Systematic review with meta-analysis: the haemodynamic effects of carvedilol compared with propranolol for portal hypertension in cirrhosis

Summary Background Propranolol is recommended for prophylaxis of variceal bleeding in cirrhosis. Carvedilol is a nonselective beta-blocker with a mild anti-alfa-1-adrenergic activity. Several studies have compared carvedilol and propranolol, yielding inconsistent results. Aim To perform a systematic review and meta-analysis of the randomised clinical trials comparing carvedilol with propranolol for hepatic vein pressure gradient reduction. Methods Studies were searched on the MEDLINE, EMBASE and Cochrane library databases up to November 2013. The weighted mean difference in percent hepatic vein pressure gradient reduction and the relative risk of failure to achieve a hemodynamic response (r…

The treatment of portal hypertension: a meta-analytic review.

Delayed-Onset Superior Mesenteric Artery Syndrome Presenting as Oesophageal Peptic Stricture

Superior mesenteric artery (SMA) syndrome is an infrequent cause of vomiting and weight loss due to compression of the third part of the duodenum by the SMA. We describe the case of a 17-year-old woman, admitted to our department for progressive dysphagia and severe weight loss due to an oesophageal peptic stricture, caused by chronic acid reflux secondary to duodenal compression by the SMA. Symptoms improved after (par)enteral nutrition and repeated oesophageal dilatation, thus supporting the role of intensive medical and endoscopic intervention as an alternative to surgery, at least in some cases.

An open-safety study of dual antiviral therapy in real-world patients with chronic hepatitis C

Purpose Treatment of patients with chronic hepatitis C with alpha-interferon and ribavirin usually produces adverse events within the first 3 months. We aimed to assess safety and predictors of discontinuation or dose modification of these drugs. Methods Observational study of 312 patients with predominantly genotype 1 chronic hepatitis C treated openly along 5 years in a clinical practice setting. Results Eighty-four percent of patients experienced at least one adverse event (853 events in total, 3.3 per patient on average). Incidence rate was higher during the first 90 days and decreased thereafter (<5%). Discontinuation rates at 30 and 90 days and at end of treatment were 2, 4 and 8%, re…

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…

Reply to Dr. Lo’s letter

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.…

W1113 Efficacy and Safety of Endoscopic Balloon Dilation of Symptomatic Intestinal Crohn's Disease Strictures

Aim: To evaluate prospectively the clinical efficacy and safety of endoscopic hydrostatic balloon dilation in a consecutive cohort of symptomatic intestinal Crohn’s disease strictures. Methods: Between September 2003 and December 2008 we performed endoscopic balloon dilations in 37 Crohn’s disease patients with 39 intestinal symptomatic strictures (4 naive and 35 postoperative). Dilations were performed using a Rigiflex through-the-scope balloon. Clinical success rate was claimed if a patient remained asymptomatic and did not require surgery or further endoscopic dilation, following technical success. Actuarial curves of clinical, endoscopic (redilation) and surgical recurrence were obtaine…

Emergency sclerotherapy or band ligation combined with vasoactive drugs for bleeding esophageal varices in cirrhosis

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the efficacy as well as adverse events of emergency sclerotherapy (or band ligation) combined with pharmacological treatments versus sclerotherapy (or band ligation) alone or vasoactive drugs alone for acute variceal bleeding in cirrhotic patients based on the results of randomised clinical trials (RCTs).

A simplified clinical risk score predicts the need for early endoscopy in non-variceal upper gastrointestinal bleeding

Abstract Background Pre-endoscopic triage of patients who require an early upper endoscopy can improve management of patients with non-variceal upper gastrointestinal bleeding. Aims To validate a new simplified clinical score (T-score) to assess the need of an early upper endoscopy in non variceal bleeding patients. Secondary outcomes were re-bleeding rate, 30-day bleeding-related mortality. Methods In this prospective, multicentre study patients with bleeding who underwent upper endoscopy were enrolled. The accuracy for high risk endoscopic stigmata of the T-score was compared with that of the Glasgow Blatchford risk score. Results Overall, 602 patients underwent early upper endoscopy, and…

Portal Hypertension and Ascites: Patient-and Population-centered Clinical Practice Guidelines by the Italian Association for the Study of the Liver (AISF)

Abstract Portal hypertension and ascites are two crucial events in the natural history of liver cirrhosis, whose appearance marks a downward shift in the prognosis of the disease. Over the years, several international and national societies have issued clinical practice guidelines for the diagnosis and management of portal hypertension and ascites. The present document addresses the needs of an updated guidance on the clinical management of these conditions. Accordingly, the AISF Governing Board appointed a multi-disciplinary committee of experts for drafting an update of the most recent EASL Clinical Practice Guidelines. The aim of this work was to adapt the EASL recommendations to nationa…

Emergency sclerotherapy versus vasoactive drugs for bleeding oesophageal varices in cirrhotic patients.

Background Emergency sclerotherapy is still widely used as a first line therapy for variceal bleeding in patients with cirrhosis, particularly when banding ligation is not available or feasible. However, pharmacological treatment may stop bleeding in the majority of these patients. Objectives To assess the benefits and harms of emergency sclerotherapy versus vasoactive drugs for variceal bleeding in cirrhosis. Search methods Search of trials was based on The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index Expanded through January 2010. Selection criteri…

Fatal necrotising fasciitis associated with intramuscular injection of nonsteroidal anti-inflammatory drugs after uncomplicated endoscopic polypectomy.

Summary Necrotising fasciitis is a life-threatening infection of the superficial muscle fascia and the adjacent deep layer of subcutaneous tissue that is often fatal. A 46-year-old woman was admitted to the intensive care unit (ICU) three days after an uncomplicated endoscopic polypectomy because of necrotising fasciitis of left tight, buttock and retroperitoneal space and septic shock. Six hours after the polypectomy she was given an intramuscular injection of ketorolac in the left tight because of moderate low abdominal pain. Twelve and 24h later she was treated with another two intramuscular injection of diclofenac in the left tight for severe pains in the left hip joint region. The shoc…

Octreotide compared with placebo in a treatment strategy for early rebleeding in cirrhosis. A double blind, randomized pragmatic trial.

beta-Blockers and sclerotherapy prevent long-term upper digestive rebleeding in cirrhosis but they seem ineffective for early rebleeding. We compared octreotide with a placebo for the prevention of early rebleeding in cirrhotic patients. After control of acute upper digestive bleeding, 262 consecutive cirrhotic patients were randomized to octreotide 100 microgram subcutaneously three times a day for 15 days (n = 131) or to the placebo (n = 131), in a double blind pragmatic trial in which beta-blockers and/or sclerotherapy were allowed together with the experimental treatment. Separate randomization and analysis were performed according to whether patients were eligible for beta-blockers and…

Efficacy and safety of endoscopic balloon dilation of symptomatic intestinal Crohn's disease strictures

Abstract Aim To evaluate prospectively the clinical efficacy and safety of endoscopic hydrostatic balloon dilation in a consecutive cohort of symptomatic intestinal Crohn's disease strictures. Methods Between September 2003 and December 2008 we performed endoscopic balloon dilations in 37 Crohn's disease patients with 39 intestinal symptomatic strictures (4 naive and 35 postoperative). Dilations were performed using a Rigiflex through-the-scope balloon. Clinical success rate was claimed if a patient remained asymptomatic and did not require surgery or further endoscopic dilation, following technical success. Actuarial curves of clinical, endoscopic (redilation) and surgical recurrence were …

New clinical and pathophysiological perspectives defining the trajectory of cirrhosis

Traditionally, the complications of cirrhosis, namely variceal bleeding, ascites and hepatic encephalopathy, were thought to result predominantly from circulatory dysfunction and altered organ perfusion arising as a result of portal hypertension. Over the past 20 years, large, international prospective studies have indicated the importance of systemic inflammation and organ immunopathology as additional determinants of organ dysfunction in cirrhosis, which not only manifests in the liver, brain, circulation and the kidneys, but also the immune system, gut, muscles, adrenal glands, reproductive organs, heart and lungs. This review provides an overview of the traditional and emerging concepts…

TIPS for Prevention of Recurrent Bleeding in Patients with Cirrhosis: Meta-analysis of Randomized Clinical Trials

To compare the effects of transjugular intrahepatic portosystemic shunt (TIPS) creation with those of endoscopic treatment with or without propranolol administration (i.e, conventional treatment) on recurrent bleeding, encephalopathy, and mortality by using meta-analysis of 11 published randomized clinical trials.Data from 11 relevant studies were retrieved by means of computerized and manual search. The combinability of the studies was assessed in terms of clinical and statistical criteria. Data were extracted on the basis of the intention-to-treat principle, and treatment effects were measured as risk differences between TIPS creation and conventional treatment. Pooled estimates were comp…

White Paper of Italian Gastroenterology: Delivery of services for digestive diseases in Italy: Weaknesses and strengths

In 2011 the three major Italian gastroenterological scientific societies (AIGO, the Italian Society of Hospital Gastroenterologists and Endoscopists; SIED, the Italian Society of Endoscopy; SIGE, the Italian Society of Gastroenterology) prepared their official document aimed at analysing medical care for digestive diseases in Italy, on the basis of national and regional data (Health Ministry and Lombardia, Veneto, Emilia-Romagna databases) and to make proposals for planning of care. Digestive diseases were the first or second cause of hospitalizations in Italy in 1999–2009, with more than 1,500,000 admissions/year; however only 5–9% of these admissions was in specialized Gastroenterology un…

Long-term sequential deferiprone-deferoxamine versus deferiprone alone for thalassemia major patients: a randomised clinical trial

A multicentre randomized open-label trial was designed to assess the effectiveness of long-term sequential deferiprone–deferoxamine (DFO–DFP) versus DFP alone to treat thalassaemia major (TM). DFP at 75 mg/kg, divided into three oral daily doses, for 4 d/week and DFO by subcutaneous infusion (8–12 h) at 50 mg/kg per day for the remaining 3 d/week was compared with DFP alone at 75 mg/kg, administered 7 d/week during a 5-year follow-up. The main outcome measures were differences between multiple observations of serum ferritin concentrations. Secondary outcomes were survival analysis, adverse events, and costs. Consecutive thalassaemia patients (275) were assessed for eligibility; 213 of these…

Sequential alternating deferiprone and deferoxamine treatment compared to deferiprone monotherapy: main findings and clinical follow-up of a large multicenter randomized clinical trial in -thalassemia major patients.

In β-thalassemia major (β-TM) patients, iron chelation therapy is mandatory to reduce iron overload secondary to transfusions. Recommended first line treatment is deferoxamine (DFO) from the age of 2 and second line treatment after the age of 6 is deferiprone (L1). A multicenter randomized open-label trial was designed to assess the effectiveness of long-term alternating sequential L1-DFO versus L1 alone iron chelation therapy in β-TM patients. Deferiprone 75 mg/kg 4 days/week and DFO 50 mg/kg/day for 3 days/week was compared with L1 alone 75 mg/kg 7 days/week during 5-year follow-up. A total of 213 thalassemia patients were randomized and underwent intention-to-treat analysis. Statisticall…

Efficacy of pneumatic dilatation for the treatment of idiopatic achalasia: a single-center experience

Pneumatic dilatation (PD) and Surgical Miotomy (SM) are presently the best treatments for untreated achalasia, with similar efficacy. There is no information on the relative efficacy of PD in younger compared to older patients. Aim of our study was to compare success rate and safety of PD in patients under fifty years old and in those over fifty years old affected by achalasia. Twenty consecutive symptomatic patients were treated in our Unit with graded PD under fluoroscopic view. Five male and 15 female with a median age of 47 years were treated. Twelve patients were less than fifty years old (group I) while 8 were older (group II). Median dysphagia questionnaire score was 14 and13 ingroup…

Prevention of upper gastrointestinal bleeding from portal hypertension in cirrhosis: rationale for medical treatment.

We updated meta-analysis and critical descriptive analysis of randomized clinical trials (RCTs) assessing the value of beta-blockers in preventing first bleeding (prophylactic) or rebleeding (therapeutic) and on survival of patients with cirrhosis. Both the methods of Peto-Mantel-Haenszel and DerSimonian-Laird were used to assess the heterogeneity and obtain cumulative estimates of treatment effects; the L'Abbé plot was also used for a visual assessment of heterogeneity in the direction of treatment effect. Seven prophylactic and nine therapeutic RCTs were analysed. beta-Blockers uniformly reduced the bleeding risk and revealed a trend toward improved survival in non-ascitic, well-compensat…

Variceal ulceration following sclerotherapy: normal consequence or complication?

Natural history and prognostic indicators of survival in cirrhosis: A systematic review of 118 studies

Liver transplantation significantly improves the survival and quality of life of patients with end-stage cirrhosis. However, a large proportion of cirrhotic patients still die while on the transplant list because of an insufficient number of donors and because of the lack of an accurate prediction of life expectancy. Although many prognostic models have been proposed in the last two decades to predict mortality in cirrhosis, the Child–Pugh score [1] is by far the most largely used both in clinical practice and in clinical research. Recently, the model for end stage liver disease (MELD) has replaced the Child–Pugh score in the United States for prioritizing liver donor allocation [2]. MELD i…

Emergency sclerotherapy versus vasoactive drugs for variceal bleeding in cirrhosis

Abstract Background & aims: Emergency sclerotherapy is used as a first-line therapy for variceal bleeding in cirrhosis, although pharmacologic treatment stops bleeding in most patients. We performed a meta-analysis comparing emergency sclerotherapy with pharmacologic treatment. Methods: MEDLINE (1968–2002), EMBASE (1986–2002), and the Cochrane Library (2002;4) were searched to retrieve randomized controlled trials comparing sclerotherapy with vasopressin (± nitroglycerin), terlipressin, somatostatin, or octreotide for variceal bleeding in cirrhosis. Outcome measures were failure to control bleeding, rebleeding, blood transfusions, adverse events, and mortality. Results: Fifteen trials were …

Deferiprone versus deferoxamine in patients with thalassemia major: a randomized clinical trial.

Deferiprone has been suggested as an effective oral chelation therapy for thalassemia major. To assess its clinical efficacy, we compared deferiprone with deferoxamine in a large multicenter randomized clinical trial. One-hundred forty-four consecutive patients with thalassemia major and serum ferritin between 1500 and 3000 ng/ml were randomly assigned to deferiprone (75 mg/kg/day) (n = 71) or deferoxamine (50 mg/kg/day) (n = 73) for 1 year. The main measure of efficacy was the reduction of serum ferritin. Liver and heart iron contents were assessed by magnetic resonance. Liver iron content and fibrosis stage variations were assessed on liver biopsy by the Ishak score in all patients willin…

Terlipressin or vasopressin plus transdermal nitroglycerin in a treatment strategy for digestive bleeding in cirrhosis

Between 1988 and 1990 an unblinded, randomized trial of terlipressin or vasopressin plus transdermal nitroglycerin, as part of a treatment strategy including emergency sclerotherapy for actively bleeding varices, was conducted during 165 admissions in 137 patients with cirrhosis and upper digestive bleeding. Eighty-four patient admissions were assigned to terlipressin (2 mg every 6 h) and 81 to vasopressin (0.4 to 0.8 unit per min) plus transdermal nitroglycerin (20 to 80 mg). The two groups were comparable for relevant clinical data, but there were slightly more patients with hepatocellular carcinoma or terminal conditions in the terlipressin group. After the 24-h study period, failure to …

Natural history of congestive gastropathy in cirrhosis

In a prospective study of the natural history of congestive gastropathy, 212 consecutive cirrhotic patients (75 treated with sclerotherapy) were included. Mean follow-up was 46 months. Mild gastropathy (mosaiclike pattern) was found in 110 patients and severe gastropathy (granular mucosa with cherry spots) was found in 20. Prevalence of Helicobacter pylori, formerly Campylobacter pylori, was 50% in patients without, 43% in those with mild, and 28% in those with severe gastropathy. Congestive gastropathy was significantly more frequent in patients treated with sclerotherapy (83% vs. 50%, P less than 10(-5)). Sixty-month actuarial proportions of patients free of anemia (in the absence of hema…

First meta-analysis of octreotide for variceal bleeding. A lost opportunity

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…

Clinical states of cirrhosis and competing risks.

The clinical course of cirrhosis is mostly determined by the progressive increase of portal hypertension, hyperdynamic circulation, bacterial translocation and activation of systemic inflammation. Different disease states, encompassing compensated and decompensated cirrhosis and a late decompensated state, are related to the progression of these mechanisms and may be recognised by haemodynamic or clinical characteristics. While these disease states do not follow a predictable sequence, they correspond to varying mortality risk. Acute-on-chronic liver failure may occur either in decompensated or in compensated cirrhosis and is always associated with a high short-term mortality. The increasin…

Screening and surveillance for hepatocellular carcinoma: perspective of a new era?

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer-related death with an increasing prevalence worldwide. Early diagnosis of HCC is important since observational studies have reported that, in patients undergoing surveillance, cancer is diagnosed at an earlier stage with increased chances of curative therapies. Anyway, despite the extensive use of screening for HCC, its effectiveness is still a controversial topic since supporting evidence is not unequivocal and some issues need to be explored. Areas covered: The aim of this paper is to review main literature data supporting performance and effectiveness of screening for early detection …

Survival and prognostic indicators in compensated and decompensated cirrhosis

Six-year survival of cirrhosis was assessed in a series of 1155 consecutive patients (751 men, 404 women). Among the men, 33% were alcoholics and 18% were HBsAg positive; corresponding figures for the women were 15% and 6%, respectively. Features of decompensation at first presentation were observed in 63% of the patients. Six-year survival was 54% in compensated and 21% in decompensated patients. No significant differences in survival were found between alcoholics and nonalcoholics. Leading causes of death were liver failure (49%), hepatocellular carcinoma (22%), and bleeding (13%). The prognostic role of 21 variables was evaluated separately in compensated and decompensated patients by th…

MTHFR C677T homozygous as risk factor for complications after OLT for cryptogenic cirrhosis

JC Virus, Helicobacter pylori, and Oesophageal Achalasia: Preliminary Results from a Retrospective Case-Control Study.