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…

Transmission of hepatitis B and hepatitis delta viruses in the households of chronic hepatitis B surface antigen carriers: A regression analysis of indicators of risk

Abstract To evaluate whether clinical and laboratory features of a hepatitis B surface antigen (HBsAg) carrier can predict risks of infection, its chronicity, and the development of liver disease among close contacts, the authors studied a cohort of 994 first degree relatives or cohabitants (household contacts) of 226 non-drug-addicted chronic HBsAg carriers (index cases), of whom 77% had liver disease and 26% were superinfected by hepatitis D virus (HDV). A logistic form of regression analysis was used to assess the role of each feature in the index case as predictor of hepatitis B virus (HBV)- and HDV-related outcomes among household contacts. Six models of risk, expressed as odds ratios,…

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…

Interferon for non-A, non-B chronic hepatitis

Abstract We reviewed randomised clinical trials evaluating the effect of lymphoblastoid or recombinant α-interferon in non-A, non-B chronic hepatitis. The outcomes assessed were the rates of serum alanine aminotransferase normalization and relapse during and after stopping interferon. Data were pooled by meta-analysis and a 50% overall rate difference, favouring treated patients, was found. Results showed homogeneity in direction of treatment effect both after short-term (2–6 months, ≥ 2 mega-units thrice weekly) and long-term (9–18 months, variable dose) interferon course. Moreover, results did not change when type of publication (abstracts vs. full reports) and treatment duration or sched…

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.…

Sustained response after lamivudine treatment in HBe minus chronic hepatitis B

A performance evaluation of the expert system 'Jaundice' in comparison with that of three hepatologists.

The diagnostic performance of an Expert System (Jaundice) designed to discriminate between different causes of jaundice was evaluated in a test sample of 200 consecutive in-patients with serum bilirubin greater than or equal to 51 mumol/l. The average probability assigned to true diagnosis, the non-error rate and the overall accuracy were, respectively, 55%, 77% and 70%. The Expert System's discriminatory ability in probabilistic prediction, assessed by a method based on continuous functions of the diagnostic probabilities (Brier score) was good. We also compared the ability of our Expert System to that of three experienced hepatologists, who were required to give a diagnosis in 20 cases fo…

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…

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…

Beta-blockers for preventing variceal bleeding

Evidence of bias in randomized clinical trials of hepatitis C interferon therapies

Introduction: Bias may occur in randomized clinical trials in favor of the new experimental treatment because of unblinded assessment of subjective endpoints or wish bias. Using results from published trials, we analyzed and compared the treatment effect of hepatitis C antiviral interferon therapies experimental or control. Methods: Meta-regression of trials enrolling naïve hepatitis C virus patients that underwent four therapies including interferon alone or plus ribavirin during past years. The outcome measure was the sustained response evaluated by transaminases and/or hepatitis C virus-RNA serum load. Data on the outcome across therapies were collected according to the assigned arm (exp…

Lactitol in treatment of chronic hepatic encephalopathy. A meta-analysis.

The efficacy and side effects of lactitol in the treatment of chronic hepatic encephalopathy was compared to that of other disaccharides in a meta-analysis of published randomized clinical trials (RCTs). The outcomes assessed were: (1) the rate of patients free from episodes of clinically detectable encephalopathy, and (2) the rate of patients free from one or more side effects in the different treatment groups. Four RCTs were eligible for analysis; in three lactitol was compared to lactulose, in one the alternative treatment was lactose in lactase-deficient patients. The methodological quality of these studies was high. Meta-analysis showed that lactitol was as effective as other disacchar…

Interferon-α for chronic hepatitis C: An analysis of pretreatment clinical predictors of response

To identify predictors of short-term and sustained ALT normalization after interferon treatment in adult patients with chronic hepatitis C, we performed a metanalysis of individual patients'data, with construction and cross-validation of a prediction rule, in 361 patients from two randomized trials. In one trial, 116 subjects with transfusion-related chronic hepatitis C were treated with lymphoblastoid interferon (5 MU/m 2 three times a week for 2 mo, then 3 MU/m 2 three times a week for 4 or 10 mo)

A decade of trials of interferon-alpha for chronic hepatitis C. A meta-regression analysis

The most relevant randomized controlled trials of interferon-alpha (IFN) for naive patients with chronic hepatitis C (CHC) published in a decade, just before appearance of pegylated IFN trials in 2000, were included in this paper. Its purpose is to review the relationship between sustained biochemical response in active versus control group versus usual clinical variables as IFN regimens, cirrhosis, genotype and versus less frequently addressed variables as funding, methodological quality or location of principal author. Meta-analysis estimates of global treatment effect varied according to trial design: group 1=IFN versus placebo/no treatment, 32 RCTs, 2499 pts, OR 9.5 (6.3-14.2); group 2a…

Treatment of elderly HCV patients with severe fibrosis: safety and efficacy data from RESIST-HCV, a large regional database

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 …

Polyalbumin receptors, hepatitis B surface antigen (HBsAg), and HBsAg/IgM complexes in HBsAg positive patients with and without delta superinfection.

Receptors for polymerized human albumin are found at high litres during high-level hepatitis B virus (HBV) replication and in small amounts in chronic low-level infection. Complexes between hepatitis B surface antigen (HBsAg) and IgM without specificity for HbsAg are expressed in a pattern similar to that of receptors. Anti-albumin antibodies could be involved in their formation. Delta infection depresses the synthesis of gene products of HBV. To assess whether delta modifies the expression of receptors on HBsAg and the level of HBsAg/IgM complexes, and if anti-albumin antibodies are actually part of the complex, we tested sera from 86 subjects with acute and chronic HBV infection. Our find…

Biliary sludge and gallstones in pregnancy: Incidence, risk factors, and natural history

To evaluate the incidence and symptoms of and risk factors for biliary sludge and gallstones during pregnancy and to assess the natural history of these conditions in the first year after delivery.Cohort study.A total of 272 pregnant women recruited in the first trimester.Biliary sludge and gallstones were diagnosed using ultrasonography, both during pregnancy and after delivery. Predictors of the presence or disappearance of sludge and stones were examined.Overall, from the first trimester of pregnancy until the immediate postpartum period, 67 women were newly diagnosed with biliary sludge, and 6 women were newly diagnosed with gallstones. The respective incidence rates were 31% (95% Cl, 2…

Assessing covariate imbalance in meta-analysis studies.

The main goal of meta-analysis is to combine data across studies or data sets to obtain summary estimates. In this paper, the novelty is to propose a statistical tool to assess a possible covariate imbalance in baseline variables to investigate similarity of trials. We conducted the detection of the covariate imbalance, first, through some graphical comparison of the empirical cumulative distribution functions or ECDFs, which are built by putting together arms or trials according to some risk factor, and second, through some non-parametric tests such as the Kolmogorov–Smirnov and the Anderson–Darling tests. To overcome the huge presence of ties, we conducted the statistical tests on perturbe…