Role of NKT Cells in the Pathogenesis of NAFLD

Nonalcoholic fatty liver disease (NAFLD) is the most frequent chronic liver disease and shows various inflammatory changes in the liver. Among those inflammatory cells, natural killer T (NKT) cells are found to have a critical role during the disease progression. NKT cells may have a protective role at the early stage with simple steatosis through modification of insulin resistance, whereas they act as a progression factor at the advanced stage with fibrosis. Those processes are thought to depend on interaction between NKT cells and CD1d molecule in the liver

A Case of Immune-Related Aseptic Meningitis during Atezolizumab plus Bevacizumab for Hepatocellular Carcinoma

Introduction: Immune checkpoint inhibitors are sometimes associated with immune-related adverse events during or after treatment. Among these, aseptic meningitis is a rare and serious complication. We report the first case of atezolizumab-induced aseptic meningitis, which occurred during treatment for advanced hepatocellular carcinoma (HCC). Case Presentation: A 74-year-old woman diagnosed with advanced HCC and treated with first-line atezolizumab plus bevacizumab developed anorexia, fatigue, and fever, after three treatment cycles. Cerebrospinal fluid examination showed slightly increased cell count and protein level but no infection or malignancy. Contrast enhancement along the cerebral sulcus was evident in contrast-enhanced magnetic resonance imaging, and the patient was diagnosed with aseptic meningitis associated with atezolizumab. Steroid therapy soon improved her clinical symptoms, and the contrast enhancement along the cerebral sulcus disappeared. Conclusion: Clinicians should monitor to avoid serious immune-related adverse events, such as aseptic meningitis, in patients during treatment of HCC with immune checkpoint inhibitors and make the diagnosis as soon as possible

An Autopsy Case of Ruptured Hepatic Angiosarcoma Treated by Transcatheter Arterial Embolization

An 80-year-old Japanese man presented to our hospital with intra-abdominal hemorrhage due to a ruptured liver tumor. Transcatheter arterial embolization (TAE) temporarily achieved hemostasis, but he died following re-rupture 4 days later. Based on autopsy findings, the liver tumor was diagnosed as hepatic angiosarcoma. Embolic agents used during embolization were identified within the hepatic small interlobular arteries. However, there were no findings of tumor cell necrosis or ischemic change in the angiosarcoma. In the present case, TAE alone did not induce ischemia-induced tumor necrosis, suggesting that TAE might be unsuitable to treat hepatic angiosarcoma. Treatment optimization for ruptured hepatic angiosarcoma is desired

Serum microRNA profiles in patients with chronic hepatitis B, chronic hepatitis C, primary biliary cirrhosis, autoimmune hepatitis, nonalcoholic steatohepatitis, or drug-induced liver injury

金沢大学医薬保健研究域薬学系Purpose: Some blood biomarkers or histological examination by liver biopsy are used for the diagnosis of liver diseases in clinics. However, conventional blood biomarkers show poor specificity and sensitivity, and liver biopsy is highly invasiveness. Therefore, to overcome such disadvantages, specific/sensitive and noninvasive options are desirable. In recent years, circulating microRNAs (miRNAs) have been acknowledged for their potential as disease markers. Actually, several miRNAs have been reported to be biomarker candidates of liver diseases. However, these earlier studies were performed for one disease. Therefore, the specificity as biomarkers was not guaranteed, because they didn\u27t study for the other types of liver injury. In this study, we examined if circulating miRNA could distinguish different types of liver diseases. Methods: Serum miRNA profiles in 28 patients with chronic hepatitis B, chronic hepatitis C, primary biliary cirrhosis, autoimmune hepatitis, nonalcoholic steatohepatitis or drug-induced liver injury as well as 4 control subjects were determined by TaqMan MicroRNA Array analysis. Principal component analysis (PCA) of selected miRNAs was performed. Results: We identified 37 miRNAs whose levels were significantly different between any of the groups. Although individual miRNAs could not distinguish different types of liver diseases, probably because of similar liver pathology, their profiling by PCA could classify different liver disease groups. Conclusions: The profiling of the selected miRNAs can be useful to distinguish different types of liver diseases. © 2017 The Canadian Society of Clinical Chemists.Embargo Period 12 month

Sequential therapies after atezolizumab plus bevacizumab or lenvatinib first-line treatments in hepatocellular carcinoma patients

Introduction: The aim of this retrospective proof-of-concept study was to compare different second-line treatments for patients with hepatocellular carcinoma and progressive disease (PD) after first-line lenvatinib or atezolizumab plus bevacizumab.Materials and methods: A total of 1381 patients had PD at first-line therapy. 917 patients received lenvatinib as first-line treatment, and 464 patients atezolizumab plus bevacizumab as first-line.Results: 49.6% of PD patients received a second-line therapy without any statistical difference in overall survival (OS) between lenvatinib (20.6 months) and atezolizumab plus bev-acizumab first-line (15.7 months; p = 0.12; hazard ratio [HR] = 0.80). After lenvatinib first-line, there wasn't any statistical difference between second-line therapy subgroups (p = 0.27; sorafenib HR: 1; immunotherapy HR: 0.69; other therapies HR: 0.85). Patients who under-went trans-arterial chemo-embolization (TACE) had a significative longer OS than patients who received sorafenib (24.7 versus 15.8 months, p < 0.01; HR = 0.64). After atezolizumab plus bevacizumab first-line, there was a statistical difference between second-line therapy subgroups (p < 0.01; sorafenib HR: 1; lenvatinib HR: 0.50; cabozantinib HR: 1.29; other therapies HR: 0.54). Patients who received lenvatinib (17.0 months) and those who under-went TACE (15.9 months) had a significative longer OS than patients treated with sorafenib (14.2 months; respectively, p = 0.01; HR = 0.45, and p < 0.05; HR = 0.46).Conclusion: Approximately half of patients receiving first-line lenvatinib or atezolizumab plus bevacizumab access second-line treatment. Our data suggest that in patients progressed to atezolizumab plus bevacizumab, the systemic therapy able to achieve the longest survival is lenvatinib, while in patients progressed to lenvatinib, the systemic therapy able to achieve the longest survival is immunotherapy