Determining the lower limit of detection required for HCV viral load assay for test of cure following direct-acting antiviral-based treatment regimens: Evidence from a global data set.

Achieving global elimination of hepatitis C virus requires a substantial scale-up of testing. Point-of-care HCV viral load assays are available as an alternative to laboratory-based assays to promote access in hard to reach or marginalized populations. The diagnostic performance and lower limit of detection are important attributes of these new assays for both diagnosis and test of cure. Therefore, our objective was to determine an acceptable LLoD for detectable HCV viraemia as a test for cure, 12 weeks post-treatment (SVR12). We assembled a global data set of patients with detectable viraemia at SVR12 from observational databases from 9 countries (Egypt, the United States, United Kingdom, Georgia, Ukraine, Myanmar, Cambodia, Pakistan, Mozambique) and two pharmaceutical-sponsored clinical trial registries. We examined the distribution of HCV viral load at SVR12 and presented the 90th, 95th, 97th and 99th percentiles. We used logistic regression to assess characteristics associated with low-level virological treatment failure (defined as <1000 IU/mL). There were 5973 cases of detectable viraemia at SVR12 from the combined data set. Median detectable HCV RNA at SVR12 was 287,986 IU/mL. The level of detection for the 95th percentile was 227 IU/mL (95% CI 170-276). Females and those with minimal fibrosis were more likely to experience low-level viraemia at SVR12 compared to men (adjusted odds ratio AOR = 1.60 95% confidence interval [CI] 1.30-1.97 and those with cirrhosis (AOR = 1.49 95% CI 1.15-1.93). In conclusion, an assay with a level of detection of 1000 IU/mL or greater may miss a proportion of those with low-level treatment failure.

Recurrence of hepatitis C virus (genotype 4) infection after living-donor liver transplant in Egyptian patients.

OBJECTIVES: The recurrence of hepatitis C virus infection after liver transplant is common and may endanger both graft and patient survival. We investigated the frequency and outcome of and risk factors for the recurrence of that virus after living-donor liver transplant in hepatitis C virus positive recipients. MATERIALS AND METHODS: Seventy-four adult hepatitis C virus positive subjects were monitored for 36 months after living-donor liver transplant and demographic and laboratory data for the recipients and donors were evaluated. Recurrent hepatitis C virus infection was diagnosed on the basis of viral replication revealed by polymerase chain reaction after transplant, elevated levels of transaminases, and the results of liver biopsy. RESULTS: Hepatitis C virus recurrence was identified in 31.1% of the patients studied. Histopathologic recurrence was mild, and 91% of the subjects had a fibrosis score of < or = F2. No recipient exhibited cirrhosis or clinical decompensation during followup. Recurrent hepatitis C virus infection was associated with pretransplant and posttransplant viral load and antibody positive to hepatitis B core antigen. No other risk factors (sex, donor or recipient age, pretransplant Child-Pugh or Model for End-Stage Liver Disease scores, immunosuppressive drug therapy, and treatment with pulse steroids) were significantly correlated with the frequency of hepatitis C virus recurrence, the grade of the histologic activity index, or the stage of fibrosis. CONCLUSIONS: In living-donor liver transplant recipients, patient and graft survival rates associated with hepatitis C virus (genotype 4) related cirrhosis were comparable to those in deceased-donor liver transplant recipients reported in the literature. Recurrent infection with hepatitic C virus after living-donor liver transplant was mild. After transplant, a higher viral load and the presence of antibody to hepatitis B core antigen could be risk factors for hepatitis C virus recurrence. Long-term follow-up in a large number of patients is required.