Alcohol Abstinence Improves Prognosis Across All Stages of Portal Hypertension in Alcohol-Related Cirrhosis.

BACKGROUND AND AIMS: Alcohol-related liver disease is a leading cause of liver-related mortality. The effect of alcohol abstinence on the natural history of alcohol-related cirrhosis across distinct stages of portal hypertension has not been thoroughly investigated. In this study, we assessed the clinical implications of abstinence in patients with alcohol-related cirrhosis and clinically significant portal hypertension. METHODS: Alcohol abstinence, hepatic decompensation, and mortality were assessed in patients with alcohol-related cirrhosis who underwent a baseline hepatic venous pressure gradient (HVPG) measurement and were diagnosed with clinically significant portal hypertension (HVPG ≥10 mm Hg). RESULTS: A total of 320 patients with alcohol-related cirrhosis (median age: 57 [interquartile range (IQR), 49.7-63.1] years; 75.6% male; 87.5% decompensated) and a median HVPG of 20 (IQR, 17-23) mm Hg were followed up for a median of 36 (IQR, 14-80) months. Overall, 241 (75.3%) patients remained abstinent, while 79 (24.7%) patients had active alcohol consumption. Alcohol abstinence was linked to a significantly reduced risk of hepatic decompensation (adjusted hazard ratio [aHR], 0.391; P < .001), as well as liver-related (aHR, 0.428; P < .001) and all-cause (aHR, 0.453; P < .001) mortality, after adjusting for baseline HVPG, MELD, and previous decompensation. Importantly, alcohol abstinence significantly reduced the cumulative incidence of hepatic decompensation in both groups with HVPG 10-19 mm Hg (P < .001) and HVPG ≥20 mm Hg (P = .002). The 3-year decompensation probability was 32.4% vs 60.0% in HVPG 10-19 mm Hg and 57.5% vs 82.6% in HVPG ≥20 mm Hg for abstinent patients vs active drinkers, respectively. CONCLUSIONS: Alcohol abstinence improves prognosis across all stages of portal hypertension in alcohol-related cirrhosis, including in patients who have already progressed to high-risk portal hypertension. (ClinicalTrials.gov, Number: NCT03267615).

Early virologic response and IL28B polymorphisms in patients with chronic hepatitis C genotype 3 treated with peginterferon alfa-2a and ribavirin.

BACKGROUND & AIMS: Polymorphisms of the IL28B gene (rs12979860 and rs8099917) are associated with high sustained virological response (SVR) rates in HCV genotype 1 patients. This study analyzes the impact of these IL28B polymorphisms on early treatment response (weeks 2 and 4) and SVR in HCV genotype 3 patients. METHODS: rs12979860 and rs8099917 were analyzed by the Step-OnePlus Real-time PCR system in 71 out of 72 Caucasian HCV genotype 3 patients participating, at our center, in a randomized study comparing 400mg with 800 mg ribavirin/day. HCV RNA was determined at weeks 2 and 4 of 180 µg/week peginterferon alfa-2a/ribavirin treatment. Sixty-nine patients completed the treatment and follow-up. RESULTS: rs12979860 genotyping revealed that 27 (37.5%) patients had C/C, 39 (54.2%) T/C, and 5 (6.9%) T/T. Thirteen patients (18.1%) became HCV RNA negative at week 2 and an additional 30 (41.7%) at week 4 (rapid virologic response; RVR); thus a total of 43 had a RVR (C/C: 77.8%; T/C or T/T: 50.0%). Irrespective of the ribavirin dose, the viral load decline was larger than in those with the T allele (T/C or T/T) (week 2: 4.46; [0.36-6.02] median; [range] vs. 3.50; [0.14-5.62]; log IU HCV-RNA/ml; p<0.001; week 4: 4.97; [1.21-6.20] vs. 4.49; [1.16-6.23]; p=0.003). Despite the faster initial viral response in C/C carriers, SVR rates were not different compared to T-allele carriers. Results of the SNP in the rs8099917 region were similar. CONCLUSIONS: IL28B polymorphisms modulate early virologic response to peginterferon/ribavirin treatment. In contrast to HCV genotype 1 patients, no effect on SVR rates was observed in genotype 3 patients. The clinical relevance of an earlier viral decline in C/C patients needs to be determined.