on liver disease and pregnancy.

Abstract The relationship between liver disease and pregnancy is of great clinical impact. Severe liver disease in pregnancy is rare; however, pregnancy-related liver disease is the most frequent cause of liver dysfunction during pregnancy and represents a severe threat to foetal and maternal survival. A rapid differential diagnosis between liver disease related or unrelated to pregnancy is required in women who present with liver dysfunction during pregnancy. This report summarizes the recommendation of an expert panel established by the Italian Association for the Study of the Liver (AISF) on the management of liver disease during pregnancy. The article provides an overview of liver disea…

Micro-albuminuria in obese subjects: relationship among body fat distribution, blood pressure and left ventricular structure and function.

OBJECTIVE: To evaluate the relationships among micro-albuminuria, blood pressure and measurements of left ventricular structure and function in centrally and peripherally obese subjects compared with members of a lean control group. METHODS: Centrally obese subjects were subdivided according to whether they had levels of micro-albuminuria higher than 30 mg/24 h (micro-albuminuric group) or lower than or equal to 30 mg/24 h (normo-albuminuric group). For all the subjects we measured heart rate, casual mean blood pressure (MBP), 24 h MBP, total cholesterol level, high-density lipoprotein cholesterol, lipoprotein (a) level, fasting immunoreactive insulin level, plasma renin activity, plasma al…

A woman with a long history of abdominal pain

C4BQ0: a genetic marker of familial HCV-related liver cirrhosis

Source Department of Medicine and Pneumology, V Cervello Hospital, Via Trabucco 180, 90146 Palermo, Italy. lindpas@yahoo.it Abstract BACKGROUND AND METHODS: Host may have a role in the evolution of chronic HCV liver disease. We performed two cross-sectional prospective studies to evaluate the prevalence of cirrhosis in first degree relatives of patients with cirrhosis and the role of two major histocompatibility complex class III alleles BF and C4 versus HCV as risk factors for familial clustering. FINDINGS: Ninety-three (18.6%) of 500 patients with cirrhosis had at least one cirrhotic first degree relative as compared to 13 (2.6%) of 500 controls, (OR 7.38; CI 4.21-12.9). C4BQ0 was signifi…

The course of oesophagogastric varices in patients with cirrhosis after DAA-induced HCV clearance

Background and aims: Use of direct acting antivirals (DAAs) has allowed to clear HCV in almost all patients even in the presence of advanced cirrhosis. Although it has been suggested that cirrhotic portal hypertension may regress after SVR, the ultimate effect of HCV clearance on the development and progression of oesophagogastric varices (OV) is still unexplored. We assessed in a prospective cohort of patients with cirrhosis the evolution of endoscopic features of portal hypertension induced by SVR obtained with DAAs. Method: 321 consecutive patients (mean age: 65.1 ± 10.5, males: 58%) with HCV Child-Pugh A cirrhosis treated with DAAs were enrolled between January 2015 and May 2016. All pa…

What changed in the Italian internal medicine and geriatric wards during the lockdown

A total of 48 internal medicine or geriatric wards among the 93 adhering to the register REPOSI answered an online questionnaire aimed to investigate the characteristics and activities of converted and non-converted wards in the crucial period of the first wave of the epidemic, 22 February-4 May 2020

Patologie da sovraccarico di ferro:recenti acquisizioni

Acute hepatitis C: in search of the optimal approach to cure.

Abstract IFN monotherapy for acute hepatitis C can be supported, but a strategy taking into account both baseline (clinical presentation, genotype, HIV coinfection) and early (spontaneous viral decay) virologic response should be developed from carefully conducted, controlled prospective studies comparing a “wait and see strategy”, and different schedules of PEG IFN monotherapy to optimize adherence and costs and to reduce the number needed to treat. The price of the ultimate success of therapy for AVH due to HCV, i.e. a stable and definitive clearance of HCV with no residual liver disease in the long term, should not be paid by a high number of patients who are treated needlessly.

A Case of Fatal Drug Rash Eosinophilia and Systemic Symptoms from Allopurinol

Hypereosinophilia is a systemic condition that has several possible etiologies: allergies, medications, infectious, autoimmune or other systemic diseases, and finally idiopathic forms. Skin involvement seems to relate to subcutaneous inflammatory infiltration in this condition, as can be observed in parasitic, autoimmune and bullous diseases, as well as in drug reactions. Generalizing, a severe adverse drug-induced reaction may cause a systemic inflammatory disease: Drug Rash with Eosinophilia and Systemic Symptoms (DRESS). Its diagnosis requires the application of a complex diagnostic algorithm and immediate identification to prevent inauspicious evolution. The prognosis is severe; drug di…

Clinical Trial Results of Peginterferons in Combination with Ribavirin

Of the large number of patients chronically infected with hepatitis C virus (HCV), only about one third have progressive liver disease, and will eventually develop cirrhosis and hepatocellular carcinoma. These are the patients for whom effective antiviral treatment is most needed. Therapy is currently recommended for patients with chronic hepatitis C who have abnormal alanine aminotransferase (ALT) levels, detectable hepatitis C virus ribonucleic acid (HCV RNA) in the blood, and significant necroinflammatory changes and/or fibrosis on liver biopsy. The current gold standard in terms of treatment efficacy is the combination of peginterferon (PEG-IFN) and ribavirin. The overall sustained viro…

Letter: effect of HCV eradication on cardiovascular disease-Authors' reply

no abstract available

Is losartan able to improve renal haemodynamics in hypertensives? a long term study

Clinical course and outcomes of drug-induced liver injury: Nimesulide as the first implicated medication

Abstract Background and aims Drug-induced liver injury (DILI) is the most common cause of death from acute liver failure, and accounts for approximately 13% of cases of acute liver failure in the United States. The clinical presentation of DILI covers a wide spectrum, from asymptomatic liver test abnormalities to symptomatic acute liver disease, prolonged jaundice and disability, or overt acute or subacute liver failure. The aim of our study was to evaluate the number of DILI cases admitted to our Unit and to identify the drugs responsible. Thus, we reviewed all clinical records of patients with DILI admitted to our Unit from 1996 to 2006. Patients and methods A database was constructed, re…

Competing risks and prognostic stages of cirrhosis: A 25-year inception cohort study of 494 patients

Summary Background Morphological, haemodynamic and clinical stages of cirrhosis have been proposed, although no definite staging system is yet accepted for clinical practice. Aim To investigate whether clinical complications of cirrhosis may define different prognostic disease stages. Methods Analysis of the database from a prospective inception cohort of 494 patients. Decompensation was defined by ascites, bleeding, jaundice or encephalopathy. Explored potential prognostic stages: 1, compensated cirrhosis without oesophago-gastric varices; 2, compensated cirrhosis with varices; 3, bleeding without other complications; 4, first nonbleeding decompensation; 5, any second decompensating event.…

COVID in 2022. Clinical risk management of sars-cov-2 positive patients admitted to an internal medicine ward

HBV reactivation in patients with HCV/HBV cirrhosis on treatment with direct-acting antivirals

Anecdotal reports suggest that patients with chronic hepatitis C virus (HCV) hepatitis and overt or occult hepatitis B virus (HBV) coinfection may reactivate HBV when HCV is suppressed or cleared by direct-acting antivirals (DAAs). We assessed the prevalence of overt or previous HBV coinfection and the risk of HBV reactivation in patients with HCV cirrhosis treated with DAAs. This was a retrospective cohort of 104 consecutive patients with HCV cirrhosis treated with DAAs. Serum HCV-RNA and HBV-DNA were tested at weeks 4, 8 and 12 of DAAs therapy and at week 12 of follow-up. At the start of DAAs, eight patients (7.7%) were HBsAg positive/HBeAg negative with undetectable HBV-DNA and low level…

Is vitamin D deficiency predictor of complications development in patients with HCV-related cirrhosis?

not available

Disease outcomes after DAA-induced SVR: Data from the resist-HCV cohort

Background and aims: Large scale, real life data on the long term course of liver disease after HCV clearance obtained with DAAs are still scanty, and the separate effects on hepatic and non-hepatic causes of death still unclear. Method: We evaluated 4147 patients (mean age: 65.7 ± 11.5 years, 57.6% males) included in the prospective RESIST-HCV cohort who started DAAs treatment in 22 centres between March 2015 and April 2017. All patients were follow after SVR to register liver-related and unrelated outcomes. The primary endpoint was the evaluation of survival since starting DAAs. Cox regression analysis was used to assess the predictors of liver-related and unrelated death. Results: Patien…

Increased expression of markers of early atherosclerosis in patients with inflammatory bowel disease.

Recent studies documented an increased cardiovascular risk in patients with inflammatory bowel disease (IBD). Our study aimed at investigating the prevalence of intima-media thickness (IMT) of the carotid arteries and the arterial stiffness indices as markers of early atherosclerosis in young IBD patients.We recruited 68 consecutive IBD patients, and 38 matched healthy controls less than 45years old (median age 31.6±8.1years). Clinical and demographic features, cardiovascular risk factors, history of cardiovascular events, concomitant therapies were registered on a dedicate database. Carotid IMT was evaluated by using high resolution B-mode ultrasonography. Arterial stiffness was assessed b…

Platelet changes in patients with hepatitis C virus-related liver cirrhosis after directly acting antiviral therapy

Background and Purpose of the study:Thrombocytopenia is the most common haematological abnormality in patients with Liver Cirrhosis and it is caused by multiple factors. This study evaluated platelets (PLT) count changes in patients with HCV related LC after DAAs therapy. Materials and Methods: We enrolled 83 patients with LC. In all patients were evaluated liver function tests and PLT count at baseline (BL), at end of therapy (ET) and three months post treatment (PostT), Elastography and ultrasound (US) at BL, and US at PostT. LC diagnosis was histological in 13 patients, in 71 with liver stiffness >12 kPa. All patients were SVR (58 patients had DAAs therapy without, 25 with Ribavirin).…

SYNTHESIS AND SAR STUDIES OF NEW 3-METHYL-5-(5-PROPYL-1H-1-R'-3-PYRAZOLYL)-1H-1-R-4-NITROSOPYRAZOLES AS ANTIMICOTIC AGENTS.

Emocromatosi

Scompenso Cardiaco da disfunzione sistolica

Subclinical cardiovascular damage in patients with HCV cirrhosis before and after treatment with direct antiviral agents: a prospective study

BACKGROUND Cirrhosis is associated with morpho-functional cardiovascular alterations. AIMS To detect early features of cardiovascular damage in HCV-compensated cirrhotic patients using myocardial deformation indices and carotid arterial stiffness, and, further, to evaluate their short-term behaviour after HCV eradication with direct antiviral agents (DAAs). METHODS Thirty-nine consecutive patients with HCV cirrhosis, without previous cardiovascular events, were studied and matched for age, gender and cardiovascular risk factors to 39 controls without liver or cardiovascular disease. Patients and controls underwent a baseline echocardiographic evaluation including global longitudinal strain …

Imaging features of pancreatic metastases: A comparison with pancreatic ductal adenocarcinoma

Purpose: To compare imaging features of pancreatic metastases (PM) with those of pancreatic ductal adenocarcinomas (PDAC). Methods: CT and MR scans of 24 patients with 54 PM and 30 patients with PDAC were reviewed to evaluate the imaging features, which were compared by using a Chi square test. Results: We found a statistically significant difference between PM and PDAC based on location (P < 0.001), margins (P < 0.001), arterial enhancement (P = 0.004), rim enhancement (P < 0.001), pancreatic duct dilatation (P = 0.01), common bile duct dilatation (P = 0.003), vascular involvement (P = 0.02), parenchymal atrophy (P < 0.001), peripancreatic fluid (P = 0.03). Conclusion: Imaging features mig…

Fluoroquinolone-induced liver injury: three new cases and a review of the literature.

PURPOSE: Fluoroquinolones are popular and widely used in primary care and hospital settings. Premarketing studies showed a favourable side-effect profile. However, significant morbidity and the need for liver transplantation for acute liver failure have been reported. We reviewed the available data on liver damage linked to fluoroquinolones. METHODS: A systematic search of case reports on the MEDLINE database encompassing the years 2000-2011 was carried out. Additional references were found by a manual search of the retrieved paper. We also describe three new cases of hepatotoxicity attributable to fluoroquinolones seen at our Unit. RESULTS: Thirty-five cases were retrieved from MEDLINE (51…

Serum BLyS/BAFF predicts the outcome of acute hepatitis C virus infection.

Summary.  B-lymphocyte stimulator/B activating factor (BLyS/BAFF) is a tumour necrosis factor-family cytokine that plays a key role in generating and maintaining the mature B-cell pool. BLyS/BAFF expression by macrophages is stimulated by interferon-γ and interleukin-10, and its serum levels are increased in chronic hepatitis C (CHC). The aim of this study was to assess serum levels of BLyS/BAFF in patients with acute hepatitis C (AHC) and correlate them with disease outcome. We studied 28 patients with AHC (14 males, mean age 59.3 ± 15 years), followed for at least 7 months since onset, comparing them with 86 CHC patients and 25 healthy blood donors (HBD). BLyS/BAFF levels were assessed at…

Clinical course and prognostic factors of hepatorenal syndrome: A retrospective single-center cohort study

AIM: To investigate clinical and biochemical features of hepatorenal syndrome (HRS), to assess short and long-term survival evaluating potential predictors of early mortality. METHODS: Sixty-two patients with liver cirrhosis and renal failure, defined as a serum creatinine value > 1.5 mg/dL on at least two measurements within 48 h, admitted to our tertiary referral Unit from 2001 to 201, were retrospectively reviewed. Among them, 33 patients (53.2%) fulfilled the revised criteria of the International Ascites Club for the diagnosis of HRS. Twenty-eight patients were treated with combinations of terlipressin and albumin, two with dopamine and albumin, and three with albumin alone. No patients…

Fecal Calprotectin in Clinical Practice

Background: Surrogate markers of colorectal inflammation are increasingly being recognized as important in differentiating organic from functional intestinal disorders. Fecal calprotectin (FC) can be easily measured in the stool, being released by leukocytes in inflammatory conditions. Aim: We evaluated FC as an index of inflammation in consecutive outpatients referred for colonoscopy for chronic, nonbloody diarrhea. Methods: Stool specimens of 346 outpatients with chronic, nonbloody diarrhea, referred for colonoscopy, were measured for FC levels. The proportion of patients correctly diagnosed with the test and the relationship with endoscopic and histologic findings were measured. Results:…

Is Transient Elastography Needed for Noninvasive Assessment of High-Risk Varices? The REAL Experience

INTRODUCTION: The Baveno VI consensus guidelines and an expanded algorithm suggest that transient elastography (TE) and platelet (PLT) count can be used to identify patients with cirrhosis who can avoid esophagogastroduodenoscopy (EGD). The primary aims of this study were to assess the ability of a simple algorithm, which uses only laboratory parameters, to predict medium/large esophageal varices (EV) in patients with hepatitis C virus (HCV) and cirrhosis from the Rete Sicilia Selezione Terapia-HCV (RESIST-HCV) cohort and to compare the performance of the algorithm with Baveno VI and Expanded Baveno VI criteria. The secondary aim was to assess the role of TE in ruling out large EV. METHODS:…

Clinical Trial: High-dose furosemide plus small-volume hypertonic saline solutions vs. repeated paracentesis as treatment of refractory ascites.

Summary Background  In patients with cirrhosis, ascites is defined as refractory when it cannot be mobilized or recurs early in standard diuretic therapy. Aim  To compare the safety and efficacy of intravenous high-dose furosemide + hypertonic saline solutions (HSS) with repeated paracentesis in patients with cirrhosis and refractory ascites. Patients and methods  Eighty-four subjects (59/25 M/F) with cirrhosis, mostly of viral aetiology, admitted for refractory ascites, were randomly assigned to receive furosemide (250–1000 mg/bid i.v.) plus HSS (150 mL H2O with NaCl 1.4–4.6% or 239–187 mEq/L) (60 patients, Group A) or to repeated paracentesis and a standard diuretic schedule (24 patients,…

Retinol-binding protein 4 (RBP4) : a new marker of G1 HCV-induced steatosis

Il carcinoma dell'esofago

Sarcopenia is associated with severe liver fibrosis in patients with non-alcoholic fatty liver disease

Background: Sarcopenia recognises insulin resistance and obesity as risk factors, and is frequently associated with cardiometabolic disorders, including non-alcoholic fatty liver disease (NAFLD). Aim: To test the prevalence of sarcopenia and its relation with the severity of fibrosis (main outcome) and the entire spectrum of liver histology in patients with NAFLD. Methods: We considered 225 consecutive patients with histological diagnosis of NAFLD (Kleiner score). The skeletal muscle index (%) (total appendicular skeletal muscle mass (kg)/weight (kg) × 100), a validated measure of sarcopenia, was assessed by bioelectrical impedance analysis. Sarcopenia was defined as a skeletal muscle mass…

Optimizing diagnostic approach to drug-induced liver injury

Drug-induced liver injury (DILI) is often a trial even to expert clinicians, because sometimes diagnosis is not easy to be made. Guidelines of the American College of Gastroenterology (ACG) yielded in 2014, help to better understand the problem. The diagnosis of DILI is made through a detailed evaluation of clinical, serological, radiological and histological aspects. Biochemical data include liver function tests that allow to assess the pattern of damage, such as hepatocellular, cholestatic and mixed liver injury; serological data include testing for major and possibly minor hepatotropic viruses, non-organ specific autoantibodies. Clinical scenario might include jaundice, nausea, vomiting …

Gender differences in chronic liver diseases in two cohorts of 2001 and 2014 in Italy

Background: Gender differences in chronic liver disease (CLD) have been partially investigated. To extend the present knowledge, we evaluated 12,263 patients with CLD enrolled in two national surveys (9997 in 2001 and 2557 in 2014). Methods: The two surveys prospectively recruited patients aged ≥ 18 referring to Italian liver units throughout the country using a similar clinical approach and analytical methods. Results: The overall male to female ratio (M/F) was 1.4 (7138/5124). Compared with females, males were significantly more likely to be younger (52.9 vs. 58.7 yrs.), with HBV infection alone (13.2% vs. 9.2%) and with alcoholic liver disease alone (11.4% vs. 6.9%), but less likely t…

Can chemotherapy concomitantly delivered with radiotherapy improve survival of patients with resectable rectal cancer? A meta-analysis of literature data

Summary Background There is clear evidence from two systematic reviews that radiotherapy (RT) reduces the risk of local recurrence in patients with resectable rectal cancer, though the data on survival are still equivocal. Objective To assess the effects of chemotherapy combined concomitantly with radiotherapy (CRT) on the increase of overall survival, and on the prevention of local recurrence and distant metastases. Data sources Computerized bibliographic searches of MEDLINE and CANCERLIT (1970–2008) were supplemented with hand searches of reference lists. Study selection Studies were included if they were randomized controlled trials (RCTs) comparing preoperative or postoperative CRT to p…

Lymphocyte beta-adrenergic receptors in young subjects with peripheral or central obesity: relationship with central haemodynamics and left ventricular function

This study was designed to evaluate total (t) and surface (s) β-adrenergic receptor (BAR) density and their relationship with central haemodynamics and left ventricular function in young subjects with central or peripheral obesity. A total of 31 obese subjects (BMI ≥30.5 kg. m−2 for males and >27.3 kg. m−2 for females) aged less than 40 years and without other risk factors for cardiovascular diseases (smoking, hypertension, diabetes and lipid abnormalities) were studied. Nine had peripheral obesity and 22 central obesity according to WHR values; there were 20 lean controls (BMI <25 kg. m−2 for males and <24.7 kg. m−2 for females). Casual (c) and 24 h ambulatory mean blood pressures (MBP-24 …

PNPLA3 GG genotype and carotid atherosclerosis in patients with non-alcoholic fatty liver disease.

Background and Aim To evaluate if the presence of carotid atherosclerosis in patients with NAFLD, could be related to gene variants influencing hepatic fat accumulation and the severity of liver damage. Methods We recorded anthropometric, metabolic and histological data(Kleiner score) of 162 consecutive, biopsy-proven Sicilian NAFLD patients. Intima-media thickness(IMT), IMT thickening(IMT≥1 mm) and carotid plaques(focal thickening of >1.3 mm at the level of common carotid artery) were evaluated using ultrasonography. IL28B rs12979860 C>T, PNPLA3 rs738409 C>G, GCKR rs780094 C>T, LYPLAL1 rs12137855 C>T, and NCAN rs2228603 C>T single nucleotide polymorphisms were also assessed. The results we…

Cardiac involvement in rheumatoid arthritis: Evidence of silent heart disease

Background : Rlieumatoid arthritis (RA) is a systemic disease involving many organ systems and is frequently accompanied by cardiac alterations. However, there is considerable disagreement concerning the cardiac abnormalities found in patients with RA. The purpose of our investigation was to determine, by a non-invasive method such as echocardiography, the nature and extent of cardiac involvement in RA patients with no symptoms of cardiac disease, in comparison with a control sample. Methods : We selected 35 patients affected by rheumatoid arthritis (five men, 30 women), aged 51 ± 11 years. No patient had either symptoms of cardiac disease or extra cardiac complaint. As a control group we s…

Transforming growth factor β1 and additional renoprotective effect of combination ACE inhibitor and angiotensin II receptor blocker in hypertensive subjects with minor renal abnormalities: A 24-week randomized controlled trial

Objective To verify the benefit of renin–angiotensin system blockade in hypertension, the effects of 24 weeks’ losartan and ramipril treatment, both alone and in combination, on urinary albumin excretion (UAE) and circulating transforming growth factor b1 (TGFb1) have been evaluated in hypertensive subjects with minor renal abnormalities. Design and methods Fifty-one patients with stage 1 and 2 essential hypertension and with UAE &gt;—20 mg/24 h but with maintained renal function have been included. After a 4-week run-in with placebo administration, a randomized double-blind, three-arm double-dummy trial was used. All the hypertensives (HT) were allocated randomly to three treatment arms (1…

Retinol-binding protein 4: a new marker of virus-induced steatosis in patients infected with hepatitis C virus genotype 1.

Retinol-binding protein 4 (RBP4) is an adipocytokine associated with insulin resistance (IR). We tested serum levels of RBP4 to assess its link with steatosis in patients with genotype 1 chronic hepatitis C (CHC) or nonalcoholic fatty liver disease (NAFLD). Nondiabetic patients with CHC (n = 143) or NAFLD (n = 37) were evaluated by liver biopsy and anthropometric and metabolic measurements, including IR by the homeostasis model assessment. Biopsies were scored by Scheuer classification for CHC, and Kleiner for NAFLD. Steatosis was tested as a continuous variable and graded as absent-mild &lt;30%, or moderate-severe &gt; or =30%. Thirty nondiabetic, nonobese blood donors served as controls. …

Analysis of TCR Vbeta repertoire and cytokine gene expression in patients with idiopathic dilated cardiomyopathy

Although the etiopathogenesis of idiopathic dilated cardiomyopathy (IDC) is still unclear, it is widely accepted that a complex interplay between viral infections and immune mechanisms is the basis of disease genesis. Previously, we showed that heart-infiltrating T cells of patients suffering from acute, fulminant Coxsackie virus B3+-IDC shared a preferential usage of three variable gene segments of the T cell receptor beta chain-(TCR-Vbeta) encoding families Vbeta3, 7 and 13.1. This indicated the possible presence of a superantigen-driven immune response. Here, we further investigated the IDC immunological scenario by analysing different phenotypes of heart-infiltrating cells: TCR repertoi…

Mortality in patients with hepatocellular carcinoma predicted by six scoring: none is the winner

Genetic association of interleukin-6 polymorphism (-174 G/C) with chronic liver diseases and hepatocellular carcinoma

Interleukin-6 (IL-6) is a pleiotropic cytokine which is expressed in many inflammatory cells in response to different types of stimuli, regulating a number of biological processes. The IL-6 gene is polymorphic in both the 5’ and 3’ flanking regions and more than 150 single nucleotide polymorphisms have been identified so far. Genetic polymorphisms of IL-6 may affect the outcomes of several diseases, where the presence of high levels of circulating IL-6 have been correlated to the stage and/or the progression of the disease itself. The -174 G/C polymorphism is a frequent polymorphism, that is located in the upstream regulatory region of the IL-6 gene and affects IL-6 production. However, the…

Profiling the risk of hepatocellular carcinoma after long-term HCV eradication in patients with liver cirrhosis in the PITER cohort

Background and aims: Severe liver disease markers assessed before HCV eradication are acknowledged to usually improve after the SVR. We prospectively evaluated, in the PITER cohort, the long-term HCC risk profile based on predictors monitored after HCV eradication by direct-acting antivirals in patients with cirrhosis. Methods: HCC occurrence was evaluated by Kaplan-Meier analysis. Cox regression analysis identified the post-treatment variables associated with de-novo HCC; their predictive power was presented in a nomogram. Results: After the end of therapy (median follow-up:28.47 months), among 2064 SVR patients, 119 (5.8%) developed de-novo HCC. The HCC incidence was 1.90%, 4.21%, 6.47% a…

N-Acetylcysteine for Preventing Acetaminophen-Induced Liver Injury: A Comprehensive Review.

Aims: N-Acetylcysteine (NAC) is used as an antidote in acetaminophen (APAP) overdose to prevent and mitigate drug-induced liver injury (DILI). Our objective was to systematically review evidence of the use of NAC as a therapeutic option for APAP overdose and APAP-related DILI in order to define the optimal treatment schedule and timing to start treatment.Methods: Bibliographic databases (PubMed, Web of Science, Embase, and MEDLINE) were searched for retrospective and prospective cohort studies, case series, and clinical trials. The prespecified primary outcomes were DILI-related mortality, hepatotoxicity, and adverse events (AEs).Results: In total, 34 studies of NAC usage in APAP-related DI…

Oxidative stress inhibits IFN-α-induced antiviral gene expression by blocking the JAK–STAT pathway

Abstract BACKGROUND/AIMS: Unresponsiveness to IFN-alpha is common in chronic hepatitis C. Since conditions associated with an increased oxidative stress (advanced age, steatosis, fibrosis, iron overload, and alcohol consumption) reduce the likelihood of response, we hypothesized that oxidative stress may affect the antiviral actions of IFN-alpha. METHODS: We examined in a human hepatocellular carcinoma cell line (Huh-7) the effect of hydrogen peroxide (H2O2), as a generator of oxidative stress, on the IFN-alpha signaling pathway. RESULTS: Pretreatment of Huh-7 cells with 0.5-1 mM H2O2 resulted in the suppression of the IFN-alpha-induced antiviral protein MxA and of IRF-9 mRNA expression. Th…

A patient with acute hepatitis C and possible IFN toxicity

Epidemiology, Diagnosis, and Non-Pharmacological Treatment of HCC

ABSTRACT: Hepatocellular carcinoma (HCC) is still one of the most common tumors, ranking first among all cancers in relation to its frequency and mortality. Only very recently has there been a deceleration in the incidence and mortality of this neoplasia, which suggests that we may be close to the peak of the HCC epidemic, at least in the Western population. Risk factors are well known, and the hepatitis B and hepatitis C viruses are the main etiologic factors. Indeed, liver cirrhosis (LC) of any etiology is the main cause of predisposition to the neoplastic degeneration of the liver; an underlying LC is present in most cases of HCC. For this reason, a surveillance program has been establis…

Nontumorous portal vein thrombosis in liver cirrhosis: Possible role of β-blockers

&lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; Nonselective β-blockers (NSBB) are used in liver cirrhosis (LC) to prevent variceal bleeding because they decrease portal pressure. A main risk factor for the development of portal vein thrombosis (PVT) in LC is decreased portal vein inflow velocity. The aim of our study was to examine retrospectively the incidence of PVT and its correlation with the use of β-blockers in a cohort of LC patients. &lt;b&gt;&lt;i&gt;Subjects and Methods:&lt;/i&gt;&lt;/b&gt; Data from 230 LC patients (90% Child-Pugh class A), who had been followed up for at least 5 years, were reviewed. The diagnosis of PVT was made by ultrasound. The presence of PVT was evaluate…

Insulin-resistance HCV infection-related affects vascular stiffness in normotensives

BACKGROUND AND AIMS. Arterial stiffness evaluated as pulse wave velocity, is an early marker of vascular damage and an independent predictor for cardiovascular events. We investigated if the insulin resistance/hyperinsulinemia chronic hepatitis C virus infection-related could influence arterial stiffness. METHODS. We enrolled 260 outpatients matched for age, body mass index, gender, ethnicity: 52 with never-treated uncomplicated chronic hepatitis C virus infection (HCV(+)), 104 never-treated hypertensives (HT) and 104 healthy subjects (NT). Pulse wave velocity was evaluated by a validated system employing high-fidelity applanation tonometry. We also measured: fasting plasma glucose and insu…

Inflammation and Aortic Stiffness: An Individual Participant Data Meta‐Analysis in Patients With Inflammatory Bowel Disease

Background The recent finding that aortic pulse wave velocity ( aPWV ) is increased in patients with inflammatory bowel disease may explain why the cardiovascular risk is increased despite the low prevalence of traditional cardiovascular risk factors. We aimed to test whether inflammation is associated with aortic stiffening in this setting after adjustment for major confounders and to perform subgroup analyses. Methods and Results A systematic literature search for aPWV in inflammatory bowel disease was performed using PubMed, Scopus, Web of Science, and Google Scholar databases (last accessed May 7, 2017). Inclusion criterion was peer‐reviewed publications on clinical studies reporting o…

Obstructive Sleep Apnea Is Associated with Liver Damage and Atherosclerosis in Patients with Non-Alcoholic Fatty Liver Disease

Background/Aims We assessed whether obstructive sleep apnea (OSA) and nocturnal hypoxemia are associated with severity of liver fibrosis and carotid atherosclerosis in patients with biopsy-proven NAFLD and low prevalence of morbid obesity. Secondary aim was to explore the association of OSA and hypoxemia with NASH and severity of liver pathological changes. Methods Consecutive patients (n = 126) with chronically elevated ALT and NAFLD underwent STOP-BANG questionnaire to estimate OSA risk and ultrasonographic carotid assessment. In patients accepting to perform cardiorespiratory polygraphy (PG, n = 50), OSA was defined as an apnea/hypopnea index ≥5. A carotid atherosclerotic plaque was defi…

Relationship between circulating E-selectin, DD genotype of angiotensin-converting-enzyme, and cardiovascular damage in central obese subjects

Fifty-six young central obese patients were investigated to evaluate relationships between soluble E-selectin (sE-S), angiotensin-converting enzyme (ACE) gene polymorphism, left ventricular function and structure, and carotid morphology by determination of sE-S and ACE genotypes. Our results indicated that central obese subjects with concomitant higher levels of sE-S and ACE DD genotype may be characterized by early cardiovascular alterations and then considered a particular subset of subjects at higher risk of cardiovascular disease.

Waiting-time and quality of care deserved to patients with early stage hepatocellular carcinoma undergoing RFA treatment

Hepatitis C Virus Infection Is Associated With Increased Cardiovascular Mortality: A Meta-Analysis of Observational Studies

There have been many studies of the effects of hepatitis C virus (HCV) infection on cardiovascular risk, but these have produced ambiguous results. We performed a meta-analysis of these studies to systematically assess the risk of HCV infection on cardiovascular disease (CVD)-related morbidity and mortality.We searched PubMed Central, Medline, Embase, and Cochrane Library, as well as reference lists of articles, for studies published through July 2015 that compared the occurrence of CVD between HCV-infected and HCV-uninfected subjects, or assessed the prevalence of HCV infection among subjects with CVDs. In total, 22 studies were analyzed. Data on the patient populations and outcomes were e…

Case report: acute portal vein thrombosis associated with acute cytomegalovirus infection in an immunocompetent adult

Cytomegalovirus (CMV) infection is usually asymptomatic and self-limiting in healthy individuals, but significant complications can develop in immunosuppressed patients. Venous or arterial thromboembolic phenomena are uncommon yet very serious complications of CMV infection. Most published reports describe immunosuppressed patients, but thrombotic events in CMV-infected immunocompetent individuals may also occur. We describe the case of an immunocompetent young man with acute CMV hepatitis that was complicated with portal vein thrombosis (PVT). We also review the literature regarding the association between PVT and CMV in immunocompetent patients. Thromboembolism is an underestimated but si…

Hospital Care of Older Patients With COPD: Adherence to International Guidelines for Use of Inhaled Bronchodilators and Corticosteroids

Abstract Objectives We aimed to analyze the prevalence and impact of COPD in older patients hospitalized in internal medicine or geriatric wards, and to investigate adherence to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, associated clinical factors, and outcomes. Design Data were obtained from REgistro POliterapie SIMI (REPOSI), a prospective multicenter observational registry that enrolls inpatients aged ≥65 years. Setting and Participants Older hospitalized patients enrolled from 2008 to 2016 with a diagnosis of COPD. Measures We evaluated adherence to the 2018 GOLD guidelines at admission and discharge, by examining the prescription of inhaled bronchodi…

SURVEILLANCE PROGRAM FOR DIAGNOSIS OF HCC IN LIVER CIRRHOSIS: ROLE OF ULTRASOUND ECHOPATTERNS

The Role of Vitamin Deficiency in Liver Disease: To Supplement or Not Supplement?

Over the past few years, growing interest has been shown for the impact of dietary requirements and nutritional factors on chronic diseases. As a result, nutritional programs have been reinforced by public health policies. The precise role of micronutrients in chronic liver disease is currently receiving particular attention since abnormalities in vitamin levels are often detected. At present, treatment programs are focused on correcting vitamin deficiencies, which are frequently correlated to higher rates of comorbidities with poor outcomes. The literature reviewed here indicates that liver diseases are often related to vitamin disorders, due to both liver impairment and abnormal intake. M…

Renal function is impaired in normotensive chronic HCV patients: role of insulin resistance.

Renal dysfunction is an independent predictor for cardiovascular morbidity and mortality. We investigated whether chronic hepatitis C virus (HCV) infection and the related insulin resistance/hyperinsulinemia influence renal function in comparison with a group of healthy subjects and with another group with metabolic syndrome. We enrolled 130 newly diagnosed HCV outpatients matched for age and gender with 130 patients with metabolic syndrome and 130 healthy subjects. Renal function was evaluated by calculation of glomerular filtration rate (e-GFR, mL/min/1.73 m2) using the CKD-EPI equation. The following laboratory parameters were measured: fasting plasma glucose and insulin, total, LDL- and…

IL-10 and TNF-α polymorphisms and the recovery from HCV infection

Hepatitis C virus (HCV) infection becomes chronic in about 85% of infected individuals, whereas only 15% of infected people clear spontaneously the virus. It is conceivable that the host immunogenetic background influences the course of infection in term of recovery. Thus, in this study we have evaluated the effect of functionally relevant polymorphisms at tumor necrosis factor-alpha (TNF-alpha, i.e., 2 biallelic polymorphisms at nt -863 and nt-308 of the promoter) and interleukin-10 (IL-10) loci (i.e., 1 biallelic polymorphism at nt -1082 of the promoter), on the clearance of HCV infection. To this purpose, we compared 18 Sicilian patients who had spontaneously recovered from previous HCV …

Analysis of 24-h noninvasive ambulatory blood pressure profiles by a third-degree polynomial approach

Extensive experience of the circadian variation of blood pressure (BP) has been reported. But some problems exist concerning the correct and satisfactory evaluation of 24-h BP profiles. A well-known approach is the Halberg's 'cosinor' method. But it could be considered inadequate for blood pressure recordings because it is based on a rigid model that does not practically fit empirical data. We suggest an approach based on a cubic function as a suitable method for such an analysis. Our investigation studied the behavior of 24-h blood pressure by a model where the function f(t) is a third-degree polynomial. We recruited 52 untreated patients affected by essential hypertension. Ambulatory BP r…

Cardiac involvement in patients with cirrhosis: a focus on clinical features and diagnosis

Cirrhotic heart has been traditionally considered protected from cardiovascular disease, even if a large amount of literature has recently shown that patients affected by chronic liver disease are exposed to cardiovascular events, as well. Since the first recognition of cardiac involvement in cirrhosis, all published studies explain that decompensated cirrhotic patients suffer from haemodynamic changes, currently known as hyperdynamic syndrome, which finally lead to cirrhotic cardiomyopathy. This is defined by the presence of a subclinical systolic dysfunction unmasked under stress conditions, impaired diastolic function and electrophysiological abnormalities, in the absence of any known ca…

Il carcinoma del colon-retto: Un approccio basato sulle evidenze

Efficacy of 8 weeks elbasvir/grazoprevir regimen for naïve-genotype 1b, HCV infected patients with or without glucose abnormalities: Results of the EGG18 study.

Background and aim: Direct Acting Antivirals(DAAs) achieve the highest rate of sustained viral re- sponse(SVR) in patients with genotype-1b(G1b) Hepatitis C virus(HCV) infection. Reducing treatment du- ration can simplify the management and improve adherence of therapy. Patients and methods: The study evaluates the efficacy of 8 weeks of elbasvir/grazoprevir regimen in 75 treatment-naïve(TN), G1b patients with mild-moderate fibrosis(Liver Stiffness by Fibroscan®&lt; 9.0 kPa). Viral load(VL) has been evaluated by Roche TaqMan RT-PCR(LLOQ &lt; 15 IU/ml). Results: Mean age was 61.0 ±14.2 years, 44% were male, mean LS by Fibroscan®was 6.1 ±1.8 kPa. Twenty-eight patients(37.3%) had an HOMA &gt; …

When and how to treat acute hepatitis C?

Background: Appropriate treatment of acute hepatitis C is still a matter of controversy due to the lack of large controlled trials. Aim: To assess the effectiveness of interferon as treatment for acute hepatitis C by meta-analysis. Methods: MEDLINE search (1985-2002) was supplemented with manual searches of reference lists. Studies were included if they were controlled trials comparing interferon to no treatment and if they included patients with either post-transfusion or sporadic acute hepatitis C. Twelve trials were analyzed (414 patients). The outcome assessed was the sustained virological response (SVR) rate (undetectable hepatitis C virus RNA in serum at least 6 months after cessation…

Sex-Differences in the Pattern of Comorbidities, Functional Independence, and Mortality in Elderly Inpatients: Evidence from the RePoSI Register

Background: The RePoSi study has provided data on comorbidities, polypharmacy, and sex dimorphism in hospitalised elderly patients. Methods: We retrospectively analysed data collected from the 2010, 2012, 2014, and 2016 data sets of the RePoSi register. The aim of this study was to explore the sex-differences and to validate the multivariate model in the entire dataset with an expanded follow-up at 1 year. Results: Among 4714 patients, 51% were women and 49% were men. The disease distribution showed that diabetes, coronary artery disease, chronic obstructive pulmonary disease, chronic kidney disease, and malignancy were more frequent in men but that hypertension, anaemia, osteoarthritis, de…

Heredity and obesity-associated hypertension: impact of hormonal characteristics and left ventricular mass. J Hypertens

OBJECTIVES: To investigate the influence of heredity on obesity-associated hypertension, we evaluated casual and 24-h blood pressure, left ventricular mass and some metabolic and hormonal measurements in normotensive obese subjects. DESIGN: Healthy, normotensive obese subjects (n = 81) with positive or negative family history of hypertension were studied. Both groups were also subdivided according to a positive or a negative family history of obesity. Accordingly, 45 obese subjects had a positive family history of hypertension, 25 of these having a positive (subgroup A) and 20 having a negative family history of obesity (subgroup B). The other 36 obese subjects had a negative family history…

Effetti cardioprotettivi del Blocco del Sistema Renina-Angiotensina-Aldosterone tramite l’associazione ACE-inibitore – Sartani: Relazione con i livelli circolanti di Transforming Growth Factor ß1.

Disseminated non-Hodgkin's lymphoma and chronic hepatitis C: a case report.

Hepatitis C virus (HCV) infection is occasionally associated to B-cell type non-Hodgkin's lymphoma. Evidence showing a possible etiological link between HCV and lymphoma has been reported from areas of high HCV prevalence. We describe the case of a 68-year-old woman with B-cell non-Hodgkin's lymphoma mainly involving the skin. Typical manifestations of disease were cutaneous nodules, red-violet in color, scattered on the entire body and adherent to the subcutaneous tissue. A 3-cm nodule excised from the leg was found at histology to consist of centroblastic-like B cells, which stained positively for CD45, CD20 and CD79a. Although the patient was treated with different chemotherapy schedules…

Survival of patients with hepatocellular carcinoma in cirrhosis: a comparison of BCLC, CLIP and GRETCH staging systems

Summary Background  A major problem in assessing the likelihood of survival of patients with hepatocellular carcinoma (HCC) arises from a lack of models capable of predicting outcome accurately. Aim  To compare the ability of the Italian score (CLIP), the French classification (GRETCH) and the Barcelona (BCLC) staging system in predicting survival in patients with HCC. Methods  We included 406 consecutive patients with cirrhosis and HCC. Seventy-eight per cent of patients had hepatitis C. Independent predictors of survival were identified using the Cox model. Results  One-hundred and seventy-eight patients were treated, while 228 were untreated. The observed mortality was 60.1% in treated p…

Carotid atherosclerosis and chronic hepatitis C: A prospective study of risk associations

BACKGROUND AND AIMS: There are contrasting results in studies of cardiovascular risk in patients with genotype 1 chronic hepatitis C (G1 CHC). We evaluated the prevalence of carotid atherosclerosis compared with a control population in order to assess the potential association between atherosclerosis, host and viral factors, and liver histological features. MATERIALS AND METHODS: One hundred seventy-four consecutive biopsy-proven G1 CHC patients were evaluated by anthropometric and metabolic measurements. One hundred seventy-four patients attending an outpatient cardiology unit were used as controls. Intima-media thickness (IMT) and carotid plaques, defined as focal thickening of > 1.3 mm a…

Association between reduced lymphocyte beta-adrenergic receptors and left ventricular dysfunction in young obese subjects

This study was designed to evaluate total (t) and surface (s) beta-adrenergic receptors (BAR) density and their relationships with left ventricular function in young obese subjects. BAR density, plasma insulin, catecholamines and left ventricular function were evaluated in 27 young obese subjects (BMI30.5 kg/m2 for males and27.3 kg/m2 for females) without other risk factors for cardiovascular diseases (smoking, hypertension, diabetes and lipid abnormalities) and in 20 lean controls (BMI25 kg/m2 for males and24.7 kg/m2 for females). Both groups were matched for gender, age and body height. BAR density was evaluated according to Böyum and De Blasi methods. Plasma catecholamines by high perfus…

Characteristics of liver cirrhosis in Italy: Evidence for a decreasing role of HCV aetiology

Previous cross-sectional studies have shown that hepatitis C virus (HCV) infection had been the main agent associated with liver cirrhosis in Italy. Abstract BACKGROUND: Previous cross-sectional studies have shown that hepatitis C virus (HCV) infection had been the main agent associated with liver cirrhosis in Italy. AIM: To assess epidemiological, laboratory and clinical features of liver cirrhosis in Italy in 2014. PATIENTS: Out of the 2557 consecutive subjects evaluated in 16 hospitals located throughout Italy in 2014, 832 (32.6%) had liver cirrhosis and were enrolled in this study. RESULTS: The mean age of subjects was 60.3years, with a male/female ratio of 1.7; 74.9% of cases had Child…

Incidence of Hepatocellular Carcinoma in Patients With HCV-Associated Cirrhosis Treated With Direct-Acting Antiviral Agents.

Background &amp; Aims: Studies have produced conflicting results of the incidence of hepatocellular carcinoma (HCC) in patients with hepatitis C virus–associated cirrhosis treated with direct-acting antivirals (DAAs). Data from clinics are needed to accurately assess the occurrence rate of HCC in patients with cirrhosis in the real world. Methods: We collected data from a large prospective study of 2,249 consecutive patients (mean age = 65.4 years, 56.9% male) with hepatitis C virus–associated cirrhosis (90.5% with Child-Pugh class A and 9.5% with Child-Pugh class B) treated with DAAs from March 2015 through July 2016 at 22 academic and community liver centers in Sicily, Italy. HCC occurren…

Time-course of insulin resistance during antiviral therapy in non-diabetic non-cirrhotic patients with genotype 1 HCV infection

Retinol-binding protein 4 (RBP4): A new marker of G1 HCV-induced steatosis

Liver injury, SARS‐COV‐2 infection and COVID‐19: What physicians should really know?

Abstract Background & Aims Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) is responsible for coronavirus disease 2019 (COVID‐19), which in males, especially in advanced age, can sometimes evolve into acute respiratory distress syndrome. In addition, mild to moderate alterations in liver function tests (LFTs) have been reported in the worst affected patients. Our review aims to analyse data on the incidence and prognostic value of LFT alterations, the underlying mechanisms and the management of pre‐existing liver disease in COVID‐19 affected patients. Methods We searched available literature through online PubMed database using terms as “SARS‐CoV‐2,” “Liver damage,” “Liver Func…

Pattern of comorbidities and 1-year mortality in elderly patients with COPD hospitalized in internal medicine wards: data from the RePoSI Registry

Currently, chronic obstructive pulmonary disease (COPD) represents the fourth cause of death worldwide with significant economic burden. Comorbidities increase in number and severity with age and are identified as important determinants that influence the prognosis. In this observational study, we retrospectively analyzed data collected from the RePoSI register. We aimed to investigate comorbidities and outcomes in a cohort of hospitalized elderly patients with the clinical diagnosis of COPD. Socio-demographic, clinical characteristics and laboratory findings were considered. The association between variables and in-hospital, 3-month and 1-year follow-up were analyzed. Among 4696 in-patient…

Liver and Statins: A Critical Appraisal of the Evidence.

Adverse drug reactions (ADRs) represent an important cause of morbidity and mortality worldwide. Statins are a class of drugs whose main adverse effects are drug-induced liver injury (DILI) and myopathy. Some of these may be predictable, due to their pharmacokinetic and pharmacodynamic properties, while others, unfortunately, are idiosyncratic. Genetic factors may also influence patient susceptibility to DILI and myopathy in the case of statins. This review will first discuss the role of statins in cardiovascular disease treatment and prevention and the underlying mechanisms of action. Furthermore, to explore the susceptibility of statin-induced adverse events such as myopathy and hepatoto…

Survival of patients with hepatocellular carcinoma in cirrhosis: a comparison of BCLC, CLIP and GRETCH staging systems

A major problem in assessing the likelihood of survival of patients with hepatocellular carcinoma (HCC) arises from a lack of models capable of predicting outcome accurately.To compare the ability of the Italian score (CLIP), the French classification (GRETCH) and the Barcelona (BCLC) staging system in predicting survival in patients with HCC.We included 406 consecutive patients with cirrhosis and HCC. Seventy-eight per cent of patients had hepatitis C. Independent predictors of survival were identified using the Cox model.One-hundred and seventy-eight patients were treated, while 228 were untreated. The observed mortality was 60.1% in treated patients and 84.9% in untreated patients. Among…

Treatment of hepatitis C: critical appraisal of the evidence

Chronic hepatitis C virus infection is currently the most common cause of end stage liver disease worldwide. Although the conclusions of the last National Institutes of Health Consensus Development Conferences on Hepatitis C have recently been published, several important issues remain unanswered. This paper reviews the available data using an evidence-based approach. Current evidence is sufficient to recommend IFN treatment for all patients with acute hepatitis. A later initiation of therapy yields the same likelihood of response as early treatment. A daily induction dose during month 1 is the best treatment option. The current gold standard of efficacy for treatment-naive patients with ch…

Liver Function Test Abnormalities in Patients with Inflammatory Bowel Diseases: A Hospital-based Survey

Background and Aims Inflammatory bowel diseases (IBD) are frequently associated with altered liver function tests (LFTs). The causal relationship between abnormal LFTs and IBD is unclear. The aim of our study was to evaluate the prevalence and etiology of LFTs abnormalities and their association with clinical variables in a cohort of IBD patients followed up in a single center. Materials and Methods A retrospective review was undertaken of all consecutive IBD in- and outpatients routinely followed up at a single referral center. Clinical and demographic parameters were recorded. Subjects were excluded if they had a previous diagnosis of chronic liver disease. LFT abnormality was defined as …

Genetic predisposition to thrombophilia in inflammatory bowel disease

BACKGROUND Inflammatory bowel disease (IBD) is linked to a definite risk of thromboembolic events (TE), but data on the role of prothrombotic genetic mutations are conflicting. STUDY Fourteen genetic factors involved in TE pathogenesis were investigated in a homogeneous cohort of Sicilian patients with IBD with and without history of TE and in healthy controls. Forty IBD patients (21 CD, 19 UC) and 20 healthy individuals were enrolled. Genetic testing was based on the reverse hybridization principle by a commercial assay that analyzes 14 polymorphisms involved in thrombophilia and cholesterol metabolism. The rate of genetic polymorphisms and mutations was compared between IBD patients and h…

Considerations regarding the alleged association between Herbalife products and cases of hepatotoxicity: a rebuttal.

We thank Dr. K Appelhans et al. for their comments [1] on our paper [2], published online first in April 2012. In our review, we aimed to draw the attention of physicians to the uncontrolled and increasingly alarming use of herbal products and dietary supplements in the general population. In fact, in Italy this phenomenon, though still limited, has rapidly increased over the last few years. Here, use of herbal medicine products has increased to 3.7 %, while in other countries consumption is higher, reaching 20 % in the UK, and 40 % in the USA. Young non-smoking women with a high level of education appear to be the most common consumers [3]. It seems that women use these products more than …

The impact of radiotherapy on survival in resectable gastric carcinoma: A meta-analysis of literature data.

Summary Background The benefit of external radiotherapy for gastric carcinoma has been extensively studied, but data on survival are still equivocal. Objective To assess the effectiveness of surgery combined with preoperative radiotherapy or postoperative chemoradiotherapy in the reduction of all-cause mortality in patients with resectable gastric carcinoma. Methods Computerised bibliographic searches of MEDLINE and CANCERLIT (1970–2006) were supplemented with hand searches of reference lists. Study selection Studies were included if they were randomised controlled trials (RCTs) comparing mortality of surgery combined with preoperative radiotherapy or postoperative chemoradiotherapy to surg…

Clinical course and management of acute and chronic viral hepatitis during pregnancy.

Summary Pregnancy is a para-physiologic condition, which usually evolves without any complications in the majority of women, even if in some circumstances moderate or severe clinical problems can also occur. Among complications occurring during the second and the third trimester very important are those considered as concurrent to pregnancy such as hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, HELLP syndrome and acute fatty liver of pregnancy. The liver diseases concurrent to pregnancy typically occur at specific times during the gestation and they may lead to significant maternal and foetal morbidity and mortality. Commonly, delivery of the foetus, even preterm, usually te…

Retreatment with pegylated interferon plus ribavirin of chronic hepatitis C non-responders to interferon plus ribavirin: A meta-analysis

Efficacy of retreatment with pegylated interferon (PEG-IFN) plus ribavirin of non-responders to standard or pegylated IFN plus ribavirin has been assessed in various studies, but sustained virologic response (SVR) rates are variable and factors influencing efficacy and tolerability still remain incompletely defined. We aimed to focus on SVR rates and to identify factors influencing them in this meta-analysis.MEDLINE as well as a manual search were used. Studies were included if they were controlled or uncontrolled trials, if they had been published as full-length papers and if they included non-responders to standard or pegylated IFN and ribavirin therapy. Fourteen trials were included in t…

Early carotid atherosclerosis and cardiac diastolic abnormalities in hypertensive subjects

Despite the fact that it is known that hypertension may be associated to early atherosclerosis manifestations, few data are to date available on the relationship between early carotid abnormalities and left ventricular diastolic dysfunction. To address this issue, 142 hypertensive patients (64 females and 78 males) younger than 55 years, at the first diagnosis of mild-to-moderate essential hypertension (WHO/ISH criteria), were selected from a database consisting of 3541 subjects referred to ultrasound cardiovascular laboratory in the last 5 years. Carotid intima-media thickness (IMT) was detected by high-resolution vascular ultrasound and left ventricular structure and function by the use o…

Sulodexide versus calcium heparin in the medium-term treatment of deep vein thrombosis of the lower limbs.

Thirty adult patients with distal, monolateral deep vein thrombosis of the lower limbs were randomly treated for sixty days either with subcutaneous Ca-Heparin or with Sulodexide, administered IM for ten days and orally for fifty days. The thrombus accretion above the knee, the venous pressures of the affected leg, the clinical sympto matology, and some laboratory coagulative tests were monitored throughout the admin istration period. Local tolerability of the two treatments was also evaluated.The two applied treatments evidenced a net antithrombotic activity, preventing thrombus accretion above the knee, improving with the same efficacy the venous pressures in the affected legs, and simila…

Effects of a short-term hypoenergetic diet on morphofunctional left ventricular parameters in centrally obese subjects

BACKGROUND: We aimed to study centrally obese subjects without other diseases, to establish whether a short-term hypoenergetic balanced regimen is able to positively modify left ventricular (LV) patterns. METHODS: We studied 32 obese subjects (out of 52 recruited for this study) with central fat distribution and without associated diseases. Each subject had undergone a moderately hypoenergetic diet for a four-month follow-up period and had a regular loss in weight. Some relevant clinical and echocardiographic parameters were evaluated. Baseline data and those evaluated at the end of the follow-up period were used for outcome analysis. RESULTS: We found a considerable reduction in LV mass an…

Elderly Onset Celiac Disease: A Narrative Review.

Celiac sprue is a chronic disease, which usually occurs in children and young adults. However, it can develop in any age group, and the prevalence is increasing even in the elderly population. The atypical patterns of clinical presentation in this age group sometimes can cause a delay in diagnosis. Given the lower sensitivity and specificity of serological tests in the aged population, clinical suspect often arises in the presence of complications (autoimmune disorders, fractures, and finally, malignancy) and must be supported by endoscopic and imaging tools. In this review, we highlight the incidence and prevalence of celiac disease in the elderly, the patterns of clinical presentation, d…

751 RETINOL-BINDING PROTEIN 4 (RBP4): A NEW MARKER OF G1 HCV-INDUCED STEATOSIS

Outcome predictors in SARS-CoV-2 disease (COVID-19): The prominent role of IL-6 levels and an IL-6 gene polymorphism in a western Sicilian population

Interferon therapy: the other face of the medal. Ann Ital Med Int. 2004;19(1):5-7.

Clinical Course and Genetic Susceptibility of Primary Biliary Cirrhosis: Analysis of a Prospective Cohort

Background: Natural history of primary biliary cirrhosis (PBC) is partially characterized in patients from the Mediterranean area whose genetic background differs from that of Northern Europeans. Objectives: We aimed to describe genetic susceptibility and clinical course of PBC in patients from Southern Italy. Methods: Socio-demographic, clinical, biochemical and histological data at diagnosis as well as disease progression of 81 PBC consecutive patients were collected. All subjects were treated with Ursodeoxycholic acid at a dose of 15 mg/kg. HLA class II DRB1 alleles were compared with those of 237 healthy control subjects. IL28B genotyping for IL28B rs12979860 C/T and rs80899917 G/T was …

Time course of insulin resistance during antiviral therapy in non-diabetic, non-cirrhotic patients with genotype 1 HCV infection

Background Genotype 1 (G1) hepatitis C virus (HCV) is associated with insulin resistance (IR) and its clearance seems to improve insulin sensitivity. We aimed to evaluate the time course of IR in response to antiviral therapy in non-diabetic, non-cirrhotic G1 HCV patients and to assess the effect of metabolic factors on sustained virological response (SVR). Methods A total of 83 consecutive treatment-naive G1 chronic hepatitis C (CHC) patients were evaluated by anthropometric and metabolic measurements, including IR using the homeostasis model assessment (HOMA). Patients were considered to have IR if HOMA was &gt;2.7. All cases had a liver biopsy scored for staging, grading and steatosis. A…

The Presence of White Matter Lesions Is Associated With the Fibrosis Severity of Nonalcoholic Fatty Liver Disease

Abstract We tested whether nonalcoholic fatty liver disease (NAFLD) and/or its histological severity are associated with vascular white matter lesions (WML) in patients with biopsy-proven NAFLD and in non-NAFLD controls. Data were recorded in 79 consecutive biopsy-proven NAFLD, and in 82 controls with normal ALT and no history of chronic liver diseases, without ultrasonographic evidence of steatosis and liver stiffness value  45 years (OR 3.09, 95% CI: 1.06–9.06, P = 0.03; and OR 11.1, 95% CI: 1.14–108.7, P = 0.03), and F2–F4 fibrosis (OR 3.36, 95% CI: 1.29–8.73, P = 0.01; and OR 5.34, 95% CI: 1.40–20.3, P = 0.01) were independently associated with WML (mostly of mild grade) by multivariate…

Central obesity and hypertensionThe role of plasma endothelin

Hypertension and central obesity are two conditions closely linked, but the mechanisms responsible for obesity-associated hypertension are still unclear. In the last few years, several studies addressed the role of endothelin-1 (ET-1) in the development and maintenance of hypertension. This study was designed to evaluate plasma ET-1 in normotensive and hypertensive central obese subjects compared with a lean healthy group. Our final goal was to analyze the relationship between plasma ET-1, blood pressure, and left ventricular structure and function in central obese subjects (both normotensives and hypertensives). ET-levels have been assessed by the radioimmunoassay method in 20 lean normote…

EVOO's Effects on Incretin Production: Is There a Rationale for a Combination in T2DM Therapy?

Type 2 diabetes mellitus (T2DM) is a serious public health concern as it is one of the most common chronic diseases worldwide due to social and economic developments that have led to unhealthy lifestyles, with a considerable impact both in terms of morbidity and mortality. The management of T2DM, before starting specific therapies, includes cornerstones such as healthy eating, regular exercise and weight loss. Strict adherence to the Mediterranean diet (MedDiet) has been related to an inverse association with the risk of T2DM onset, as well as an improvement in glycaemic control; in particular, thanks to the consumption of extra virgin olive oil (EVOO). Agonists of gut-derived glucagon-like…

Hemostatic balance in patients with liver cirrhosis: Report of a consensus conference.

Abstract Patients with cirrhosis present with hemostatic alterations secondary to reduced availability of pro-coagulant and anti-coagulant factors. The net effect of these changes is a rebalanced hemostatic system. The Italian Association of the Study of the Liver (AISF) and the Italian Society of Internal Medicine (SIMI) promoted a consensus conference on the hemostatic balance in patients with cirrhosis. The consensus process started with the review of the literature by a scientific board of experts and ended with a formal consensus meeting in Rome in December 2014. The statements were graded according to quality of evidence and strength of recommendations, and approved by an independent …

Clinical features and comorbidity pattern of HCV infected migrants compared to native patients in care in Italy: A real-life evaluation of the PITER cohort

Background: Direct-acting antivirals are highly effective for the treatment of hepatitis C virus (HCV) infection, regardless race/ethnicity. We aimed to evaluate demographic, virological and clinical data of HCV-infected migrants vs. natives consecutively enrolled in the PITER cohort. Methods: Migrants were defined by country of birth and nationality that was different from Italy. Mann-Whitney U test, Chi-squared test and multiple logistic regression were used. Results: Of 10,669 enrolled patients, 301 (2.8%) were migrants: median age 47 vs. 62 years, (p &lt; 0.001), females 56.5% vs. 45.3%, (p &lt; 0.001), HBsAg positivity 3.8% vs. 1.4%, (p &lt; 0.05). Genotype 1b was prevalent in both gro…

Mortality in patients with hepatocellular carcinoma predicted by six scoring systems: None is the winner

Reactive hyperemia index (RHI) and cognitive performance indexes are associated with histologic markers of liver disease in subjects with non-alcoholic fatty liver disease (NAFLD): a case control study

BACKGROUND: No study evaluated vascular health markers in subjects with non-alcoholic fatty liver disease (NAFLD) through a combined analysis of reactive hyperemia peripheral arterial tonometry (RH-PAT) and arterial stiffness indexes. AIM OF THE STUDY: We aimed to assess whether NAFLD and its histological severity are associated with impairment of arterial stiffness and RH-PAT indexes in a mixed cohort of patients with biopsy-proven NAFLD. MATERIALS AND METHODS: The Kleiner classification was used to grade NAFLD grade. Pulse wave velocity (PWV) and augmentation index (Aix) were used as markers of arterial stiffness, whereas endothelial function was assessed using reactive hyperemia index (R…

Central obesity and hypertension: the role of plasma endothelin. Am J Hypertens

Hypertension and central obesity are two conditions closely linked, but the mechanisms responsible for obesity-associated hypertension are still unclear. In the last few years, several studies addressed the role of endothelin-1 (ET-1) in the development and maintenance of hypertension. This study was designed to evaluate plasma ET-1 in normotensive and hypertensive central obese subjects compared with a lean healthy group. Our final goal was to analyze the relationship between plasma ET-1, blood pressure, and left ventricular structure and function in central obese subjects (both normotensives and hypertensives). ET-levels have been assessed by the radioimmunoassay method in 20 lean normote…

Herbal hepatotoxicity: a hidden epidemic

Complementary and alternative therapies, including herbal products, have become increasingly popular in the general population and among patients and physicians. Regulations and pharmacovigilance regarding herbal drugs are still incomplete and need to be improved. In fact, herbals are commonly marketed on the Internet, and in many countries they are sold as food supplements, which are beyond the control of drug regulatory agencies. In Europe and the U.S., reports of hepatotoxicity from these products, including those advertised for liver diseases, are accumulating. Many herbal drugs are also commonly used in children, and in women during pregnancy and lactation, because they are believed to…

The presence of white matter lesions is not associated with non-alcoholic fatty liver disease but with its histological severity

[Prevalence of pericardial effusion in subjects with rheumatoid arthritis: an echocardiographic study].

We used echocardiography to determine the prevalence of pericardial effusion in rheumatoid arthritis (RA) patients without cardiac systems and compared our results to those obtained in a control group of age-matched subjects. Thirty-six patients with RA (6 men, 30 women; mean age 51 +/- 11 years) were selected from a patient population in treatment at our outpatient Rheumatology Clinic. None of the patients had any symptoms of cardiac disease, and all patients with signs and/or systems of extracardiac disease were excluded from the study. The control group consisted of 60 volunteers (mean age 51 +/- 12 years) randomly selected from a larger group of subjects with neither symptoms, signs and…

Polypharmacy in older people: lessons from 10 years of experience with the REPOSI register

As a consequence of population aging, we have witnessed in internal medicine hospital wards a progressive shift from a population of in-patients relatively young and mainly affected by a single ailment to one of ever older and more and more complex patients with multiple chronic diseases, followed as out-patients by many different specialists with poor integration and inevitably treated with multiple medications. Polypharmacy (defined as the chronic intake of five or more drugs) is associated with increased risks of drug-drug interactions and related adverse effects, prescription and intake errors, poor compliance, re-hospitalization and mortality. With this background, the Italian Society …

Oxidative stress inhibits expression of alfa-IFN induced antiviral genes by suppressing tyrosine phosphorylation of Stat-1 in huh 7 cells

Clinical features and outcomes of patients with drug-induced autoimmune hepatitis: a retrospective cohort study.

Abstract Background Drugs and herbal products can induce autoimmune hepatitis. We assessed frequency and clinical outcomes of patients suffering from drug-induced autoimmune hepatitis. Methods All patients with drug-induced liver injury admitted between 2000 and 2011 were retrospectively studied. Diagnoses of drug-induced autoimmune hepatitis and idiopathic autoimmune hepatitis were made according to simplified criteria. After discharge, all patients had regular follow-up and were contacted to update outcomes. Results Among 10,270 in-hospital patients, 136 (1.3%) were diagnosed with drug-induced liver injury. Among them, 12 (8.8%) were diagnosed as drug-induced autoimmune hepatitis (41.7% m…

The presence of White Matter Lesions is not associated with Non-alcoholic Fatty Liver Disease but with its histological severity

Hyperferritinemia is a risk factor for steatosis in chronic liver disease.

AIM: To investigate the relationship between ferritin and steatosis in patients with chronically abnormal liver function tests (LFTs) and high ferritin level. METHODS: One hundred and twenty-four consecutive patients with hyperferritinemia (male > 300 ng/mL, female > 200 ng/mL) were evaluated; clinical, biochemical and serological data, iron status parameters, HFE gene mutations and homeostasis model assessment score were obtained. Steatosis was graded by ultrasound as absent or present. Histology was available in 53 patients only. RESULTS: Mean level of ferritin was 881 ± 77 ng/mL in men and 549 ± 82 ng/mL in women. The diagnosis was chronic hepatitis C in 53 (42.7%), non-alcoholic fatty l…

SGLT2 Inhibitors as the Most Promising Influencers on the Outcome of Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD), the most frequent liver disease in the Western world, is a common hepatic manifestation of metabolic syndrome (MetS). A specific cure has not yet been identified, and its treatment is currently based on risk factor therapy. Given that the initial accumulation of triglycerides in the liver parenchyma, in the presence of inflammatory processes, mitochondrial dysfunction, lipotoxicity, glucotoxicity, and oxidative stress, can evolve into non-alcoholic steatohepatitis (NASH). The main goal is to identify the factors contributing to this evolution because, once established, untreated NASH can progress through fibrosis to cirrhosis and, ultimately, be co…

Rivaroxaban-induced hepatotoxicity

Aim/Objective/Background Direct-acting oral anticoagulant drugs are marketed worldwide for the primary and secondary prevention and treatment of thromboembolic disorders. Rivaroxaban, an oral, direct factor Xa inhibitor, is one of the most used. Rivaroxaban-induced hepatotoxicity is unusual, although a number of adverse reports have recently been reported. Here, we report two new cases of rivaroxaban-induced hepatitis. Methods A systematic search of case reports on the MEDLINE database encompassing the years 2008–2016 was carried out.Additional references were obtained following a manual search of the retrieved papers. We report two new cases of adverse events occurred in patients treated w…

Sympathovagal balance and 1-h postload plasma glucose in normoglucose tolerant hypertensive patients.

AIMS: Normoglucose tolerant (NGT) subjects with a 1-h postload plasma glucose (PLPG) value ≥155 mg/dL have an increased risk of type-2 diabetes and subclinical organ damage. Heart rate variability (HRV) reflects cardiac autonomic balance, frequently impaired in course of diabetes. At this time, no data support the association between 1-h PLPG and HRV; thus, we investigated the possible association between 1-h PLPG and HRV. METHODS: We enrolled 92 never-treated hypertensive subjects (56 women, 36 men), aged 55 ± 9.8 years. During OGTT, the patients underwent electrocardiographic recordings to evaluate HRV in the time domain (SDNN). Insulin sensitivity was assessed by Matsuda index. RESULTS: …

Real life data on elbasvir/grazoprevir efficacy, safety and drug-drug interaction profile in patients with chronic hepatitis C viral infection: a prospective analysis in the PITER cohort

Introduction: In a previous study, based on PITER cohort data, it was reported that of patients, undergoing direct acting antiviral (DAA) therapy, 30%-44%, are at risk of potential drug-drug interactions (DDI). Aim: We aimed to evaluate the prospective profile of elbasvir/grazoprevir (EBR/GZR) efficacy and safety combined with real life comedication profile. Method: Data from 312 patients (mean age 63 ± 10 years; 44% male, 90% of genotype 1.85% fibrosis stage ≤ F3, 15% with child A cirrhosis), enrolled in PITER by 15 clinical centers and treated with EBR/GZR, with at least three months of follow up after the end of treatment, were evaluated. Comedication profiles (no changes, drugs interrup…

CLINICAL COURSE OF NIMESULIDE-INDUCED LIVER INJURY

Serum BLYS/BAFF levels in acute hepatitis C predict clinical outcome

The SIMI Gender '5 Ws' Rule for the integration of sex and gender-related variables in clinical studies towards internal medicine equitable research

AbstractBiological sex and sociocultural gender matter when it comes to health and diseases. They have been both proposed as the undeniable gateways towards a personalized approach in care delivery. The Gender Working Group of the Italian Society of Internal Medicine (SIMI) was funded in 2019 with the aim of promoting good practice in the integration of sex and gender domains in clinical studies. Starting from a narrative literature review and based on regular meetings which led to a shared virtual discussion during the national SIMI congress in 2021, the members of the WG provided a core operational framework to be applied by internal medicine (IM) specialists to understand and implement t…

Adverse drug reaction and organ damage: the liver

Drug-induced liver injury (DILI) is among the most challenging acute or chronic liver conditions to be handled by physicians. Despite its low incidence in the general population, DILI is a frequent cause of acute liver failure. As such, the possibility of DILI should be considered in all patients who present with acute liver damage, independent of any known pre-existing liver disease. DILI can be classified as intrinsic/dose-dependent (e.g., acetaminophen toxicity) or idiosyncratic/dose-independent, with the latter form being relatively uncommon. Amoxicillin-clavulanate is the antimicrobial that is most frequently associated with idiosyncratic DILI. Large, ongoing, prospective studies in we…

Prevalence of use and appropriateness of antidepressants prescription in acutely hospitalized elderly patients.

Depression is often under-recognized in older patients, even if antidepressants (AD) are commonly prescribed, with a prevalence of use that increase with ageing [ 1 ]. Nevertheless, even if a diagnosis of depression is established, inappropriate treatment can occur [ 2 ]. Beers criteria are the most widely screening tools used to detect inappropriate prescription of drugs in people aged 65 years or more [ 3 ]. Since 2010, attempts to adapt the Beers' criteria have been made in Europe [ 4 , 5 ]. Tricyclic drugs are the ADs to be always avoided in the elderly, owing to their anticholinergic side effects, such as cognitive impairment, delirium, urinary retention and falls [ 3 ]. Selective sero…

Direct-acting antivirals after successful treatment of early hepatocellular carcinoma improve survival in HCV-cirrhotic patients

Background &amp; Aims: The effectiveness of direct-acting antivirals (DAAs) against hepatitis C virus (HCV), following successful treatment of early hepatocellular carcinoma (HCC), has been studied extensively. However, the benefit in terms of overall survival (OS) remains to be conclusively demonstrated. The aim of this study was to assess the impact of DAAs on OS, HCC recurrence, and hepatic decompensation. Methods: We prospectively enrolled 163 consecutive patients with HCV-related cirrhosis and a first diagnosis of early Barcelona Clinic Liver Cancer stage 0/A HCC, who had achieved a complete radiologic response after curative resection or ablation and were subsequently treated with DAA…

Acute polymyositis during treatment of acute hepatitis C with pegylated interferon alpha-2b.

Hepatitis C virus is not cleared after primary infection in 50-85% of subjects exposed to hepatitis C virus. Anti-viral treatment during the early phase of infection significantly enhances the likelihood of a sustained clearance of hepatitis C virus. Although, a variety of autoimmune-related side effects have been observed during interferon therapy for chronic hepatitis, immuno-mediated adverse reactions have not been reported during treatment of acute hepatitis C. We describe the case of a patient who developed acute hepatitis C virus infection and, while receiving pegylated interferon alpha-2b monotherapy, developed a severe polymyositis. This case illustrates the potential risk of autoim…

Prognostic indicators of successful endoscopic sclerotherapy for prevention of rebleeding from oesophageal varices in cirrhosis: a long-term cohort study

Abstract Background. Although band ligation is now recommended for prevention of rebleeding from oesophageal varices in cirrhosis, sclerotherapy is still widely used. Patients submitted to chronic sclerotherapy undergo several endoscopies and experience a large number of serious complications. However, long-term outcome is poorly defined. Aims. To assess the clinical course and prognostic indicators of patients undergoing chronic sclerotherapy for prevention of variceal rebleeding as a basis for future evaluation of long-term band ligation outcome. Methods. Prospective cohort study prognostic analysis by the Cox proportional hazards model. Results. A total of 218 consecutive cirrhotic patie…

Liver and cardiovascular mortality after hepatitis C virus eradication by DAA: Data from RESIST-HCV cohort

Real-world evidence on the course of Hepatitis C Virus (HCV) chronic liver disease after Sustained Virologic Response (SVR) obtained with direct-acting antiviral drugs (DAAs) are still limited, and the effects on mortality remain unclear. We evaluated the post-treatment survival of 4307 patients in the RESIST-HCV cohort (mean age 66.3 ± 11.6 years, 56.9% males, 24.7% chronic hepatitis, 66.9% Child-Pugh A cirrhosis and 8.4% Child-Pugh B cirrhosis) treated with DAAs between March 2015 and December 2016 and followed for a median of 73 weeks (range 16–152). Proportional cause-specific hazard regression for competing risks was used to evaluate the survival and to assess the predictors of liver a…

Plasma adiponectin: a contributing factor for cardiac changes in visceral obesity-associated hypertension.

This study has been designed to evaluate the impact of adiponectin levels on left ventricular geometry and function in visceral obesity-associated hypertension. 94 consecutive subjects, 53 of them were hypertensives and 41 normotensives with age <= 65 years, subgrouped according to the presence or absence of visceral obesity, were studied. Total adiponectin levels were measured by a validated competitive radioimmunoassay. Left ventricular telediastolic internal diameter, interventricular septum, posterior wall thickness, total left ventricular mass (LVM) and normalized for height to the 2.7 power (LVM/h(2.7)), relative wall thickness, left ventricular ejection fraction by echocardiography a…

Pancreatic cancer: risk and preventive factors

In Asian countries, the increasing incidence of obesity has only recently opened a debate that has been ongoing in the West for a long time, not only regarding its cardiovascular consequences, but also the relationship between obesity, non-alcoholic fatty liver disease (NAFLD), and cancer

Left ventricular filling abnormalities and obesity-associated hypertension: relationship with overproduction of circulating transforming growth factor β1

This study has been designed to evaluate the relationship among transforming growth factor beta1 (TGFbeta1) and some measurements of diastolic function in a population of hypertensive subjects with normal left ventricular ejection fraction. We studied 67 hypertensive outpatients who according to their BMI levels were subdivided into three groups: lean (L), overweight (OW) and obese (OB) hypertensives (HT). Circulating TGFbeta1 and M- and B-mode echocardiography was determined. All hypertensives were further subgrouped, according to European Society of Cardiology Guidelines, into two subsets of patients with normal diastolic function or with diastolic dysfunction. Prevalence of left ventricu…

Weight-loss supplementation and acute liver failure: the case of Garcinia Cambogia

Surveillance Program for Diagnosis of HCC in Liver Cirrhosis: Role of Ultrasound Echo Patterns

International guidelines suggest ultrasound surveillance for hepatocellular carcinoma (HCC) early diagnosis in liver cirrhosis (LC) patients, but 40% of nodules &lt;2 cm escape detection. We investigated the existence of an ultrasound pattern indicating a higher risk of developing HCC in patients under surveillance. 359 patients with LC (Child-Pugh A-B8) underwent ultrasound screening (median follow-up 54 months, range 12–90 months), liver function tests, alpha-fetoprotein assay, and portal hypertension evaluation. Echo patterns were homogeneous, bright liver, coarse, coarse small nodular pattern, and coarse large nodular pattern. During follow-up 13.9% developed HCC. At multivariate analys…

Hepatitis delta infection in Italian patients: towards the end of the story?

Background: The endemicity of hepatitis delta virus infection in Italy has decreased in the last decades. Aim: To evaluate the current epidemiology of chronic delta infection in Italy and to compare the present findings with the corresponding figures from the previous studies. Methods: A cross-sectional study involving 16 referral centres scattered all over the country in 2014. Results: Out of the 513 hepatitis B surface antigen-positive subjects enrolled, 61 (11.9%) were anti-delta positive, with a sex ratio (M/F) of 2.05. The majority (80.3%) of them was 50 years or older, while the proportion of subjects younger than 30 years of age was as low as 3.3%. No difference was detected by geogr…

Meccanismi immunologici e molecolari del danno epatico da farmaci

I polimorfismi genetici e/o i fattori ambientali, ad esempio l’alcol e/o i farmaci concomitanti, contribuiscono alla suscettibilità individuale nel determinare il danno epatico da farmaci. L’HLA si è dimostrato essere uno dei più importanti predittore di suscettibilità individuale anche per quei farmaci per i quali questa non era stata mai sospettata.

Expression of Cytokeratin 7 and 20 in Pathological Conditions of the Bile Tract

Expression of cytokeratin 7 (CK7) and cytokeratin 20 (CK20) helps to establish the origin of biliary and metastatic carcinomas. We investigated the expression of CK7 and CK20 in inflammatory, metaplastic and neoplastic conditions of the bile ducts, and evaluated possible relationships between the CK expression pattern and extrahepatic bile duct/gallbladder carcinomas (EBDCs) or intrahepatic bile duct carcinomas (IBDCs). We used immunohistochemistry for the investigation of 48 formalin-fixed, paraffin-embedded specimens grouped as: A) lithiasic or inflamed surgically resected extrahepatic bile ducts/gallbladders: all were CK7+/CK20+; B) percutaneous liver biopsies from patients with chronic …

Copper/MYC/CTR1 interplay: A dangerous relationship in hepatocellular carcinoma

Free serum copper correlates with tumor incidence and progression of human cancers, including hepatocellular carcinoma (HCC). Copper extracellular uptake is provided by the transporter CTR1, whose expression is regulated to avoid excessive intracellular copper entry. Inadequate copper serum concentration is involved in the pathogenesis of Non Alcoholic Fatty Liver Disease (NAFLD), which is becoming a major cause of liver damage progression and HCC incidence. Finally, MYC is over-expressed in most of HCCs and is a critical regulator of cellular growth, tumor invasion and metastasis. The purpose of our study was to understand if higher serum copper concentrations might be involved in the prog…

The aetiological pattern of hepatocellular carcinoma ( HCC) in Italy is changing

The aetiological pattern of hepatocellular carcinoma ( HCC) in Italy is changing.

N-Acetylcysteine for the Management of Non-Acetaminophen Drug-Induced Liver Injury in Adults: A Systematic Review

Introduction: Idiosyncratic drug-induced liver injury (DILI) is a rare adverse reaction to drugs and other xenobiotics. DILI has different grades of severity and may lead to acute liver failure (ALF), for which there is no effective therapy. N-acetylcysteine (NAC) has been occasionally tested for the treatment of non-acetaminophen drug-induced ALF. However, limited evidence for its efficacy and safety is currently available. Our aim was to elucidate the benefit and safety of NAC in DILI and evaluate its hepatoprotective effect.Methods: We conducted a systematic review to evaluate the management and prevention focused on NAC in idiosyncratic DILI. The main outcomes included mortality due to …

High rate of spontaneous viral clearance in patients with iatrogenic acute hepatitis C

Influence of universal HBV vaccination on chronic HBV infection in Italy: Results of a cross-sectional multicenter study

Background and Aim The universal hepatitis B vaccination for infants and 12-year-old adolescents (the latter limited to the first 12 years of application) was launched in Italy in 1991. Twenty-three years later we evaluated the impact of the vaccination campaign on the burden of HBsAg-positive chronic liver diseases (CLD). Material and Methods 513 HBsAg-positive chronic carriers referring to 16 Italian liver units were investigated and compared with HBsAg carriers enrolled in previous surveys. Results The proportion of inactive carriers decreased from 20.0% in 2001 to 3.3% in 2014, while that of cirrhotic patients increased from 22.6 to 33.2%. Regarding the age class 0–33 (fully covered by …

Hepatitis C Virus Eradication by Direct Antiviral Agents Improves Carotid Atherosclerosis in patients with Severe Liver Fibrosis.

Abstract BACKGROUND AND AIM: Recent studies suggest an association between HCV infection and cardiovascular damage, including carotid atherosclerosis, with a possible effect of HCV clearance on cardiovascular outcomes. We aimed to examine whether HCV eradication by direct antiviral agents (DAA) improves carotid atherosclerosis in HCV-infected patients with advanced fibrosis/compensated cirrhosis. MATERIALS AND METHODS: One hundred eighty-two consecutive HCV patients with advanced fibrosis or compensated cirrhosis were evaluated by virological, anthropometric and metabolic measurements. All patients underwent DAA-based antiviral therapy according to AISF/EASL guidelines. Intima-media thickne…

Synthesis and structure-activity relationship studies of new 3-methyl-5-(5-propyl-1H-1-R'-3-pyrazolyl)-1H-1-R-4-nitrosopyrazoles as antimicotic agents

We have reported that some 4-nitrosopyrazoles derivatives displayed in vitro and in vivo potent antifungal activity at no cytotoxic concentration and some of these compounds were 4 times more potent than Amphotericine B and Fluconazole respectively against Cryptococcus.Neoformans and C. Krusei.We reported also that the absence of NO group or its replacement with NO2 or NH2 groups gave compounds devoid of antimycotical activity. To better understand the mechanism of action and with the aim of identifying the chemical features responsible for the action, we synthesized and tested a new class of compounds in which the 4-NO group was replaced with 4-CN group having, these last, similar steric a…

Tumor Necrosis Factor Alpha Antagonists and Occurrence of Autoantibodies in Inflammatory Bowel Disease Patients: A Single Center Experience

Background & Aims: Appearance of auto antibodies have been described during anti-tumor necrosis factor (TNF) alpha therapy; however, their prevalence and clinical relevance are still unclear. We investigated prevalence of autoantibodies in inflammatory bowel diseases (IBD) patients on anti-TNFα treatment and occurrence of clinical symptoms. Methods: Titers of ANA, anti-dsDNA, SMA, AMA, LKM were evaluated from blood samples in patients receiving anti-TNFα inhibitor (adalimumab, infliximab). Results: Among 39 patients treated with anti-TNFα therapy, twenty of them developed ANA, mostly induced by infliximab. 55% ANA positive patients developed peripheral polyarthralgias with no need for inter…

The Ionic Hypothesis of Aging

The clinical association of essential hypertension with metabolic abnormalities, such as hyperinsulinemia, insulin resistance, obesity, altered glucose tolerance and/or frank non-insulin dependent diabetes mellitus (NIDDM) has long been appreciated(1). Each of the above clinical conditions is extremely frequent in the elderly. The association of these different clinical states, that is also common at younger ages, has been termed “Syndrome X” and more recently “Generalized Cardiovascular-Metabolic Disease.”(2,3) Although several hypothesis have been proposed, including a primary role of hyperinsulinemia and insulin resistance, the mechanism(s) of this linkage has not been established. This …

NT pro BNP plasma level and atrial volume are linked to the severity of liver cirrhosis.

BACKGROUND AND AIMS: Plasma levels of NT-pro-BNP, a natriuretic peptide precursor, are raised in the presence of fluid retention of cardiac origin and can be used as markers of cardiac dysfunction. Recent studies showed high levels of NT pro BNP in patients with cirrhosis. We assessed NT pro-BNP and other parameters of cardiac dysfunction in patients with cirrhosis, with or without ascites, in order to determine whether the behaviour of NT pro BNP is linked to the stage of liver disease or to secondary cardiac dysfunction. METHODS: Fifty eight consecutive hospitalized patients mostly with viral or NAFLD-related cirrhosis were studied. All underwent abdominal ultrasound and upper GI endoscop…

Clinical implications of the hyperdynamic syndrome in cirrhosis.

Abstract The hyperdynamic syndrome is a late consequence of portal hypertension in cirrhosis. The principal hemodynamic manifestations of the hyperdynamic syndrome are high cardiac output, and increased heart rate and total blood volume, accompanied by reduced total systemic vascular resistance. Pathophysiology involves a complex of humoral and neural mechanisms that can determine hemodynamic changes, and lead to hyperdynamic circulation. In this review we focus our attention on the manifestations of the hyperdynamic syndrome. Some of these are well described and directly related to portal hypertension (varices, ascites, hepatic encephalopathy, and hepatorenal syndrome), while others, such …

Transforming growth factor beta1 ed effetto nefroprotettivo dell’associazione ACE-inibitori-AT1 antagonista in soggetti ipertesi con iniziale danno renale