Liver enzyme normalization predicts success of Hepatitis C oral direct-acting antiviral treatment

Sarwat T Khan, Michaeline McGuinty, Daniel J Corsi, Curtis L Cooper


Purpose: Monitoring of hepatitis C virus (HCV) treatment response is performed by serial HCV RNA measurements; however, this may not be useful for predicting treatment success or failure with oral direct-acting antiviral agent (DAA) therapies. Liver enzyme levels, which are elevated in chronic HCV and tend to decline on therapy, may serve as a more logistically and economically feasible alternative for monitoring treatment response.

Source: The Ottawa Hospital Viral Hepatitis Clinic patients (n=219), receiving interferon-free oral DAA treatments, were assessed for liver enzymes and HCV RNA levels at baseline, week 4 and ≥12 weeks post-treatment. Suppression cut points used for this analysis were ALT ≤ 40U L-1 and AST ≤ 30U L-1. The primary outcome was week 12 sustained virologic response (SVR). By our analysis, all indicators had strong PPV (>90%) but limited NPV (<25%).

Principal findings: Along with week 4 HCV RNA, AST ≤ 30U L-1 and AST:ALT ratio at week 4 were associated with SVR in univariate analysis with similar PPV and NPV to HCV RNA. ALT was not predictive of DAA outcome. In multivariate models, adjusting for cirrhosis and genotype, baseline AST:ALT ratio<0.9 (but none of the week 4 indicators) was significantly associated with SVR.

Conclusion: Our analysis suggests that enzyme levels (particularly AST and AST:ALT ratio) provide a viable alternative to HCV RNA, with robust predictive value in determining treatment success of DAA therapies.

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