Retreatment of patients with chronic hepatitis C, subtype 1b and cirrhosis, who failed previous direct-acting antiviral therapy including first- and second-generation NS5A inhibitors with ombitasvir/paritaprevir/ritonavir, dasabuvir + sofosbuvir + ribavirin.

The use of direct-acting antiviral agents (DAAs) in patients with chronic HCV genotype 1 infection results in sustained virologic response (SVR) rates of 95%-97%, but 3%-5% of patients experience virologic failure. We observed 17 patients infected with HCV subtype 1b who failed previous treatment with DAA, including 13 subjects (76.5%) with liver cirrhosis. Twelve subjects (70.6%) previously received NS5A inhibitors of the first generation (ledipasvir or daclatasvir) and five subjects (29.4%) - the second generation (velpatasvir). All patients were retreated with a combination of ombitasvir/paritaprevir/ritonavir and dasabuvir (3D) with sofosbuvir (SOF) and ribavirin (RBV). We compared SVR12 rates depending on fibrosis stage, presence of just single or double NS5A mutations (L31M/V/I and/or Y93H), and on the generation of previously used NS5A inhibitor. Observed SVR12 rates were as follows: 94.1% (16/17 patients) overall; 100% in patients without cirrhosis (n = 4) vs 92.3% in those with cirrhosis (n = 13); 100% with single L31M/V/I or Y93H mutation (n = 7) vs 88.9% with double mutations (n = 9); 100% in patients who previously failed first generation (n = 12) vs 80.0% in those failed second-generation NS5A inhibitors (n = 5). Retreatment with 3D + 0SOF + RBV was highly effective and safe in patients with chronic HCV GT1b infection who failed previous use of NS5A inhibitors. Fibrosis stage, baseline presence of NS5A RAS mutations and the generation of previously used NS5A inhibitors may impact the probability of achieving SVR12 , but statistical significance was not demonstrated in our small retrospective cohort. Further studies in a larger population are needed to confirm or not the predictive value of these baseline factors.

IL-28B genetic variation, gender, age, jaundice, hepatitis C virus genotype, and hepatitis B virus and HIV co-infection in spontaneous clearance of hepatitis C virus.

BACKGROUND/AIMS: Spontaneous viral clearance observed in some patients is one of the variants of the hepatitis C virus (HCV) infection natural history. We aimed to look at the complexity of factors affecting the spontaneous clearance of HCV (SC HCV). MATERIALS AND METHODS: A total of 357 anti-HCV positive patients (309 with chronic hepatitis C and 48 patients with SC HCV) were included into the study. We studied the effects of the interleukin-28B (IL-28B) gene polymorphism, gender, age, the routes of virus transmission, past hepatitis C with jaundice, HCV genotype, and hepatitis B virus (HBV) and HIV co-infection on the outcome of HCV infection. RESULTS: Based on the study results, the SC HCV was found in 48 individuals (13.4%). The most significant positive factors affecting the SC HCV included IL-28B single nucleotide polymorphism (SNP) rs12979860 (CC) and SNP rs8099917 (TT) (OR 4.03, p<0.001) and (OR 3.14, p<0.002), female gender (OR 2.72, p<0.001), young age (OR 2.30, p<0.008), and past history of jaundice (OR 5.12, p<0.001). The markers of a past HBV infection were found significantly more often in SC. CONCLUSION: Positive predictors of the SC HCV include favorable IL-28B genotype, female gender, young age, a history of jaundice, markers of a past HBV infection, the absence of HIV infection, but not the viral genotype.