We describe a patient with chronic hepatitis C virus (HCV) infection who had severe hepatic injury during interferon- therapy and who was successfully treated with prostaglandin E₁ and prednisone.

A 54-year-old man with chronic active HCV infection received intramuscular interferon- 2a (Canferon A, Takeda Pharmaceutical Company, Japan), 9 x 10⁶/U three times a week, in March 1992. The patient's serum alanine aminotransferase (ALT) level returned to normal in April. In May, he reported an itchy eruption, and his serum ALT level began to increase. On 15 June, his serum ALT level reached 811 kU, and interferon therapy was discontinued. On hospitalization, he showed severe hepatic injury: His total bilirubin level was 4.9 mg/dL; his conjugated bilirubin level was 4.3 mg/dL; his ALT level was 885 kU; his aspartate aminotransferase level was 940 kU (normal, 10 to 26 kU); and his prothrombin time was 32% of normal. Test results were negative for hepatitis B virus, hepatitis A virus, cytomegalovirus, and Epstein-Barr virus. Autoantibodies, such as antinuclear, anti-smooth muscle, antimitochondrial, and anti-liver-kidney microsomal antibodies, as well as anti-interferon- antibody, were not detected in the serum. The serum IgG concentration was 1850 mg/dL. Test results showed that HCV-RNA in the serum obtained on 4 June 1992 was negative. Continuous infusion of prostaglandin E₁ [1] was begun, and the patient's prothrombin time improved rapidly. However, his serum ALT levels remained high, and prednisone therapy was initiated. His serum ALT level decreased to 103 kU after 2 weeks of prednisone administration.

Patients with fatal liver failure induced by interferon administration have been described [2, 3]. Our patient showed no autoantibodies, and superinfection with other viruses was excluded. Negativity of serum HCV-RNA at the time of exacerbation makes it unlikely that HCV caused severe hepatic injury. Itchy eruptions appeared before the increase in the ALT level, and the rapid decrease in serum ALT levels after prednisone administration may suggest an immunologic mechanism induced by interferon, given that he had not received any concurrent drugs or allergens. Close monitoring of liver function test results during interferon therapy is recommended, and combination therapy with prostaglandin E₁ and prednisone at an early phase of severe hepatic injury should be considered, even when no autoantibodies are detected in the serum.