Objective Autoimmune hepatitis (AIH) is a chronic inflammatory disorder of unknown etiology that may proceed to cirrhosis, although some patients already have cirrhosis at the time of AIH diagnosis. The aim of this study was to clarify the clinical characteristics of AIH patients with cirrhosis in Japan. Methods Questionnaires were sent to liver specialists at four research facilities. Data for 250 patients diagnosed with AIH using the scoring system of the International Autoimmune Hepatitis Group (IAIHG) between 1975 and 2010 were collected and analyzed. Results The male-to-female ratio was 1:8.3 and the average patient age was 55.6 years. Liver cirrhosis was found in 51 AIH patients (20.4%). Of these, 43 patients (84.3%) had cirrhosis at presentation and eight patients (15.7%) developed cirrhosis during the follow-up period (average follow-up of 82.1 months). There were significant differences between the two groups with and without cirrhosis at presentation with regard to age and biochemical parameters at presentation. There were no significant differences in histology, with the exception of liver fibrosis. The overall 10-year probability of survival was 71.2% vs. 99.3% in the patients with and without cirrhosis (log-rank test, p<0.001). The relapse rate was significantly higher in the patients who developed cirrhosis during treatment than in those who did not develop cirrhosis during treatment (100% vs. 7.5%, p<0.001). Conclusion Since liver cirrhosis has already developed at presentation in many AIH patients with cirrhosis, it is important to diagnose the disease in the early stage and administer treatment rapidly with corticosteroids or immunosuppressants. In addition, a history of relapse is a risk factor for the development of cirrhosis in Japanese patients with AIH.

GCAP is recommended as a potential therapeutic option for severe alcoholic hepatitis.

Breakthroughs during lamivudine therapy were assessed according to hepatitis flares and mutational polymorphism of hepatitis B virus (HBV) infecting patients. Of 42 patients with chronic hepatitis B and positive for hepatitis B e antigen in serum, 13 (30%) harbored HBV mutants with lamivudine resistance after a mean duration of 29 months on lamivudine. The virological breakthrough occurred 14.5 months after the start of lamivudine treatment, and all the patients with it developed breakthrough hepatitis 3 months later. The clinical course of breakthrough hepatitis was self-limited except in one patient who had already developed cirrhosis at the baseline. One year after breakthrough hepatitis, serum ALT, albumin, prothrombin time and platelet counts were maintained well on conventional treatments without resorting to interferon. Major HBV mutants during breakthrough hepatitis were those with M552I in the YMDD motif of viral DNA polymerase/reverse transcriptase in 7 patients (54%), M552I/L528M in 4 patients (31%) and M552V/L528M in 2 patients (15%). There were no patients in whom mutations at nucleotide 529 occurred including the 2 who later developed hepatocellular carcinoma. There was no clear relationship between distinct mutational patterns and clinical courses. Further studies are needed for making out the effects of lamivudine-resistant mutants on clinical outcomes, taking into considerations genotypes of HBV.

Agaricus blazei Murill (ABM) is one of the most popular complementary alternative medicines (CAM). We experienced a case of a 60-year-old woman with severe hepatitis associated with extract of ABM and extract of Ganoderma lucidum, and a case of a 75-year-old man with drug-induced liver injury (DILI) associated with extract of ABM and fucoidan. Their clinical courses from the start of CAM until the onset of DILI were observed unexpectedly, because they were under observation for stable malignant neoplasms: stage III malignant thymoma and stage IV lung cancer, respectively. However, they did not talk about taking CAM with their physicians. There were two common points between these two cases. First, they were diagnosed as compatible with DILI by using an international diagnostic scale, the Roussel Uclaf Causality Assessment Method. The second point was that histological findings of the liver were very similar to autoimmune hepatitis (AIH). In addition, serum immunoglobulin G and zinc sulfate turbidity tests gradually increased from the start of CAM to the onset of DILI. Their clinical course and liver histology suggested that the immunostimulating action of ABM caused liver injury which was very similar to that seen in AIH.

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