Normalization of Alanine Aminotransferase Levels at the End of Treatment with Direct-Acting Antiviral Therapy for Chronic Hepatitis C Infection Is Associated with Sustained Virological Response

Abstract

Introduction: All oral treatment regimens for chronic Hepatitis C (HCV) infection offer high rates of sustained virological response(SVR) but there are no guidelines for on-treatment monitoring to predict SVR. The purpose of this study was to determine if alanine aminotransferase (ALT) levels during the treatment with direct acting antiviral therapy (DAA) predict response to treatment and if normalization of ALT at the end of treatment (EOT) predicts SVR. Methods: Charts of the patients treated with DAA's between February 2014 and September 2014 were reviewed. Patients with HCV genotype 1, 2 and 3 were included. Treatment regimens included sofosbuvir plus simeprevir or sofosbuvir plus weight based ribavirin for duration of 12 to 24 weeks. Age, gender, BMI, genotype (GT), +/- cirrhosis and prior treatment status were recorded. ALT levels were recorded pretreatment, at weeks 2, 4, 8, 12, 16, 24 or EOT and at 3 months' post treatment. HCV RNA levels were recorded pretreatment, week 4, EOT and at 3 months' post treatment. Normalization of ALT was defined as levels.Table 1: Association of End of Treatment Normalized ALT levels and HCV RNA levels at 3 months post treatmentTable 2: Association of End of Treatment Normalized ALT levels and HCV RNA levels at 3 months post treatment in patients with cirrhosisResults: 67 patients were treated with DAAs during the study period. 3 patients were excluded. 39 had HCV GT1 and 25 had HCV GT2 or 3 infection.Twenty-eight were cirrhotic. Normalization of ALT at week 4 did not predict the HCV suppression at the end of treatment (p=0.4). Overall, patients with normalized ALT level at the end of treatment had a 6-fold increase in the rates of SVR12 (p < 0.02). With each unit increase in the ALT at the end of treatment, patients were 14% less likely to achieve SVR12 (p=0.0009). Among patients with cirrhosis, normalized ALT level at the end of treatment was associated with 25-fold increase in the rates of SVR12 (p=0.04). With each unit increase in ALT, cirrhotic patients were 18% less likely to achieve SVR12 (p=0.009). In patients without cirrhosis ALT levels at the end of treatment did not predict SVR12. Conclusion: The ALT level at the end of treatment with DAA can help predict the SVR12, particularly in patients with cirrhosis. Increase in the ALT levels while on treatment or at the end of treatment should alert the physician of possible treatment failure.