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      Review of hepatocellular carcinoma: Epidemiology, etiology, and carcinogenesis

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          Abstract

          Since the 1970s, the epidemic of hepatocellular carcinoma (HCC) has spread beyond the Eastern Asian predominance and has been increasing in Northern hemisphere, especially in the United States (US) and Western Europe. It occurs more commonly in males in the fourth and fifth decades of life. Among all cancers, HCC is one of the fastest growing causes of death in the US and poses a significant economic burden on healthcare. Chronic liver disease due to hepatitis B virus or hepatitis C virus and alcohol accounts for the majority of HCC cases. Incidence of nonalcoholic fatty liver disease has been on the risem and it has also been associated with the development of HCC. Its pathogenesis varies based on the underlying etiological factor although majority of cases develop in the setting of background cirrhosis. Carcinogenesis of HCC includes angiogenesis, chronic inflammation, and tumor macroenvironment and microenvironment. There is a significant role of both intrinsic genetic risk factors and extrinsic influences such as alcohol or viral infections that lead to the development of HCC. Understanding its etiopathogenesis helps select appropriate diagnostic tests and treatments.

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          Most cited references56

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          Integrated analysis of somatic mutations and focal copy-number changes identifies key genes and pathways in hepatocellular carcinoma.

          Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. Here, we performed high-resolution copy-number analysis on 125 HCC tumors and whole-exome sequencing on 24 of these tumors. We identified 135 homozygous deletions and 994 somatic mutations of genes with predicted functional consequences. We found new recurrent alterations in four genes (ARID1A, RPS6KA3, NFE2L2 and IRF2) not previously described in HCC. Functional analyses showed tumor suppressor properties for IRF2, whose inactivation, exclusively found in hepatitis B virus (HBV)-related tumors, led to impaired TP53 function. In contrast, inactivation of chromatin remodelers was frequent and predominant in alcohol-related tumors. Moreover, association of mutations in specific genes (RPS6KA3-AXIN1 and NFE2L2-CTNNB1) suggested that Wnt/β-catenin signaling might cooperate in liver carcinogenesis with both oxidative stress metabolism and Ras/mitogen-activated protein kinase (MAPK) pathways. This study provides insight into the somatic mutational landscape in HCC and identifies interactions between mutations in oncogene and tumor suppressor gene mutations related to specific risk factors.
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            Rising incidence of hepatocellular carcinoma in the United States.

            Clinical observations have suggested that the number of cases of hepatocellular carcinoma has increased in the United States. We analyzed data from the Surveillance, Epidemiology, and End Results (SEER) data base to determine the age-adjusted incidence of hepatocellular carcinoma from 1976 to 1995, data from the U.S. vital-statistics data base to determine age-adjusted mortality rates from 1981 to 1995, and data from the Department of Veterans Affairs to determine age-adjusted rates of hospitalization for the disease from 1983 to 1997. The incidence of histologically proved hepatocellular carcinoma increased from 1.4 per 100,000 population (95 percent confidence interval, 1.3 to 1.4) for the period from 1976 to 1980 to 2.4 per 100,000 (95 percent confidence interval, 2.3 to 2.4) for the period from 1991 to 1995. Among black men, the incidence was 6.1 per 100,000 for the period from 1991 to 1995, and among white men, it was 2.8 per 100,000. There was a 41 percent increase in the mortality rate from primary liver cancer and a 46 percent increase in the proportion of hospitalizations attributable to this disease during the periods studied. The incidence increased significantly among younger persons (40 to 60 years old) during the period from 1991 to 1995 as compared with earlier periods. An increase in the number of cases of hepatocellular carcinoma has occurred in the United States over the past two decades. The age-specific incidence of this cancer has progressively shifted toward younger people.
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              Immunology of hepatitis B virus and hepatitis C virus infection.

              More than 500 million people worldwide are persistently infected with the hepatitis B virus (HBV) and/or hepatitis C virus (HCV) and are at risk of developing chronic liver disease, cirrhosis and hepatocellular carcinoma. Despite many common features in the pathogenesis of HBV- and HCV-related liver disease, these viruses markedly differ in their virological properties and in their immune escape and survival strategies. This review assesses recent advances in our understanding of viral hepatitis, contrasts mechanisms of virus-host interaction in acute hepatitis B and hepatitis C, and outlines areas for future studies.
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                Author and article information

                Journal
                J Carcinog
                J Carcinog
                JC
                Journal of Carcinogenesis
                Medknow Publications & Media Pvt Ltd (India )
                1477-3163
                2017
                29 May 2017
                : 16
                : 1
                Affiliations
                [1] Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Texas Medical Branch, Galveston, Texas, USA
                [1 ] Department of Hematology and Oncology, National Institute of Health, Bethesda, Maryland, USA
                [2 ] Department of Internal Medicine, Division of Oncology, University of Texas Health Science Center, McGovern Medical School, Houston, Texas, USA
                Author notes
                Address for correspondence: Julie H. Rowe, Department of Internal Medicine, Division of Oncology, University of Texas Health Science Center, McGovern Medical School, Houston, Texas, USA. E-mail: Julie.Rowe@ 123456uth.tmc.edu
                Article
                JC-16-1
                10.4103/jcar.JCar_9_16
                5490340
                28694740
                26cfd4e9-39e0-48d5-aa8f-15c546ee8ce3
                Copyright: © 2017 Journal of Carcinogenesis

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

                History
                : 23 December 2016
                : 11 April 2017
                Categories
                Review Article

                Oncology & Radiotherapy
                carcinogenesis,epidemiology,etiology,hepatocellular carcinoma,pathogenesis
                Oncology & Radiotherapy
                carcinogenesis, epidemiology, etiology, hepatocellular carcinoma, pathogenesis

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