Atezolizumab plus bevacizumab treatment for unresectable hepatocellular carcinoma progressing after molecular targeted therapy: A multicenter prospective observational study.

To evaluate the efficacy of atezolizumab plus bevacizumab treatment in patients with hepatocellular carcinoma (HCC) previously treated with molecular targeted agents (MTAs). Thirty-one patients treated with atezolizumab plus bevacizumab for unresectable HCC and previously treated with MTAs were enrolled in this study. The treatment lines ranged from second to sixth lines.

[A case of swallow syncope with transient congestive liver caused by esophageal dilatation associated with huge hiatal hernia].

A 76-year-old woman suffered from repeated postprandial syncope of unknown cause. Computed tomography scanning revealed an enlarged hiatal hernia sac with food residues that compressed both the left atrium and inferior vena cava. As soon as the hernia cavity expanded during an upper gastrointestinal X-ray examination, she experienced a deterioration of her level of consciousness.

Analysis of renal function during telaprevir-based triple therapy for chronic hepatitis C.

Telaprevir (TVR) is used for the treatment of chronic hepatitis C in a combination therapy with pegylated-interferon and ribavirin. Although renal dysfunction is one of the critical adverse outcomes of this treatment, little is known regarding the mechanism of its onset. The present study assessed the association of renal function with TVR dose and viral response.

Hepcidin/ferroportin expression levels involve efficacy of pegylated-interferon plus ribavirin in hepatitis C virus-infected liver.

Aim: To investigate the relationship between the iron-metabolism-related gene expression profiles and efficacy of antiviral therapy in chronic hepatitis C patients.

Methods: The hepatic expression profile of iron-metabolism-related genes was analyzed and its association with virological response to pegylated-interferon plus ribavirin combination therapy was evaluated. A hundred patients with chronic hepatitis C (genotype1b, n = 50; genotype 2, n = 50) were enrolled and retrospectively analyzed.

Functional evaluation and characterization of a newly developed silicone oil-free prefillable syringe system.

The functionality of a newly developed silicone oil-free (SOF) syringe system, of which the plunger stopper is coated by a novel coating technology (i-coating™), was assessed. By scanning electron microscopy observations and other analysis, it was confirmed that the plunger stopper surface was uniformly covered with the designed chemical composition. A microflow imaging analysis showed that the SOF system drastically reduced both silicone oil (SO) doplets and oil-induced aggregations in a model protein formulation, whereas a large number of subvisible particles and protein aggregations were formed when a SO system was used.

Pathophysiological analysis of primary biliary cirrhosis focusing on choline/phospholipid metabolism.

Background & Aims: Injury to biliary epithelial cells caused by disorders in bile composition may be the initial step in the pathogenesis of primary biliary cirrhosis (PBC). We therefore examined choline/phospholipid metabolism in livers of patients with PBC.

Methods: Hepatic levels of mRNA encoded by choline metabolism-related genes in early stage PBC patients were quantified by real-time RT-PCR.

Association of ITPA polymorphism with outcomes of peginterferon-α plus ribavirin combination therapy.

Aim: To analyzed the association between inosine triphosphatase (ITPA) (rs1127354) genotypes and sustained virological response (SVR) rates in peginterferon (Peg-IFN)α + ribavirin (RBV) treatment.

Methods: Patients who underwent Peg-IFNα + RBV combination therapy were enrolled (n = 120) and they had no history of other IFN-based treatments. Variation in hemoglobin levels during therapy, cumulative reduction of RBV dose, frequency of treatment withdrawal, and SVR rates were investigated in each ITPA genotype.

Add-on therapy of pitavastatin and eicosapentaenoic acid improves outcome of peginterferon plus ribavirin treatment for chronic hepatitis C.

Despite the use of pegylated-interferon (peg-IFN) plus ribavirin combination therapy, many patients infected with hepatitis C virus (HCV)-1b remain HCV-positive. To determine whether addition of pitavastatin and eicosapentaenoic acid (EPA) is beneficial, the "add-on" therapy option (add-on group) was compared retrospectively with unmodified peg-IFN/ribavirin therapy (standard group). Association of host- or virus-related factors with sustained virological response was assessed.

[A case of protein-losing gastroenteropathy accompanied by Sjögren syndrome and mixed connective tissue disease].

Case reports of protein-losing gastroenteropathy (PLGE) associated with not only mixed connective tissue disease (MCTD) but also Sjögren syndrome (SjS) are very rare. We report a first case of PLGE in a patient with both MCTD and SjS. A 58-year-old Japanese woman was referred and admitted to our hospital because of abdominal fullness and lower leg edema.

[A case of Cowden disease with a germline mutation in exon5 of PTEN gene diagnosed based on typical esophageal multiple polypoid lesions observed on a medical checkup].

A man in his fifties had a medical checkup. Mucosal papillomatosis in his oral cavity and palmoplantar keratosis were observed. Esophagogastroduodenoscopy revealed multiple polypoid lesions both in the esophagus and stomach.

Acute liver failure caused by drug-induced hypersensitivity syndrome associated with hyperferritinemia.

Drug-induced hypersensitivity syndrome (DIHS) is a severe reaction usually characterized by fever, rash, and multiorgan failure, occurring 2-6 wk after drug introduction. It is an immune-mediated reaction involving macrophage and T-lymphocyte activation and cytokine release. A 54-year-old woman was diagnosed with rheumatic arthritis and initiated salazosulfapyridine by mouth.

Expression profile of lipid metabolism-associated genes in hepatitis C virus-infected human liver.

Aim:   Recent studies have shown that lipid metabolic pathways are required for the entry, replication and secretion of hepatitis C virus (HCV). Although little is known about the life cycle of HCV in humans, the activation of cholesterol and fatty acid biosynthesis may be critical for HCV proliferation.

Methods:   We assessed the transcription levels of genes essential for cholesterol and fatty acid biosynthesis in liver samples obtained from patients with chronic hepatitis C and determined their correlations.

Changes in the expression of cholesterol metabolism-associated genes in HCV-infected liver: a novel target for therapy?

Recent investigations indicate that hepatitis C virus (HCV) infection is closely associated with hepatocytic lipid metabolism and induces hepatic steatosis. However, the actual lipid metabolism in HCV-infected liver has not been extensively investigated in humans. In this study, we evaluated the expression of lipid metabolism-associated genes in patients with HCV infection by real-time PCR.

The state of cholesterol metabolism in the liver of patients with primary biliary cirrhosis: the role of MDR3 expression.

Aim: Because dyslipidemia, such as hypercholesterolemia, is a characteristic of primary biliary cirrhosis (PBC), hepatic lipid metabolism may be disturbed in PBC patients. We examined the expression of lipid metabolism-associated genes in PBC liver.

Methods: All of the patients examined were in stage I or II PBC and without medication.

Validity of FibroScan values for predicting hepatic fibrosis stage in patients with chronic HCV infection.

Objective: The aim of this study was to validate the FibroScan system compared with liver histology and serum markers for the diagnosis of hepatic fibrosis. We also tried to determine the cut-off levels and assess the feasibility of using FibroScan values to predict the fibrosis stage.

Methods: In 44 patients with HCV infection, liver stiffness was evaluated by FibroScan, serum fibrosis markers and a liver biopsy.

Impact of cholesterol metabolism and the LXRalpha-SREBP-1c pathway on nonalcoholic fatty liver disease.

We previously studied fatty acid metabolism in the liver of nonalcoholic fatty liver disease (NAFLD) and reported the activation of the LXRalpha-SREBP-1c pathway in hepatocytes. LXRalpha regulates cholesterol metabolism as well as fatty acid metabolism, and its agonistic ligands are oxysterols. Moreover, there is some evidence that excess cholesterol intake is involved in the onset of NAFLD.

Early decline of the HCV core antigen can predict SVR in patients with HCV treated by Pegylated interferon plus ribavirin combination therapy.

Objective: Pegylated interferon (PEG-IFN) plus ribavirin (RBV) combination therapy is now a popular treatment for patients with chronic hepatitis C; however, the reported sustained virologic response (SVR) rate remains at nearly 50% in genotype 1b infected patients. Therefore, it is of clinical benefit to be able to predict the effect of combination therapy on individual patients earlier in the treatment. We estimated the predictive serum HCV core antigen levels for SVR in the early therapeutic stage of combination therapy.

Nutritional investigation of non-obese patients with non-alcoholic fatty liver disease: the significance of dietary cholesterol.

Objective: The onset and progression of non-alcoholic fatty liver disease (NAFLD) seem to be affected by nutritive intake; however, detailed examinations have not been performed in non-obese NAFLD patients. The purpose of this study was to identify potential nutritive factors that affect NAFLD and its related nutritional problems.

Material And Methods: We investigated the distribution of abdominal fat, dietary intake, and biochemical data in patients with NAFLD and compared non-obese with obese patients.

The significance of differences in fatty acid metabolism between obese and non-obese patients with non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is considered to be associated with metabolic syndrome; however, a number of NAFLD patients are not obese. To explore any differences in lipid metabolism between obese and non-obese patients, we determined the expression of fatty acid metabolism-related genes. Expression levels of target genes were quantified by real-time PCR using liver biopsy samples from NAFLD patients and normal controls.

SREBP-1c, regulated by the insulin and AMPK signaling pathways, plays a role in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is a common liver disease whose prevalence has increased markedly. We reported previously that fatty acid synthesis was enhanced in NAFLD with the accumulation of fatty acids. To clarify the disorder, we evaluated the expression of genes regulating fatty acid synthesis by real-time PCR using samples from NAFLD (n=22) and normal liver (control; n=10).

Re-evaluation of fatty acid metabolism-related gene expression in nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is one of the most frequent causes of abnormal liver dysfunction, and its prevalence has markedly increased. We previously evaluated the expression of fatty acid metabolism-related genes in NAFLD and reported changes in expression that could contribute to increased fatty acid synthesis. In the present study, we evaluated the expression of additional fatty acid metabolism-related genes in larger groups of NAFLD (n=26) and normal liver (n=10) samples.

Decreased portal flow volume increases the area of necrosis caused by radio frequency ablation in pigs.

Background/aims: Although radio frequency ablation (RFA) has been widely accepted as an effective treatment for hepatocellular carcinoma (HCC), severe complications are not uncommon. Major complications seem to occur as a result of over-ablation beyond the intended area. As most patients with HCC have underlying cirrhosis, we speculated that decreased portal flow might cause the necrosis associated with RFA.

Comparison of tissue pressure and ablation time between the LeVeen and cool-tip needle methods.

Background: Radio frequency ablation (RFA) has been accepted clinically as a useful local treatment for hepatocellular carcinoma (HCC). However, intrahepatic recurrence after RFA has been reported which might be attributable to increase in intra-tumor pressure during RFA. To reduce the pressure and ablation time, we developed a novel method of RFA, a multi-step method in which a LeVeen needle, an expansion-type electrode, is incrementally and stepwise expanded.