Elevated ALT Following Hepatitis C Treatment May Indicate Treatment Failure

Patients with increased concentrations of alanine transaminase (ALT) following antiviral treatment for hepatitis C virus (HCV) infection may be experiencing treatment failure, according to study results presented at IDWeek 2022, held from October 19 to 23, in Washington, DC.

Nucleic acid testing is necessary to confirm sustained virologic response achievement after antiviral therapy in patients with HCV infection. This testing modality is expensive, making it unfeasible in some under-resourced settings.

This study sought to assess whether evaluating markers of liver function may be a cost-saving approach for identifying patients who should undergo nucleic acid testing. Data were sourced from the HCV treatment shortening study SEARCH, which was conducted in Vietnam. Patients (n=46) receiving direct-acting antiviral therapy for HCV infection were evaluated for changes in ALT and aspartate aminotransferase (AST) from the end of therapy to 12 weeks. Findings from the primary analysis were confirmed by evaluating a cohort of patients (n=193) who were included in STOP-HCV, a second HCV treatment shortening study that was conducted in the United Kingdom.

In the Vietnam cohort, patients had infections of HCV genotypes 1 or 6. A total of 11 patients did not achieve a sustained virologic response. Stratified by cure status, ALT concentrations decreased by a median of 1 IU/L among patients (n=25) who achieved clinical cure compared with a median increase of 24 IU/L observed among those (n=11) who experienced treatment failure (P <.001).

Any increase in ALT following treatment completion was found to be associated with treatment failure, with HCV nucleic acid testing results showing a sensitivity of 100%, a specificity of 48%, and an area under the receiver operating characteristic curve score of 0.99.

Among the UK validation cohort, patients had infections of HCV genotypes 1 or 4. A total of 60 patients failed to achieve a sustained virologic response. At week 12 following treatment completion, ALT concentrations increased by a median of 1 IU/L among patients (n=133) who achieved clinical cure compared with a median increase of 45 IU/L among those (n=60) who experienced treatment failure.

This study may have been limited by the small sample sizes and differences in HCV genotype composition.

These data suggest “only around half of treated individuals require HCV RNA testing 12 weeks after end of treatment,” the researchers concluded.