Yasuyo Morita

Association of exogenous insulin or sulphonylurea treatment with an increased incidence of hepatoma in patients with hepatitis C virus infection.

Background: Diabetes mellitus is frequently seen in hepatitis C patients and is often treated with antidiabetic agents that increase serum insulin levels. Because insulin is a growth‐promoting hormone, antidiabetic agents could pose a risk for hepatocellular carcinoma (HCC).

Interferon-γ brings additive anti-viral environment when combined with interferon-α in patients with chronic hepatitis C

Abstract T-cell hyporesponsiveness may lead to chronicity of hepatitis C virus (HCV) infection. We evaluated whether interferon (IFN)-γ injection can bring a Th1-dominant environment to patients with chronic hepatitis C. Seventeen patients with genotype 1b received natural IFN-α 5MU daily for the first 2 weeks and three times a week for the next 22 weeks followed by natural IFN-γ 1 MU daily for 2 weeks. In 4 of 17 patients (23.5%), alanine aminotransferase (ALT) was normalized and 3 of these 4 patients (75.0%) cleared HCV RNA. β2 microglobulin (BMG), neopterin and soluble (s) Fas increased with IFN-α and increased more with IFN-γ. Serum interleukin (IL)-12, CD4 and CD8 remained unchanged with IFN-α but increased after IFN-α was replaced by IFN-γ. IL-10 was not changed either with IFN-α or γ. Productions of IL-2, IFN-γ and tumor necrosis factor (TNF)-α by peripheral blood mononuclear cells did not change by IFN-α therapy, however, they were enhanced at the end of IFN-γ therapy. Productions of IL-2 and 4 were unaffected. These results show that some immune parameters become Th1-dominant by additional IFN-γ in patients with chronic hepatitis C. Combination of these two IFNs should be explored.

CD14 expression and Kupffer cell dysfunction in non-alcoholic steatohepatitis: Superparamagnetic iron oxide-magnetic resonance image and pathologic correlation

Background and Aim:  Kupffer cell (KC) function and CD14 expression contributes to pathogenesis of non‐alcoholic steatohepatitis (NASH). However, these relationships remain unclear. We investigated the relationship of KC function with superparamagnetic iron oxide‐enhanced magnetic resonance imaging (SPIO‐MRI), histopathological severity of NASH, and number of CD14‐positive KCs in NASH.

Evaluation of Resistance-Associated Substitutions in NS5A Using Direct Sequence and Cycleave Method and Treatment Outcome with Daclatasvir and Asunaprevir for Chronic Hepatitis C Genotype 1.

Background The aim of this study was to evaluate the efficacy of daclatasvir plus asunaprevir therapy in patients infected with hepatitis C virus and determine its relevance to resistant variants. Methods A total of 629 consecutive patients infected with hepatitis C virus genotype 1 were assessed. Daclatasvir (60 mg/day) plus asunaprevir (200 mg/day) was given for 24 weeks. The virological responses and resistance-associated substitutions of hepatitis C virus mutants were examined by the direct sequence and cycleave methods were evaluated. Results Overall, 89.4% (555/621) of patients exhibited a sustained virological response (SVR). The SVR rates in the patients with wild type, mixed, and mutant type Y93 by direct sequencing were 92.5% (520/562), 70.3% (26/37), and 42.9% (9/21), respectively. The SVR rates in the patients with 100%, 90%, 80%-30%, and 20%-0% Y93 wild by the cycleave method were 93.4% (456/488), 88.2%(30/34), 56.0%(14/25), and 36.8%(7/19), respectively. In contrast, the SVR rates for the wild type and mixed/mutant type L31 by direct sequencing were 90.2% (534/592) and 72.4% (21/29), respectively. In the multivariate analyses, the wild type Y93, no history of simeprevir therapy, the wild type L31, and low HCV RNA level were independent factors of SVR. Conclusion NS5A resistance-associated substitutions, especially Y93H, were major factors predicting the SVR. Although direct sequencing can predict the SVR rate, the cycleave method is considered to be more useful for predicting the SVR when used in combination.

Peginterferon‐alpha‐2b plus ribavirin therapy in patients with chronic hepatitis C as assessed by a multi‐institutional questionnaire in Japan

Background and aim:  There has so far been no questionnaire report on patients who were treated with peginterferon plus ribavirin (PEG IFN+RBV) therapy. The purpose of this study was to investigate the problems of this therapy by a questionnaire survey.

Pathogenesis and Significance of Restricted Diet and Exercise Therapy in Nonalcoholic Steatohepatitis (NASH)

The risk factors that are most strongly associated with nonalcoholic fatty liver disease (NAFLD) are: age greater than 40 to 50 years, and severe obesity, diabetes mellitus (DM), or hyperlipidemia (especially hypertriglyceridemia). The pathogenesis of nonalcoholic steatohepatitis (NASH) is multifactorial. Insulin resistance, fatty acids, and oxidant stress may be important pathogenic factors in NASH. Efforts are presently underway to define the role of these factors and to determine whether modifying them (for example, by improving insulin sensitivity) could be effective in the treatment of the condition. At present, lifestyle changes involving exercise and dietary restrictions appear to be an effective means of improving NASH. Physicians should actively check for the presence of NAFLD in those who are overweight and who have diabetes mellitus. The treatment is usually directed toward optimizing body weight. The role of pharmacological agents remains to be established, and much more work is necessary to define the pathogenesis of NASH and to develop effective treatments.