Our current study is the first to identify that HCV infection may influence methadone metabolism, particularly S-methadone metabolism. Our findings suggest that methadone dosage adjustment should be considered in HCV-infected patients in an MMT program. HCV infection may affect the liver functional enzymes toward of AST and ALT, but not ��-GT. In our present experiments, we also found that HCV antibody-positive MMT patients had higher AST and ALT levels than HCV antibody-negative patients. The liver is the primary target of HCV infection and the extent of damage to hepatocytes has been found to closely correlate with serum markers such as, AST and ALT [32]�C[35]. HCV infection has also been reported to be associated with the release of AST, ALT, and ��-GT [35]�C[37].

This may be the reason why AST and ALT were found to be significantly increased in the HCV antibody-positive patients in our current cohort. The ��-GT levels are mainly correlated with alcohol use [38], [39]. There were no differences found in our current analyses in the percentage of alcohol users between the HCV antibody-positive and HCV antibody-negative patient groups. This may be the reason why ��-GT failed to show a higher serum level in these MMT patients. When further subgrouping the severity of the liver��s infectious status among the HCV antibody-positive patients, it was found that the AST/ALT ��1 group of MMT patients had a lower BMI, but a higher percentage of combined HIV infection than the AST/ALT<1 group. Using AST/ALT ��1 as an indicator for liver cirrhosis has had both supportive [40], [41] and non-supportive reports [42].

While the predictive accuracy of AST/ALT ��1 is still in question [43], it may be an useful indicator for combined HIV infection among HCV antibody-positive MMT patients. Although it is not clear that how HCV infection alters methadone metabolism, HCV- associated hepatic inflammation has been associated with a reduction in methadone dosage requirements [44]. In our current study, our multivariate regression data also indicated that the methadone dose correlates with HCV infection (Table 3) although the reason for this correlation remains unclear. We propose that the increase in CYP2B6 enzymatic activity may be one of the reasons. The limitations of our present study include the fact that 95% of the MMT patients in our cohort were HCV antibody-positive.

This may create a statistical imbalance, however a high HCV incidence is common in heroin-dependent-patients with reported ranges from 67% to 96% [3]. HCV antibody-positivity combined with HBV presence has been reported to cause severe damage to liver tissue [45], [46]. In our present study, this combined infection status did not affect methadone metabolism. This may AV-951 be because only three of our patients had a combined HCV antibody-negative and HBV antigen presence.