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      Statin Use is Associated with Decreased Hepatocellular Carcinoma Recurrence in Liver Transplant Patients

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          Abstract

          Statins have been reported to prevent the development of hepatocellular carcinoma (HCC). We examined whether statin therapy is associated with decreased HCC recurrence in patients who underwent liver transplantation for HCC. Three hundred forty-seven patients ≥ 20 years old who underwent liver transplantation for HCC from 2006 to 2016 were enrolled in this study. Statin therapy was defined as the administration of statins for more than 30 days after liver transplantation. One hundred twelve (32.3%) patients treated with statins over 30 days were defined as the statin group, and the remaining 235 (67.7%) were defined as the non-statin group. Several risk factors reported to be associated with HCC recurrence, such as proportion of underlying liver disease, above Milan criteria, differentiation of HCC, vascular invasion, and preoperative alpha-fetoprotein level were not different between the two groups. Time-dependent Cox regression analysis showed that statin treatment was associated with significantly lower recurrence risk of HCC after adjusting for other risk factors (hazard ratio = 0.32, 95% CI = 0.11–0.89).

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          Clinical Management of Hepatocellular Carcinoma. Conclusions of the Barcelona-2000 EASL Conference

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            Statins and cancer prevention.

            Randomized controlled trials for preventing cardiovascular disease indicated that statins had provocative and unexpected benefits for reducing colorectal cancer and melanoma. These findings have led to the intensive study of statins in cancer prevention, including recent, large population-based studies showing statin-associated reductions in overall, colorectal and prostate cancer. Understanding the complex cellular effects (for example, on angiogenesis and inflammation) and the underlying molecular mechanisms of statins (for example, 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase-dependent processes that involve geranylgeranylation of Rho proteins, and HMG-CoA-independent processes that involve lymphocyte-function-associated antigen 1) will advance the development of molecularly targeted agents for preventing cancer. This understanding might also help the development of drugs for other ageing-related diseases with interrelated molecular pathways.
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              The continuing increase in the incidence of hepatocellular carcinoma in the United States: an update.

              The incidence of hepatocellular carcinoma was reported to be increasing in the United States. However, alternate explanations were diagnostic or reclassification bias and changes in the demographic features of the general population. To examine the temporal trends in the incidence of hepatocellular carcinoma. Retrospective cohort study. Information collected by population-based registries of the Surveillance, Epidemiology, and End Results (SEER) program. Persons given a diagnosis of hepatocellular carcinoma between 1975 and 1998. Linear Poisson multivariate regression model, controlling for differences in age, sex, race or ethnicity, and geographic region among patients with hepatocellular carcinoma and in the underlying population. The overall age-adjusted incidence rates of hepatocellular carcinoma increased from 1.4 per 100 000 in 1975 to 1977 to 3.0 per 100 000 in 1996 to 1998. There was a 25% increase during the last 3 years of the study compared with the preceding 3 years (1993 to 1995). The increase affected most age groups above 40 years, with the greatest increase in the 45- to 49-year-old age group. White men had the greatest increase (31%) in the last time period (1996 to 1998) compared with 1993 to 1995. The Poisson regression model confirmed an almost 2-fold increase in the incidence rate ratio for hepatocellular carcinoma between 1975 to 1978 and 1996 to 1998. The incidence of hepatocellular carcinoma continues to increase rapidly in the United States, with rates increasing the fastest in white men 45 to 54 years of age. These findings are consistent with a true increase and could be explained by consequences of hepatitis C virus acquired during the 1960s and 1970s.
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                Author and article information

                Contributors
                edgo@yuhs.ac
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                6 February 2019
                6 February 2019
                2019
                : 9
                : 1467
                Affiliations
                [1 ]ISNI 0000 0004 0470 5454, GRID grid.15444.30, Division of Endocrinology and Metabolism, Department of Internal Medicine, , Yonsei University College of Medicine, ; Seoul, Republic of Korea
                [2 ]ISNI 0000 0004 0439 4086, GRID grid.413046.4, Department of Transplantation Surgery, Severance Hospital, , Yonsei University Health System, ; Seoul, Republic of Korea
                [3 ]ISNI 0000 0004 0470 5454, GRID grid.15444.30, Department of Preventive Medicine, , Yonsei University College of Medicine, ; Seoul, Republic of Korea
                [4 ]ISNI 0000 0004 0470 5454, GRID grid.15444.30, Institute of Health Services Research, , Yonsei University College of Medicine, ; Seoul, Republic of Korea
                [5 ]ISNI 0000 0004 0470 5454, GRID grid.15444.30, Institute of Endocrine Research, , Yonsei University College of Medicine, ; Seoul, Republic of Korea
                Author information
                http://orcid.org/0000-0002-0364-4675
                Article
                38110
                10.1038/s41598-018-38110-4
                6365496
                30728421
                089e6be2-1de0-49f6-aff5-1866a25e5b5a
                © The Author(s) 2019

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 26 July 2018
                : 28 November 2018
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100003621, Ministry of Science, ICT and Future Planning (MSIP);
                Award ID: 2016R1A2B4013029
                Award Recipient :
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