Precore mutant hepatitis B virus-associated fulminant hepatitis during infliximab therapy for rheumatoid arthritis
A 73-year-old female, with a 10-year history of RA, had been treated with prednisone (5–10 mg/day) and MTX (5–8 mg/week) for 10 and 6 years, respectively. These were ineffective, and infliximab (150 mg every 8 weeks, 3 mg/kg) was added between June 2004 and May 2005, with liver function tests at each infusion. A pretreatment screening test showed that HBsAg and HBcAb were positive, and hepatitis C virus antibody was negative. Liver tests and images showed no abnormalities. MTX and prednisone were tapered, and prednisone was withdrawn in April 2005. An effective clinical improvement of joint disease was observed, and C reactive protein became normal. After the eighth infusion of infliximab, the liver function was found to be abnormal (AST 291 IU/L (normal <40), ALT 331 IU/L (<40)), and MTX therapy was withdrawn. Her liver function progressively worsened (AST 1690 IU/L, ALT 1390 IU/L), and she was admitted to our hospital in June 2005.\nOn admission, she had jaundice and mild hepatic encephalopathy. Laboratory data revealed AST 393 IU/L, ALT 544 IU/L, γGTP 130 IU/L (<30), LDH 364 IU/L (115 ∼ 245), total bilirubin 15.7 mg/dL (<1.0), prothrombin time 8% (>70), and NH3 168 µg/dL (30 ∼ 80). Her serological status was as follows: HBsAg, HBeAb, and IgM HBcAb were positive, while HBsAb and HBeAg were negative. HBV-DNA was present with a level of 4.3 log copies per milliliter (<2.6) by polymerase chain reaction assay. HBV was of genotype B and the precore mutant was 100%. She had no HIV and IgM hepatitis A virus antibodies. An abdominal computed tomography (CT) scan showed atrophic liver. Therefore, a diagnosis of fulminant hepatitis due to the reactivation of HBV from a previously asymptomatic HBV carrier state was made, and lamivudine (a reverse-transcriptase inhibitor of viral DNA polymerase) therapy (150 mg/day) and plasma exchange were immediately performed. Her condition temporarily improved, and liver transplantation was considered. However, her liver function deteriorated and an abdominal CT showed more atrophic liver. She died of liver failure 18 days after admission. A postmortem examination was performed, and the ascites volume was 170 mL. The liver was remarkably atrophied, weighing just 508 g, and more than 80% of the hepatocytes were necrotic. CD8-positive cytotoxic T lymphocytes had predominantly infiltrated, and amyloid A protein deposition as a result of RA was seen in the hepatic artery (Fig. ). Vessels in most organs showed amyloid A protein deposition.