Autoimmune Hepatic Failure Following Acute Hepatitis A is Accompanied by Inflammatory Conversion of Regulatory T Cells

To evaluate the pathophysiology of autoimmune hepatitis (AIH) following acute hepatitis A (AHA) in immunologic aspects, we performed multi-color flow cytometry with peripheral blood mononuclear cells of a patient who underwent liver transplantation due to AIH-induced liver failure. Unlike general AHA patients, the proportion of tumor necrosis factor-α-producing Treg cells remained high for 6 months after diagnosis of AHA until she underwent a liver transplantation. The conversion of Treg cells into mediators of inflammation may have played a role in the autoimmune pathogenesis following AHA.ope

The Beginning of Ending Hepatitis C Virus: A Summary of the 26th International Symposium on Hepatitis C Virus and Related Viruses

Hepatitis C virus (HCV) infects ~71 million people worldwide, and 399,000 people die annually due to HCV-related liver cirrhosis and hepatocellular carcinoma. The use of direct-acting antivirals results in a sustained virologic response in >95% of patients with chronic HCV infection. However, several issues remain to be solved to eradicate HCV. At the 26th International Symposium on Hepatitis C Virus and Related Viruses (HCV2019) held in Seoul, South Korea, October 5-8, 2019, virologists, immunologists, and clinical scientists discussed these remaining issues and how we can achieve the elimination of HCV.ope

Nivolumab for Advanced Hepatocellular Carcinoma with Multiple Lung Metastases after Sorafenib Failure

Over the past decade, standard first-line systemic treatment of advanced hepatocellular carcinoma (HCC) has been based on sorafenib, a multi-kinase inhibitor. Regorafenib, another tyrosine kinase inhibitor, is the only second-line therapy that has been globally approved after progression under sorafenib treatment. Recently, immunotherapeutic agents have emerged as promising treatment options in many different malignancies, including advanced HCC. Nivolumab is the first immunotherapy approved by the Food and Drug Administration for use in HCC patients with advanced-stage second-line after sorafenib failure. In this report, a case of advanced HCC with multiple lung metastases in which a complete response and maintained progression-free status was achieved with nivolumab, following the failure of transarterial chemoembolization and sorafenib is presented. We hope this report may help expand the clinical application of second-line treatment.ope

Risk of Hepatocellular Carcinoma in Patients with Non-alcoholic Fatty Liver Disease

비알코올 지방간질환 (non-alcoholic fatty liver disease, NAFLD) 은 비만 및 당뇨병의 증가와 맞물려 최근 한국을 포함한 전 세계적으로 유병률이 증가하고 있으며 간세포암종의 주요 원인으로 알려져 있다.1,2 현재 NAFLD 가이드라인에서는 간경변증이나 진행성 간섬유화 등 고위험군에서만 간세포암종 감시를 권고하고 있으나,3 NAFLD 환자에서 간섬유화가 진행 되지 않아도 간세포암종이 발생하는 경우도 많아 간섬유화가 심하지 않은 NAFLD 환자들에 대해서도 적절한 간세포암종 감시의 필요성이 제기되고 있다. 이에 Bianco 등4은 간내 지방 함량과 연관성이 있다고 알려진 PNPLA3, TM6SF2, GCKR, MBOAT7, 그리고 HSD17B13 등의 다섯 가지 유전변이들을 이용하여 개발한 다중유전자 위험점수 (polygenic risk score, PRS)를 통해 NAFLD 코호트와 일반 인구집단 코호트를 대상으로 간세포암종 발생 위험도 예측 모델을 제시하였다.ope

Clinical Significance of AFP and PIVKA-II Responses for Monitoring Treatment Outcomes and Predicting Prognosis in Patients with Hepatocellular Carcinoma

AIM: Recently, the utility of tumor markers in the hepatocellular carcinoma (HCC) field has received a good deal of attention. Here, we review and summarize the results of studies on the roles played by the α -fetoprotein (AFP) and prothrombin induced by the absence of vitamin K or antagonist-II (PIVKA-II) responses in terms of the monitoring of outcomes and prediction of prognosis after various HCC treatments. METHODS: Studies lodged in PUBMED and that satisfied our inclusion criteria were reviewed. RESULTS: We reviewed 12 studies measuring both AFP and PIVKA-II responses in HCC patients treated in various ways. The results are presented by treatment modality. CONCLUSION: Measurement of AFP and PIVKA II marker levels before and after HCC treatment is clinically useful in monitoring of treatment outcomes and prognosis and in predicting recurrence and survival.ope

Strategy for Hepatitis C Treatment in Liver Transplant Settings

In patients with detectable virus at the time of liver transplantation, hepatitis C virus (HCV) infection always recurs on the graft, and 30% of patients have an aggressive clinical and histologic course with increased morbidity, mortality, and graft loss. Moreover, in some transplantation patients, recurrent HCV infection leads to an aggressive course of disease known as fibrosing cholestatic hepatitis, which is characterized by hepatic decompensation and death. Liver allograft and recipient survival can be substantially improved with successful eradication of HCV. Recent advances in direct-acting antiviral agents have revolutionized the management of HCV infection, and a number of these agents have shown high sustained virological responses, shorter durations of treatment, and much improved tolerability when compared with previous pegylated interferon based therapies in liver transplant settings.ope

KASL clinical practice guidelines for management of chronic hepatitis B

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Regression of liver fibrosis and hepatocellular carcinoma development after HCV eradication with oral antiviral agents

We prospectively investigated the changes of liver stiffness (LS) and the occurrence of hepatocellular carcinoma (HCC) after hepatitis C virus (HCV) eradication using direct antiviral agents (DAA) over three years. LS measurement using transient elastography and serum fibrosis surrogate markers before treatment and at 48, 96, 144 weeks after starting direct-acting antivirals (DAA) according to the protocol were evaluated. Patients were also compared with historical cohort treated with pegylated interferon (peg-IFN). Sustained viral response (SVR) was observed in 95.8%. LS value in the patients achieving SVR significantly decreased over time (19.4 ± 12.9 kPa [baseline], 13.9 ± 9.1 kPa [48 weeks], 11.7 ± 8.2 kPa [96 weeks], 10.09 ± 6.23 [144 weeks], all p < 0.001). With matched analysis, the decrease in LS value was significantly larger in DAA group than peg-IFN group at both 48 weeks (29% vs. 9%) and 96 weeks (39% vs. 17%). The incidence of HCC was not significantly different between DAA and peg-IFN groups (5.5% vs. 5.4%) at 144 weeks. HCV eradication with DAA can lead to improvement of liver stiffness over time. The regression of fibrosis was greater in the group with DAA than peg-IFN.Clinical trials registration: ClinicalTrials.gov (NCT02865369).ope

Regulation of the hypoxic tumor environment in hepatocellular carcinoma using RNA interference

OBJECTIVES: Hypoxia is the condition where tumor cells have been deprived of oxygen and has been shown to have a role of tumor development in the hepatocellular carcinoma (HCC). METHODS: Using PubMed online database and Google scholar web site, the terms "angiogenesis", "apoptosis", "RNA interference" and/or "hepatocellular carcinoma (HCC)" were searched and analyzed. RESULTS: The hypoxia inducible factors (HIFs) are transcriptional regulators that affect a homeostatic response to oxidative stress and have been identified as a key transcription activator of angiogenesis, survival, and metabolism. Cytokines, such as IL-8, also controlled endothelia cells survival and angiogenesis. IL-8 was also overexpressed under hypoxia and induced tumor angiogenesis and growth. CONCLUSION: Therefore, regulation of HIFs and IL-8 controlled the tumor microenvironment in terms of tumor angiogenesis and apoptosis. The review summarizes the results of regulation of the hypoxic tumor environment.ope

New Concept of Hepatocellular Carcinoma Treatment with the Tumor Suppressor ‘WDR76’ through ‘RAS’ Degradation

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