Hepatocyte growth factor overexpression ameliorates liver inflammation and fibrosis in a mouse model of nonalcoholic steatohepatitis.

Background: Hepatocyte growth factor (HGF) is a potent growth factor involved in liver regeneration that has various effects on epithelial and nonepithelial cells. Although it has been demonstrated that HGF can reduce liver inflammation or fibrosis caused by pharmaceutical or chemical insult, no examination of its effect on liver injury in nonalcoholic steatohepatitis (NASH) has been reported.

Methods: To examine the effect of HGF on liver injury in NASH, we generated a murine steatohepatitis model on an HGF overexpression transgenic (Tg) background, and fed the mice a methionine- and choline-deficient diet (MCD).

Azelnidipine is a calcium blocker that attenuates liver fibrosis and may increase antioxidant defence.

Background And Purpose: Oxidative stress plays a critical role in liver fibrogenesis. Reactive oxygen species (ROS) stimulate hepatic stellate cells (HSCs), and ROS-mediated increases in calcium influx further increase ROS production. Azelnidipine is a calcium blocker that has been shown to have antioxidant effects in endothelial cells and cardiomyocytes.

Epstein-Barr virus-positive T-cell lymphoma cells having chromosome 22q11.2 deletion: an autopsy report of DiGeorge syndrome.

Reported herein was the first autopsy case of Epstein-Barr virus-associated T-cell lymphoma in a 25-year-old man with DiGeorge syndrome. Systemic lymph nodes demonstrated diffuse encasement by large lymphoma cells positive for CD45, CD2, CD3, CD5, CD7, CD8, TIA1, and granzyme B, accompanied with marked hemophagocytosis. Almost 100% of lymphoma cells were both EBER- and LMP-1-positive, and EBNA2-negative.

Optimal follow-up time to determine the sustained virological response in patients with chronic hepatitis C receiving pegylated-interferon and ribavirin.

Background And Aim: This study evaluated whether the assessment of hepatitis C virus (HCV)-RNA at 12 weeks (FW+12) post-treatment follow-up was as applicable as FW+24 to evaluate sustained virological response (SVR) using the highly sensitive real-time polymerase chain reaction (PCR) HCV assay.

Methods And Results: Two hundred and twenty-two patients with chronic hepatitis C were included in this study. Pegylated interferon (Peg-IFN) and ribavirin were administered for 24-72 weeks based on the genotype and viral load.

Nuclear receptors CAR and PXR; therapeutic targets for cholestatic liver disease.

Cholestasis results in the intrahepatic retention of cytotoxic bile acids (BA) and it can thus lead to liver injury. Hydrophilic BA ursodeoxycholic acid (UDCA) is currently used to treat cholestasis but its efficacy is limited. Nuclear receptors are key regulators of various processes including metabolism of xeno- and endobiotics such as BA and drugs.

A retrospective cohort study of partial splenic embolization for antiviral therapy in chronic hepatitis C with thrombocytopenia.

Background: Although partial splenic embolization (PSE) is reportedly effective prior to interferon (IFN)-based therapy, the number of subjects in these studies is small, and the appropriate candidates and disease prognosis remain unknown.

Methods: PSE was performed in 30 patients with advanced hepatitis C who could not receive IFN-based therapy because of thrombocytopenia, platelet counts of ≤100,000/mm(3), and hypersplenism. Also, we compared 25 PSE-treated patients with 23 PSE-untreated patients with thrombocytopenia receiving pegylated IFN (PEG-IFN)-alpha 2b plus ribavirin over the same period.

Gastric ulcer revealed by computed tomography in a patient with tongue cancer after percutaneous gastrostomy.

With the advances in computed tomography (CT) imaging, CT can result in precise imaging, even of the gastrointestinal tract. However, the diagnostic quality of endoscopy is superior to CT because of precise mucosal observations or biopsy procedure. In the present case, CT was useful in the diagnosis of a gastric ulcer because endoscopy was deemed too difficult to perform due to tongue cancer occupying the oral space.

Nuclear receptor CAR-regulated expression of the FAM84A gene during the development of mouse liver tumors.

The nuclear xenobiotic receptor CAR is a phenobarbital (PB)-activated transcription factor. Using a mouse model of two-step liver tumorigenesis, in which tumor growth was initiated by diethyl nitrosamine (DEN) and promoted by chronic treatment with PB, we previously demonstrated that tumors developed only in the presence of CAR. Here, we have identified the FAM84A (family with sequence similarity 84, member A) gene as a CAR-regulated gene that is over-expressed during development of phenobarbital-promoted mouse liver tumors.

Transforming growth factor-α attenuates hepatic fibrosis: possible involvement of matrix metalloproteinase-1.

Background: The effect of transforming growth factor (TGF)-α on fibrosis varies between cell types and the role of TGF-α in hepatic fibrosis has not been fully elucidated.

Methods: We examined the effect of TGF-α on hepatic fibrosis using TGF-α-expressing transgenic mice fed a methionine- and choline-deficient (MCD) diet and human hepatic stellate cells (HSCs) line LX-2, rat and human primary HSCs.

Results: Although the expression levels of the tissue inhibitor of metalloproteinases-1 and α1(I) collagen mRNA were unchanged, feeding the TGF-α transgenic mice the MCD diet resulted in greater expression of the murine functional analogue of matrix metalloproteinase-1 (MMP-1), MMP-13 mRNA and protein and attenuated hepatic fibrosis compared with wild-type mice.

Stricture after endoscopic submucosal dissection for early gastric cancers and adenomas.

Background And Aim:  Stricture is a complication that may occur after endoscopic submucosal dissection (ESD) of gastric neoplasms. The goal of the present study was to investigate the incidence, risk factors and management of gastric stricture after ESD.

Methods: The medical records of 308 patients who underwent ESD for gastric neoplasms were reviewed.

Clinical characteristics and treatment for patients presenting with bleeding duodenal varices.

Background And Aim: Bleeding from ectopic varices, including duodenal varices, is uncommon, but it can be difficult to manage. The clinical data of patients diagnosed and treated for duodenal varices were reviewed to investigate the strategy for treatment.

Methods: The present study reviewed the clinical data of 10 patients with duodenal varices (mean age, 58.

Clinical characteristics of null responders to Peg-IFNα2b/ribavirin therapy for chronic hepatitis C.

Aim: To predict which chronic hepatitis C patients are likely to be late-responders, we herein investigated the clinical characteristics of null-responders at 36 wk with hepatitis C virus (HCV) genotype Ib and a high viral load during the course of pegylated interferon (Peg-IFN)/ribavirin therapy.

Methods: One hundred forty-two patients with genotype Ib HCV and a high viral load were included in this study. Peg-IFNα2b (1.

Constitutive active/androstane receptor promotes hepatocarcinogenesis in a mouse model of non-alcoholic steatohepatitis.

The nuclear receptor constitutive active/androstane receptor (CAR) acts as a sensor of toxic byproducts derived from the endogenous metabolism and exogenous chemicals. We previously reported that CAR is responsible for exacerbating hepatic injury and fibrosis in a dietary model of non-alcoholic steatohepatitis (NASH) via upregulation of lipid peroxidation. In this study, we investigated the pathological roles of the CAR in the development of hepatocellular carcinoma in NASH model.

Radiation dose to the pediatric cardiac catheterization and intervention patient.

Objective: The radiation dose from cardiac catheterization is particularly relevant when treating children because of their greater radiosensitivity compared with adults. Moreover, cardiac catheterization is being used increasingly for interventional radiology procedures, possibly resulting in higher patient radiation doses. This article reports the radiation doses and related factors, such as fluoroscopy time, for children who underwent cardiac catheterization and children who underwent other interventional radiology procedures.

[A case of hepatocellular carcinoma complicated with Caroli's disease].

A 29-year-old man was admitted with right hypochondralgia and fever. Markedly dilated bile ducts were observed, mainly in the right lobe of the liver. Based on both the clinical findings and imaging, we diagnosed Caroli's disease and choledochal cyst complicated with cholangitis.

Histone deacetylase inhibitors induce cytochrome P450 2B by activating nuclear receptor constitutive androstane receptor.

Valproic acid, a histone deacetylase (HDAC) inhibitor, induces the cytochrome P450 2B subfamily. However, the effects of HDAC inhibitors on CYP2B induction are still not fully understood. Nuclear receptor constitutive androstane receptor (CAR) is a key regulator of CYP2B induction.

Endoscopic treatment of rectal carcinoid tumors.

Background: Various methods have been reported for the endoscopic treatment of rectal carcinoid tumors. The present study was designed to identify the optimal treatment strategy for an endoscopic resection.

Methods: Forty rectal carcinoid tumors of 38 patients were treated endoscopically.

Xenobiotic-sensing nuclear receptors CAR and PXR as drug targets in cholestatic liver disease.

Cholestasis results in the intrahepatic retention of cytotoxic bile acid and it can thus lead to liver injury and/or liver fibrosis. Cholestatic liver damage is counteracted by a variety of intrinsic hepatoprotective mechanisms including a complex network of drug metabolizing enzymes and transporters. During the last decade, much progress has been made in dissecting the mechanisms which regulate the hepatic xeno- and endobiotic metabolism by nuclear receptors.

[A case of autoimmune hepatitis which worsened after switching from a brand name to a generic version of prednisolone].

We recently encountered a case of autoimmune hepatitis whose symptoms worsened after switching from a brand name to a generic version of prednisolone. The patient was a 46-year-old woman. She was admitted because of elevation of alanine aminotransferase (ALT) levels during follow-up sessions.

Endoscopic submucosal dissection for colorectal tumors.

Background: Endoscopic submucosal dissection (ESD) is a state-of-the-art method that enables resection of larger tumors than those resectable by conventional endoscopic mucosal resection (EMR). However, the individual role of each method in the treatment of colorectal tumors remains undetermined.

Objective And Methods: To consider the respective indications of ESD and EMR for colorectal tumors, we analyzed the results of the two treatments retrospectively.

Fucosylated fraction of alpha-fetoprotein as a predictor of prognosis in patients with hepatocellular carcinoma after curative treatment.

Aim: The aim of this study was to evaluate the clinical usefulness of measuring the Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3) for prognostic predictor in patients with hepatocellular carcinoma (HCC).

Methods: A total of 477 HCC patients who underwent percutaneous ablative therapy or hepatectomy were enrolled. Overall survival and recurrence-free survival were respectively evaluated retrospectively and prospectively.

Hepatocyte growth factor protects against Fas-mediated liver apoptosis in transgenic mice.

Background: Apoptosis via the Fas/Fas ligand signalling system plays an important role in the development of various liver diseases. The administration of an agonistic anti-Fas antibody to mice causes massive hepatic apoptosis and fulminant hepatic failure. Several growth factors including hepatocyte growth factor (HGF) have been found to prevent apoptosis.

Marked eosinophilia as the first manifestation of sclerosing cholangitis.

We encountered a 45-year-old man who presented with marked eosinophilia as the first manifestation of sclerosing cholangitis. He was found to have a liver dysfunction during a regular physical check up and thereafter consulted our hospital. The laboratory data on admission indicated an elevation of AST (96 IU/L), ALT (136 IU/L) and ALP (1,025 IU/L).