[An anatomical case of obstructive jaundice due to the rapid enlargement of hepatic peribiliary cysts in end-stage alcoholic liver cirrhosis].

A man in his 60s had end-stage alcoholic cirrhosis. About six months before his death, hepatic peribiliary cysts (HPBC) rapidly increased, and he developed jaundice and liver failure. The pathological autopsy performed after his death revealed that his intrahepatic bile duct was pressured due to multiple cysts caused by HPBC, which resulted in liver failure.

Pretreatment with antibiotics is associated with reduced therapeutic response to atezolizumab plus bevacizumab in patients with hepatocellular carcinoma.

Aim: Alterations in microbial composition of gut microbiota due to antibiotics (ATB) may lead to resistance to immune checkpoint inhibitors (ICIs). This study aimed to assess the impact of ATB use on therapeutic response in patients with hepatocellular carcinoma (HCC) receiving atezolizumab plus bevacizumab.

Methods: This study retrospectively analyzed 105 patients with HCC treated with atezolizumab plus bevacizumab as a primary systemic therapy from prospectively-registered, multicenter, cohorts.

Two cases of delayed onset of immune-related adverse events after discontinuation of nivolumab in patients with metastatic renal cell cancer.

Introduction: Delayed onset of immune-related adverse events following immune-checkpoint inhibitor discontinuation is underrecognized because of little available evidence.

Case Presentation: A 50-year-old man with metastatic renal cell carcinoma (Case 1) and 58-year-old woman with renal cell carcinoma and retroperitoneal lymph node metastasis (Case 2) underwent nivolumab therapy. Case 1: Progressive disease forced nivolumab discontinuance after 18 months, and he underwent two courses of tyrosine kinase inhibitor therapy.

Self-expandable metallic stent placement above the papilla without endoscopic sphincterotomy in patients with distal malignant biliary obstruction.

The best method for endoscopic placement of self-expandable metallic stents (SEMS) for distal malignant biliary obstruction (MBO) has not yet been determined. The aim of this study was to evaluate how SEMS placement above the papilla and without endoscopic sphincterotomy (EST) impacts the time to recurrent biliary obstruction (RBO) in patients with distal MBO. We retrospectively reviewed data for 73 consecutive patients with unresectable distal MBO who underwent endoscopic SEMS placement for the first time at our institution between April 2014 and March 2016.

Prognostic Factors for Patients With a Large Number of Hepatocellular Carcinoma Nodules.

Background: The prognostic factors and treatment strategies for hepatocellular carcinoma (HCC) patients with a large number of tumor nodules have not been fully elucidated. Clinical factors influencing prognosis were investigated in HCC patients with 30 or more tumor nodules.

Methods: Forty-six HCC patients with 30 or more tumor nodules participated in this study.

Chemotherapy-Induced Sclerosing Cholangitis Caused by Systemic Chemotherapy.

A 61-year-old woman diagnosed with cervical cancer received systemic chemotherapy using paclitaxel and bevacizumab. Marked elevation of liver enzyme levels was observed. Ultrasonography and computed tomography showed wall thickening of the extrahepatic and intrahepatic bile ducts accompanied by stricture and dilatation.

Development of a thrombus in the superior mesenteric artery associated with sequential therapy with tyrosine kinase inhibitors for hepatocellular carcinoma.

Tyrosine kinase inhibitors (TKIs) are widely used for systemic chemotherapy of hepatocellular carcinoma (HCC). Arterial thromboembolism (ATE) has been reported to be an adverse event associated with TKI therapy, but its incidence is rare. Here, we report a case of an HCC patient who developed a thrombus in the superior mesenteric artery (SMA) while on TKI therapy.

Two-step progression of varenicline-induced autoimmune hepatitis.

We describe a rare case of drug-induced hepatitis due to the smoking cessation agent varenicline in a 46-year-old Asian woman. The liver injury progressed in two steps. First, the liver injury started in the absence of viral/autoimmune responses, and withdrawal of varenicline lowered the increase in the levels of liver enzymes immediately.

The Effectiveness of a Liver Disease Education Class for Providing Information to Patients and Their Families.

Background: We have been conducting liver disease education classes regularly in our hospital for the purpose of providing health information to patients and their families.

Methods: In order to evaluate the effectiveness of these classes, we conducted a questionnaire survey of patients and family members who attended the classes held three times in 2012. The cumulative total number of participants was 80 (49 patients, 26 family members, and five others).

CD14 monocyte-derived galectin-9 induces natural killer cell cytotoxicity in chronic hepatitis C.

Unlabelled: Natural killer (NK) cell activation is associated with both liver injury and persistent infection in chronic hepatitis C (CHC); however, the detailed mechanism of this activation has not yet been fully elucidated. Because galectin-9 (Gal-9) has been reported to be increased in the serum and liver tissue of CHC patients, we investigated the function of Gal-9 in NK cell activation in CHC. First, we evaluated the function of Gal-9 on NK cytotoxicity in vitro.

Quick and stable parallel puncture of hepatic tumors using a double-barreled needle direction system for ultrasound-guided bipolar radiofrequency ablation.

Aim: In bipolar radiofrequency ablation (RFA) therapy, insertion of multiple needles at appropriate points on a target is difficult. The aim of our study was to evaluate a simplified method for multi-electrode insertion using a newly developed double-barreled needle guidance system for percutaneous RFA of hepatic tumors.

Methods: RFA using two bipolar electrodes was performed in 15 consecutive patients (nine men, six women; mean age, 72.

The Hepatitis B Virus Genotype Affects the Persistence of Viral Replication in Immunodeficient NOG Mice.

Background & Aims: At least eight genotypes of Hepatitis B virus (HBV) have been identified. HBV genotype C is the most common genotype in Japan, although the incidence of HBV genotype A is increasing. The reason underlying the differences in viral multiplication of the HBV genotypes is unclear, especially in vivo.

S100A8 Production in CXCR2-Expressing CD11b+Gr-1high Cells Aggravates Hepatitis in Mice Fed a High-Fat and High-Cholesterol Diet.

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease with a spectrum of presentations. S100A8 has been suggested to play a pivotal role as an endogenous immune-activator in inflammatory diseases. In this study, we investigated the involvement of S100A8 in the development of NAFLD.

Emergence of hepatitis C virus NS5A L31V plus Y93H variant upon treatment failure of daclatasvir and asunaprevir is relatively resistant to ledipasvir and NS5B polymerase nucleotide inhibitor GS-558093 in human hepatocyte chimeric mice.

Background: Resistance-associated variants (RAVs) emerge at multiple positions spanning hepatitis C virus (HCV) NS3/4A and NS5A regions upon failure of asunaprevir/daclatasvir combination therapy. It has not been determined whether the emergence of such RAVs have an impact on re-treatment by a combination of ledipasvir and sofosbuvir, a potent regimen for HCV genotype 1 infection.

Methods: TK-NOG human hepatocyte chimeric mice were inoculated with sera from a patient with treatment failure of asunaprevir/daclatasvir therapy.

Invariant natural killer T cell deficiency leads to the development of spontaneous liver inflammation dependent on γδT cells in mice.

Background: Immune tolerance is maintained in the liver, and perturbation of tolerance can lead to immune-mediated liver diseases such as autoimmune hepatitis (AIH). Invariant natural killer T (iNKT) cells and γδT cells have been shown to maintain immune homeostasis as regulatory cells and to play pathogenic roles in immune-mediated diseases as effector cells. We hypothesized that iNKT cells and γδT cells are involved in the maintenance of hepatic immune tolerance and immune-mediated liver disease.

Carbamazepine promotes liver regeneration and survival in mice.

Background & Aims: Carbamazepine (CBZ), a widely used anticonvulsant and mood stabilizer, activates multiple proliferative and pro-survival pathways. Here, we hypothesize that CBZ may promote hepatocellular proliferation and ameliorate liver regeneration.

Methods: C57BL6/J mice were orally administered CBZ or vehicle and underwent a 70% partial hepatectomy (PHx), 85% PHx or treatment with carbon tetrachloride (CCl4).

Valine, the branched-chain amino acid, suppresses hepatitis C virus RNA replication but promotes infectious particle formation.

Background & Aims: Concentrations of the branched-chain amino acid (BCAA) in the serum of patients with liver cirrhosis correlate with their liver function. Oral administration of BCAA can ameliorate hypoalbuminemia and hepatic encephalopathy. In this study, we aim to clarify the role of BCAA in regulating the replication of the hepatitis C virus (HCV).

The combination therapy of α-galactosylceramide and 5-fluorouracil showed antitumor effect synergistically against liver tumor in mice.

α-Galactosylceramide (α-GalCer) has been reported to be therapeutic against metastatic liver tumors in mice. However, little is known regarding the efficacy of combined chemo-immunotherapy using α-GalCer and anticancer drugs. In this study, we evaluated the antitumor effect of the combination therapy of α-GalCer and 5-fluorouracil (5-FU) against liver tumors of MC38 colon cancer cells.

Interferon-α suppresses hepatitis B virus enhancer II activity via the protein kinase C pathway.

HBV has two enhancer (En) regions each of which promotes its own transcription. En II regulates production of pregenomic RNA, a key product of HBV replication, more strongly than En I. Although IFN-α has been found to suppress En I activity, its effect on En II activity has not been examined.

Alterations in microRNA expression profile in HCV-infected hepatoma cells: involvement of miR-491 in regulation of HCV replication via the PI3 kinase/Akt pathway.

The aim of this study was to investigate the role of microRNA (miRNA) on hepatitis C virus (HCV) replication in hepatoma cells. Using miRNA array analysis, miR-192/miR-215, miR-194, miR-320, and miR-491 were identified as miRNAs whose expression levels were altered by HCV infection. Among them, miR-192/miR-215 and miR-491 were capable of enhancing replication of the HCV replicon as well as HCV itself.

[A patient who developed diaphragmatic hernia 20 months after percutaneous radiofrequency ablation for hepatocellular carcinoma].

A 50-year-old man underwent radiofrequency ablation (RFA) for a hepatocellular carcinoma, located in the S8 area adjacent to the diaphragm. 20 months later, he was admitted because of severe right hypochondralgia and dyspnea. Computed tomography revealed a prolapsed large intestine through a defect on the right diaphragm, and emergency surgery was performed.