Fever following Treatment with Atezolizumab plus Bevacizumab Predicts Liver Injury in Patients with Unresectable Hepatocellular Carcinoma: A Prospective Observational Analysis.

Introduction: Liver injury is a treatment-related adverse event (liver-TRAE), one of the most common complications of atezolizumab plus bevacizumab (Atez/Bev) therapy, when treating unresectable hepatocellular carcinoma (uHCC). Fever following immune checkpoint inhibitor (ICI) therapy may predict ICI-induced liver injury in various malignancy types. However, the association between fever and liver-TRAEs in patients with uHCC treated with Atez/Bev has not been investigated.

Utility of MELD 3.0 and MELD-Na in Predicting Long-term Mortality and Rebleeding After Endoscopic Hemostasis for Acute Variceal Hemorrhaging in Patients with Cirrhosis.

Objective This retrospective study assessed the longitudinal prognostic accuracy of the MELD, MELD-Na, MELD 3.0, and Child-Pugh scores in predicting mortality and rebleeding risk in patients with liver cirrhosis (LC) following successful endoscopic hemostasis for acute variceal hemorrhaging (AVH). Methods Time-dependent receiver operating characteristics and survival analyses were performed to predict mortality.

Impact of alcohol consumption and muscle mass on bone mineral density in metabolic dysfunction and alcohol-associated liver disease (MetALD) and metabolic dysfunction-associated steatotic liver disease (MASLD).

Background And Aims: Metabolic dysfunction and alcohol-associated liver disease (MetALD) and metabolic dysfunction-associated steatotic liver disease (MASLD) are newly defined conditions within steatotic liver disease (SLD). We have previously reported that lean physique, hypertriglyceridemia and weak grip strength are risk factors for decreased bone mineral density (BMD) in patients with MASLD. While BMD is influenced by both alcohol consumption and metabolic dysfunction, the specific relationship between SLD and decreased BMD remains unclear.

Soluble Siglec-9 Improves Intestinal Barrier Function in a Mouse Model of Metabolic Dysfunction-Associated Steatohepatitis.

Metabolic dysfunction-associated steatohepatitis (MASH), characterized by liver inflammation, fibrosis, and fat accumulation, can develop into cirrhosis and liver cancer. Despite its increasing prevalence worldwide, there are few established therapies for advanced MASH. We previously demonstrated that stem cells from human exfoliated deciduous teeth-conditioned media (SHED-CM) exerted therapeutic effects in a MASH mouse model.

Rapid development of diffuse hepatic calcification in a patient with congenital hepatic fibrosis and secondary hyperparathyroidism.

A man in his 20 s with congenital hepatic fibrosis and polycystic kidney disease (PKD) presented with symptoms of anemia. Upper gastrointestinal endoscopy revealed mild exudative hemorrhage due to gastric antral vascular ectasia, which was treated with argon plasma coagulation. Computed tomography (CT) at admission revealed diffuse hepatic calcification and ectopic calcifications in the left buttock and bilateral inguinal regions.

Steroid initiation dose and duration of steroid reduction for immune checkpoint inhibitor-induced liver injury.

Aim: Treatment for severe immune checkpoint inhibitor (ICI)-induced liver injury (≥ Grade 3) requires prednisolone (PSL) administration and interruption of the underlying malignancy treatment. If the liver injury improves steadily, a lower initial dose of PSL is beneficial. We aimed to investigate the relationship between the initial dose of PSL and the response to PSL or the duration of PSL dose reduction.

Pathological significance of intranuclear structures in liver biopsy samples.

Aim: Glycogenated nuclei (GN) are glycogen deposits within the nuclei and are a frequent pathological finding in metabolic dysfunction-associated steatotic liver disease. This study aimed to investigate the relationship between GN and two morphologically distinct types of intranuclear lipid droplets in liver biopsy specimens and to explore their respective pathological significance.

Methods: We analyzed 135 liver biopsy specimens.

Decline of Persistent Jaundice in a Patient With Autoimmune Hepatitis and Vanishing Bile Duct Syndrome Treated With Elobixibat for Constipation.

We present the case of a 49-year-old woman with autoimmune hepatitis and persistent jaundice. On admission, pathology and laboratory results supported the diagnosis of autoimmune hepatitis-primary biliary cholangitis (AIH-PBC) overlap syndrome with vanishing bile duct syndrome (VBDS). Standard treatment, including methylprednisolone pulse therapy, prednisolone, azathioprine, bezafibrate, and ursodeoxycholic acid, failed to resolve jaundice.

Gut microbes associated with functional cure of chronic hepatitis B.

Background And Aims: Hepatitis B virus (HBV) is prevalent worldwide and is difficult to eradicate. Current treatment strategies for chronic hepatitis B ultimately seek to achieve functional cure (FC); however, the factors contributing to FC remain unclear. We aimed to investigate the gut microbiota profiles of patients with chronic hepatitis B who achieved FC.

Clinical features and pathological findings by liver biopsy in patients with immune-related sclerosing cholangitis induced by immune checkpoint inhibitors.

Background: Immune-related sclerosing cholangitis (irSC) induced by immune checkpoint inhibitors (ICIs) is relatively rare, and its clinical and pathological features are not well known.

Aims: We aimed to compare the clinical course and pathological findings of irSC with those of non-irSC liver injury.

Methods: Clinical data were retrospectively collected from 2416 patients with advanced malignancies treated with ICIs between September 2014 and October 2023.

Type 2 Diabetes and Hypertension as Risk Factors for Advanced Fibrosis in Biopsy Proven Metabolic Dysfunction-Associated Steatotic Liver Disease.

Objectives: To identify the diagnostic criteria for metabolic dysfunction-associated steatotic liver disease (MASLD) related to liver fibrosis and to characterize patients with cryptogenic steatotic liver disease (SLD) (non-MASLD) among those previously diagnosed with nonalcoholic fatty liver disease (NAFLD).

Methods: This multicenter retrospective study included 511 patients diagnosed with NAFLD via liver biopsy, and the prevalence of MASLD was assessed based on the diagnostic criteria. Patients were divided into those who met the MASLD criteria and those who did not, and the characteristics of advanced fibrosis and associated cardiometabolic factors were evaluated.

A Proposal for a Simple Subclassification of Advanced Hepatocellular Carcinoma in Systemic Treatment.

Objectives: This study focused on the presence or absence of vascular invasion and extrahepatic metastasis in hepatocellular carcinoma (HCC) and examined their impact on systemic treatment outcomes.

Methods: We retrospectively analyzed 362 patients with unresectable HCC who received first-line systemic therapy. The prognostic evaluation was based on the presence of vascular invasion and extrahepatic metastasis at the time of treatment initiation.

Activity and phosphatidylcholine transfer protein interactions of skeletal muscle thioesterase Them2 enable hepatic steatosis and insulin resistance.

Thioesterase superfamily member 2 (Them2), a long-chain fatty acyl-CoA thioesterase that is highly expressed in oxidative tissues, interacts with phosphatidylcholine transfer protein (PC-TP) to regulate hepatic lipid and glucose metabolism and to suppress insulin signaling. High-fat diet-fed mice lacking Them2 globally or specifically in skeletal muscle, but not liver, exhibit reduced hepatic steatosis and insulin resistance. Here, we report that the capacity of Them2 in skeletal muscle to promote hepatic steatosis and insulin resistance depends on both its catalytic activity and interaction with PC-TP.

Impact of BMI and Body Composition on First-line Systemic Treatment for Unresectable Hepatocellular Carcinoma.

Background/aim: The effects of body mass index (BMI) and body composition on the outcomes of systemic treatment for unresectable hepatocellular carcinoma (uHCC) remain unclear.

Patients And Methods: In this retrospective study, patients with uHCC treated with lenvatinib (LEN) or atezolizumab+bevacizumab, were classified into high- (≥25 kg/m) and low- (<25 kg/m) BMI groups and evaluated for prognosis. Prognostic impact of body composition was also evaluated.

Predicting early rebleeding and mortality after endoscopic hemostasis of esophagogastric varices: Diagnostic performance of aspartate aminotransferase-to-platelet ratio index and model for end-stage liver disease-Na score.

Background: Endoscopic variceal ligation and sclerotherapy are recommended for esophagogastric variceal bleeding (EGVB) in cirrhosis but can be complicated by early rebleeding and death. This study aimed to identify noninvasive markers accurately predicting early rebleeding and mortality after endoscopic hemostasis for EGVB.

Methods: Among 116 patients with endoscopically confirmed EGVB and endoscopic hemostasis, various noninvasive markers were calculated, and their predictive accuracy was compared by receiver-operating characteristic curve analysis.

Clinical Outcomes of Use of the Porous Glass Membrane Pumping Emulsification Device During Transarterial Chemoembolization for Hepatocellular Carcinoma.

Background/aim: The porous glass membrane pumping emulsification device enhances local therapeutic effects of transarterial chemoembolization for hepatocellular carcinoma (HCC); however, limited clinical outcomes have been reported. This study aimed to investigate the efficacy and safety of transarterial chemoembolization using the glass membrane pumping emulsification device for HCC.

Patients And Methods: Between 2019 and 2023, 58 patients (median age=73 years) with unresectable HCC underwent 73 transarterial chemoembolizations using the glass membrane pumping emulsification device at the Nagoya University Hospital.

Intestinal Microbiome Associated with Efficacy of Atezolizumab and Bevacizumab Therapy for Hepatocellular Carcinoma.

The combination of atezolizumab and bevacizumab has become the first-line treatment for patients with unresectable hepatocellular carcinoma (HCC). However, no studies have reported on specific intestinal microbiota associated with the efficacy of atezolizumab and bevacizumab. In this study, we analyzed fecal samples collected before treatment to investigate the relationship between the intestinal microbiome and the efficacy of atezolizumab and bevacizumab.

Risk factors for decreased bone mineral density in patients with metabolic dysfunction-associated steatotic liver disease: A cross-sectional study at a health examination center.

Background & Aims: Steatotic liver disease (SLD) is often detected in health examinations. However, although individuals with metabolic dysfunction-associated SLD (MASLD) may have decreased bone mineral density (BMD), the specific risk factors remain unclarified. The objective of this study was to identify the factors associated with decreased BMD in patients with MASLD.

Outcomes of immune checkpoint inhibitor-induced liver toxicity managed by hepatologists in a multidisciplinary toxicity team.

Aim: To detect immune-related adverse events (irAEs) early and treat them appropriately, our institute established an irAE-focused multidisciplinary toxicity team in cooperation with various departments. This study aimed to evaluate a consultation system involving a team of hepatologists in terms of its utility for the management of severe immune checkpoint inhibitor (ICI)-induced liver toxicity.

Methods: To analyze the diagnosis and treatment of severe ICI-induced liver toxicity (Grade 2 requiring corticosteroid therapy and Grade 3 or higher), we examined patients' clinical courses before and after the hepatologist consultation system was established (pre-period, September 2014 to February 2019; post-period, March 2019 to March 2023).

A 70-year-old Woman with Asymptomatic Ferroportin Disease.

A 59-year-old Japanese woman presented with hyperferritinemia. We decided against iron removal treatment because there were no symptoms or signs of iron-induced organ damage. A follow-up study revealed a gradual increase in transferrin saturation.