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      Lamivudine versus Entecavir for Newly Diagnosed Hepatitis B Virus-Related Hepatocellular Carcinoma

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          Abstract

          Background/Aims

          Antiviral therapy is a key component in the management of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients. However, whether the potent drug entecavir is more effective than a less potent drug, such as lamivudine, in HBV-related HCC is not clear.

          Methods

          A retrospective cohort of 451 newly diagnosed, HBV-related HCC patients without antiviral therapy at diagnosis, who started antiviral therapy with either entecavir (n=249) or lamivudine (n=202), were enrolled.

          Results

          The median survival was longer for the entecavir group than for the lamivudine group, and lamivudine use (vs entecavir) was an independent factor for mortality (hazard ratio [HR], 1.49; p=0.002). Lamivudine use (vs entecavir) was an independent risk factor for new-onset hepatic decompensation (HR, 1.67; p=0.010) in 318 patients without previous hepatic decompensation, and it was also an independent risk factor for recurrence after curative therapy (HR, 1.84; p=0.002) in 117 patients who received curative therapy. The findings were similar in a propensity score-matched cohort.

          Conclusions

          Overall survival, decompensation-free survival, and recurrence-free survival were better in the entecavir-treated patients than in the lamivudine treated-patients, indicating that the potent antiviral drug should be the preferred choice in HBV-related HCC patients.

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          Most cited references18

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          [Practice guidelines for management of hepatocellular carcinoma 2009].

          (2009)
          Hepatocellular carcinoma (HCC) is a major cancer in Korea, typically has a poor prognosis, and constitutes the majority of primary hepatic malignancies. It is the number one cause of death among people in their 50s in Korea. The five-year survival rate of liver cancer is poor; at 18.9%. Efforts to increase the survival rate through early diagnosis of HCC and optimal treatments are keenly needed. Western guideline for the management of HCC were developed, but these guidelines are somewhat unsuitable for Korean patients. Thus, the Korean Liver Cancer Study Group (KLCSG) and the National Cancer Center (NCC), Korea jointly produced the Clinical Practice Guidelines for HCC for the first time in Korea in 2003. Owing to medical advances over the following six years, diagnosis and treatment of HCC has changed considerably. As more national and foreign data are accumulated, KLCSG and NCC, Korea recently revised the Clinical Practice Guidelines for HCC. Forty or more specialists in the field of hepatology, general surgery, radiology and radiation oncology participated, and meticulously reviewed national and foreign papers, and collected opinions through advisory committee conferences. These multidisciplinary, evidence-based guidelines summarized diagnosis, surgical resection, liver transplantation, local treatments, transarterial chemoembolization, radiation therapy, chemotherapy, preemptive antiviral treatments, and response evaluation of HCC. These Korean guidelines are expected to be useful for clinical management of and research on HCC.
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            Effect of antiviral treatment with nucleotide/nucleoside analogs on postoperative prognosis of hepatitis B virus-related hepatocellular carcinoma: a two-stage longitudinal clinical study.

            Postoperative prognosis of hepatitis B virus (HBV) -related hepatocellular carcinoma (HCC) is poor. The effect of nucleotide/nucleoside analog (NA) treatment on the prognosis has not been fully clarified. We carried out a two-stage longitudinal study that included a randomized clinical trial (RCT) to evaluate the effect of NA treatment on postoperative prognosis of HBV-HCC. Seven hundred eighty patients (163 in the RCT) were enrolled onto this study following radical hepatectomy. Lamivudine, adefovir dipivoxil, or entecavir were postoperatively administered to antiviral groups. Surgical specimens were examined immunohistochemically for carboxylic acid-terminal truncated HBV X protein (Ct-HBx). In the nonrandomized cohort, high viral load (≥ 10(4) copies/mL) significantly predicted unfavorable overall survival and recurrence-free survival (RFS), whereas antiviral treatment significantly improved both types of survival. In the RCT, antiviral treatment significantly decreased HCC recurrence and HCC-related death, with hazard ratios (HRs) of 0.48 (95% CI, 0.32 to 0.70) and 0.26 (95% CI, 0.14 to 0.50), respectively, in multivariate Cox analyses. Patients who received antiviral treatment had significantly decreased early recurrence (HR, 0.41; 95% CI, 0.27 to 0.62) and improved liver function 6 months after surgery compared with the controls (P < .001). Those with recovered liver function had a higher 2-year RFS rate than those without (P = .003). Ct-HBx expression in adjacent hepatic tissues significantly predicted an unfavorable RFS in the antiviral group (P < .001). Although it might not affect the HCC-promoting potential of Ct-HBx, NA treatment is effective in normalizing liver function, decreasing HBV-HCC recurrence, and improving postoperative survival. This effect should be validated in a multicenter phase III RCT.
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              Association of nucleos(t)ide analogue therapy with reduced risk of hepatocellular carcinoma in patients with chronic hepatitis B: a nationwide cohort study.

              Treatment for hepatitis B virus infection reduces the risk of hepatocellular carcinoma (HCC). However, the long-term protective effects for subgroups of patients with chronic hepatitis B are unclear. We conducted a retrospective nationwide cohort study using data from Taiwan's National Health Insurance Research Database (from January 1, 1997, through December 31, 2010). Cumulative incidences were calculated and multivariable analyses were carried out after adjusting for competing mortality. Propensity scores were used to match 21,595 patients with chronic hepatitis B who received nucleoside analogue therapy for at least 90 days (treated cohort) with 21,595 untreated patients with chronic hepatitis B (controls), who received hepatoprotectants for at least 90 days. Data were collected from the treated cohort for a mean period of 3.46 years and from controls for 5.24 years. The treated cohort had a significantly lower 7-year incidence of HCC (7.32%; 95% confidence interval [CI], 6.77%-7.87%) than controls (22.7%; 95% CI, 22.1%-23.3%; P < .001). After adjusting for competing mortality and other confounders, nucleos(t)ide analogue treatment was associated with a reduced risk of HCC, with an adjusted hazard ratio of 0.37 (95% CI, 0.34-0.39; P < .001). Sensitivity analyses confirmed the association between nucleos(t)ide analogue treatment and reduced risk of HCC. Age, sex, cirrhosis, and diabetes mellitus modified this association. Based on a retrospective, nationwide study in Taiwan, nucleoside analogue therapy use is associated with reduced risk of HCC in patients with chronic hepatitis B virus infection. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Gut Liver
                Gut Liver
                Gut and Liver
                Editorial Office of Gut and Liver
                1976-2283
                2005-1212
                November 2016
                13 June 2016
                : 10
                : 6
                : 939-947
                Affiliations
                [1 ]Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
                [2 ]Biostatistics and Clinical Epidemiology Center, Samsung Medical Center, Seoul, Korea
                Author notes
                Correspondence to: Dong Hyun Sinn, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea, Tel: +82-2-3410-3409, Fax: +82-2-3410-6983, E-mail: dh.sinn@ 123456samsung.com

                See editorial on [Related article:]page 869.

                Article
                gnl-10-939
                10.5009/gnl15527
                5087934
                27282264
                5858d846-8060-4d4d-b654-81d35af89bb3
                Copyright © 2016 by The Korean Society of Gastroenterology, the Korean Society of Gastrointestinal Endoscopy, the Korean Society of Neurogastroenterology and Motility, Korean College of Helicobacter and Upper Gastrointestinal Research, Korean Association the Study of Intestinal Diseases, the Korean Association for the Study of the Liver, Korean Pancreatobiliary Association, and Korean Society of Gastrointestinal Cancer.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 19 October 2015
                : 30 December 2015
                : 06 January 2016
                Categories
                Original Article

                Gastroenterology & Hepatology
                antiviral agents,hepatitis b,chronic,carcinoma,hepatocellular,potency,survival

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