bms-790052 and Hepatic-Encephalopathy

The Daclatasvir and Sofosbuvir combination therapy (SOF/DCV) has shown efficacy in patients with chronic hepatitis C in clinical trials.. To investigate the efficacy and safety of SOF/DCV for treatment of patients with hepatitis C-related liver cirrhosis genotype 4.. Multicentre study involving 551 patients with liver cirrhosis genotype 4; 432 naïve patients and 119 treatment-experienced patients. All patients received SOF (400 mg) and DCV (60 mg) daily in addition to weight-based ribavirin (RBV) for 12 weeks and when RBV is contraindicated the treatment duration was extended to 24 weeks.. Sustained virological response at 12 weeks after end of treatment (SVR12) rate was 92% in naïve cirrhotic patients and 87% in previous treated patients (by ITT analysis). Virological failure was infrequent, occurring in 42 patients (8%) overall. Thirty-two (6%) were non responders; and 10 (2%) cases were relapsers, 31 patients (7%) were CTP-A and 11 (13.3%) patients were CTP-B (by ITT analysis). The most common adverse events were anaemia, fatigue, headache, pruritus. Serious side effects were recorded mainly in CTP-B cirrhotic patients including HCC and hepatic encephalopathy.. The SOF/DCV combination therapy has proven efficacy and safety in treating patients with hepatitis C-related liver cirrhosis genotype 4 in a large cohort of patients in the real world.

Topics: Adult; Aged; Antiviral Agents; Carbamates; Drug Therapy, Combination; Female; Genotype; Hepacivirus; Hepatic Encephalopathy; Hepatitis C; Humans; Imidazoles; Liver Cirrhosis; Male; Middle Aged; Pyrrolidines; Ribavirin; Sofosbuvir; Sustained Virologic Response; Valine

Medical treatment of decompensated cirrhosis due to hepatitis C virus (HCV) remains a clinical challenge even in the era of direct-acting antiviral drugs (DAAs). We evaluated the efficacy and safety of DAAs in the management of HCV genotype 4-related decompensated cirrhosis.. The study included a treatment group (n = 160) composed of HCV patients with decompensated cirrhosis who received DAAs for 3 months and a matched control group (n = 80) who preferred not to receive DAAs, follow-up was for 24-31 months.. In treatment group; there were improvements in platelet count, albumin, CTP (p = 0.001) and MELD scores (p = 0.03), a significant reduction in the frequency of hepatic encephalopathy (HE). SVR was achieved in 90%. Hepatocellular carcinoma (HCC) developed in 10% (n = 18) within 6.8 ± 2.5 months after DAAs, survival was higher in the treated vs. the control group (28.9 ± 0.95 vs. 11.4 ± 2.2 months, p = 0.001). Liver volume by ultrasound at a cutoff 495 ml was predictive of complications after DAAs therapy mainly HCC and reduced survival with sensitivity 93.2%, specificity 72%.. HCV with decompensated cirrhosis and adequate liver volume had a 90% SVR with improved CTP&MELD and survival.. (NCT03547895).

Topics: Adult; Antiviral Agents; Ascites; Carbamates; Drug Therapy, Combination; Esophageal and Gastric Varices; Female; Hepatic Encephalopathy; Hepatitis C, Chronic; Humans; Imidazoles; Liver Cirrhosis; Male; Middle Aged; Patient Selection; Pyrrolidines; Quality of Life; Ribavirin; RNA, Viral; Severity of Illness Index; Sofosbuvir; Survival Rate; Sustained Virologic Response; Ultrasonography; Valine

The efficacy of direct-acting anti-viral (DAA) therapy in patients with a history of hepatocellular carcinoma (HCC) is unknown.. We prospectively evaluated whether previously treated HCC affects DAA efficacy in a large real-life cohort of cirrhotic patients.. From January to December 2015 all consecutive HCV mono-infected patients with cirrhosis and/or history of HCC attending 10 Italian tertiary liver centres were enrolled. Baseline characteristics and response to therapy were recorded. 1927 patients were enrolled (mean age: 62.1 ± 10.9 years; 1.205 males). Genotype 1 was the most frequent (67.9%) followed by genotypes 3 (12.4%), 2 (11.2%) and 4 (8.6%). 88.4% and 10.9% of cases were classified Child A and B, respectively, and 14 (<1%) cases were classified Child C. Ascites and hepatic encephalopathy occurred in 10.7% and 3.2% of patients, respectively. Varices were detected in 39.3% of patients. Suboptimal and optimal treatment was prescribed: 15.9% of patients received sofosbuvir/simeprevir, 33.4% sofosbuvir/ledipasvir, 20.2% a Viekirax + Exviera regimen, 15.7% sofosbuvir/ribavirin, 9.9% sofosbuvir/daclatasvir and 3.4% Viekirax; 1.3% of patients received an interferon-based regimen.. The sustained virologic response (SVR) rate at intention-to-treat analysis was 95.1%. It differed significantly across Child classes, that is, 96.3%, 86.1% and 71.4% Child A, B and C, respectively (P < 0.0001) and across genotypes (P = 0.002). The SVR rate did not differ between patients with (95.0%) and those without previous HCC (95.1%). At multivariable analysis, SVR was significantly associated with HCV genotype, Child class.. This large real-life study proves that the efficacy of DAA in cirrhotic patients is not impaired by successfully treated HCC.

Topics: Aged; Antiviral Agents; Benzimidazoles; Carbamates; Carcinoma, Hepatocellular; Cohort Studies; Drug Therapy, Combination; Female; Fluorenes; Genotype; Hepacivirus; Hepatic Encephalopathy; Hepatitis C, Chronic; Humans; Imidazoles; Interferons; Italy; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Prospective Studies; Pyrrolidines; Ribavirin; Simeprevir; Sofosbuvir; Sustained Virologic Response; Uridine Monophosphate; Valine