We performed a meta-analysis of individual patient data from 11 randomized controlled trials comparing corticosteroids, pentoxifylline, or their combination in patients with severe alcoholic hepatitis. We compared the effects of the treatments on survival for 28 days or 6 months, and response to treatment based on the Lille model. We searched PubMed for randomized controlled trials of pharmacologic therapy for severe alcoholic hepatitis. Our final analysis comprised 11 studies, of 2111 patients. We performed 4 meta-analyses of the effects of corticosteroids vs placebo or control, corticosteroids vs pentoxifylline, corticosteroids and pentoxifylline vs corticosteroids and placebo or control, and pentoxifylline vs placebo. In each meta-analysis, the effect of treatment on the primary outcome (overall survival at 28 days, defined as the period from the first day of assigned treatment to 28 days) was estimated using a Cox proportional hazards regression model, including trials as random effect. Corticosteroid treatment significantly decreased risk of death within 28 days compared with controls (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.48–0.86) or to pentoxifylline (HR 0.64; 95% CI 0.43–0.95). In multiple-imputation and complete case analyses, the effect of corticosteroids compared with controls remained significant. When we compared corticosteroids vs pentoxifylline, the corticosteroid effect remained significant in the complete case analysis (HR 0.66; P = .04) but not in multiple-imputation analysis (HR 0.71; P = .08). There was no difference in 28-day mortality when patients were given a combination of corticosteroids and pentoxifylline vs corticosteroids alone or between patients given pentoxifylline vs control. In our analysis of secondary outcomes, we found no significant differences in 6-month mortality when any treatments or controls were compared. Corticosteroids were significantly associated with increased response to therapy compared with controls (relative risk 1.24; 95% CI 1.10–1.41) or pentoxifylline (relative risk 1.43; 95% CI 1.20–1.68). We found no difference in response to therapy between patients given a combination of corticosteroids and pentoxifylline vs corticosteroids alone or pentoxifylline vs controls. In a meta-analysis of 4 controlled trials, we found corticosteroid use to reduce risk of death within 28 days of treatment, but not in the following 6 months. This loss of efficacy over time indicates a need for new therapeutic strategies to improve medium-term outcomes.
The association of non-alcoholic fatty liver disease (NAFLD) with several other diseases has gained increased interest during the recent years. Among them, the association with chronic kidney disease (CKD) has emerged as an important one regarding both its prevalence and significance. The early recognition of this association is important for the prognosis of patients with NAFLD and CKD. Apart from early diagnosis, the accurate assessment of renal function is also crucial in the clinical practice of hepatologists. Several methods have been used in the literature for the evaluation of kidney function in patients with NAFLD up to now. In this respect, calculators (or formulas) for the estimation of Glomerular Filtration Rate (eGFR) and Albumin to Creatinine Ratio (ACR) are simple, practical and easily available methods for this purpose. The aim of this review is to report on the epidemiology and pathophysiology of the relationship between NAFLD and CKD and to describe the different methods of kidney function assessment in patients with NAFLD. The collection of all relevant data regarding this association will provide hepatologists with pertinent knowledge on this topic and allow them to use the most accurate methods for the assessment of kidney function in these patients in their clinical practice.
Hepatocellular carcinoma (HCC) is an aggressive tumor that frequently develops in patients with primary biliary cirrhosis (PBC). We determined the mortality of patients with PBC who develop HCC, and which interventions (surgery, radiofrequency ablation, chemoembolization, alcohol injection, or transplantation) increase survival times. We investigated whether the Milan criteria predict outcomes of these patients and are effective in selection for liver transplantation. We evaluated data from 38 patients who had a confirmed diagnosis of PBC and HCC between March 1993 and February 2011. Patients were grouped based on whether or not they met the Milan criteria. Survival was assessed using the Kaplan-Meier analysis. Eighteen of the 38 patients (47.3%) died during the follow-up period; 49.4% survived for 5 years and 31.7% survived for 10 years. Thirty-five patients (92.0%) underwent one or a combination of interventions. Liver transplantation improved survival (risk ratio, 0.06; P < .0001), whereas surgery approached significance in causing deterioration (risk ratio, 2.87; P = .07). Mortality did not appear to be affected by meeting the Milan criteria (P = .84). Five- and 10-year survival times for patients with PBC who developed HCC were 49.4% and 31.7%, respectively. Patients who meet the Milan criteria receive liver transplantation as often as those who do not; we did not observe a difference in survival time between groups. Patients with PBC who develop HCC appear to benefit from aggressive therapies.
Nonalcoholic fatty liver disease (NAFLD) is highly associated with insulin resistance (IR), type 2 diabetes mellitus and metabolic syndrome, being characterized as the hepatic component of metabolic syndrome. Despite its high prevalence, no pharmacological treatment has been established, as of yet. A growing body of evidence, however, shows that reducing IR can result in improvement of the biochemical and histological features of nonalcoholic steatohepatitis (NASH)-the aggressive form of NAFLD that can lead to cirrhosis and hepatocellular carcinoma. Unfortunately, the several trials that have assessed the effect of various antidiabetic agents to date have failed to establish an effective and safe treatment regimen for patients with NAFLD. Glucagon-like peptide-1 (commonly known as GLP-1) agonists are a novel class of antidiabetic drugs that improve insulin sensitivity and promote weight loss. They also appear to have a direct effect on the lipid metabolism of hepatocytes, reducing hepatic steatosis. Several trials have demonstrated that GLP-1 agonists can reduce aminotransferase levels and improve liver histology in patients with NAFLD, suggesting that these agents could serve as an alternative treatment option for these patients. This manuscript discusses the role and potential mechanisms of GLP-1 agonists in the treatment of NASH.
Objectives: The aim of this study was to evaluate retrospectively the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, epidemiological parameters, and the clinical data from the antiviral treatment of hepatitis C in a large cohort of intravenous drug users (IDUs) followed-up from 1994 until 2008. Patients and Methods: A total of 1179 former IDUs followed up either in the liver unit or in the context of a substitution program organization were included in this study. A retrospective chart review was prepared to retrieve data on the patients' demographic characteristics, the prevalence of viral hepatitis, and information on HCV treatment. Results: The prevalence of HBsAg positive was 5%. A substantial number of patients were anti-HCV positive (847/1170, 73%), 189 were lost to follow-up, 526 (80%) were HCV RNA positive and 132 (20%) had a self-limited disease. The most prevalent genotype was 3 (59.7%). Twenty-five percent of the study population received antiviral treatment against HCV infection. Patients seen in the Liver Unit were more likely to receive antiviral treatment. The sustained virological response (SVR) was 80% with patients treated with pegylated interferon and ribavirin having a significantly higher SVR rate. Conclusions: Our results show that (a) the majority of IDUs in Greece have chronic hepatitis C and the prevalent genotype is 3 (b) patients who complete therapy have SVR rates similar to those without drug-dependence, and (c) since IDUs constitute the core of the hepatitis C epidemic and the main route of HCV transmission, efforts to treat these patients should be made.