POGLUT1, the putative effector gene driven by rs2293370 in primary biliary cholangitis susceptibility locus chromosome 3q13.33.

Primary biliary cholangitis (PBC) is a chronic and cholestatic autoimmune liver disease caused by the destruction of intrahepatic small bile ducts. Our previous genome-wide association study (GWAS) identified six susceptibility loci for PBC. Here, in order to further elucidate the genetic architecture of PBC, a GWAS was performed on an additional independent sample set, then a genome-wide meta-analysis with our previous GWAS was performed based on a whole-genome single nucleotide polymorphism (SNP) imputation analysis of a total of 4,045 Japanese individuals (2,060 cases and 1,985 healthy controls).

HLA-DRB1 and DQB1 alleles in Japanese type 1 autoimmune hepatitis: The predisposing role of the DR4/DR8 heterozygous genotype.

Objective: Autoimmune hepatitis (AIH) is a chronic progressive liver disease. AIH is composed predominantly of type 1 in Japanese populations. The genetic and environmental factors are associated with the pathogenesis of AIH.

Ultra-deep sequencing analysis of resistance-associated variants during retreatment with simeprevir-based triple therapy after failure of telaprevir-based triple therapy in patients with genotype 1 hepatitis C virus infection.

Aim: Simeprevir (SMV)-based triple therapy is an effective retreatment option following failure of telaprevir (TVR)-based triple therapy. However, it is unclear whether the persistence of resistance-associated variants (RAVs) induced by TVR-based therapy may reduce the treatment effect of SMV-based therapy.

Methods: The factors associated with the treatment effect, including RAVs in the NS3 region, were examined in 21 patients with genotype 1b HCV infection who were treated with SMV-based therapy after failure of TVR-based therapy.

Declining incidence of hepatocellular carcinoma in Osaka, Japan, from 1990 to 2003.

Background: Japan has the highest incidence rate of primary liver cancer attributed to chronic hepatitis C virus (HCV) infection among developed countries. Molecular clock analysis of HCV sequences revealed that the spread of HCV took place earlier in Japan than in other countries. This might influence recent temporal trends in hepatocellular carcinoma (HCC) incidence.

Classification of ultrasonographic images of small hepatocellular carcinoma using galactose-based contrast agent: relation between image patterns and histologic features.

Purpose: The aim of this study was to establish the relation between observed ultrasonographic (US) images produced with a galactose-based contrast agent and histologic characteristics of small hepatocellular carcinomas (HCCs).

Materials And Methods: A total of 64 nodules in 64 patients, 22 well differentiated and 42 moderately differentiated with a histologically proven HCC, smaller than 3.0 cm in diameter and who had undergone hepatectomy were consecutively examined by contrast-enhanced US using a galactose-based contrast agent.

Frequent impairment of the spindle assembly checkpoint in hepatocellular carcinoma.

Background: Chromosomal instability (CI) leading to aneuploidy is one form of genetic instability, a characteristic feature of various types of cancers. Recent work has suggested that CI can be induced by a spindle assembly checkpoint defect. The aim of the current study was to determine the frequency of a defect of the checkpoint in hepatocellular carcinoma (HCC) and to establish whether alterations of genes encoding the checkpoint were associated with CI in HCC.

Circulating transforming growth factor beta 1 as a predictor of liver metastasis after resection in colorectal cancer.

Plasma transforming growth factor beta1 (TGF-beta1) has been reported to be correlated with the extent of disease in colorectal cancer, but it is not known whether measuring this cytokine can help predict liver metastasis after curative resection. We prospectively studied whether plasma TGF-beta1 levels could predict liver metastasis in 117 patients with colorectal cancer before and after curative resection. Blood samples were drawn before and 2 weeks after surgery to determine the cytokine levels.

Long-term responders without eradication of hepatitis C virus after interferon therapy: characterization of clinical profiles and incidence of hepatocellular carcinoma.

Aims/background: The aim of this study was to determine the characteristics of patients with chronic hepatitis C showing long-term normalization of alanine aminotransferase (ALT) without eradication of HCV RNA, as well as to investigate the incidence of hepatocellular carcinoma (HCC) in such patients.

Methods: Four hundred and nineteen patients with histologically-proven chronic hepatitis C who had received interferon (IFN) therapy were studied. Complete response (CR) was defined as persistent normalization of ALT levels with eradication of serum HCV RNA (n= 126).

Changes in serum hepatic fibrosis markers in biochemical responders to interferon therapy for chronic hepatitis C.

Serum hepatic fibrosis markers (7s domain of type IV collagen, N-terminal peptide of type III procollagen, and hyaluronate) were determined during and after a 6-month interferon treatment of patients with chronic hepatitis C. Changes in these markers were compared among the patients who showed a sustained normalization of serum alanine transaminase (ALT) levels with and without eradication of serum hepatitis C virus RNA (complete responders and biochemical responders) and nonresponders. In the case of complete responders, the serum 7s domain of type IV collagen and the N-terminal peptide of type III procollagen levels decreased at the end and 24 weeks after the end of the treatment.

Lack of frameshift mutations at coding mononucleotide repeats in hepatocellular carcinoma in Japanese patients.

Background: Microsatellite instability occurs frequently in hereditary nonpolyposis colorectal carcinoma, in sporadic gastrointestinal carcinoma, and in other tumors. In these tumors, slippage-related frameshift mutations have been detected at coding mononucleotide repeats in genes such as those for transforming growth factor-beta receptor type II (TGFbetaRII), mannose 6-phosphate/insulinlike growth factor II receptor (M6P/IGFIIR), hMSH3, hMSH6, and Bcl-2-associated X protein (BAX). Because these genes regulate cell growth or repair DNA mismatches, loss of their function is thought to promote tumor development.

Relation of interferon therapy and hepatocellular carcinoma in patients with chronic hepatitis C. Osaka Hepatocellular Carcinoma Prevention Study Group.

Background: The effect of interferon therapy on the incidence of hepatocellular carcinoma in chronic hepatitis C is poorly defined.

Objective: To compare the incidence of hepatocellular carcinoma in interferon-treated patients with chronic hepatitis C to that of historical controls and to examine whether response to therapy is related to incidence of hepatocellular carcinoma in patients with chronic hepatitis C.

Design: Retrospective cohort study.

[Properties of gas (CO2) microbubbles made by hand agitation and it's contrast enhancing effect].

The property of gas (CO2) microbubbles made by hand agitation and it's contrast enhancing effect of abdominal organs on gray scale ultrasound are here described. The size of microbubbles of CO2 gas adequately prepared with 5% human serum albumin was nearly 23 microns in mean diameter. However, the size and the density of gas microbubbles are affected with many factors, including mixing times, volume ratio of gas and liquid and the species of gas and liquid.

Elevated serum lipoprotein (a) levels associated with ulcerative colitis in a young Japanese patient.

Thromboembolism has been shown to play a role in the pathogenesis of inflammatory bowel disease (IBD). A possibility exists that lipoprotein (a) [Lp(a)], a newly-discovered prothrombotic factor, also participates in the development of at least some cases of IBD. Marked elevation of serum Lp(a) levels was observed in a young patient with ulcerative colitis.

Recombinant interferon-alpha-2a for treatment of chronic hepatitis C: results of a multicenter randomized controlled dose study.

To compare the efficacy of low and relatively high dosages of recombinant interferon (IFN)-alpha-2a in Japanese patients with chronic hepatitis C, as well as to characterize the type of patients who will respond well to a low-dosage treatment, 88 patients with histologically proven chronic hepatitis C were randomly assigned to two treatment groups; one treated with IFN-alpha-2a 6 MU daily for 2 weeks followed by 6 MU three times weekly for 22 weeks (6-MU group), and another given the same initial treatment followed by 3 MU three times weekly for 22 weeks (3-MU group). The rate of sustained normalization of ALT 6 months after the cessation of treatment was 33% in the 3-MU group and 40% in the 6-MU group (p = 0.64).

Hepatocellular carcinoma in adenomatous hyperplasia: detection with contrast-enhanced US with carbon dioxide microbubbles.

Adenomatous hyperplasia (AH) of the liver is considered a precancerous lesion because hepatocellular carcinoma (HCC) has been found in nodules of AH at histologic examination. Contrast material-enhanced ultrasound (US) with intraarterial infusion of carbon dioxide microbubbles was performed in four patients with HCC in AH lesions. In all four patients, a "hyperechoic focus in an area of hypoechoic change" in relation to the adjacent liver was demonstrated, compatible with the minimal vascular change associated with neoplastic transformation and carcinoma development.

Aromatase activity in human hepatocellular carcinoma. Relationship with the degree of histologic differentiation.

Human hepatocellular carcinomas (HCC) were examined aromatase activity, an enzyme that converts androgen into estrogen. Such activity was detected in all 13 specimens of HCC (mean activity, 120 fmol/30 min/mg microsomal protein). The activity tended to be lower in the HCC tissue than in the surrounding liver tissue (mean activity, 230 fmol/30 min/mg microsomal protein), although it was higher in the HCC tissue from three of eight patients with Edmondson's Grade 2 disease.

Elevated levels of transforming growth factor beta messenger RNA and its polypeptide in human hepatocellular carcinoma.

Malignant cells in culture express elevated levels of transforming growth factor beta 1 (TGF-beta 1) mRNA and secrete an abundant amount of TGF-beta protein, but little is known about the production of TGF-beta in human malignant tissues in vivo. We estimated the levels of TGF-beta 1 mRNA expression by Northern hybridization and measured TGF-beta protein using a radioreceptor assay in tumor tissues surgically obtained from six patients with hepatocellular carcinoma (HCC). TGF-beta 1 mRNA was expressed at much higher levels in HCC tissues from all the cases compared with normal human liver, suggesting an association of the activated TGF-beta 1 gene transcription with hepatocarcinogenesis.

Expression of transforming growth factor-beta 1 mRNA in human hepatocellular carcinoma.

We investigated the expression of transforming growth factor beta 1 (TGF-beta 1) mRNA in tumor tissues surgically removed from ten patients with hepatocellular carcinoma (HCC). All HCC tissues expressed TGF-beta 1 mRNA at different levels, indicating the presence of activated transcription of TGF-beta 1 gene in human HCC tissues in vivo. The level of TGF-beta 1 mRNA expression showed no relationship to main tumor size of plasma alpha-fetoprotein level.

Hepatic tumors: US contrast enhancement with CO2 microbubbles.

Enhancement of hepatic tumors on sonograms by injection of carbon dioxide microbubbles into the hepatic artery as a contrast material (enhanced ultrasonography) was performed in 43 patients with various histologically confirmed hepatic tumors. Enhanced sonograms were classified into five patterns according to the relative changes of the echo levels between the tumor and the nontumorous parenchyma of the liver as a result of enhancement: hyperechoic change, isoechoic change, hypoechoic change with hyperechoic rim (rim sign), marginal spotty hyperechoic change, and internal spotty hyperechoic change. Eighty-eight percent of hepatocellular carcinomas showed hyperechoic change, 70% of metastatic tumors exhibited hypoechoic change with the rim sign.