Significant association between HLA-B*35:01 and onset of drug-induced liver injury caused by Kampo medicines in Japanese patients.

Aim: Drug-induced liver injury (DILI) is a severe and life-threatening immune-mediated adverse effect, occurring rarely among treated patients. We examined genomic biomarkers in the Japanese population that predict the onset of DILI after using a certain class of drugs, such as Kampo products (Japanese traditional medicines).

Methods: A total of 287 patients diagnosed as DILI by hepatology specialists were recruited after written informed consent was obtained.

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.

Low prevalence of colonic mucosal injury and bleeding in patients taking direct oral anticoagulants for non-valvular atrial fibrillation.

Objective: Direct oral anticoagulants are frequently used to prevent systemic embolism associated with atrial fibrillation. Gastrointestinal bleeding is a common adverse event of this pharmacotherapy, especially in the lower gastrointestinal tract. However, the prevalence of mucosal injury of the colon in patients taking direct oral anticoagulants has remained unknown.

[Second-line therapy with mycophenolate mofetil in patients with autoimmune hepatitis who were intolerant or failed to respond to standard treatment].

Although standard treatment for autoimmune hepatitis (AIH) comprises prednisolone (PSL) and azathioprine (AZA), some patients are intolerant to or do not respond to PSL and/or AZA. The clinical practice guidelines of AIH in Europe and North America recommend mycophenolate mofetil (MMF) as second-line treatment in these patients. We administered MMF as second-line therapy to 7 patients with AIH (male/female 1/6, age range 27-79 years) who were intolerant to or failed to respond to standard treatment.

Plasma Lipid Profiling of Three Types of Drug-Induced Liver Injury in Japanese Patients: A Preliminary Study.

Drug-induced liver injury (DILI) is a major adverse event caused by drug treatment, which can be categorized into three types: hepatocellular, mixed, and cholestatic. Although nearly every class of drugs can cause DILI, an overall understanding of lipid profiles in DILI patients is lacking. We used lipidomics to analyze the plasma lipid profiles of patients to understand their hepatic pathophysiology and identify DILI biomarkers.

Extracellular Vesicles Produced by Bifidobacterium longum Export Mucin-Binding Proteins.

Extracellular proteins are important factors in host-microbe interactions; however, the specific factors that enable bifidobacterial adhesion and survival in the gastrointestinal (GI) tract are not fully characterized. Here, we discovered that NCC2705 cultured in bacterium-free supernatants of human fecal fermentation broth released a myriad of particles into the extracellular environment. The aim of this study was to characterize the physiological properties of these extracellular particles.

A validation study of the Ursodeoxycholic Acid Response Score in Japanese patients with primary biliary cholangitis.

Background/purpose: Although ursodeoxycholic acid (UDCA) is a first-line treatment for primary biliary cholangitis (PBC), 20%-30% of patients with PBC exhibit an incomplete response to UDCA. Recently, the UDCA Response Score was proposed for predicting response to UDCA using pretreatment parameters in patients with PBC. We aimed to validate the UDCA Response Score in Japanese patients with PBC.

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.

Gilbert Syndrome with Concomitant Hereditary Spherocytosis Presenting with Moderate Unconjugated Hyperbilirubinemia.

We experienced a case of a 19-year-old man with Gilbert syndrome with concomitant hereditary spherocytosis. The patient presented with moderate unconjugated hyperbilirubinemia, and inherited etiology was strongly suspected. The diagnosis of Gilbert syndrome was confirmed by the genetic analysis of the UGT1A1 gene, demonstrating UGT1A1*28 and compound heterozygote UGT1A1*6.

Validation of the Japanese version of the Chronic Liver Disease Questionnaire for the assessment of health-related quality of life in patients with chronic viral hepatitis.

Aim: Patients with chronic liver diseases (CLD) suffer from a variety of subjective symptoms, and the assessment of health-related quality of life (HRQOL) is crucial. The Chronic Liver Disease Questionnaire (CLDQ) is the first liver disease-specific instrument for this purpose. In this study we aimed to develop the Japanese version of CLDQ and to assess its validity and reliability in Japanese patients with chronic viral hepatitis.

Benefit of cystatin C in evaluation of renal function and prediction of survival in patients with cirrhosis.

Aim: The assessment of renal function is of vital importance in management of patients with cirrhosis. While serum creatinine (Cr) is routinely used for this purpose, Cr-based estimated glomerular filtration rate (eGFR) does not reflect true renal function because of muscle wasting and impaired liver function. By contrast, cystatin C (CysC) is unrelated to muscle volume and liver function.

Endoscopic removal of a denture with clasps impacted in the ileocecum.

We report a case of endoscopic removal of a denture with clasps impacted in the ileocecum. The patient was a 63-year-old man hospitalized at another center with aspiration pneumonia. He had a history of cerebral bleeding, inflicted permanent damage with left hemiplegia, and dysphagia.

Carcinosarcoma of the liver.

Herein we present a 73-year-old man with primary carcinosarcoma of the liver, a rare malignant tumor of the liver. The case was followed up due to HBV-related liver cirrhosis. Regular check-up by ultrasound demonstrated a hyperechoic tumor in the left lobe of the liver, and he was referred and admitted to our hospital.

Autoimmune neutropenia due to antineutrophil antibodies in a patient with primary sclerosing cholangitis.

Autoimmune neutropenia (AIN) is defined as a decrease in the circulating absolute neutrophil count (ANC) to less than 1500/μl caused by serum antineutrophil antibodies. Secondary AIN is associated with various autoimmune diseases. Herein we present the case of a patient with primary sclerosing cholangitis (PSC) who developed secondary AIN.

The clinical significance of IgA antimitochondrial antibodies in sera and saliva in primary biliary cirrhosis.

It still remains unclear how antimitochondrial autoantibodies (AMA) are involved with immunopathogenesis of primary biliary cirrhosis (PBC). We have suggested the potential role of IgA-AMA in damage to epithelial cells in PBC. In the current study, we investigated whether IgA-AMA were detectable in sera and saliva of PBC patients, to examine the association between detectable IgA-type autoantibodies in sera or saliva and progression of liver diseases.

Liver injury induced by levothyroxine in a patient with primary hypothyroidism.

We report a patient with primary hypothyroidism, who developed hepatocellular injury due to levothyroxine, synthetic thyroxine. A 63-year-old male was admitted to our hospital due to elevation of liver enzymes. The patient was diagnosed as having hypothyroidism and had been treated with levothyroxine for almost two months until admission.

Comparison of urinary excretion of pravastatin and temocapril in bile duct-ligated rats and Eisai hyperbilirubinemic rats (EHBR).

Background/purpose: In patients with complete bile duct obstruction, the only pathway for the elimination of cholephilic compounds is through the urine. Although changes in various transporters in the liver and kidney in cholestasis have been elucidated, little is known about how effectively the elimination of these compounds is compensated for by urinary excretion.

Methods: In the present study, the urinary excretion of pravastatin and temocapril was studied in bile-duct-ligated rats (BDLR) for 3 days and in Eisai hyperbilirubinemic rats (EHBR).

Serum soluble interleukin-2 receptor in eosinophilia.

The relationship between soluble interleukin-2 receptor (sIL-2R) levels and clinical characteristics was evaluated in patients with eosinophilia. Thirty-eight out of 60 patients showed sIL-2R levels of more than 800 U/ml. In these patients, sIL-2R was closely related to the eosinophil count, but not the IgE level.

Biliary excretion of bile acids and organic anions in zone 1- and zone 3-injured rats.

Aims: Hepatocytes in zone 1 of the hepatic lobule play a role in the uptake and biliary excretion of bile acids and organic anions under physiological conditions, and those in zone 3 may play a role only with a high-dose load. To further elucidate the role of hepatic zonation on the handling of bile acids and organic anions, biliary excretion of these compounds was studied in zone 1- and zone 3-injured rats.

Methods: Biliary excretion of bile acids and organic anions was studied in zone 1- and zone 3-injured rats, caused by allyl alcohol and bromobenzene, respectively.

Effect of tauro-alpha-muricholate and tauro-beta-muricholate on oestradiol-17 beta-glucuronide-induced cholestasis in rats.

The effect of tauro-beta-muricholate (beta MC-tau) and tauro-alpha-muricholate (alpha MC-tau) on oestradiol-17 beta-glucuronide (E217G)-induced cholestasis was compared with that of tauroursodeoxycholate (UDC-tau) in rats. Like UDC-tau, alpha MC-tau and beta MC-tau infused at the rate of 0.2 mumol/min per 100 g bodyweight (BW) completely inhibited the cholestasis induced by E217G infused at the rate of 0.

[Aspergillus lumbar discitis in a patient with acute lymphoblastic leukemia following induction therapy].

A 47-year-old female was admitted in October 1988 because of anemia and lymphoblastic cells in peripheral blood. A bone marrow aspirate was hypercellular with 93.9% lymphoblasts negative for peroxidase staining.

[A "retinoic acid syndrome" observed in two cases of acute promyelocytic leukemia].

Two cases of acute promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA) developed fever, dyspnea and chest pain. A chest roentgenogram showed bilateral pleural effusion (case 1) and bilateral interstitial infiltration (case 2). The first case was a 50-year-old female in her first relapse, who was initially diagnosed as having pleuritis tuberculosa and was treated with anti-tuberculotic agents.

Interstitial pneumonitis possibly due to mitoxantrone.

A 41-year-old patient with chronic myelogenous leukemia in the accelerated phase was treated with mitoxantrone. She developed pyrexia 7 days after receiving the third administration of mitoxantrone. After 3 more days, she experienced dry cough and dyspnea.