Letter: psoriasiform eruption during vedolizumab therapy
Steatosis affects the performance of liver stiffness measurement for fibrosis assessment in patients with genotype 1 chronic hepatitis C.
Background & Aims: In Chronic Hepatitis C (CHC), the influence of steatosis on liver stiffness measurement (LSM) is still debated. We assessed the impact of steatosis and its ultrasonographical sign – bright liver echo pattern (BLEP) – on LSM values and on transient elastography (TE) accuracy for the diagnosis of liver fibrosis, in a cohort of consecutive patients with Genotype 1 (G1) CHC. Methods: Patients (n = 618) were assessed by clinical, ultrasonographic and histological (Scheuer score) features. TE was performed using the M probe. Results: Male gender (p = 0.04), steatosis as continuous variable (p <0.001), severity of necroinflammation (p = 0.02) and stage of fibrosis (p <0.001) wer…
Mycophenolate mofetil is a valid option in patients with inflammatory bowel disease resistant to TNF-α inhibitors and conventional immunosuppressants.
Abstract Background Few studies investigated the role of mycophenolate mofetil in inflammatory bowel disease, and none of them had specifically focused on patients with previous multiple intolerances and/or nonresponses to conventional immunosuppressants and biologics. Aims To evaluate clinical benefit and tolerability profile of mycophenolate mofetil in patients with inflammatory bowel disease and limited treatment options. Methods All consecutive patients with previous multiple intolerances and/or nonresponses to immunosuppressants and biologics who started an off-label treatment with mycophenolate mofetil from January 2014 to February 2016 were entered in a prospectively maintained datab…
P215 Blood-based prognostic biomarkers in Crohn’s patients treated with biologics: a new promising tool to predict endoscopic outcomes
Abstract Background There is a growing need for biomarkers of inflammation to monitor and predict therapeutic outcome in Crohn’s disease (CD) patients. We aimed to evaluate whether the level of circulating blood cells, expressed as ratios (NLR, neutrophil-to-lymphocyte ratio; PLR, platelet-to-lymphocyte ratio; ELR, eosinophil-to-lymphocyte ratio and ENLR, eosinophil*neutrophil-to-lymphocyte ratio), could be used as early prognostic biomarker of endoscopic response (ER) in patients starting biological therapy with infliximab, adalimumab, vedolizumab and ustekinumab. Association with steroid-free clinical remission at week 54 and endoscopic disease activity at baseline, as well as other varia…
Letter: switching from one to another anti-tumour necrosis factor alpha agent, and the risks of an overlap of exposure
The histological or ultrasonographic detection of steatosis affects the performance of LSM in patients with chronic HCV genotype 1 infection
Cardiovascular diseases and HCV infection: a simple association or more?
HCV infection, metabolic disorders and cardiovascular alterations, considered alone or in combination, are common conditions in a large proportion of the general population. Consequently, determining whether the association of HCV infection with cardiometabolic disorders is simply coincidental or, conversely, caused by pathogenetic mechanisms (in)directly linking chronic HCV infection to these disorders, would be of extreme relevance. Several clinical studies have shown that metabolic disorders—namely, type 2 diabetes,1 insulin resistance (IR)2 and hepatic steatosis3—are highly prevalent in patients with chronic hepatitis C (CHC) compared with non-infected patients. Experimental and clinica…
Screening of colorectal cancer: present and future
Colorectal cancer (CRC) is the third most common cancer in males and second in females, and the fourth most common cause of cancer death worldwide. Currently, about 60-70% of diagnosed cases in symptomatic patients are detected at an advanced stage of disease. Earlier stage detection through the use of screening strategies would allow for better outcomes in terms of reducing the disease burden. Areas covered: The aim of this paper is to review the current published evidence from literature which assesses the performance and effectiveness of different screening tests for the early detection of CRC. Expert commentary: Adequate screening strategies can reduce CRC incidence and mortality. In th…
Association of vitamin D serum levels and its common genetic determinants, with severity of liver fibrosis in genotype 1 chronic hepatitis C patients.
Background and aims: Lower 25-Hydroxyvitamin D (25[OH]D) serum lev- els have been associated with the severity of liver fibrosis in genotype 1 chronic hepatitis C patients (G1CHC). In addition, a recent genome-wide study identified genetic variants (rs12785878, near dehydrocholesterol reduc- tase, DHCR7; rs10741657, near CYP2R1; and rs7041, near vitamin D binding protein, GC) affecting 25(OH)D serum levels in healthy populations. We aimed to assess the association between vitamin D serum levels and its genetic determinants, with the severity of liver fibrosis. Material and methods: Two hundred sixty patients with biopsy-proven G1CHC were consecutively evaluated. The 25(OH)D serum levels wer…
Genetic background in nonalcoholic fatty liver disease: A comprehensive review
In the Western world, nonalcoholic fatty liver disease (NAFLD) is considered as one of the most significant liver diseases of the twenty-first century. Its development is certainly driven by environmental factors, but it is also regulated by genetic background. The role of heritability has been widely demonstrated by several epidemiological, familial, and twin studies and case series, and likely reflects the wide inter-individual and inter-ethnic genetic variability in systemic metabolism and wound healing response processes. Consistent with this idea, genome-wide association studies have clearly identified Patatin-like phosholipase domain-containing 3 gene variant I148M as a major player i…
Primary biliary cirrhosis and hereditary hemorrhagic telangiectasia: When two rare diseases coexist
Primary biliary cirrhosis is a slowly progressive cholestatic autoimmune liver disease that mainly affects middle- aged women with an estimated prevalence ranging from 6.7 to 402 cases per million. Hereditary hemorrhagic telangiectasia, or Rendu-Osler-Weber disease, is an autosomal dominant disorder characterized by angiodysplastic lesions (telangiectases and arteriovenous malformations) that can affect many organs, including liver, with a prevalence of 1-2 cases per 10000. We describe the coexistence, for the first time to our knowledge, of these two rare diseases in a 50-year old Caucasian woman. In this setting, the relevance of an accurate medical history, the role of liver histology an…
Psoriasis and Inflammatory Bowel Disease.
<b><i>Background:</i></b> Inflammatory bowel disease (IBD) and psoriasis (PS) are associated conditions. The reason for this association lies in the sharing of predisposition genes and common immunological mechanisms. <b><i>Summary:</i></b> This review will focus on the interplay between IBD and PS, with details on prevalence and phenotype of PS in IBD, genetics, pathogenetic pathways, and therapy. <b><i>Key Messages:</i></b> Microbiome seems relevant in both conditions: a reduction of beneficial bacteria has been observed. IBD and PS have in common some comorbidities like cardiovascular disease, similar risk of cancer …
Clinical benefit of vedolizumab on articular manifestations in patients with active spondyloarthritis associated with inflammatory bowel disease.
Vedolizumab (VDZ) is a new biological agent which was recently approved for the treatment of inflammatory bowel disease (IBD)1 following the good clinical responses reported by clinical trials for both Crohn's disease2 and ulcerative colitis.3 However, the effects of VDZ on extraintestinal manifestations were not reported in these trials, and the ‘real life’ experience is still limited. On these premises, we read with interest the recent work by Varkas et al 4 reporting a series of five patients with IBD who were treated with VDZ and promptly developed new onset or exacerbation of spondyloarthritis (SpA), irrespective of the response to treatment on intestinal symptoms. Although the hypothe…
Physicians’ Knowledge and Application of Immunization Strategies in Patients with Inflammatory Bowel Disease: A Survey of the Italian Group for the Study of Inflammatory Bowel Disease
<b><i>Background:</i></b> No data on European countries about knowledge and application of immunization strategies in patients with inflammatory bowel disease (IBD) are available. <b><i>Objectives:</i></b> We designed a questionnaire aimed at exploring these issues among Italian gastroenterologists dealing with adult and paediatric IBD. <b><i>Methods:</i></b> An anonymous, 24-item, questionnaire was sent via e-mail to all members of the Italian Group for the study of Inflammatory Bowel Disease. Three sets of questions were formulated: (1) Characteristics of respondents; (2) General opinions on the role of vaccines in IB…
The METEOR Trial: The Burial of Methotrexate in Ulcerative Colitis?
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…
Metabolic Factors and Chronic Hepatitis C: A Complex Interplay
In the last years, several lines of evidence showed how metabolic factors may influence the natural history of patients with chronic hepatitis C. Chronic HCV infection is able to perturb the metabolic homeostasis of the host, in a context of complex interactions where pre-existent metabolic status and genetic background play an important role, allowing us to state that HCV infection is a systemic disease. In this review, we discuss the most recent lines of evidence on the main metabolic factors that are known to be associated with CHC, namely, insulin resistance/type 2 diabetes, steatosis, visceral obesity, atherosclerosis, vitamin D, menopause, fructose and coffee intake, lipoproteins, met…
P717 Ustekinumab in Crohn’s disease: Real-world outcomes from the Sicilian Network for inflammatory bowel diseases (SN-IBD):–Preliminary results
Abstract Background Ustekinumab is approved in Europe for the treatment of moderate-to-severe Crohn’s disease (CD) since 2016. Italian real-life data on efficacy and safety are scarce. The aim of this study was to assess effectiveness, safety and usage of Ustekinumab in an Italian cohort of patients. Methods Data of patients with moderate-to-severe CD who started Ustekinumab in Sicily were extracted from the database of the SN-IBD. Demographic data, disease-related data (disease duration, location, clinical activity) and previous therapies with biologics were collected. The primary study endpoints were steroid-free clinical remission and steroid-free clinical response at week 12, 24 and 52 …
Progressive multi-organ expression of immunoglobulin G4-related disease: A case report.
A 63-year-old Caucasian man presented with a cholestatic syndrome, renal failure and arthralgias. A laboratory examination revealed high immunoglobulin G (IgG) and IgG4 levels (5.95 g/L; normal range: 0.08-1.4 g/L), pointing to a diagnosis of systemic IgG4-related disease, with definite radiological evidence of biliary and pancreatic expression, and plausible renal, articular, salivary and lacrimal glands involvement. Due to the rarity of the condition, there are currently no random control trials to point to the optimal therapeutic approach. The patient has been on steroid therapy with the subsequent introduction of azathioprine, with a complete resolution of all symptoms, a rapid reductio…
Diagnostic and vaccine strategies to prevent infections in patients with inflammatory bowel disease.
Summary Objectives The treatment of inflammatory bowel disease (IBD) has been revolutionized by the use of immunomodulatory agents. Although these potent drugs are effective in controlling disease activity, they also cause an increased risk of new infections or reactivation of latent infections. On these premises, we aimed to provide guidance on the definitions of immunocompromised patients, opportunistic infections and the risk factors associated with their occurrence in an IBD context, and to suggest the proper screening tests for infectious diseases and the vaccination schedules to perform before and/or during therapy with immunomodulators. Methods All the most recent evidences – filtere…
Body Mass Index and Liver Stiffness Affect Accuracy of Ultrasonography in Detecting Steatosis in Patients With Chronic Hepatitis C Virus Genotype 1 Infection
Background & Aims: Few studies have evaluated the accuracy of ultrasonography in detecting steatosis in patients with chronic hepatitis C. We assessed its accuracy in detecting steatosis and factors that affect its diagnostic performance in consecutive patients with chronic hepatitis C virus genotype 1infection. Methods: We analyzed data from 515 patients with chronic hepatitis C, confirmed by liver biopsy, assessing anthropometric, biochemical, metabolic, virologic, and ultrasonography features. Transient elastography was performed to measure liver stiffness. Steatosis was identified with ultrasonography based on detection of a bright liver echo pattern. Results: Ultrasonography identified…
A real life comparison of the effectiveness of adalimumab and golimumab in moderate-to-severe ulcerative colitis, supported by propensity score analysis
Abstract Background Adalimumab and golimumab are effective in the treatment of moderate to severe ulcerative colitis. Aims We reported the comparative effectiveness of adalimumab and golimumab in ulcerative colitis. Methods 118 patients treated with adalimumab and 79 treated with golimumab were included and evaluated at 8 weeks and at the end of follow up. Results Overall clinical benefit was 72.6% at 8 weeks and 58.9% at the end of follow up. Patients with longer disease duration and those treated with adalimumab had a better outcome. Clinical benefit was 78.8% in adalimumab patients and 63.3% in golimumab patients (p = 0.026) after 8 weeks; it was 66.9% in adalimumab patients and 46.8% in…
Industrial, not fruit fructose intake is associated with the severity of liver fibrosis in genotype 1 chronic hepatitis C patients.
Background & Aims: Unhealthy food intake, specifically fructose, has been associated with metabolic alterations and with the severity of liver fibrosis in patients with non-alcoholic fatty liver disease. In a cohort of patients with genotype 1 chronic hepatitis C (G1 CHC), we tested the association of fructose intake with the severity of liver histology. Methods: Anthropometric and metabolic factors, including waist circumference (WC), waist-to-hip ratio (WHR), dorso-cervical lipohypertrophy and HOMA were assessed in 147 consecutive biopsy-proven G1 CHC patients. Food intake, namely industrial and fruit fructose, was investigated by a three-day structured interview and a computed database. …
Persistence on Anti-Tumour Necrosis Factor Therapy in Older Patients with Inflammatory Bowel Disease Compared with Younger Patients: Data from the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD)
BACKGROUND AND OBJECTIVE: Older people with inflammatory bowel disease (IBD) appear to have a lower response to anti-tumour necrosis factor (TNF) therapy, with more frequent complications than younger patients. The objective of this study was to assess persistence on therapy and the safety of anti-TNF therapy in older patients (aged ≥ 60 years). METHODS: We retrospectively reviewed the database of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD), extracting data regarding IBD patients aged ≥ 60 years and controls < 60 years of age at their first course of anti-TNF treatment. Data concerning persistence on therapy over the first year of treatment (primary objective) together …
Personalized cost-effectiveness of boceprevir-based triple therapy for untreated patients with genotype 1 chronic hepatitis C
Abstract Background We assessed the cost-effectiveness of boceprevir-based triple therapy compared to peginterferon alpha and ribavirin dual therapy in untreated patients with genotype 1 chronic hepatitis C; patients were discriminated according to the combination of baseline plus on-treatment predictors of boceprevir-based triple therapy. Methods Cost-effectiveness analysis performed according to data from the available published literature. The target population was composed of untreated Caucasian patients, aged 50 years, with genotype 1 chronic hepatitis C, and these were evaluated over a lifetime horizon by Markov model. The study was carried out from the perspective of the Italian Nati…
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…
Hepatobiliary and Pancreatic: Portal hypertensive biliopathy presenting as acute cholangitis
P255 Efficacy and safety of a restrictive ferric carboxymaltose infusion strategy for iron deficiency anemia in inflammatory bowel disease patients
Abstract Background Iron deficiency anemia (IDA) is a common condition in patients with inflammatory bowel disease (IBD) and ferric carboxymaltose (FCM) has shown fast correction of hemoglobin (Hb) levels and good tolerability. We evaluated the response to FCM in IBD patients with IDA. The primary outcome was the assessment of the rate of response to single or multiple FCM infusions after 12 months from the first infusion. Secondary outcomes were the response to a single FCM infusion after 3 months and the assessment of FCM safety. Methods We retrospectively included 185 consecutive patients from IBD Unit of “Villa Sofia-V. Cervello” Hospital who received at least a dose of 500 mg FCM infus…
The severity of steatosis influences liver stiffness measurement in patients with nonalcoholic fatty liver disease
In nonalcoholic fatty liver disease, the influence of severity of steatosis on liver stiffness measurement (LSM) is poorly studied and still debated. We assessed the impact of steatosis severity and its ultrasonographic (US) sign, severe bright liver echo pattern, on LSM values and on transient elastography accuracy for the diagnosis of liver fibrosis in a cohort of consecutive patients with nonalcoholic fatty liver disease. Patients (n = 253) were assessed by clinical, US, and histological (Kleiner score) features. Transient elastography was performed using the M probe. Among patients with low amounts of fibrosis (F0-F1 and F0-F2), median LSM values, expressed in kilopascals, were signific…
PNPLA3 rs738409 I748M is associated with steatohepatitis in 434 non-obese subjects with hepatitis C
Summary Background The PNPLA3/Adiponutrin rs738409 C/G single nucleotide polymorphism is associated with the severity of steatosis, steatohepatitis and fibrosis in patients with non-alcoholic fatty liver disease, as well as the severity of steatosis and fibrosis in patients with chronic hepatitis C (CHC). Aim To test in genotype 1(G1)-CHC patients, the putative association between the PNPLA3 variant and histological features of steatohepatitis, as well as their impact on the severity of fibrosis. Methods Four hundred and thirty-four consecutively biopsied Caucasian G1-CHC patients were genotyped for PNPLA3 rs738409, its effect evaluated by using an additive model. Histological features of s…
Safety and potential interaction of immunosuppressive drugs for the treatment of inflammatory bowel disease in elderly patients
Inflammatory bowel diseases, including Crohn's disease and ulcerative colitis, are chronic diseases associated with increased morbidity and reduced quality of life. Age may represent a risk factor for adverse events, due to the multimorbidity and polypharmacy, common in elderly patients. Elderly are often not included in clinical trials evaluating efficacy and safety of study drugs for the treatment of inflammatory bowel diseases. Several drugs, such as aminosalicylates, systemic corticosteroids, immunosuppressant drugs, biological drugs and Janus Kinase inhibitors, are available for the management of inflammatory bowel diseases. With the increasing spectrum of therapeutic options, it is th…
Residual risk of hepatocellular carcinoma after HCV eradication: more than meets the eye.
ABSTRACT Eradication of HCV in patients with advanced liver fibrosis or cirrhosis reduces, but does not altogether abolish, the risk of development of hepatocellular carcinoma. The reasons underlying this residual risk remain elusive. Even if HCV clearance eliminates its direct and indirect carcinogenic effects, the persistence of cirrhosis and the possible coexistence of metabolic factors (diabetes, obesity and insulin resistance) and of alcohol abuse can promote the development of hepatocellular carcinoma acting as autonomous, nonviral carcinogenic factors. Lessons learned in the IFN era may still assist in predicting the forthcoming scenario, when IFN-free regimens will obtain high rat…
The complex interplay between vitamin D deficiency and diabetes
It has been recently highlighted the link between vitamin D and metabolic and immunological pro- cesses, which established its role as an essential component of human health preservation. Vitamin D has been defined as natural immune modulators, and through the activation of its receptors (VDRs), it regulates calcium metabolism, cellular growth, proliferation and apoptosis, and other immunological functions. In this setting, vita- min D has also been reported to influence glucose regulation via effects on insulin secretion and action. Vitamin D deficiency is strongly associated with obesity mostly due to the storage of vitamin D in adipose tissue because of its lipophilic properties. The dec…
P288 Vedolizumab May Be An Effective Option For The Management Of Postoperative Recurrence Of Crohn’s Disease
Abstract Background The role of Vedolizumab (VDZ) as therapeutic option for the postoperative recurrence of Crohn’s disease (CD) following ileocolonic resection is currently unknown. We aimed to assess the effectiveness of VDZ in this setting. Methods All consecutive CD patients with an available baseline colonoscopy at 6-12 months from the ileocolonic resection and treated with VDZ for the postoperative recurrence after the baseline colonoscopy were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Diseases (SN-IBD). The primary outcome was endoscopic success, assessed at the first colonoscopy following initiation of VDZ. In patients with Rutgeerts score i0 or i1 at …
Serum γ-glutamyl transferase levels, insulin resistance and liver fibrosis in patients with chronic liver diseases.
Background and Aims: Serum levels of γ-glutamyl-transpeptidase(γ-GT) were associated with liver disease severity and metabolic alterations, which in turn are able to affect hepatic damage. In patients with nonalcoholic fatty liver disease (NAFLD), genotype 1 chronic hepatitis C (G1CHC) and chronic hepatitis B (CHB), we assessed the link between liver fibrosis and γ-GT serum levels, and we evaluated if normal or high γ-GT serum levels affect the association between insulin resistance (IR) and severity of liver fibrosis. Methods: 843 consecutive patients with chronic liver disease (CLD)(193 NAFLD, 481 G1CHC, 169 CHB) were evaluated by liver biopsy (Kleiner and Scheuer scores) and clinical and…
Suboptimal performance of APRI and FIB-4 in ruling out significant fibrosis and confirming cirrhosis in HIV/HCV co-infected and HCV mono-infected patients
Purpose: We aimed to assess the diagnostic reliability of two indirect biomarkers, APRI and FIB-4, for the staging of liver fibrosis using transient elastography (TE) as reference standard, among HIV/HCV co-infected and HCV mono-infected patients. Methods: This is an observational, retrospective study on subjects who had access to the RESIST HCV from October 2013 to December 2016, a regional network encompassing 22 hospitals and academic centers throughout Sicily. Sensitivity, specificity and diagnostic accuracy of indirect biomarkers for liver stiffness measurement (LSM) < 9.5 kPa (significant fibrosis) and LSM ≥ 12.5 kPa (cirrhosis) were determined by receiver operator characteristics …
Cost-effectiveness of sofosbuvir-based triple therapy for untreated patients with genotype 1 chronic hepatitis C
We assessed the cost-effectiveness of sofosbuvir (SOF)-based triple therapy (TT) compared with boceprevir (BOC)- and telaprevir (TVR)-based TT in untreated genotype 1 (G1) chronic hepatitis C (CHC) patients discriminated according to IL28B genotype, severity of liver fibrosis, and G1 subtype. The available published literature provided the data source. The target population was made up of untreated Caucasian patients, aged 50 years, with G1CHC and these were evaluated over a lifetime horizon by Markov model. The study was carried out from the perspective of the Italian National Health Service. Outcomes included discounted costs (in euros at 2013 value), life-years gained (LYG), quality-adju…
AISF position paper on HCV in immunocompromised patients.
Abstract This report summarizes the clinical features and the indications for treating HCV infection in immunocompromised and transplanted patients in the Direct Acting Antiviral drugs era.
High sCD36 plasma level is associated with steatosis and its severity in patients with genotype 1 chronic hepatitis C
Soluble CD36 (sCD36) plasma levels, a known marker of cardiometabolic disorders, are associated with surrogate markers of steatosis, while experimental and human studies show a link between CD36 expression in the liver and steatosis. In a cohort of patients with genotype 1 chronic hepatitis C (G1 CHC), we tested the association of sCD36 plasma levels with host and viral factors and sustained virological response (SVR). One hundred and seventy-five consecutive biopsy-proven patients were studied. sCD36 plasma levels were assessed by an in-house ELISA. All biopsies were scored by one pathologist for staging and grading (Scheuer) and graded for steatosis, which was considered moderate-severe i…
The Hepatic Expression of Vitamin D Receptor Is Inversely Associated With the Severity of Liver Damage in Genotype 1 Chronic Hepatitis C Patients
BACKGROUND/AIMS: Low 25-hydroxyvitamin D serum levels have been associated with the severity of liver fibrosis in genotype 1 chronic hepatitis C patients (G1CHC), and experimental evidence suggested a hepatoprotective role of vitamin D via interaction with hepatic vitamin D receptor (VDR). We assessed the hepatic expression of VDR protein and its association with liver disease severity. METHODS: Ninety-one consecutive patients with biopsy-proven G1CHC and available frozen liver tissue were evaluated. Ten subjects without chronic liver diseases and nine patients with autoimmune hepatitis served as controls. The hepatic expression of VDR protein was assessed by Western blot for quantification…
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 …
Hepatic steatosis and insulin resistance are associated with severe fibrosis in patients with chronic hepatitis caused by HBV or HCV infection.
BACKGROUND AND AIMS: Steatosis and insulin resistance (IR) are the major disease modifying in patients with chronic hepatitis C (CHC). Only few studies evaluated these features in patients with chronic hepatitis B (CHB). We aimed to assess the prevalence and the factors related to steatosis and IR in CHB patients, compared with CHC subjects, and to evaluate the potential association between these features and fibrosis severity. MATERIAL AND METHODS: One hundred and seventy consecutive patients with CHB (28 HBeAg positive, 142 HBeAg negative), were evaluated using liver biopsy and metabolic measurements and matched for sex, age and body mass index with 170 genotype 1 CHC patients. IR was def…
The Selective Use of Combination Therapy in Patients with Inflammatory Bowel Disease Resistant to Anti-TNF: to Whom, How and How Long?
Sir, We read with interest the recent work by Peyrin-Biroulet and colleagues on the long-term outcome for patients starting anti-TNF monotherapy for Crohn’s disease [CD] and for those needing the addition of an immunomodulator [IM].1 We agree with the main finding of the study, i.e. starting with anti-TNF monotherapy does not worsen long-term disease outcomes. This is in line with data from the literature2 and with our recent prospective study on the concomitant use of an IM and infliximab [IFX] in patients with CD or ulcerative colitis who have had a primary or secondary non-response to IFX monotherapy3: …
A Propensity Score-matched Comparison of Infliximab and Adalimumab in Tumour Necrosis Factor-α Inhibitor-naïve and Non-naïve Patients with Crohn's Disease: Real-Life Data from the Sicilian Network for Inflammatory Bowel Disease
Background and aims There is an unmet need to better understand the effectiveness of different biologics in inflammatory bowel diseases. We aimed at performing a multicentre, real-life comparison of the effectiveness of infliximab [IFX] and adalimumab [ADA] in Crohn's disease [CD]. Methods Data of consecutive patients with CD treated with IFX and ADA from January 2013 to May 2017 were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Disease. We used propensity score-matching accounting for the main baseline characteristics in TNF-α inhibitor-naive and non-naive patients. Results A total of 632 patients [735 total treatments] were included. Among naive patients, a cli…
Hyperuricaemia: another metabolic feature affecting the severity of chronic hepatitis because of HCV infection.
Background Several works observed a link between uric acid serum levels and clinical and histological features of nonalcoholic fatty liver disease. An association between chronic hepatitis C (CHC) and uric acid levels has been poorly investigated. Aims To assess the potential association between uric acid serum levels and both histological features of liver damage and sustained virological response (SVR) in a homogeneous cohort of CHC patients. Methods Consecutive biopsy-proven CHC patients were included. Hyperuricaemia was diagnosed with uric acid serum levels >7 mg/dl in men, and >6 mg/dl in women. Patients underwent therapy with pegylated interferon plus ribavirin. Results Hyperuricaemia…
Antimitochondrial antibody -M2 positive autoimmune hepatitis during standard of care for chronic hepatitis C
The current standard of care (SoC) for chronic hepatitis C, i.e. the combination of a pegylated-interferon (PEG-IFN) with ribavirin (RBV), may activate underlying autoimmune conditions. Particularly, interferon (IFN) has been known to induce or exacerbate autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) in hepatitis C virus patients. We describe a severe, acute-onset antimitochondrial antibody (AMA)-M2 positive AIH appearing during the last weeks of SoC in a woman with chronic hepatitis C and no previous history of autoimmunity, and resolving on protracted steroids. In this context, the relevance of the characterization of the immunoglobulin isotype of portal plasma cells for …
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…
Is Epstein-Barr virus infection associated with the pathogenesis of microscopic colitis?
Abstract Background Epstein-Barr virus (EBV) has been associated with inflammation in the colon, particularly in patients with inflammatory bowel disease (IBD). Even if a relevant plasmocytosis, similar to IBD, is present in microscopic colitis (MC), the frequency of EBV infection in this setting is unknown. Objectives We aimed to compare the frequency of colonic EBV infection in patients with MC, ulcerative colitis (UC), and irritable bowel syndrome (IBS). Study design The frequency of colonic EBV infection in biopsies of 30 patients with MC, 30 patients with UC, and 30 controls with IBS was retrospectively assessed. PCR was performed to detect viral EBV DNA in colonic biopsies. In situ hy…
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…
Cost-effectiveness of sofosbuvir-based triple therapy for untreated patients with genotype 1 chronic hepatitis C
We assessed the cost-effectiveness of sofosbuvir (SOF)-based triple therapy (TT) compared with boceprevir (BOC)- and telaprevir (TVR)-based TT in untreated genotype 1 (G1) chronic hepatitis C (CHC) patients discriminated according to IL28B genotype, severity of liver fibrosis, and G1 subtype. The available published literature provided the data source. The target population was made up of untreated Caucasian patients, aged 50 years, with G1CHC and these were evaluated over a lifetime horizon by Markov model. The study was carried out from the perspective of the Italian National Health Service. Outcomes included discounted costs (in euros at 2013 value), life-years gained (LYG), quality-adju…
P0760 : PNPLA3 rs738409 I748M is associated with steatohepatitis in non obese subjects with hepatitis C
Blood-based prognostic biomarkers in Crohn’s Disease patients on biologics: a promising tool to predict endoscopic outcomes
There is a growing need for biomarkers to predict therapeutic outcome in Crohn's disease (CD).The aim was to evaluate whether NLR (neutrophil-to-lymphocyte ratio), PLR (platelet-to-lymphocyte ratio), ELR (eosinophil-to-lymphocyte ratio), and ENLR (eosinophil*neutrophil-to-lymphocyte ratio), could be prognostic biomarkers of endoscopic response (ER) when starting biologics.Patients with CD who started biologics were enrolled. Multivariate analysis was used to evaluate whether NLR, PLR, ELR and ENLR at baseline and at w12 could predict ER (Simple Endoscopic Score for Crohn's disease [SES-CD] ≤2 or SES-CD≤2 and Rutgeerts i0-i1) after 52 weeks of treatment. Area under the curve (AUC) was calcul…
The Addition of an Immunosuppressant After Loss of Response to Anti-TNFα Monotherapy in Inflammatory Bowel Disease: A 2-Year Study
Background The addition of an immunosuppressant (IM) after loss of response to anti-TNFα monotherapy is an emerging strategy of therapeutic optimization in patients with inflammatory bowel disease (IBD). However, few clinical data have been reported to date. We aimed to evaluate the efficacy and safety of this selective combination therapy in patients with IBD. Methods All consecutive patients with loss of response to anti-TNFα monotherapy despite an intensive dose optimization who added an IM from October 2014 to October 2016 were entered into a prospective database. Results Among 630 patients treated with anti-TNFα agents during the study period, 46 (7.3%) added an IM. A total of 31 patie…
TM6SF2 rs58542926 is not associated with steatosis and fibrosis in largecohort of patients with genotype 1 chronic hepatitis C
Background & Aims We tested the putative association of the rs58542926 variant of TM6SF2, a recently described genetic determinant of nonalcoholic fatty liver disease, with steatosis and fibrosis in genotype 1(G1) chronic hepatitis C(CHC) patients. Methods A total of 694 consecutively biopsied Caucasian G1 CHC patients were genotyped for TM6SF2 rs58542926, IL28B rs12979860 and PNPLA3 rs738409. Steatosis was classified as absent (<5%), mild-moderate(5–29%) and severe(≥30%), Fibrosis was considered severe if=F3-F4. Results Carriers of TM6SF2 rs58542926 (6.3% of patients) exhibited lower serum levels of cholesterol (P = 0.04) and triglycerides (P = 0.01), but a similar distribution of steatosi…
Hepatocellular carcinoma and synchronous liver metastases from colorectal cancer in cirrhosis: A case report.
A 68-year-old Caucasian man with hepatitis C virus-related cirrhosis was admitted to our Unit in February 2010 for a diagnostic evaluation of three centimetric hypoechoic focal liver lesions detected by regular surveillance ultrasound. The subsequent computer tomography (CT) led to a diagnosis of unifocal hepatocellular carcinoma (HCC) in VI hepatic segment, defined the other two nodules in the VI and VII segment as suspected metastases, and showed a luminal narrowing with marked segmental circumferential thickening of the hepatic flexure of the colon. Colonoscopy detected an ulcerated, bleeding and stricturing lesion at the hepatic flexure, which was subsequently defined as adenocarcinoma …
Non-Invasive Assessment of Liver Injury in Non-Alcoholic Fatty Liver Disease: A Review of Literature.
NAFLD (Non-Alcoholic Fatty Liver Disease) is an increasingly significant public health issue, regarded as the most relevant liver disease of the twenty-first century. Approximately 20%-30% of NAFLD subjects develop a NASH (Non-Alcoholic Steato-Hepatitis), a condition which can potentially evolve to liver cirrhosis and hepatocellular carcinoma. For these reasons a proper evaluation of liver damage is a key point for diagnosis and prognosis and liver biopsy still remains the "gold standard" procedure both for discrimination between steatosis and steatohepatitis and assessment of the degree of liver fibrosis. Nonetheless, given it is an invasive, painful and costly procedure, a great research …
PNPLA3 rs738409 C>G SNP is associated with histological features of NASH in genotype 1 chronic hepatitis C patients
Long-term use of human albumin for the treatment of ascites in patients with hepatic cirrhosis: The interim analysis of the ANSWER study
s / Digestive and Liver Disease 47S (2015) e1–e18 e7 (months; 95% CI): CPT 0 62 (52.9–71.1), A 44 (41.6–46.4), B 22 (19.7–24.3), C 9 (6.6–11.3), p<0.0001. Comparisons between survivals of CTP 0 vs A, B and C were also statistically different (p<0.0001 in all associations). The prognosis of patients in the intermediateBCLCstagealsodifferedaccording to the liver function (0 vs A vs B, p<0.0001). Conclusions: The newly proposed CTP class 0 identifies a different subgroup of patientswith a better prognosis, alsowhen applied in a European cohort, where HCV aetiology is predominant. This new approach impacts not only on outcome prediction but also, potentially, on treatment allocation, better str…
Risk of Pneumonia Caused by Pneumocystis jiroveci in Inflammatory Bowel Disease: The Role of Concomitant Pulmonary Comorbidities
Hepatic steatosis and insulin resistance are associated with severe fibrosis in patients with chronic hepatitis caused by HBV or HCV infection
Background and aims: Steatosis and insulin resistance (IR) are the major disease modifying in patients with chronic hepatitis C (CHC). Only few studies evaluated these features in patients with chronic hepatitis B (CHB). We aimed to assess the prevalence and the factors related to steatosis and IR in CHB patients, compared with CHC subjects, and to evaluate the potential association between these features and fibrosis severity. Material and methods: One hundred and seventy consecutive patients with CHB (28 HBeAg positive, 142 HBeAg negative), were evaluated using liver biopsy and metabolic measurements and matched for sex, age and body mass index with 170 genotype 1 CHC patients. IR was def…
Tolerability profile of thiopurines in inflammatory bowel disease: a prospective experience
The occurrence of thiopurine-related adverse events (AEs) may complicate the management of patients with inflammatory bowel disease (IBD). We aimed to evaluate the tolerability of thiopurines in a current IBD setting.All consecutive patients who started a treatment with azathioprine (AZA) from January 2010 to March 2016 were entered in a prospectively maintained database, and the AEs which led to the permanent discontinuation of the drug were reported.Two hundred and fifty three patients were included. Median total follow-up was 32 months (range: 0.2-75 months). At the end of the study, AZA was discontinued in 160 patients (63.2%). The main reason leading to drug withdrawal was the occurren…
P801 Physicians’ knowledge and application of immunisation strategies in patients with inflammatory bowel disease: a survey by the Italian Group for the study of inflammatory bowel disease (IG-IBD)
Blood-based prognostic biomarkers in Crohn’s Disease patients on biologics: a promising tool to predict endoscopic outcomes
There is a growing need for biomarkers to predict therapeutic outcome in Crohn’s disease (CD). The aim was to evaluate whether NLR (neutrophil-to-lymphocyte ratio), PLR (platelet-to-lymphocyte ratio), ELR (eosinophil-to-lymphocyte ratio), and ENLR (eosinophil*neutrophil-to-lymphocyte ratio), could be prognostic biomarkers of endoscopic response (ER) when starting biologics. Patients with CD who started biologics were enrolled. Multivariate analysis was used to evaluate whether NLR, PLR, ELR and ENLR at baseline and at w12 could predict ER (Simple Endoscopic Score for Crohn’s disease [SES-CD] ≤2 or SES-CD≤2 and Rutgeerts i0-i1) after 52 weeks of treatment. Area under the curve (AUC) was calc…