Safety and tolerance of sorafenib in Japanese patients with advanced hepatocellular carcinoma.

PURPOSE: Sorafenib provides a survival benefit for patients with advanced hepatocellular carcinoma (HCC). However, there has been little experience with it in Japan. This study evaluated the safety and tolerance of sorafenib in Japanese patients with HCC. METHODS: Clinical data for patients given sorafenib for advanced HCC were captured from eight institutions. All patients were classified as Child-Pugh A and the treatment was started at 400 mg twice daily. We recorded adverse events, treatment duration, and survival retrospectively. Adverse events were graded using Common Terminology Criteria, version 3.0; tumor response was assessed according to Response Evaluation Criteria in Solid Tumor, version 1.1. RESULTS: Of the 54 patients treated, their median age was 69 years (range 48-82), 91% were males, 52% had HCV infection, and 22% had HBV infection. The most common drug-related adverse events were hand-foot skin reactions (HFSR) (72%), aspartate transaminase elevation (55%), alanine aminotransferase elevation (52%), rash (50%), fatigue (41%), and diarrhea (32%). Liver failure occurred in 19%. The median time to treatment failure was 2 months. Dose reduction was required in 83% of the patients, and this occurred within 2 weeks in 44%. The median overall survival was 6.9 months. CONCLUSIONS: These data suggest that sorafenib is generally tolerated in Japanese patients with HCC. Nevertheless, the majority needed a dose reduction. Adverse events including HFSR, rash, and liver failure occurred more frequently in our patients than those reported elsewhere. Careful attention must be paid to these adverse events during sorafenib administration.

Clinical and histological recovery from "life-threatening" severe acute alcoholic hepatic failure with complete hepatofugal portal blood flow.

A 25-year-old man who was a heavy alcohol drinker was admitted to our hospital after presenting with general malaise, dyspnea, abdominal distension, systemic edema and jaundice. His liver function tests showed hyperbilirubinemia and prolonged prothrombin time, and a computed tomography scan and ultrasound showed liver atrophy and massive ascites. Furthermore, Doppler ultrasound revealed complete hepatofugal portal blood flow in the portal trunk and intrahepatic portal branches. Causes other than alcohol were excluded, and he was diagnosed as having severe acute alcoholic hepatic failure (Maddrey's discriminant function score 43.3, MELD score 21), although not clinically typical. He was treated with anti-coagulation therapy according to the precise evaluation of portal blood flow by Doppler ultrasound, and marked clinical, biochemical and hemodynamic improvements were observed. Liver biopsy performed 2 months after onset showed submassive necrosis with pericellular fibrosis. Liver biopsy performed three years after onset showed mild portal fibrosis with a marked improvement. Doppler ultrasound is an indispensable tool for evaluating patients with severe acute hepatitis.