scholarly journals Molecular Mechanisms Driving Progression of Liver Cirrhosis towards Hepatocellular Carcinoma in Chronic Hepatitis B and C Infections: A Review

2019 ◽  
Vol 20 (6) ◽  
pp. 1358 ◽  
Author(s):  
Tatsuo Kanda ◽  
Taichiro Goto ◽  
Yosuke Hirotsu ◽  
Mitsuhiko Moriyama ◽  
Masao Omata
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Hepatitis B ◽  
Molecular Mechanisms ◽  
Kinase Inhibitors ◽  
Primary Liver Cancer ◽  
Immune Checkpoints ◽  
Major Type ◽  
Advanced Stages ◽  
Almost All

Almost all patients with hepatocellular carcinoma (HCC), a major type of primary liver cancer, also have liver cirrhosis, the severity of which hampers effective treatment for HCC despite recent progress in the efficacy of anticancer drugs for advanced stages of HCC. Here, we review recent knowledge concerning the molecular mechanisms of liver cirrhosis and its progression to HCC from genetic and epigenomic points of view. Because ~70% of patients with HCC have hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection, we focused on HBV- and HCV-associated HCC. The literature suggests that genetic and epigenetic factors, such as microRNAs, play a role in liver cirrhosis and its progression to HCC, and that HBV- and HCV-encoded proteins appear to be involved in hepatocarcinogenesis. Further studies are needed to elucidate the mechanisms, including immune checkpoints and molecular targets of kinase inhibitors, associated with liver cirrhosis and its progression to HCC.

scholarly journals The impact of FGF19/FGFR4 signaling inhibition in antitumor activity of multi-kinase inhibitors in hepatocellular carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hiroaki Kanzaki ◽  
Tetsuhiro Chiba ◽  
Junjie Ao ◽  
Keisuke Koroki ◽  
Kengo Kanayama ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Molecular Mechanisms ◽  
Kinase Inhibitors ◽  
Progression Free Survival ◽  
Erk Signaling ◽  
Enzyme Linked Immunosorbent Assay ◽  
Antitumor Effects ◽  
The Impact

AbstractFGF19/FGFR4 autocrine signaling is one of the main targets for multi-kinase inhibitors (MKIs). However, the molecular mechanisms underlying FGF19/FGFR4 signaling in the antitumor effects to MKIs in hepatocellular carcinoma (HCC) remain unclear. In this study, the impact of FGFR4/ERK signaling inhibition on HCC following MKI treatment was analyzed in vitro and in vivo assays. Serum FGF19 in HCC patients treated using MKIs, such as sorafenib (n = 173) and lenvatinib (n = 40), was measured by enzyme-linked immunosorbent assay. Lenvatinib strongly inhibited the phosphorylation of FRS2 and ERK, the downstream signaling molecules of FGFR4, compared with sorafenib and regorafenib. Additional use of a selective FGFR4 inhibitor with sorafenib further suppressed FGFR4/ERK signaling and synergistically inhibited HCC cell growth in culture and xenograft subcutaneous tumors. Although serum FGF19high (n = 68) patients treated using sorafenib exhibited a significantly shorter progression-free survival and overall survival than FGF19low (n = 105) patients, there were no significant differences between FGF19high (n = 21) and FGF19low (n = 19) patients treated using lenvatinib. In conclusion, robust inhibition of FGF19/FGFR4 is of importance for the exertion of antitumor effects of MKIs. Serum FGF19 levels may function as a predictive marker for drug response and survival in HCC patients treated using sorafenib.

scholarly journals Hepatitis B Virus Pre-S Gene Deletions and Pre-S Deleted Proteins: Clinical and Molecular Implications in Hepatocellular Carcinoma

Viruses ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 862
Author(s):  
Yueh-Te Lin ◽  
Long-Bin Jeng ◽  
Wen-Ling Chan ◽  
Ih-Jen Su ◽  
Chiao-Fang Teng
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Molecular Mechanisms ◽  
Incidence Rates ◽  
Gene Deletions ◽  
S Gene ◽  
B Virus ◽  
Potential Applications ◽  
Prevention And Therapy

Hepatocellular carcinoma (HCC) is one of the most frequent and fatal human cancers worldwide and its development and prognosis are intimately associated with chronic infection with hepatitis B virus (HBV). The identification of genetic mutations and molecular mechanisms that mediate HBV-induced tumorigenesis therefore holds promise for the development of potential biomarkers and targets for HCC prevention and therapy. The presence of HBV pre-S gene deletions in the blood and the expression of pre-S deleted proteins in the liver tissues of patients with chronic hepatitis B and HBV-related HCC have emerged as valuable biomarkers for higher incidence rates of HCC development and a higher risk of HCC recurrence after curative surgical resection, respectively. Moreover, pre-S deleted proteins are regarded as important oncoproteins that activate multiple signaling pathways to induce DNA damage and promote growth and proliferation in hepatocytes, leading to HCC development. The signaling molecules dysregulated by pre-S deleted proteins have also been validated as potential targets for the prevention of HCC development. In this review, we summarize the clinical and molecular implications of HBV pre-S gene deletions and pre-S deleted proteins in HCC development and recurrence and highlight their potential applications in HCC prevention and therapy.

scholarly journals Viral hepatitis and liver cancer

2017 ◽  
Vol 372 (1732) ◽  
pp. 20160274 ◽  
Author(s):  
Marc Ringehan ◽  
Jane A. McKeating ◽  
Ulrike Protzer
Keyword(s):  
Liver Cirrhosis ◽  
Liver Cancer ◽  
Hepatitis B ◽  
Viral Infections ◽  
Current Knowledge ◽  
Primary Liver Cancer ◽  
Oncogenic Viruses ◽  
Chronic Infections ◽  
Future Design ◽  
End Stage

Hepatitis B and C viruses are a global health problem causing acute and chronic infections that can lead to liver cirrhosis and hepatocellular carcinoma (HCC). These infections are the leading cause for HCC worldwide and are associated with significant mortality, accounting for more than 1.3 million deaths per year. Owing to its high incidence and resistance to treatment, liver cancer is the second leading cause of cancer-related death worldwide, with HCC representing approximately 90% of all primary liver cancer cases. The majority of viral-associated HCC cases develop in subjects with liver cirrhosis; however, hepatitis B virus infection can promote HCC development without prior end-stage liver disease. Thus, understanding the role of hepatitis B and C viral infections in HCC development is essential for the future design of treatments and therapies for this cancer. In this review, we summarize the current knowledge on hepatitis B and C virus hepatocarcinogenesis and highlight direct and indirect risk factors. This article is part of the themed issue ‘Human oncogenic viruses’.

scholarly journals Clinical characteristics of patients with hepatitis B virus related liver cirrhosis and primary liver cancer

2015 ◽  
Vol 23 (17) ◽  
pp. 2798
Author(s):  
Feng Lv ◽  
Yu-Feng Gao ◽  
Jian-Guo Rao ◽  
Wei Zhang ◽  
Gui-Zhou Zou ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Hepatitis B Virus ◽  
Liver Cancer ◽  
Hepatitis B ◽  
Clinical Characteristics ◽  
Primary Liver Cancer ◽  
B Virus

scholarly journals YinQiSanHuang Jiedu decoction for the treatment of hepatitis B-related compensated liver cirrhosis: study protocol for a multicentre randomised controlled trial.

2021 ◽  
Author(s):  
Qing-Juan Wu ◽  
Wen-Liang Lv ◽  
Juan-Mei Li ◽  
Ting-Ting Zhang ◽  
Wen-Hui Zhou ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Placebo Group ◽  
Chinese Medicine ◽  
Randomised Controlled Trial ◽  
Traditional Chinese Medicine ◽  
Liver Fibrosis ◽  
Hepatitis B ◽  
Controlled Trial ◽  
Randomised Controlled

Abstract Introduction: Hepatitis B-related compensated liver cirrhosis is related to higher risk of hepatocellular carcinoma, anti-viral therapy is the preferred method. As the pathological mechanisms of liver fibrosis are complex, drugs developed for a single target are difficult to be effective in clinical practice, so there are no chemical drugs or biological drugs with clear efficacy available for clinical application at present. Traditional Chinese medicine is a kind of medical science that has been gradually formed during thousands of years and continuously enriched by the people of all ethnic groups in China. Traditional chinese medicine shows curative effects in the treatment of liver diseases, especially in the field of liver fibrosis prevention and treatment. This study aim to test the integrative medicine (chinese medicine plus anti-riral therapy) effective on lowing hepatocellular carcinoma risk among patients with hepatitis B-related compensated liver cirrhosis.Methods and Analysis: This is a multicentre randomised controlled trial, total 5 hospitals and 802 patients will involved in. All the subjects are randomly allocated to the YinQiSanHuang Jiedu decoction(YQSHD) group (n=401) or the placebo group (n=401). The YQSHD group receives YQSHD granule with Entecavir(ETV), the placebo group receives YQSHD placebo with ETV. Treatment period will last for 52 weeks, and follow-up period for 52±2 weeks. The primary outcome measure is the annual incidence of HCC. Outcomes will be assessed at baseline and after treatment. Objective of this trial is “the integrative of YQSHD with ETV reduce the annual incidence of HCC to 1%”.Ethics and dissemination:The protocol has been approved by the Medical Ethics Committee of Guang’anmen Hospital, China (No.2019-006-KY), and the other centres in the trial will not begin recruiting until local ethical approval has been obtained.Trial final results will be disseminated via publication. Trial registration: ChiCTR1900021532, this protocol was registered in the Chinese Clinical Trial Registry (URL: http://www.chictr.org.cn/searchproj.aspx) on February 26th, 2019.

Identification of a liver cirrhosis signature in plasma for predicting hepatocellular carcinoma risk in a population-based cohort of hepatitis B carriers

2012 ◽  
Vol 53 (1) ◽  
pp. 58-66 ◽  
Author(s):  
Chia-Chi Liu ◽  
Ya-Hui Wang ◽  
Eric Y Chuang ◽  
Mong-Hsun Tsai ◽  
Ya-Hui Chuang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Hepatitis B ◽  
Population Based ◽  
Carcinoma Risk
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