Purpose: Alanine aminotransferase (ALT) levels are monitored during the course of treatment for hepatitis C virus (HCV), although their utility to predict response remains unclear. According to a prior study, in which standard interferon and ribavirin were used, sustained virological response (SVR) did not correlate with early ALT normalization. We hypothesize that more potent treatments used currently for HCV may result in more profound declines of ALT levels, and therefore, better predict treatment outcomes. This study examines the trends of ALT throughout HCV treatment course, factors determining them, and their relationship with virological response. Methods: In this retrospective study, all HCV-infected patients from the hepatitis clinic of our hospital who completed HCV therapy from 2008 to 2013 were included. Patients were treated with pegylated interferon and ribavirin, with or without protease inhibitors (boceprevir or telaprevir), following the recommended futility rules. We collected ALT and HCV RNA data at weeks 0, 4, 12, 24, end of treatment, and 12 or 24 weeks post-treatment completion. ALT upper limit of normal was defined as 40 IU/mL. Chi-square was used to compare proportions and logistic regression to identify factors associated with early ALT normalization. Results: Seventy patients were included in the study. The majority was male (64%), Caucasian (74%), mean age of 52, with genotype 1 (64%), and underwent therapy without protease inhibitors (59%). SVR was achieved by 64% of patients. Fifty-three percent and 74% of patients had ALT normalization by week 4 and week 12, respectively. There was no significant difference in SVR between patients with and without ALT normalization by week 4 (69% vs. 59%, p=0.39) and by week 12 (67% vs. 53%, p=0.29). Similarly, there were no significant differences in the proportions of patients achieving undetectable RNA level between these two subgroups at week 4 (72% vs. 72%, p=0.98) and at week 12 (90% vs. 76%, p=0.17). Several patterns of ALT during treatment were observed; none of them reliably predicted SVR. Factors such as gender, race, genotype, high pretreatment RNA level, presence of steatosis, advanced fibrosis, and use of protease inhibitors were not associated with early ALT normalization. Conclusion: Normalization of ALT during HCV treatment course does not correlate well with on-treatment virological response, and is not a reliable predictor of SVR, with poor negative predictive value. Our data suggests that besides HCV replication, other individual factors not fully understood determine ALT levels during HCV treatment.
Read full abstract