Hepatic Safety of Methotrexate in Rheumatoid Arthritis Patients with Hepatitis B Surface Antigen

Park, Yong Wook; Park, Jae Hong; Bae, Yun Sang; Kim, Tae Hwan; Jun, Jae Bum; Jung, Sungsoo; Bae, Sang Cheol; Kim, Seong Yoon; Yoo, Dae Hyun

Abstract

OBJECTIVE
To investigate the hepatic safety of methotrexate (MTX)and useful parameters to assess the risk of hepatotoxicity in rheumatoid arthritis (RA) patients with hepatitis B surface antigen (HBsAg).
METHODS
19 HBsAg positive (B group)and 54 HBsAg negative (non-B group)RA patients taking MTX were prospectively followed up for 2 years. Aspartate aminotransferase (AST)and alanine aminotransferase (ALT)were checked at 2-month interval.In B group,HBeAg,HBeAb and levels of hepatitis B virus DNA (HBV DNA)were additionally checked,and liver biopsy was performed in seventeen of 19 patients.Change of AST or ALT to more than 1.5 times the upper limit of normal were considered as a hepatic event.The data were analyzed by stepwise linear and logistic regression method.
RESULTS
The findings of liver biopsy in B group were classified as grade I (n=8),II (n=6),and IIIA (n=3)according to the Roenigk Classification Scale. Mean cumulative dose of MTX in B group was 2054mg in cases with hepatic event and 1780mg in cases who stopped taking MTX.The frequency of hepatic event (47.4%vs 7.4%,p=0.0001)and MTX withdrawal (26.3%vs 1.9%, p=0.0008)was higher in B group than in non-B group.HBV DNA (+)group (n=9)showed the increased tendency of hepatic event and MTX withdrawal compared with HBV DNA (-)group (n=10).Baseline HBV DNA was negative in all HBeAg (-)patients (n=14),but HBV DNA was positive during MTX therapy in 7 of 14 HBeAg (-)patients.Serum levels of AST and ALT returned to normal range within 2 months after MTX withdrawal in twelve of 13 patients with hepatic event.
CONCLUSION
The use of MTX in HBsAg positive RA patients requires close monitoring of AST and ALT.HBV DNA seems to be a useful marker to predict hepatic event and viral replication,especially in HBeAg (-)patients.