Real‐world re‐treatment outcomes of direct‐acting antiviral therapy failure in patients with chronic hepatitis C

Abstract

Direct‐acting antiviral (DAA) drugs are associated with high (>95%) sustained virological response at 12 weeks (SVR12) in chronic hepatitis C (CHC) patients. There is a paucity of data regarding the characteristics and re‐treatment outcomes of DAA treatment failure patients. In a retrospective analysis of the prospectively collected database, we assessed the outcomes of re‐treatment among patients with previous DAA failure. Patients' characteristics, viral characteristics, including resistance‐associated substitutions (RAS) in a subgroup of patients, SVR12, and clinical outcomes were studied. Of 40 patients with DAA failure, among whom 36 were retreated, mean age was 45.7 years, 63.9% (n = 23) were male, 63.9% (n = 23) had a genotype‐3 infection and 63.9% (n = 23) were cirrhotic. The re‐treatment regimens included a combination of pan‐genotypic DAA, mainly sofosbuvir and velpatasvir with or without ribavirin. Three patients who declined retreatment and one who was still on treatment was excluded. For patients who completed re‐treatment, SVR12 was 100% irrespective of genotypes. SVR12 among genotype 3 was 75% (15 of 20) when lost to follow‐up was considered a treatment failure. Six patients died due to liver‐related causes, including five (83.3%) with hepatocellular carcinoma. RAS analysis in 17 randomly selected patients did not reveal any dominant substitutions in NS5A or NS5B region affecting SVR12, though several novel mutations were observed. In conclusion, re‐treatment of CHC patients with prior DAA failure using pan‐genotypic DAA is associated with high SVR12 rates irrespective of genotype or the presence of RAS.

Comments on “Real‐world re‐treatment outcomes of direct‐acting antiviral therapy failure in patients with chronic hepatitis C”

“…Of them, 62 ( were lost to follow-up, while the last was still on treatment at the time of analysis. 1 Our findings in a large multicenter cohort confirm that the risk of nonadherence to the retreatment schedule is high in patients with previous VF. Patients with previous VF are a hard-to-treat population.…”

Retreatment of patients with chronic hepatitis C, subtype 3a, and cirrhosis, who previously failed a regimen containing second-generation NS5A inhibitors with sofosbuvir + glecaprevir/pibrentasvir and ribavirin for 16-24 weeks

“…These very emerging mutations are most often registered, with more than 80% resistance, in patients with HCV subtype 3a in case of failure of the most commonly used second -generation DAAs treatment regimens:, SOF/VEL, and GLE/PIB [31,32,33]. As mentioned above, the most common cause of failures of DAA treatment are RASs in the NS5А region, with A30K, L31M and Y93H being the most signi cant of them.…”

Effects of comorbid conditions and prescribed chronic medications on the treatment plan for chronic hepatitis C infection: A cross‐sectional retrospective study

“…These findings suggest that despite the challenges posed by cirrhosis, tailored treatment approaches using specific DAAs can still yield favorable outcomes in terms of achieving sustained virological response. 22 , 23 , 24 , 25 …”