Effectiveness and safety of daclatasvir/sofosbuvir with or without ribavirin in genotype 3 hepatitis C virus infected patients. Results in real clinical practice.

OBJECTIVE: Direct-acting antivirals have shown high efficacy in all hepatitis C virus (HCV) genotypes, but genotype 3 (G3) treatments continue to be a challenge, mainly in cirrhotic patients. The aim of this study is to analyse effectiveness and safety of daclatasvir associated with sofosbuvir with or without ribavirin in G3-HCV infected patients in real clinical practice. METHODS: An observational, prospective, cohort study over 2.5 years, in G3-HCV infected adult patients, in all fibrosis stages including patients with decompensated cirrhosis. Treatment was a combination of sofosbuvir 400 mg/day + daclatasvir 60 mg/day, with or without a weight-adjusted dosing of ribavirin for 12 or 24 weeks. The primary efficacy endpoint was sustained virologic response rates 12 weeks after therapy (SVR12). The primary safety endpoint was treatment withdrawal rates secondary to severe adverse events. RESULTS: A total of 111 patients were enrolled, 32.4% cirrhotics and 29.9% treatment-experienced. The global SVR12 rate was 94.6%, while the SVR12 rate in F3-4 fibrosis stage patients was 90.8% versus 100% in patients with F0-2 fibrosis (p=0.03). In cirrhotic patients, SVR12 was 100% versus 40% depending on whether ribavirin was added or not to daclatasvir/sofosbuvir (p=0.001). No other patient or treatment basal variables influenced the treatment effectiveness. No patient treatment withdrawal secondary to severe adverse events was observed. CONCLUSIONS: Daclatasvir/sofosbuvir ± ribavirin is highly effective in G3-HCV infected patients. Advanced degrees of fibrosis significantly decrease the effectiveness of this treatment, which motivates the need for the addition of ribavirin in cirrhotic patients. The regimen was safe and well tolerated.

Liver-related mortality and hospitalizations attributable to chronic hepatitis C virus coinfection in persons living with HIV.

OBJECTIVES: The aim of this study was to compare liver-related mortality and liver-related hospitalizations for persons living with HIV (PLWH) with and without hepatitis C virus (HCV) exposure, and to estimate the fraction of liver disease attributable to chronic HCV coinfection. METHODS: An ambispective cohort study followed PLWH between 1993 and 2014. PLWH were classified into three groups: those who were HIV-monoinfected, those who cleared HCV spontaneously and those with chronic HCV coinfection. Liver-related mortality was estimated for the three groups and compared with the adjusted standardized mortality ratio. RESULTS: Data for 2379 PLWH were included in the study (1390 monoinfected individuals, 146 spontaneous HCV resolvers and 843 with chronic HCV coinfection). Global mortality was 33.8%, 21.4% of which was liver-related. Patients who died from liver-related causes were mostly on antiretroviral therapy and had an undetectable HIV viral load when they died. The liver-related mortality rate in those with chronic HCV coinfection was 10.01 per 1000 patient-years vs. 3.84 per 1000 patient-years in the HIV-monoinfected group (P < 0.001). The adjusted standardized mortality ratio in the chronically HCV-coinfected group was 4.52 (95% confidence interval 2.98-5.86). The fractions of liver-related mortality and liver-related hospitalizations attributable to chronic HCV coinfection were 0.61 and 0.74, respectively. There were no differences in liver-related events between HIV-monoinfected individuals and those who spontaneously cleared HCV. CONCLUSIONS: Chronic HCV infection increases the risk of liver-related mortality and liver-related hospitalizations in PLWH, despite good control of HIV infection. Sixty per cent of liver-related mortality in chronically HCV-coinfected PLWH could be attributable to chronic HCV infection. The effect of mass HCV eradication with new therapies should be evaluated.