Efficacy and safety of telaprevir, pegylated interferon α-2b and ribavirin triple therapy in Japanese patients infected with hepatitis C virus genotype 1b.

Objective This study evaluated the efficacy and safety of triple therapy with telaprevir (TVR), pegylated interferon α-2b (PegIFN-α-2b) and ribavirin (RBV) in Japanese patients chronically infected with hepatitis C virus (HCV) genotype 1b in real-world clinical practice. Methods A total of 106 consecutive patients with HCV genotype 1b were treated with triple therapy for 12 weeks followed by dual therapy with PegIFN-α-2b and RBV for 12 weeks. The primary end point was sustained virological response (SVR), defined as undetectable serum HCV RNA at 24 weeks after the end of treatment.

Presence of esophageal varices is a risk factor for non-hemorrhagic death of hepatocellular carcinoma patients treated with radiofrequency ablation.

Background/aims: The presence of esophageal varices (EVs) is believed to be a factor that affects the prognosis of patients with hepatocellular carcinoma (HCC). We examined whether the presence and severity of EVs affected either survival prognosis or the cause of death in HCC patients treated with radiofrequency ablation (RFA).

Methodology: The study included 89 HCC patients treated with RFA who were endoscopically evaluated for EVs before treatment.

Interaction between cytochrome P450 1A2 genetic polymorphism and cigarette smoking on the risk of hepatocellular carcinoma in a Japanese population.

Limited epidemiological evidence suggests that genetic polymorphisms of drug-metabolizing enzymes such as cytochrome P450 (CYP), glutathione S-transferase (GST) and N-acetyltransferase (NAT) may be involved in tobacco-related hepatocarcinogenesis. We conducted a case-control study, including 209 incident cases with hepatocellular carcinoma (HCC) and two different control groups [275 hospital controls and 381 patients with chronic liver disease (CLD) without HCC], to investigate whether CYP1A1, CYP1A2, CYP2A6, CYP2E1, GSTM1 and NAT2 polymorphisms are related to the risk of HCC with any interaction with cigarette smoking. Overall, no significant associations with HCC were observed for any genotypes against either control group.

Hepatitis C virus infection enhances insulin resistance induced by visceral fat accumulation.

Background/aims: To clarify the impact of visceral obesity on hepatitis C virus (HCV)-infected patients, we examined the relationship between insulin resistance development and visceral fat accumulation.

Methods: We analyzed 87 HCV-infected patients with mild fibrosis (stage 1 or 2) in comparison with 125 sex- and age-matched patients with non-alcoholic fatty liver disease (NAFLD). The degree of visceral fat area (VFA; cm(2)) at the umbilical level was measured by abdominal computed tomography and divided into two grades: no visceral obesity, VFA<100 and visceral obesity, VFA>/=100.

Interaction between interleukin-1beta -31T/C gene polymorphism and drinking and smoking habits on the risk of hepatocellular carcinoma among Japanese.

The risk of hepatocellular carcinoma (HCC) increases with the severity of hepatic inflammation. Interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha are proinflammatory cytokines with multiple biological effects and may play essential roles in inflammation-linked tumor development. We conducted a case-control study including 209 incident HCC cases and two control groups (275 hospital controls and 381 patients with chronic liver disease [CLD] without HCC) to investigate whether IL-1B and TNF-A gene polymorphisms influence HCC susceptibility with any interaction with alcohol and tobacco.

Radiofrequency ablation with the real-time virtual sonography system for treating hepatocellular carcinoma difficult to detect by ultrasonography.

Radiofrequency ablation has been applied to treat hepatocellular carcinoma, with favorable therapeutic outcomes. Nevertheless, practitioners have approached radiofrequency ablation with some reluctance due to the difficulty of identifying isoechoic tumors and recurrent tumors. The aim of the present study is to investigate the efficacy of Real-time Virtual Sonography to treat hepatocellular carcinoma difficult to detect by conventional ultrasonography.

Waist circumference correlates with hepatic fat accumulation in male Japanese patients with non-alcoholic fatty liver disease, but not in females.

Background And Aim: Abdominal obesity, a component of metabolic syndrome, is a major risk factor for non-alcoholic fatty liver disease (NAFLD). In recent worldwide definitions of metabolic syndrome, waist measurement has been proposed as a simple and useful estimate of abdominal obesity, taking into account gender differences in waist circumference. The present cross-sectional study investigated the correlation of hepatic fat accumulation and waist circumference in Japanese NAFLD patients to determine if there are gender differences in this relationship.

[Late-onset type ornitine transcarbamirase deficiency (OTCD) with fulminant onset following a fatal prognosis].

A 16-year-old man was admitted to our hospital with nausea, general fatigue, and consciousness disturbance along with extreme hyperammoniemia eight days after the onset of symptoms. Familial history and the high concentration of orotic acid in urine lead us to a diagnosis of OTCD. We immediately initiated intensive treatment such as continuous hemodiafiltration and sodium benzoate administration; however, the patient died twelve days after admission.

Paternal transmission and slow elimination of mutant alleles associated with late-onset ornithine transcarbamylase deficiency in male patients.

In ten families with late-onset ornithine transcarbamylase (OTC) deficiency in male patients, three mutant alleles-R40H, R277W, and Y55D-were identified. In a total of 20 informative parent-offspring pairs, father-to-daughter transmission and mother-to-offspring transmission occurred in five (25%) and 15 (75%), respectively, indicating that paternal transmission contributes substantially to the pool of these mutant alleles. Relative reproductive fitness of males and females carrying the mutant alleles was calculated to be 0.

Case-control study on cigarette smoking and the risk of hepatocellular carcinoma among Japanese.

Emerging epidemiologic data suggest that cigarette smoking may increase the risk of hepatocellular carcinoma (HCC), yet considerable controversies (e.g. inconsistent dose-response relationships) still exist with this association.

High-dose vitamins E and C supplementation prevents ribavirin-induced hemolytic anemia in patients with chronic hepatitis C.

Aim: In combination therapy using interferon (IFN) and ribavirin for chronic hepatitis C, reduced doses should be used due to ribavirin-induced hemolytic anemia. The present study aimed to elucidate whether high-dose vitamins E and C supplementation attenuated ribavirin-induced hemolytic anemia.

Methods: Twenty-one consecutive patients with chronic hepatitis C were enrolled in this study between July 2003 and December 2004, and received high-dose vitamins E (2000 mg) and C (2000 mg) supplementation, daily, in addition to IFN alfa-2b and ribavirin combination therapy (vitamins E/C group).

Menatetrenone, a vitamin K2 analogue, inhibits hepatocellular carcinoma cell growth by suppressing cyclin D1 expression through inhibition of nuclear factor kappaB activation.

Purpose: Menatetrenone, a vitamin K2 analogue, plays an important role in the production of blood coagulation factors. Menatetrenone has also bee shown to have antineoplastic effects against several cancer cell lines including hepatocellular carcinoma (HCC) cells. However, the mechanisms by which vitamin K2 inhibits HCC cell growth have not bee fully clarified, and we therefore investigated the molecular basis of vitamin K2-induced growth inhibition of HCC cells.

Inverse association between coffee drinking and the risk of hepatocellular carcinoma: a case-control study in Japan.

Coffee use has consistently been associated with lower serum liver enzyme levels and a reduced risk of liver cirrhosis. A limited number of cohort and case-control studies also suggest a decreased risk of hepatocellular carcinoma (HCC) among coffee drinkers, but mostly without consideration of hepatitis virus infection. In the present case-control study, we recruited 209 incident HCC cases and three different controls (1308 community controls, 275 hospital controls, and 381 patients with chronic liver disease [CLD] without HCC), all of whom were aged 40-79 years and residents of Saga Prefecture, Japan.

hOGG1 Ser326Cys polymorphism and risk of hepatocellular carcinoma among Japanese.

Background: The Ser326Cys polymorphism in human oxoguanine glycosylase 1 (hOGG1), which is involved in the repair of 8-hydroxy-2-deoxyguanine in oxidatively damaged DNA, has been associated with susceptibility to certain cancers, but has not been examined in causation of hepatocellular carcinoma (HCC).

Methods: We conducted a case-control study to investigate whether this polymorphism was related to HCC risk with any interaction with alcohol consumption and cigarette smoking. Genotyping was performed by a polymerase chain reaction with confronting two-pair primers among 209 newly diagnosed HCC cases, 275 hospital controls, and 381 patients with chronic liver disease (CLD) without HCC.

Visceral fat accumulation and insulin resistance are important factors in nonalcoholic fatty liver disease.

Background: Nonalcoholic fatty liver diseases are often associated with obesity, insulin resistance, and excessive visceral fat accumulation. The aims of this study were (1) to evaluate the relationship between the severity of fatty liver and visceral fat accumulation in nonalcoholic fatty liver diseases, and (2) to investigate the relationships of fatty liver with biochemical data and insulin resistance.

Methods: One hundred twenty-nine subjects (63 women) with fatty liver diagnosed by ultrasonography were enrolled.

High serum leptin is an independent risk factor for non-response patients with low viremia to antiviral treatment in chronic hepatitis C.

Aim: To determine whether body weight and/or serum leptin were independent predictors of response to antiviral treatment in patients with chronic hepatitis C.

Methods: A retrospective evaluation was performed in 139 patients with chronic hepatitis C treated with interferon (IFN) from 1996 to 2000. Sustained response was defined as negative by hepatitis C virus (HCV) RNA analysis using PCR and normal transaminase at 24 wk after cessation of IFN therapy.

The effect of menatetrenone, a vitamin K2 analog, on disease recurrence and survival in patients with hepatocellular carcinoma after curative treatment: a pilot study.

Background: The high recurrence rate of hepatocellular carcinoma (HCC) determines the long-term prognosis for patients with HCC. In the current study, the authors tested the effects of menatetrenone, a vitamin K2 analog, on recurrent HCC and survival after curative treatment.

Methods: Sixty-one patients who were diagnosed as free of HCC after surgical resection or percutaneous local ablation were assigned randomly assigned to either a menatetrenone group (n = 32 patients) or a control group (n = 29 patients).

Influence of alcohol consumption and gene polymorphisms of ADH2 and ALDH2 on hepatocellular carcinoma in a Japanese population.

Although alcohol intake as well as hepatitis viruses has been associated with hepatocellular carcinoma (HCC), gene-alcohol interactions on HCC risk remain to be elucidated. We conducted a case-control study to examine whether polymorphisms of alcohol dehydrogenase 2 (ADH2) and aldehyde dehydrogenase 2 (ALDH2) modified the HCC risk depending on the amount of alcohol intake. ADH2 and ALDH2 genotyping was performed by a duplex polymerase chain reaction with confronting two-pair primers in 209 newly diagnosed HCC cases and 2 different controls [275 hospital controls and 381 patients with chronic liver disease (CLD)].

Transforming growth factor-beta 1-induced apoptosis is blocked by beta 1-integrin-mediated mitogen-activated protein kinase activation in human hepatoma cells.

Growth factors and extracellular matrices cooperatively regulate cellular behavior. However, the interactions between transforming growth factor-beta 1 (TGF-beta 1) and integrins in hepatic cells are not fully understood. We investigated the effects of beta 1-integrin on TGF-beta 1-regulated growth of hepatoma cells.

Induction of multiple matrix metalloproteinase genes in human hepatocellular carcinoma by hepatocyte growth factor via a transcription factor Ets-1.

Matrix metalloproteinases (MMPs) have been implicated in progression of hepatocellular carcinoma (HCC), as have hepatocyte growth factor (HGF) and its c-Met receptor. We investigated regulation of MMP gene expression by HGF in human HCC. Expression of mRNAs encoding MMPs, HGF and c-Met receptor was examined by quantitative reverse transcription-polymerase chain reaction (RT-PCR) in human HCC and in five human HCC cell lines.

The relationship between insulin resistance and polymorphisms of the endothelial nitric oxide synthase gene in patients with coronary artery disease.

Nitric oxide (NO) regulates endothelial function and is believed to prevent atherogenesis. In endothelial cells, endothelial nitric oxide synthase (eNOS) is expressed constitutively, and regulates NO synthesis. A mutation of the eNOS gene has been associated with the development of coronary artery disease (CAD).