Sphingosine-1-phosphate promotes liver fibrosis in metabolic dysfunction-associated steatohepatitis.

Aim: Metabolic dysfunction-associated steatohepatitis (MASH) is one of the most prevalent liver diseases and is characterized by steatosis and the accumulation of bioactive lipids. This study aims to understand the specific lipid species responsible for the progression of liver fibrosis in MASH.

Methods: Changes in bioactive lipid levels were examined in the livers of MASH mice fed a choline-deficient diet (CDD).

Cases of Rapid Hepatitis B Surface Antigen Reduction after COVID-19 Vaccination.

Objective One of the therapeutic goals for chronic infection with hepatitis B virus is the clearance of hepatitis B surface antigen (HBsAg) from the blood, as a high load of HBsAg has been proposed to induce antigen-specific immunotolerance. To achieve HBsAg reduction, Pegylated interferon and nucleos (t) ide analogs are used to treat chronic hepatitis B. Following the coronavirus disease 2019 (COVID-19) outbreak, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has rapidly spread worldwide, and vaccination with mRNA COVID-19 vaccines has been conducted since 2021 in Japan.

Iron chelator deferasirox inhibits NF-κB activity in hepatoma cells and changes sorafenib-induced programmed cell deaths.

Objective: The improvements of antitumor effects and tolerability on chemotherapy for advanced hepatocellular carcinoma (HCC) are warranted. Here, we aimed to elucidate the mechanism of the combining effect of tyrosine kinase inhibitor sorafenib (SOR) and iron chelator deferasirox (DFX) in human hepatoma cell lines, HepG2 and Huh-7.

Methods: The types of programmed cell deaths (PCDs); necrosis/necroptosis and apoptosis, were evaluated by flow cytometry and fluorescent microscopy.

Real-world efficacy and safety of 12-week sofosbuvir/velpatasvir treatment for patients with decompensated liver cirrhosis caused by hepatitis C virus infection.

Aim: This study aimed to evaluate the real-world efficacy and safety of 12-week sofosbuvir/velpatasvir (SOF/VEL) treatment for patients with decompensated liver cirrhosis caused by hepatitis C virus (HCV) infection.

Methods: A total 72 of patients with Child-Pugh (CP) class B or C were enrolled. We evaluated the sustained virologic response at 12 weeks after the end of treatment (SVR12), adverse events (AEs), and changes in the liver function.

Identification of heterozygous p.Y150C and p.V274M mutations in the HJV gene in a Japanese patient with a mild phenotype of juvenile hemochromatosis: A case report.

Juvenile hemochromatosis (JH) is known as a progressive iron-storage disease, and causes severe organ impairments, including cardiomyopathy and liver cirrhosis. However, JH is a rare genetic disorder, and information for genetic mutations and phenotypes is limited. Here, we report a case of JH with heterozygous p.

Hypozincemia is associated with human hepatocarcinogenesis in hepatitis C virus-related liver cirrhosis.

Aim: Hypozincemia is associated with the progression of chronic liver diseases, but it is unknown whether hypozincemia promotes human hepatocarcinogenesis. Our aim is to evaluate the serum zinc levels in liver cirrhosis (LC) patients and clarify the relationship between the serum zinc levels and the development of hepatocellular carcinoma (HCC).

Methods: Cirrhotic patients without HCC (n = 299) were enrolled from 14 medical institutes in Japan as a multicenter prospective study (No.

Splicing variant of hepcidin mRNA.

Hepcidin is a main regulator of iron metabolism, of which abnormal expression affects intestinal absorption and reticuloendothelial sequestration of iron by interacting with ferroportin. It is also noted that abnormal iron accumulation is one of the key factors to facilitate promotion and progression of cancer including hepatoma. In this study, we firstly revealed that a new alternative HAMP transcript was found in hepatoma-derived cell line HLF, which was identical to the wild-type preprohepcidin sequence except lacking of an internal 60 bases.

Iron-induced epigenetic abnormalities of mouse bone marrow through aberrant activation of aconitase and isocitrate dehydrogenase.

Iron overload remains a concern in myelodysplastic syndrome (MDS) patients. Iron chelation therapy (ICT) thus plays an integral role in the management of these patients. Moreover, ICT has been shown to prolong leukemia-free survival in MDS patients; however, the mechanisms responsible for this effect are unclear.

Bone morphogenetic protein-binding endothelial regulator of liver sinusoidal endothelial cells induces iron overload in a fatty liver mouse model.

Background: Non-alcoholic fatty liver disease (NAFLD) is frequently accompanied by iron overload. However, because of the complex hepcidin-regulating molecules, the molecular mechanism underlying iron overload remains unknown. To identify the key molecule involved in NAFLD-associated iron dysregulation, we performed whole-RNA sequencing on the livers of obese mice.

A selective splicing variant of hepcidin mRNA in hepatocellular carcinoma cell lines.

Hepcidin is a main regulator of iron metabolism, of which abnormal expression affects intestinal absorption and reticuloendothelial sequestration of iron by interacting with ferroportin. It is also noted that abnormal iron accumulation is one of the key factors to facilitate promotion and progression of cancer including hepatoma. By RT-PCR/agarose gel electrophoresis of hepcidin mRNA in a hepatocellular carcinoma cell line HLF, a smaller mRNA band was shown in addition to the wild-type hepcidin mRNA.

A Bamboo Joint-Like Appearance is a Characteristic Finding in the Upper Gastrointestinal Tract of Crohn's Disease Patients: A Case-Control Study.

The clinical importance of Crohn's disease (CD)-specific lesions in the upper gastrointestinal tract (upper GIT) has not been sufficiently established. The aim of this case-control study is to investigate the characteristic findings of CD in the upper GIT. In 2740 patients who underwent gastroduodenoscopy at Asahikawa Medical University between April 2011 and December 2012, 81 CD patients, 81 gender- and age-matched non-IBD patients, and 66 ulcerative colitis (UC) patients were investigated in the present study.

Heterogeneous Nuclear Ribonucleoprotein A1 Improves the Intestinal Injury by Regulating Apoptosis Through Trefoil Factor 2 in Mice with Anti-CD3-induced Enteritis.

Background: The role of hnRNP A1 in the onset of intestinal inflammation remains unclear. This study investigated the function of hnRNP A1 in mice enteritis models.

Methods: C57Bl6/J mice were intraperitoneally injected with anti-CD3 antibodies to develop enteritis.

Polyphosphate, an active molecule derived from probiotic Lactobacillus brevis, improves the fibrosis in murine colitis.

Inflammatory bowel disease frequently causes intestinal obstruction because of extensive fibrosis. This study investigated whether polyphosphate (poly P), an active molecule derived from Lactobacillus brevis, could improve the fibrosis in a model of chronic colitis. In this study, dextran sodium sulfate (DSS)-induced chronic colitis models and trinitrobenzene sulfonic acid (TNBS)-induced colitis models were used as models of fibrosis.

A randomized study on the effectiveness of prophylactic clipping during endoscopic resection of colon polyps for the prevention of delayed bleeding.

Backgrounds: The efficacy of clipping for preventing the delayed bleeding after the removal of colon polyps is still controversial. In order to clarify this efficacy, a randomized controlled study was performed.

Methods: One hundred and fifty-six patients with colon neoplasms (288 lesions) were enrolled in the study.

Hepatic nerve growth factor induced by iron overload triggers defenestration in liver sinusoidal endothelial cells.

The fenestrations of liver sinusoidal endothelial cells (LSECs) play important roles in the exchange of macromolecules, solutes, and fluid between blood and surrounding liver tissues in response to hepatotoxic drugs, toxins, and oxidative stress. As excess iron is a hepatotoxin, LSECs may be affected by excess iron. In this study, we found a novel link between LSEC defenestration and hepatic nerve growth factor (NGF) in iron-overloaded mice.

Effective control of relapsing disseminated intravascular coagulation in a patient with decompensated liver cirrhosis by recombinant soluble thrombomodulin.

A 70-year-old Japanese man was hospitalized for expanding purpura and chronic disseminated intravascular coagulation (DIC) caused by decompensated liver cirrhosis. As there are no effective treatments for chronic DIC caused by liver cirrhosis, we decided to administer recombinant human soluble thrombomodulin (rhsTM) after he provided informed consent. The DIC was rapidly improved; however, the purpura and coagulopathy recurred after two months, and repeated rhsTM treatments were required.

Infliximab extends the duration until the first surgery in patients with Crohn's disease.

Background/aims: While biological drugs are useful for relieving the disease activity and preventing abdominal surgery in patients with Crohn's disease (CD), it is unclear whether the use of biological drugs in CD patients with no history of abdominal surgery is appropriate. We evaluated the effects of infliximab and other factors on extending the duration until the first surgery in CD patients on a long-term basis.

Methods: The clinical records of 104 CD patients were retrospectively investigated.

Branched-chain amino acids prevent hepatocarcinogenesis and prolong survival of patients with cirrhosis.

Background & Aims: Although a low plasma level of branched-chain amino acids (BCAAs) is a marker of cirrhosis, it is not clear whether BCAA supplements affect disease progression. We performed a multicenter study to evaluate the effects of BCAA supplementation on hepatocarcinogenesis and survival in patients with cirrhosis.

Methods: We enrolled 299 patients from 14 medical institutions in Japan in a prospective, multicenter study in 2009; 267 patients were followed through 2011.

Upregulation of iron regulatory hormone hepcidin by interferon α.

Background And Aim: Interferon (IFN) activates various immune systems in vivo and is administered to patients with diseases such as viral hepatitis B, C, and malignant tumors. Iron dysregulation has been reported during treatment with IFN; however, it remains unclear whether IFN itself affects iron metabolism. We therefore determined the effect of IFN on iron metabolism.

Augmented hepatic Toll-like receptors by fatty acids trigger the pro-inflammatory state of non-alcoholic fatty liver disease in mice.

Aim: There is considerable evidence that intestinal microbiota are involved in the development of metabolic syndromes and, consequently, with the development of non-alcoholic fatty liver disease (NAFLD). Toll-like receptors (TLRs) are essential for the recognition of microbiota. However, the induction mechanism of TLR signals through the gut-liver axis for triggering the development of non-alcoholic steatohepatitis (NASH) or NAFLD remains unclear.

MicroRNA-146b improves intestinal injury in mouse colitis by activating nuclear factor-κB and improving epithelial barrier function.

Background: The precise role of microRNAs in inflammatory disease is not clear. The present study investigated the effect of microRNA (miR-146b) with respect to improving intestinal inflammation.

Methods: The microRNA profile in interleukin-10 deficient mice was examined using microRNA arrays and miR-146b was selected for the subsequent experiments.

Survey of non-B, non-C liver cirrhosis in Japan.

Aim: The aim of this survey was to reveal clinical features for each etiology of non-B, non-C liver cirrhosis (NBNC LC) in Japan.

Methods: In a nationwide survey of NBNC LC in Japan at the 15th General Meeting of the Japan Society of Hepatology, 6999 NBNC LC patients were registered at 48 medical institutions. Epidemiological and clinical factors were investigated.