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Hepatitis C virus-associated hepatocellular carcinoma after sustained virologic response

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      Abstract

      The introduction of a direct-acting antiviral (DAA) for patients with hepatitis C virus (HCV) infection, could lead to higher sustained virologic response (SVR) rates with fewer adverse events, and it could shorten the treatment duration relative to the interferon era. Although most recent clinical studies have demonstrated that the occurrence rates of hepatocellular carcinoma (HCC) are decreased by SVR with both interferon-based and interferon-free-regimens, there are several reports about the unexpected observation of high rates of early tumor occurrence and recurrence in patients with HCV-related HCC undergoing interferon-free therapy despite SVR. Several mechanisms of HCC occurrence and rapid immunological changes, including cytokines and chemokines during and after DAA treatment, have also been reported. We focused on the possibilities that HCC occurs or recurs during and after DAA treatment, based on the reported clinical and basic studies. Further studies and observations will be needed to determine the short-term and long-term effects on hepatocarcinogenesis caused by the eradication of HCV with DAAs. New serum biomarkers and a follow-up system for HCV-patients with SVR should be established.

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      Most cited references 67

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      Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008.

      Estimates of the worldwide incidence and mortality from 27 cancers in 2008 have been prepared for 182 countries as part of the GLOBOCAN series published by the International Agency for Research on Cancer. In this article, we present the results for 20 world regions, summarizing the global patterns for the eight most common cancers. Overall, an estimated 12.7 million new cancer cases and 7.6 million cancer deaths occur in 2008, with 56% of new cancer cases and 63% of the cancer deaths occurring in the less developed regions of the world. The most commonly diagnosed cancers worldwide are lung (1.61 million, 12.7% of the total), breast (1.38 million, 10.9%) and colorectal cancers (1.23 million, 9.7%). The most common causes of cancer death are lung cancer (1.38 million, 18.2% of the total), stomach cancer (738,000 deaths, 9.7%) and liver cancer (696,000 deaths, 9.2%). Cancer is neither rare anywhere in the world, nor mainly confined to high-resource countries. Striking differences in the patterns of cancer from region to region are observed. Copyright © 2010 UICC.
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        Hepatocellular carcinoma.

        Hepatocellular carcinoma is the sixth most prevalent cancer and the third most frequent cause of cancer-related death. Patients with cirrhosis are at highest risk of developing this malignant disease, and ultrasonography every 6 months is recommended. Surveillance with ultrasonography allows diagnosis at early stages when the tumour might be curable by resection, liver transplantation, or ablation, and 5-year survival higher than 50% can be achieved. Patients with small solitary tumours and very well preserved liver function are the best candidates for surgical resection. Liver transplantation is most beneficial for individuals who are not good candidates for resection, especially those within Milano criteria (solitary tumour ≤5 cm and up to three nodules ≤3 cm). Donor shortage greatly limits its applicability. Percutaneous ablation is the most frequently used treatment but its effectiveness is limited by tumour size and localisation. In asymptomatic patients with multifocal disease without vascular invasion or extrahepatic spread not amenable to curative treatments, chemoembolisation can provide survival benefit. Findings of randomised trials of sorafenib have shown survival benefits for individuals with advanced hepatocellular carcinoma, suggesting that molecular-targeted therapies could be effective in this chemoresistant cancer. Research is active in the area of pathogenesis and treatment of hepatocellular carcinoma. Copyright © 2012 Elsevier Ltd. All rights reserved.
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          Hepatocellular carcinoma in cirrhosis: incidence and risk factors.

          Emerging data indicate that the mortality rate of hepatocellular carcinoma (HCC) associated with cirrhosis is rising in some developed countries, whereas mortality from non-HCC complications of cirrhosis is decreasing or is stable. Cohort studies indicate that HCC is currently the major cause of liver-related death in patients with compensated cirrhosis. Hepatitis C virus (HCV) infection is associated with the highest HCC incidence in persons with cirrhosis, occurring twice as commonly in Japan than in the West (5-year cumulative incidence, 30% and 17%, respectively), followed by hereditary hemochromatosis (5-year cumulative incidence, 21%). In hepatitis B virus (HBV)-related cirrhosis, the 5-year cumulative HCC risk is 15% in high endemic areas and 10% in the West. In the absence of HCV and HBV infection, the HCC incidence is lower in alcoholic cirrhotics (5-year cumulative risk, 8%) and subjects with advanced biliary cirrhosis (5-year cumulative risk, 4%). There are limited data on HCC risk in cirrhosis of other causes. Older age, male sex, severity of compensated cirrhosis at presentation, and sustained activity of liver disease are important predictors of HCC, independent of etiology of cirrhosis. In viral-related cirrhosis, HBV/HCV and HBV/HDV coinfections increase the HCC risk (2- to 6-fold relative to each infection alone) as does alcohol abuse (2- to 4-fold relative to alcohol abstinence). Sustained reduction of HBV replication lowers the risk of HCC in HBV-related cirrhosis. Further studies are needed to investigate other viral factors (eg, HBV genotype/mutant, occult HBV, HIV coinfection) and preventable or treatable comorbidities (eg, obesity, diabetes) in the HCC risk in cirrhosis.
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            Author and article information

            Affiliations
            Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba 260-8670, Japan
            Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba 260-8670, Japan
            Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Itabashi-ku 173-8610, Japan. kandat-cib@ 123456umin.ac.jp
            Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba 260-8670, Japan
            Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba 260-8670, Japan
            Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Itabashi-ku 173-8610, Japan
            Author notes

            Author contributions: All authors contributed to all aspects of this paper.

            Corresponding author: Tatsuo Kanda, MD, PhD, Associate Professor, Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, 30-1 Oyaguchi-Kamicho, Tokyo, Itabashi-ku 173-8610, Japan. kandat-cib@ 123456umin.ac.jp

            Telephone: +81-3-39728111 Fax: +81-3-39568496

            Contributors
            Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba 260-8670, Japan
            Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba 260-8670, Japan
            ,
            Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Itabashi-ku 173-8610, Japan. kandat-cib@ 123456umin.ac.jp
            Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba 260-8670, Japan
            Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba 260-8670, Japan
            Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Itabashi-ku 173-8610, Japan
            Journal
            World J Hepatol
            WJH
            World Journal of Hepatology
            Baishideng Publishing Group Inc
            1948-5182
            27 December 2018
            27 December 2018
            : 10
            : 12
            : 898-906
            6323517 jWJH.v10.i12.pg898 10.4254/wjh.v10.i12.898
            ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.

            This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.

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