Highlights• HBV viral load is an important predictor of adverse outcomes in patients with chronic HBV (CHB).• Liver steatosis may co-occur with CHB but its effect on all-cause mortality and cancer has not been determined.• Liver steatosis is significantly associated with allcause mortality and cancer in patients with CHB.• The effect of liver steatosis on mortality and cancer is stronger than the effect of HBV viral load.• Patients with CHB and liver steatosis should be closely monitored, irrespective of their viral load.

Sustained virological response (SVR) results in reduced incidence of hepatocellular carcinoma (HCC) and mortality among chronic hepatitis C (CHC) patients with advanced fibrosis. Since both advanced fibrosis and liver steatosis (LS) may coexist in CHC patients, we evaluated their individual effects on a composite outcome of all‐cause mortality and HCC in CHC patients with SVR following direct‐acting antivirals (DAA) treatment. We retrospectively evaluated inception cohort of 515 CHC patients who achieved SVR following treatment with DAA, with a mean follow‐up of 24 months. Baseline liver fibrosis was assessed by transient elastography, and LS was validated by at least three independent ultrasonographic examinations. 211 of 515 patients (41%) had baseline LS. Patients with LS had a higher cumulative rate of all‐cause mortality and HCC at 2 years of follow‐up compared to patients without LS (15.75% and 2.79%, respectively, P < 0.001), although they did not have increased incidence of advanced fibrosis or cirrhosis. Consistently, multivariate analysis showed that LS was associated with a significant 7.5‐fold increased risk of all‐cause mortality and HCC (HR 7.51, 95% C.I 3.61‐13.36, P < 0.001) even upon adjustment to components of the metabolic syndrome, whereas advanced fibrosis showed only a trend towards statistical significance (HR 2.32, 95% C.I 0.97‐6.59, P = 0.06). In conclusion, LS is a major predictor of all‐cause mortality and HCC in patients who achieved SVR following DAA treatment regardless of fibrosis stage. These patients should be rigorously screened for HCC.

BackgroundLiver fibrosis predicts liver-related morbidity and mortality in patients with non-alcoholic fatty liver disease (NAFLD). Non-invasive scores correlate with the degree of liver fibrosis in these patients.Aims and methodsTo investigate the accuracy of noninvasive scoring systems in predicting long-term outcomes and cancer incidence of patients with NAFLD, we performed a single-center retrospective study of patients with biopsy proven NAFLD. Mean follow up period was 100 months. Outcomes included liver-related complications, hospitalizations, overall mortality and the development of any malignancies.Results32 patients had advanced fibrosis (F3-F4) per biopsy at baseline and 121 patients had mild to moderate fibrosis (F0-F2). Both advanced histologic fibrosis stage as well as higher non-invasive scores predicted repeated hospitalizations and longer hospitalization stays. In a multivariate analysis, liver fibrosis (p = 0.002), FIB-4 score (p<0.001), NFS (p<0.001) but not APRI score (p = 0.07) were predictors of overall mortality, and the occurrence of malignancies was associated with higher APRI (p<0.001), FIB-4 (p<0.001) and NFS (p = 0.008) scores, but not with advanced fibrosis, as determined by liver biopsy (p = 0.105).ConclusionsIn NAFLD patients, noninvasive scoring systems are good predictors of morbidity and mortality and may have an additive value in predicting the development of hepatic and extra-hepatic cancers.

The advent of direct-acting antivirals (DAAs) has transformed the landscape of hepatitis C virus (HCV) management. We aimed to prospectively (real-time) evaluate the feasibility of using a response-guided therapy approach, based on mathematical modeling of early viral kinetics, to reduce the duration of DAAs therapy. Patients were treated with DAAs according to the physicians’ preference. HCV was measured at baseline and at day 2 and weeks 1, 2 and 4 after treatment initiation. The primary endpoint was the proportion of patients with sustained-virological response (SVR) at 12 and/or 24 weeks post-treatment. Twenty-nine patients (mean age 54 ± 16, 44% females, 73% with HCV genotype 1), were enrolled and all completed therapy. Treatment duration was shortened in 11 of the 29 patients (38%). SVR was achieved in 28 of the 29 patients (97%). Relapse occurred post treatment in a single case of a non-cirrhotic male with genotype 3, who was treated with sofosbuvir/velpatasvir for 6 weeks. Virus sequencing did not identify baseline or treatment emergent resistance associated substitutions. Real-time mathematical modeling of early HCV kinetics can be utilized for shortening DAAs duration in approximately 40% of patients without compromising treatment efficacy. Clinical trial registration: ClinicalTrials.gov Identifier: NCT03603327.

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