Suspected de novo Hepatitis B in a Patient Receiving Anti-Tumor Necrosis Factor Alpha Therapy for the Treatment of Crohn's Disease
A 41-year-old woman had abdominal pain, diarrhea and fever in July 2006. Because of persistent symptoms, she was hospitalized in August 2006. A cobblestone-like appearance was seen in the sigmoid colon upon colonoscopy. On the basis of the results of detailed examination, she was diagnosed as having colonic CD. Since she had severe CD with a Crohn's disease activity index (CDAI) of 373 and needed prompt and effective treatment, treatment with IFX at 5 mg/kg and 6-mercaptopurine (6-MP) at 30 mg/day was initiated in September 2006. Laboratory findings at the initiation of treatment included an aspartate transaminase (AST) level of 22 IU/l, an alanine transaminase (ALT) level of 22 IU/l and negative HBsAg. She was not tested for anti-HBsAb and anti-HBcAb. At week 10 of IFX therapy, symptoms were alleviated (CDAI: 56), and remission was successfully induced. IFX was administered at weeks 0, 2 and 6 and every 8 weeks thereafter, and remission was successfully maintained. Colonoscopy about 1 year after the initiation of treatment revealed colonic mucosal healing with scarring. However, about 1 year after the initiation of IFX therapy, she began to experience delayed-onset hypersensitivity reactions to IFX such as fever and joint pain. We thus considered switching biologic therapy from IFX to ADA. On October 8, 2010, 4 years and 1 month after the first administration of IFX, the 30th and final administration of IFX was given, and her hepatic function was normal (AST 16 IU/l, ALT 21 IU/l). On December 12, 2010, hepatic function test immediately before the first administration of ADA revealed mild hepatic dysfunction (AST 61 IU/l, ALT 54 IU/l). Since no abnormal hepatic function had been found before and the cause was unknown, she received 160 mg of ADA on that day and was followed up thereafter. On December 17, 2010, although hepatic enzyme levels were still high, she received 80 mg of ADA.\nOn January 4, 2011, since she felt generalized malaise with an AST of 322 IU/l and an ALT of 527 IU/l, she was hospitalized for detailed examination and treatment (fig. ). Examinations revealed HBsAg of 250 IU/ml and HBV DNA of >9.0 log copies/ml. HBV genotype was type C, and anti-hepatitis C virus antibody (anti-HCVAb) was negative (table ). Virological testing of a sample obtained from her husband revealed negative results for HBsAg and anti-HBcAb and no detection of HBV DNA. Sexual transmission of HBV from her husband and others was ruled out. Abdominal echo and computed tomography examination showed no evidence of chronic hepatic disorder. Liver biopsy revealed mild fibrosis (A2/F1). These findings supported the presence of hepatic disorder due to HBV. Although no data on HBV DNA and anti-HBcAb before onset were available, her clinical course suggested de novo hepatitis B due to reactivation of HBV related to the treatment with IFX and 6-MP.\nOn January 5, 2011, antiviral treatment with ETV at 0.5 mg/day was initiated. Treatment with ADA was suspended after the first two administrations, but treatment with 6-MP was continued. Ten sessions of granulocytapheresis were conducted to maintain remission of CD. AST and ALT levels peaked at 440 IU/l and 624 IU/l, respectively, on January 14, 2011, and then decreased gradually over time. On March 29, 2011, hepatic function returned to normal (AST 30 IU/l, ALT 24 IU/l). Since negative HBV DNA results were obtained in June 2011, treatment with ADA was reintroduced (fig. ). Since then she has continued treatment with ETV and has maintained normal levels of AST, ALT and HBV DNA without recurrence of hepatitis B. 10 months after treatment with ETV, her anti-HBsAb turned positive. She has also continued ADA and has maintained mucosal integrity and clinical remission without gastrointestinal symptoms.