Drug-induced liver injury associated with Agaricus blazei Murill which is very similar to autoimmune hepatitis.

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.

Clinical features of cirrhosis in Japanese patients with type I autoimmune hepatitis.

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.

Risk factors for hepatocellular carcinoma in Japanese patients with autoimmune hepatitis type 1.

BACKGROUND: Hepatocellular carcinoma (HCC) is occasionally seen even in patients with autoimmune hepatitis (AIH) without prior infection either with hepatitis C virus (HCV) or hepatitis B virus. The aim of this study was to identify the incidence of and risk factors for HCC with AIH in a large-scale population with a long-term follow-up in Japan. METHODS: One hundred and eighty patients diagnosed with AIH were enrolled (F/M = 159/21; mean age, 59.9 years; mean observation period, 80.2 months). Patients with positive HCV antibody/serum HCV RNA and/or positive HBs Ag were excluded. Initial treatment included immunosuppressant therapy (n = 147), other drugs (n = 28), and no drug (n = 5). Patients underwent abdominal ultrasonography at intervals of 3-6 months during observation. Patients' demographic factors, biochemical data, liver histology, medications, response to treatment, and complications were evaluated in relation to HCC. RESULTS: During the observation period, six patients (3.3%) developed HCC. Univariate analysis showed that risk factors for HCC were cirrhosis at diagnosis with AIH (p = 0.0002), absence of a treatment response (p = 0.033), abnormal alanine aminotransferase (ALT) at the final observation (p = 0.0002), and diabetes (p = 0.0015). Multivariate analysis showed that risk factors for HCC were cirrhosis at diagnosis of AIH (odds ratio 4.08) and abnormal ALT at final observation (odds ratio 3.66). CONCLUSION: This retrospective study showed that cirrhosis at diagnosis of AIH and abnormal ALT at final observation were independently associated with HCC development. It is important to pay attention to the presence of cirrhosis at diagnosis of AIH and to normalize ALT.

The importance of a prior psychiatric examination in pegylated interferon and ribavirin combination treatment for chronic hepatitis C.

UNLABELLED: Some patients receiving pegylated interferon and ribavirin treatment for chronic hepatitis C are forced to discontinue the treatment due to psychiatric disorders. We performed a retrospective study to evaluate whether pre-treatment psychiatric examinations could increase successful completion rates for this treatment. METHODS: A total of 535 patients who started pegylated interferon-α-2b and ribavirin treatment at 6 hospitals affiliated with our hospital were included in this study. The patients were divided into two groups. Those who had visited a psychiatric clinic before treatment were Group A (N=223), and those who did not visit a psychiatric clinic before treatment were Group B (N=312). We analyzed the rate of discontinuation due to psychiatric disorders in the two groups. RESULTS: The rate of discontinuation due to psychiatric disorders in Group A was found to be significantly lower than that of Group B (1.8% (4/223) vs. 6.1% (19/312), P=0.035). In Group A, 6.1% (4/65) discontinued the treatment due to psychiatric disorders, while the comparable rate in Group B was 27% (19/68) (P=0.0004). Among patients who presented with psychiatric symptoms during treatment, the rate of treatment completion was significantly higher in Group A than in Group B (69.2% (18/26) vs. 5.0% (1/20), P=0.0067). In patients with a history of psychiatric symptoms, no discontinuation due to psychiatric disorder was observed in Group A. CONCLUSIONS: A psychiatric examination before pegylated interferon and ribavirin treatment was found to positively contribute to the successful completion of the treatment.

[A case of hepatic eosinophilic granuloma, which needs distinction with metastatic liver cancer].

A 68-year-old man was referred to our hospital because of eosinophilia in peripheral blood and pancreatic tumor on abdominal US. He was accustomed to eating the raw flesh of wild boar and keeping wild boar, and under medical treatment for Diabetes. Pancreatic tumor was diagnosed to the pancreatic ductal cancer by the imaging examination and endoscopic transpapillary brushing cytology for pancreatic duct. The diagnosis of hepatic eosinophilic granuloma was done by aspiration biopsy for hepatic multiple small nodules. Because of the strong positive finding for nematose in the assay of multi dot-ELISA for parasite, hepatic eosinophilic granuloma caused by visceral larva migrans was accidentally complicated by pancreatic cancer, and operation for the pancreatic cancer was done. To bear this disease in mind and to research his life history, is important to diagnose hepatic multiple nodules with eosinophilia.

Subclones of drug-resistant hepatitis B virus mutants and the outcome of breakthrough hepatitis in patients treated with lamivudine.

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.

Severe alcoholic hepatitis successfully treated by leukocytapheresis: a case report.

BACKGROUND: The prognosis of severe alcoholic hepatitis is poor, and there is no established method for a cure. METHODS: A 34-year-old man was admitted to Kurume University Hospital because of severe liver dysfunction due to excess alcohol intake. He was treated with prednisolone and two sessions of granulocyte and monocyte adsorption apheresis (GCAP) using an Adacolumn, which removes leukocytes--especially granulocytes and monocytes--from the peripheral blood. We evaluated the changes in the serum levels of interleukin-6, interleukin-8, tumor necrosis factor-alpha, and soluble intercellular adhesion molecule-1, as well as the conventional liver tests and peripheral white blood cell count. RESULTS: Prednisolone was effective in the short term but resulted in an increase in C-reactive protein (CRP), peripheral leukocytes, and serum total bilirubin. GCAP performed on the 34th and 41st hospital days produced decreases in the white blood cell count, total bilirubin, and intercellular adhesion molecule-1. The patient survived, despite the expected poor prognosis on admission. CONCLUSIONS: GCAP is recommended as a potential therapeutic option for severe alcoholic hepatitis.