岡本 宏明

A 56-year-old man receiving immunosuppressive therapy with methotrexate (MTX) for a T-cell lymphoproliferative disorder developed acute hepatitis caused by hepatitis E virus (HEV). Persistent HEV viremia was observed, and the patient was diagnosed with chronic HEV infection based on the continued presence of HEV RNA in both serum (106-107 copies/mL) and feces (~ 109 copies/mL in 15% suspensions) 6 months after the initial infection. A 12-week course of ribavirin (RBV) therapy, combined with gradual tapering of MTX, resulted in undetectable HEV RNA levels in serum and feces at the end of the RBV treatment. However, 6 months after completion of RBV therapy and MTX cessation, HEV RNA reappeared at low levels in serum (10 copies/mL) and feces (~ 103 copies/mL in 15% suspensions). This low-level viremia persisted for approximately 4 months without any clinical symptoms or additional treatment. Eventually, HEV RNA became spontaneously undetectable in both serum and feces, and the patient was considered cured based on sustained HEV RNA negativity 1129 days after the onset of hepatitis. This case highlights the importance of extended follow-up-beyond the standard 6 months-when assessing the viral clearance in HEV-infected patients following antiviral therapy.

Hepatitis A virus (HAV) infection sometimes results in the occurrence of acute liver failure and acute-on-chronic liver failure (ACLF), which is often fatal, especially in patients with diabetes mellitus or elderly individuals. ACLF is observed in patients with cirrhosis who occasionally have zinc deficiency. However, effective drugs for hepatitis A are currently unavailable. Glucose-regulated protein 78 (GRP78) is an antiviral agent that has been reported to prevent HAV replication. The effects of zinc acetate on HAV HA11-1299 genotype IIIA replication and changes in GRP78 levels in human hepatocytes with or without HAV infection were examined. Zinc acetate inhibited HAV HA11-1299 genotype IIIA replication in both Huh7 and GL37 cells. Zinc acetate also inhibited HAV replication in both low- and high-glucose media. Zinc acetate increased the expression of GRP78, in response to HAV replication. The combination of zinc acetate with ribavirin led to greater suppression of both HAV HA11-1299 genotype IIIA and HAV HM175/18f genotype IB replication in Huh7 cells than that of ribavirin alone. In conclusion, zinc acetate inhibits HAV replication in accompany with the elevation of GRP78 expression without causing cellular toxicity. Zinc compounds may be useful for the treatment of ACLF caused by HAV infection.