<i>Objective:</i> This study was aimed at evaluating the effects of interferon (IFN)-α on survival rate after resection of hepatocellular carcinoma. <i>Methods:</i> In a randomized, controlled trial by the University Hospital, Medical Center and affiliated hospital in Osaka, Japan, 30 men were after surgery randomly allocated to an IFN-α group (15 patients) and to a control group. Patients in the IFN group received 6 MIU of IFN-α intramuscularly daily for 2 weeks, then three times a week for 14 weeks, and finally twice a week for 88 weeks. The incidence of recurrence and survival rate were then studied. <i>Results:</i> The response to IFN was sustained viral response (SVR) in 2 patients, biochemical response (BR) in 6, partial response (PR) in 5, and no response (NR) in 2. In the control, 8 of the 15 patients demonstrated continuous abnormally high levels of ALT. At the end point of the study, intrahepatic recurrence was detected in 9 of the IFN group and in 13 of the control (p = 0.065, log-rank test). The cumulative survival rate was higher in the IFN group than in the controls (p = 0.041). <i>Conclusion:</i> Postoperative IFN therapy improves the outcome after resection of hepatitis C virus-related hepatocellular carcinoma.
Aim: The Japanese Nutritional Study Group for Liver Cirrhosis (JNUS) was assembled in 2008 with the support of a Health Labor Sciences Research Grant from the Ministry of Health, Labor and Welfare of Japan. The goal of the study group was to propose new nutritional guidelines for Japanese patients with liver cirrhosis (LC), with the aim of preventing hepatocellular carcinoma. Methods: Between 2008 and 2010, the member investigators of JNUS conducted various clinical and experimental studies on nutrition on LC. These included anthropometric studies, a questionnaire study on daily nutrient intake, clinical trials, experimental studies using animal models, re‐evaluation of previous publications and patient education. Over this 3‐year period, the group members regularly discussed the nutritional issues related to LC, and a proposal was finally produced. Results: Based on the results of JNUS projects and discussions among the members, general recommendations were made on how Japanese patients with LC should be managed nutritionally. These recommendations were proposed with a specific regard to the prevention of hepatocarcinogenesis. Conclusion: The new JNUS guidelines on nutritional management for Japanese patients with LC will be useful for the actual nutritional management of patients with LC. The JNUS members hope that these guidelines will form the basis for future discussions and provide some direction in nutritional studies in the field of hepatology.
Effective prophylactic therapies have not been established for hepatocellular carcinoma recurrence. Peretinoin represents one novel option for patients with hepatitis C virus-related hepatocellular carcinoma (HCV-HCC), and it was tested in a multicenter, randomized, double-blind, placebo-controlled study. Patients with curative therapy were assigned to one of the following regimens: peretinoin 600, 300 mg/day, or placebo for up to 96 weeks. The primary outcome was recurrence-free survival (RFS). Of the 401 patients initially enrolled, 377 patients were analyzed for efficacy. The RFS rates in the 600-mg group, the 300-mg group, and the placebo group were 71.9, 63.6, and 66.0 % at 1 year, and 43.7, 24.9, and 29.3 % at 3 years, respectively. The primary comparison of peretinoin (300 and 600-mg) with placebo was not significant (P = 0.434). The dose–response relationship based on the hypothesis that "efficacy begins to increase at 600 mg/day" was significant (P = 0.023, multiplicity-adjusted P = 0.048). The hazard ratios for RFS in the 600-mg group vs. the placebo group were 0.73 [95 % confidence interval (CI) 0.51–1.03] for the entire study period and 0.27 (95 % CI 0.07–0.96) after 2 years of the randomization. Common adverse events included ascites, increased blood pressure, headache, presence of urine albumin, and increased transaminases. Although the superiority of peretinoin to placebo could not be validated, 600 mg/day was shown to be the optimal dose, and treatment may possibly reduce the recurrence of HCV-HCC, particularly after 2 years. The efficacy and safety of peretinoin 600 mg/day should continue to be evaluated in further studies.
Background/Aim: Hepatoma-derived growth factor (HDGF) is involved in the progression of hepatocellular carcinoma (HCC). The present study assessed the epigenomic changes in hepatoma-derived cells through HDGF stimulation. Materials and Methods: We used two hepatoma-derived cell lines (HepG2 and SK-Hep1) and searched for microRNAs whose expression commonly changed in response to HDGF administration. We further explored a genetic database to investigate the association of the candidate microRNAs with the survival of HCC patients. Results: Despite both HepG2 and SK-Hep1 cells being categorized as hepatoma-derived cells, the microRNA profile differed between these two lines. However, HepG2 and SK-Hep1 cells shared 30 up-regulated and 2 down-regulated microRNAs. Of these, miR-6072 and miR-3137 were significantly associated with a poor prognosis in HCC patients. Conclusion: We identified two candidate microRNAs whose expression increased in response to HDGF stimulation. Both these molecules were associated with a poor prognosis of HCC patients.
Abstract Background and aim: Thiopurine S‐methyltransferase (TPMT) genotypes or phenotypes may be a predictive factor for azathioprine‐induced toxicities. We investigated the genotypic status of TPMT to evaluate the risk of azathioprine‐related adverse effects in Japanese patients with different liver diseases, including autoimmune hepatitis (AIH). Methods: 49 patients with AIH, 67 with primary biliary cirrhosis (PBC), and 120 with hepatitis C virus (HCV) were examined. TPMT genotypes were determined by PCR‐restriction fragment length polymorphism‐based assays. Results: The distribution of TPMT genotypes was 90% TPMT * 1/TPMT * 1, 8% TPMT * 1/TPMT * 3C, and 2% TPMT * 3C/TPMT * 3C in AIH, and 94% TPMT * 1/TPMT * 1, 4.5% TPMT * 1/TPMT * 3C, and 1.5% TPMT * 3C/TPMT * 3C in PBC. All except 1 patient with HCV had the TPMT * 1/TPMT * 1 genotype. Severe myelosuppression occurred in two of nine patients with AIH who received azathioprine, one of whom was homozygous for TPMT * 3C. Conclusions: TPMT * 3C variants are more frequent in patients with AIH or PBC than in patients with viral hepatitis or healthy volunteers in Japan. Pharmacogenetic screening for TPMT polymorphisms before commencing azathioprine therapy may help to prevent severe hematotoxicity in patients with TPMT deficiency.
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