Background and Aims: Ledipasvir/Sofosbuvir (LDV/SOF) with or without Ribavirin (RBV) has shown good results in terms of efficacy and safety in clinical trials in advanced liver cirrhosis, but real-life data are still needed in order to confirm this profile. We investigated the efficacy and safety of LDV/SOF in a large Romanian population with liver cirrhosis and genotype 1b hepatitis C virus (HCV). Methods: We analyzed a multicentric retrospective cohort enrolling 349 patients with decompensated liver cirrhosis due to HCV who received LDV/SOF±RBV 12/24 weeks (301/48). Patients were included between 2017-2018, all with genotype 1b. Main inclusion criteria were liver cirrhosis and detectable HCV RNA. The cases were followed-up monthly during therapy and 12 weeks after the end of therapy. Results: The cohort included 60% females with a median age of 61, 16% interferon (IFN) pre-treated, 53% with comorbidities, 40/53/7 % with Child Pugh A/B/C, 4% with virus B co-infection and 8% with previously treated hepatocellular carcinoma. Mean initial MELD score was 11.92 (6.82÷ 24.5). Six patients were lost during follow-up. Sustained virologic response (SVR) in intention-to-treat was reported in 85.1%. Predictive factors of SVR in decompensated cirrhosis were female gender (p=0.01), advanced age (p<0.001), lower bilirubin levels (p=0.002) and lower CTP score (p=0.02). In patients with CTP score B or C low bilirubin levels (p=0.003), low INR (p<0.001), increased platelet count (p=0.04), low CTP score (p<0.001), lack of encephalopathy (p=0.02), serum albumin >3.5g/dl (p=0.002) predicted improvement of liver function. Serious adverse events were reported in 16/349 (4.6%), most of them due to severe liver decompensation (9/16). Conclusions: LDV/SOF±RBV proved to be highly efficient in our difficult to treat population with 85.1% SVR.

The combination paritaprevir/ritonavir, ombitasvir, and dasabuvir (PrOD), which achieves a high sustained virologic response (SVR) rate and few side effects, has dramatically changed the outcome of hepatitis C virus (HCV) infection. The risk of hepatocellular carcinoma (HCC) and variceal bleeding in patients treated with interferon (IFN)free direct-acting antivirals (DAAs) is unknown. The aim of this prospective study was to evaluate the rate of HCC and variceal bleeding and identify prognostic factors for decompensation/complications in HCV-1b-infected patients with compensated liver cirrhosis following treatment with PrOD with or without ribavirin. Material and methods: A total of 483 HCV patients received PrOD treatment. Patients with a history of HCC were excluded from the study. Prior antiviral therapy was identified in 59% of patients. Patient data were collected at baseline, at the end of treatment (EoT), at 3 months after EOT (SVR) and during an 18-month surveillance period. Patients were divided into two age groups: <60 years (233 patients) and ≥60 years (250 patients). Results: The median observation period was 540 days. During this period, HCC developed in 18 patients (3.7%) and variceal bleeding developed in 9 patients (1.9%). A Propensity score matching analysis found no significant difference in the incidence of HCC (p= 0.078) or variceal bleeding (p=0.426) between the two groups. The mean serum AFP levels decreased in the young group (baseline=19.44 ng/dL, SVR=4.57 ng/dL) and the elderly group (baseline=4.52 ng/dL, SVR=10.69 ng/dL). Edge of decompensation and previous esophageal varices were significantly associated with the risk of variceal bleeding. Conclusions: The risk of HCC (5.3%) and variceal bleeding (2%) development in elderly patients (≥60years) following viral eradication by IFN-free DAA therapy may follow a specific pattern.