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Summary: Risk of hepatocellular carcinoma (HCC) in hepatitis C virus cirrhotic patients treated with direct‐acting antiviral agents (DAA) is still debating. We investigated it in a large cohort. The cohort comprised 1045 cirrhotic patients who completed treatment with DAA, with a median follow‐up of 17.3 months after end of treatment (EOT), including 943 patients without history of HCC and 102 previously treated for HCC. The majority were men (59.9%), with compensated cirrhosis (88.8%), genotype 1b (44.7%). Univariate, multivariate analysis and Kaplan‐Meier curves were performed to detect predictors of HCC in patients with and without reduction in alpha‐fetoprotein (AFP) during treatment. SVR12 was 95.6%. HCC developed in 95 (9.9%), including 54 of 943 (5.7%) occurrent and 41 of 102 (39%) recurrent tumours. De novo were more often unifocal (P = 0.01) and curable (P = 0.03). AFP decreased from 16.1 ± 36.2 mg/dL (baseline) to 11.4 ± 55 mg/dL (EOT). At univariate analysis, predictors were a previous HCC, older age, higher model for end‐stage liver disease, prolonged INR, lower platelets, baseline and EOT AFP, virological failure and no reduction in AFP during treatment. Kaplan‐Meier curves showed lower incidence of HCC in patients showing any reduction in AFP (P = 0.001). Those with AFP <6 ng/mL had the lowest risk (P = 0.0002). At logistic regression, platelets (P = 0.009, OR 0.99 CI: 0.99‐1.00), previous HCC (P < 0.000 01, OR: 10.76, 95% CI: 5.89‐19.34) and no reduction in AFP during treatment (P = 0.0005, OR: 2.98, CI: 1.60‐5.54) were independent predictors of HCC. In conclusion, risk of HCC after DAA treatment remains substantial. It is higher among patients with previous HCC, low platelets and without reduction in AFP during treatment. [ABSTRACT FROM AUTHOR]

Background & Aims The proportion of HCV-infected patients over age 65 years in Western countries is increasing. This growth and the advent of new antiviral therapy bring into the question the real-world efficacy and safety of the combination of sofosbuvir ( SOF) and simeprevir ( SMV) plus a flat dose of 800 mg/d ribavirin ( RBV) in elderly patients with cirrhosis compared to younger patients. Methods Retrospective observational multicentre real-life investigation study of SOF/ SMV/ RBV for a duration of 12 weeks in HCV genotype 1-infected patients with cirrhosis. Results Of the 270 patients enrolled in this study, with compensated cirrhosis, 133 (49.2%) were ≥65 years of age. Sustained virological response at 12 weeks ( SVR12) was achieved by 94.2% (129/137) of those aged <65 years and 97.7% (130/133) of those ≥65 years. Diabetes was the most common comorbidity in patients ≥65 years compared to younger patients (26.3% vs 12.4% P<.003). The most common adverse event ( AE) in elderly patients was a grade 2 anaemia (35.3% vs 19.9% P<.004). Conclusions Sofosbuvir/simeprevir plus a daily flat dose of RBV 800 mg for 12 weeks was highly effective and safe in genotype 1 elderly patients with compensated cirrhosis. [ABSTRACT FROM AUTHOR]

Background & Aims Despite the excellent efficacy of direct-acting antivirals ( DAA) reported in clinical trials, virological failures can occur, often associated with the development of resistance-associated substitutions ( RASs). This study aimed to characterize the presence of clinically relevant RASs to all classes in real-life DAA failures. Methods Of the 200 virological failures that were analyzed in 197 DAA-treated patients, 89 with pegylated-interferon+ribavirin (Peg IFN+ RBV) and 111 without ( HCV-1a/1b/1g/2/3/4=58/83/1/6/24/25; 56.8% treatment experienced; 65.5% cirrhotic) were observed. Sanger sequencing of NS3/ NS5A/ NS5B was performed by home-made protocols, at failure (N=200) and whenever possible at baseline (N=70). Results The majority of the virological failures were relapsers (57.0%), 22.5% breakthroughs, 20.5% non-responders. RAS prevalence varied according to IFN/ RBV use, DAA class, failure type and HCV genotype/subtype. It was 73.0% in IFN group vs 49.5% in IFN free, with the highest prevalence of NS5A- RASs (96.1%), compared to NS3- RASs (75.9% with IFN, 70.5% without) and NS5B- RASs (66.6% with IFN, 20.4% without, in sofosbuvir failures). In the IFN-free group, RASs were higher in breakthrough/non-responders than in relapsers (90.5% vs 40.0%, P<.001). Interestingly, 57.1% of DAA IFN-free non-responders had a misclassified genotype, and 3/4 sofosbuvir breakthroughs showed the major- RAS-S282T, while RAS-L159F was frequently found in sofosbuvir relapsers (18.2%). Notably, 9.0% of patients showed also extra target RASs, and 47.4% of patients treated with ≥2 DAA classes showed multiclass resistance, including 11/11 NS3+ NS5A failures. Furthermore, 20.0% of patients had baseline- RASs, which were always confirmed at failure. Conclusions In our failure setting, RAS prevalence was remarkably high in all genes, with a partial exception for NS5B, whose limited resistance is still higher than previously reported. This multiclass resistance advocates for HCV resistance testing at failure, in all three genes for the best second-line therapeutic tailoring. [ABSTRACT FROM AUTHOR]

Background/Aims: To evaluate, in clinical practice, the efficacy and safety of combined antiviral treatment in hepatitis C virus (HCV) carriers with normal alanine aminotransferase (ALT) levels. Methods: Eighty-eight HCV carriers with persistently normal ALT levels were enrolled. All patients received peginterferon (PEG-IFN) α-2a 180 μg once weekly plus ribavirin (RBV) 800 mg/day for 24 weeks (HCV-2 and -3) or 1000–1200 mg/day for 48 weeks (HCV-1). Results: Rapid virological response (RVR) was seen in 66/88 patients (75%): 19/32 HCV-1 (59%), 40/46 HCV-2 (87%) and 7/10 HCV-3 patients. Younger patients, leaner subjects and patients with non-1 genotype or lower baseline HCV RNA levels were more likely to achieve an RVR. Sustained virological response (SVR) was seen in 69/88 patients (78%): 20/32 HCV-1 patients (62%), 41/46 HCV-2 patients (89%) and 8/10 (80%) HCV-3 patients. The overall SVR rate was 88% in patients with RVR (58/66) and 50% in those without RVR. Conclusions: The combination of PEG-IFN α-2a and RBV produces, in patients with normal ALT, virological response rates that are comparable or even higher than those obtained in patients with elevated ALT levels. Thus, we suggest that in selected cases immediate therapy might be preferred to a ‘wait-and-see’ policy. [ABSTRACT FROM AUTHOR]

The article discusses a study on the relation of epicardial fat tissue and alanine aminotransferase (ALT) in patients with increased visceral fat. It notes that increased visceral adipose tissue (VAT) is a risk factor for an unfavorable cardio-metabolic profile and fatty liver. Based on the results, human immunodeficiency virus (HIV)-infected patients with metabolic syndrome (MS) showed higher magnetic resonance imaging (MRI)-VAT, waist circumference and epicardial fat thickness.

The article reports on research which was conducted to investigate the safety of sorafenib therapy in adults with advanced hepatocellular carcinoma. Researchers evaluated the use of sorafenib with 51 patients. They found that the drug was well tolerated and had a positive effect on quality of life in elderly patients with advanced hepatocellular carcinoma.