The effect of alanine aminotransferase dynamics on predicting sustained virological response in chronic hepatitis C virus infection

which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The sustained virological response (SVR) of the combination of both pegylated interferon alfa (PegIFN) and ribavirin (RBV) in patients with chronic hepatitis C virus (HCV) infection is heterogeneous. 1 The therapeutic approach has been more individualized to obtain the better outcomes of patients with chronic HCV infection, and clinicians need to know the factors for predicting SVR. 2 The viral factors are HCV genotype and serum HCV RNA levels at baseline, and numerous host factors include age, sex, race, weight, liver fibrosis, and insulin resistance. 1 Recently, an interleukin-28 polymorphism has been acknowledged as powerful pretrea-tment predictor of SVR. 3,4 Once treatment is initiated, the monitoring of on-treatment viral responses such as rapid virological response (RVR) and early virological response (EVR) can further aid in predicting treatment response. 5 However, there was little data evaluated the relationship between on-treatment ALT changes and therapeutic outcome of PegIFN and RBV in chronic HCV. Kim et al 6 reported interesting evidence showing that the rapid normalization of serum ALT after start of treatment may play an additional role on predicting SVR. Serum ALT levels are usually elevated in patients with chronic HCV, but more than half of patients may have a normal ALT level at some point due to its fluctuation. 7 In patients with persistently normal ALT levels, the median ALT levels remains stable for prolonged period, but transient elevations occur about 50% of cases. 8 Sustained normal serum ALT levels were associated with female, lower serum HCV RNA titer, and less inflammation and fibrosis on biopsy. 8 During chronic infection, serum HCV RNA levels remain relatively constant without significant fluctuation in untreated individuals. 9 This suggests that the process of viral production and clearance has been relatively balanced. To investigate the effect ALT dynamics on SVR, we need to know the relationship with viral kinetics. Viral kinetic profiles show that the appearance of HCV RNA after initiation of standard therapy can be biphasic in the first 4 weeks. 10,11 The final slope reflects the net loss of infected cells, and a rapid loss of infected cells is strongly associated with end treatment of response and SVR. 12,13 Serum ALT, a surrogate marker of hepatocyte damage or death, decreases during antiviral treatment, and shows the lowest activity at the end of treatment. 14 The …