Frequency of null genotypes of glutathione S-transferase M1 and T1 in Japanese patients with drug-induced liver injury.

Aim: Previous reports suggest that the null genotype (*0/*0) of glutathione S-transferase (GST) M1 and/or GSTT1 could be risk factors for drug-induced liver injury (DILI). However, multi-institutional pharmacogenetic research with various suspected drugs has rarely been performed in Japan. Therefore, the aim of this study was to investigate the role of GSTM1 and GSTT1 null genotype in the occurrence of DILI in Japanese patients.

Hepatocellular carcinoma development in diabetic patients: a nationwide survey in Japan.

Background: Although type 2 diabetes mellitus (T2DM) is a known risk factor for hepatocellular carcinoma (HCC) development, the annual incidence in diabetes patients is far below the threshold of efficient surveillance. This study aimed to elucidate the risk factors for HCC in diabetic patients and to determine the best criteria to identify surveillance candidates.

Methods: The study included 239 patients with T2DM who were diagnosed with non-viral HCC between 2010 and 2015, with ≥ 5 years of follow-up at diabetes clinics of 81 teaching hospitals in Japan before HCC diagnosis, and 3277 non-HCC T2DM patients from a prospective cohort study, as controls.

Development and course of diabetes according to genetic factors and diabetes treatment among patients with nonalcoholic fatty liver disease.

Objectives: Many patients with nonalcoholic fatty liver disease (NAFLD) also have diabetes. However, the genetic factors associated with diabetes in NAFLD are unclear. In this study, we investigated the clinical course and risk factors of diabetes development.

Bardet-Biedl Syndrome Caused by Skipping of SCLT1 Complicated by Microvesicular Steatohepatitis.

We treated the case of a 22-year-old male patient with liver dysfunction. At 1 year of age, hepatic fibrosis was suspected. In addition, due to the presence of retinitis pigmentosa, renal failure, obesity, mental retardation, and hypogonadism, he was diagnosed with Bardet-Biedl syndrome (BBS).

Outcomes of Japanese patients with non-alcoholic fatty liver disease according to genetic background and lifestyle-related diseases.

Introduction And Objectives: Genetic background may be involved in the mechanisms of liver injury and the development of non-alcoholic fatty liver disease (NAFLD). However, its contributions to the long-term outcome of NAFLD have been unclear.

Methods: We enrolled 314 Japanese patients with biopsy-confirmed NAFLD from 2000 to 2018 (161 men [51.

Hepatocellular carcinoma in young morbid obese patients with non-alcoholic fatty liver disease.

We report the two youngest cases of hepatocellular carcinoma (HCC) in non-alcoholic fatty liver disease (NAFLD) among our 119 NAFLD-HCC patients. A 36-year-old man was referred to our hospital due to a 5 cm in diameter liver tumor with elevation of α-fetoprotein and des-γ-carboxy prothrombin found at his annual health check. He had no symptoms other than 20 kg weight loss.

Characteristics of hepatocellular carcinoma arising from Fontan-associated liver disease.

Aim: Hepatocellular carcinoma (HCC) can arise from Fontan-associated liver disease (FALD); this is known as FALD-HCC. The clinical features of FALD-HCC are unclear. Thus, we examined the incidence and clinical characteristics of FALD-HCC.

Long-term outcomes of non-alcoholic fatty liver disease and the risk factors for mortality and hepatocellular carcinoma in a Japanese population.

Background And Aim: The incidence of mortality and hepatocellular carcinoma (HCC) in patients with non-alcoholic fatty liver disease (NAFLD) has been reported, but the long-term outcomes of Japanese patients with NAFLD are not fully evaluated.

Methods: We enrolled 365 Japanese patients with biopsy-confirmed NAFLD (1990-2008) followed for ≥ 6 months: 185 males (50.7%); median age (54 years); advanced fibrosis 108 (29.

Characteristic Features of Nonalcoholic Fatty Liver Disease in Japan with a Focus on the Roles of Age, Sex and Body Mass Index.

This review provides an update on the characteristics of nonalcoholic fatty liver disease (NAFLD), with a focus on the effects of age, sex, and body mass index. Age is a risk factor for NAFLD progression; however, extremely old patients have unique features, namely, the associations between metabolic comorbidities and NAFLD are weaker and NAFLD is not a risk factor for mortality. The prevalence of NAFLD is higher in men than in premenopausal women, whereas the reverse is true after menopause.

The characteristics and risk factors of hepatocellular carcinoma in nonalcoholic fatty liver disease without cirrhosis.

Background And Aim: We evaluated the characteristics of hepatocellular carcinoma (HCC) in patients who had non-alcoholic fatty liver disease (NAFLD) without cirrhosis.

Methods: We prospectively followed NAFLD patients at our University hospital. NAFLD was diagnosed from detection of steatosis by histology or imaging, no alcohol intake, and exclusion of other liver diseases.

High Throughput Screening of Serum γ-Glutamyl Dipeptides for Risk Assessment of Nonalcoholic Steatohepatitis with Impaired Glutathione Salvage Pathway.

Nonalcoholic fatty liver disease (NAFLD) is the most common preventable chronic liver disorder in developed countries, the prevalence of which is increasing worldwide due to its association with obesity and type 2 diabetes. However, the exact mechanisms of NAFLD pathophysiology remain poorly understood including its progression to the more severe nonalcoholic steatohepatitis (NASH). New advances for early detection and monitoring of NASH progression are limited due to the lack of specific blood biomarkers, thus requiring invasive liver biopsies for histopathology.

Differences in the genetic backgrounds of patients with alcoholic liver disease and non-alcoholic fatty liver disease.

Background And Aim: Alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) have common hepatic histological features, but few studies have compared the genomic backgrounds of these two diseases. Here, we compared the genetic differences between ALD and NAFLD.

Methods: This study enrolled 318 Japanese patients with ALD ( = 118; male, 86%; median age, 62 years; liver cirrhosis, 58%; hepatocellular carcinoma [HCC], 31%) and NAFLD ( = 200; male, 55%; age, 61 years; cirrhosis, 19%; HCC, 12%).

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).

Characteristics of non-alcoholic steatohepatitis among lean patients in Japan: Not uncommon and not always benign.

Background And Aim: To elucidate features of nonobese non-alcoholic fatty liver disease (NAFLD), we assessed Japanese patients with NAFLD stratified by body mass index (BMI) and by sex.

Methods: Biopsy-proven 762 NAFLD patients (404 men) were classified into three groups by the Japanese criteria: nonobese group (BMI < 25 kg/m ), obese group (25 to 30), and severely obese group (≥ 30). Clinicopathological features and single nucleotide polymorphism of patatin-like phospholipase 3 (PNPLA3) rs738409 were investigated, and body composition analysis was performed by bioelectrical impedance analysis and computed tomography.

Analysis of 307 cases with drug-induced liver injury between 2010 and 2018 in Japan.

Aim: In order to know the present status of drug-induced liver injury (DILI) in Japan, we present the data of prospectively collected DILI cases between 2010 and 2018 from 27 hospitals.

Methods: Drug-induced liver injury cases diagnosed by DILI experts from 27 hospitals all over Japan have been prospectively collected since 2010. Alanine aminotransferase level ≥150 U/L and/or alkaline phosphatase ≥2× upper limit of normal were inclusion criteria.

Clinicopathological investigation of steatohepatitic hepatocellular carcinoma: A multicenter study using immunohistochemical analysis of adenoma-related markers.

Aims: Steatohepatitic hepatocellular carcinoma (SH-HCC) is a newly proposed concept, which shows histological features of steatohepatitis in HCC lesions, and it is strongly associated with metabolic syndrome (MS) and steatosis/steatohepatitis in non-cancerous lesions. Recently, a substantial number of HCC associated with MS were reported to have developed from pre-existing inflammatory hepatocellular adenoma (HCA). To elucidate the characteristic features of SH-HCC, we clinicopathologically investigated strictly diagnosed SH-HCC and non-SH-HCC (standard HCC).

A Data Mining-based Prognostic Algorithm for NAFLD-related Hepatoma Patients: A Nationwide Study by the Japan Study Group of NAFLD.

The prognosis of patients with nonalcoholic fatty liver disease-related hepatocellular carcinoma (NAFLD-HCC) is intricately associated with various factors. We aimed to investigate the prognostic algorithm of NAFLD-HCC patients using a data-mining analysis. A total of 247 NAFLD-HCC patients diagnosed from 2000 to 2014 were registered from 17 medical institutions in Japan.

Hormone-replacement Therapy for Hepatopulmonary Syndrome and NASH Associated with Hypopituitarism.

The patient was a 23-year-old man who was diagnosed with severe hypoxemia and liver dysfunction after suffering from sudden difficulty breathing. At 2 years of age, he had been diagnosed with hypopituitarism, and had received hormone-replacement until he was 18 years of age. Echocardiography using micro bubbles and pulmonary scintigraphy indicated intrapulmonary shunt and a liver biopsy showed steatohepatitis.

Copper deposition in oligodendroglial cells in an autopsied case of hepatolenticular degeneration.

We present a case of hepatolenticular degeneration, so-called Wilson's disease (WD), in a 31-year-old Japanese man with broader deposition of copper in the liver, kidney and brain. The liver showed severe cirrhotic changes with macronodular pseudolobule formation, but there was little difference in immunohistochemical expression patterns of the copper transporter ATP7B between the control and present case. In the brain, there were both WD-related lesions such as the scattering of Opalski cells and changes caused by hepatic encephalopathy including the appearance of Alzheimer type II glia.

Risk factors for recurrence of primary biliary cholangitis after liver transplantation in female patients: A Japanese multicenter retrospective study.

Primary biliary cholangitis (PBC) is diagnosed mainly in female individuals, and risk factors for PBC recurrence (rPBC) after liver transplantation (LT) from cadaveric donors have been reported. We conducted a retrospective multicenter study of rPBC in female patients after living-donor LT (LDLT). A total of 388 female patients undergoing LDLT for end-stage PBC were enrolled, and the effects of preoperative and operative factors were evaluated.

Risk estimation model for nonalcoholic fatty liver disease in the Japanese using multiple genetic markers.

Unlabelled: The genetic factors affecting the natural history of nonalcoholic fatty liver disease (NAFLD), including the development of nonalcoholic steatohepatitis (NASH) and NASH-derived hepatocellular carcinoma (NASH-HCC), are still unknown. In the current study, we sought to identify genetic factors related to the development of NAFLD, NASH, and NASH-HCC, and to establish risk-estimation models for them. For these purposes, 936 histologically proven NAFLD patients were recruited, and genome-wide association (GWA) studies were conducted for 902, including 476 NASH and 58 NASH-HCC patients, against 7,672 general-population controls.

The Clinical Difference in the Platelet Counts between Liver Cirrhosis with Nonalcoholic Fatty Liver Disease and Hepatitis C Virus.

Objective The rate of platelet count reduction appears to differ among different liver diseases. In the present study, we investigated the difference in the platelet counts of patients with nonalcoholic fatty liver disease (NAFLD) and those with chronic liver disease due to hepatitis C virus (CLD-HCV). Methods The study population included 620 patients with NAFLD and 405 patients with CLD-HCV, all of whom were diagnosed by liver biopsy.

The Outcome of Cirrhotic Patients with Ascites Is Improved by the Normalization of the Serum Sodium Level by Tolvaptan.

Objective Hyponatremia is frequently observed in patients with decompensated liver cirrhosis and it is also related to a poor prognosis. The vasopressin V2-receptor antagonist tolvaptan is used to treat cirrhotic patients with ascites and increases the serum sodium (Na) level. In this study, we investigated (i) whether or not correction of the Na level improves the prognosis of cirrhotic patients with ascites and (ii) predictors of normalization of the serum Na level after tolvaptan therapy.