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Abstract
This article synthesises the current evidence on the risk of de novo extrahepatic cancer in people living with a liver transplant after hepatocellular carcinoma, the risk factors for cancer, and the recommended approaches to cancer prevention and surveillance. People living with a transplanted liver have an elevated risk of cancer and cancer death, and the indication for transplantation does not markedly alter the cancer risk. The excess risk of cancer is double that of the age- and sex-matched general population. Virus-related cancers, especially non-Hodgkin lymphoma, Kaposi sarcoma, Merkel cell carcinoma, oral, and anogenital cancers occur at increased risk, as do cancers causally associated with high prior sun exposure, smoking and excessive alcohol consumption, including skin, oesophageal, larynx, lung, kidney, and bladder cancer. The risk of incident breast and prostate cancer is not increased. Cancer-related deaths largely mirror that for cancer incidence, and extend to include the more common malignancies such as breast, colorectal, prostate cancer and non-melanoma skin cancer. As medical immunosuppression is the principal risk factor for cancer, the regimen should be reviewed on a regular basis to achieve immunosuppression minimisation. An individual, risk-based approach to cancer screening according to test characteristics and personal and family cancer history, medical history, lifestyle factors, and life expectancy is recommended. Multicomponent interventions may achieve the best results in supporting the adoption and maintenance of cancer risk-reducing behaviours. Regular, empowering patient counselling and education is a cornerstone for the care of people living with a liver transplant.
Keywords
Cancer
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risk
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prevention
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screening
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surveillance
/
cohort
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Claire M. Vajdic, Marina T. van Leeuwen, Geoffrey W. McCaughan.
Extrahepatic cancer risk after liver transplantation for hepatocellular carcinoma: incidence, risk and prevention.
Hepatoma Research, 2021, 7: 34 DOI:10.20517/2394-5079.2020.159
| [1] |
Dantal J,Cantarovich D.Effect of long-term immunosuppression in kidney-graft recipients on cancer incidence: randomised comparison of two cyclosporin regimens.Lancet1998;351:623-8
|
| [2] |
Grulich AE,Falster MO.Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis.Lancet2007;370:59-67
|
| [3] |
Na R,Meagher NS,Keogh AM.Comparison of de novo cancer incidence in Australian liver, heart and lung transplant recipients.Am J Transplant2013;13:174-83
|
| [4] |
Na R,Grulich AE.High azathioprine dose and lip cancer risk in liver, heart, and lung transplant recipients: a population-based cohort study.J Am Acad Dermatol2016;74:1144-1152.e6
|
| [5] |
Na R,Grulich AE.Iatrogenic immunosuppression and risk of non-Hodgkin lymphoma in solid organ transplantation: a population-based cohort study in Australia.Br J Haematol2016;174:550-62
|
| [6] |
Mehta N,Yao FY.Liver transplantation for hepatocellular carcinoma. Working Group Report from the ILTS Transplant Oncology Consensus Conference.Transplantation2020;104:1136-42
|
| [7] |
Dageforde LA,Chapman WC.Liver transplantation for hepatocellular carcinoma: current update on treatment and allocation.Curr Opin Organ Transplant2017;22:128-34
|
| [8] |
Xu X,Ling Q.Liver transplantation for hepatocellular carcinoma beyond the Milan criteria.Gut2016;65:1035-41 PMCID:PMC4893115
|
| [9] |
OPTN/SRTR 2018 Annual Data Report: Liver. Available from https://srtr.transplant.hrsa.gov/annual_reports/2018/Liver.aspx. [Last accessed on 5 May 2021]
|
| [10] |
Bouvard V,Straif K.A review of human carcinogens-Part B: biological agents.Lancet Oncol2009;10:321-2
|
| [11] |
Sérée O,Guillaume E.Longterm risk of solid organ de novo malignancies after liver transplantation: a French national study on 11,226 Patients.Liver Transpl2018;24:1425-36
|
| [12] |
Aberg F,Höckerstedt K,Isoniemi H.Risk of malignant neoplasms after liver transplantation: a population-based study.Liver Transpl2008;14:1428-36
|
| [13] |
Haagsma EB,Schaapveld M.Increased cancer risk after liver transplantation: a population-based study.J Hepatol2001;34:84-91
|
| [14] |
Nordin A,Pukkala E.Decreasing incidence of cancer after liver transplantation-a Nordic population-based study over 3 decades.Am J Transplant2018;18:952-63
|
| [15] |
Jiang Y,Fenton SS,Lilly L.Liver transplantation and subsequent risk of cancer: findings from a Canadian cohort study.Liver Transpl2008;14:1588-97
|
| [16] |
Collett D,Banner NR,Watson C.Comparison of the incidence of malignancy in recipients of different types of organ: a UK Registry audit.Am J Transplant2010;10:1889-96
|
| [17] |
Krynitz B,Lindelöf B.Risk of skin cancer and other malignancies in kidney, liver, heart and lung transplant recipients 1970 to 2008--a Swedish population-based study.Int J Cancer2013;132:1429-38
|
| [18] |
Taborelli M,Ettorre GM.Italian Transplant & Cancer Cohort StudyRisk of virus and non-virus related malignancies following immunosuppression in a cohort of liver transplant recipients. Italy, 1985-2014.Int J Cancer2018;143:1588-94
|
| [19] |
van Leeuwen MT,Webster AC.Immunosuppression and other risk factors for early and late non-Hodgkin lymphoma after kidney transplantation.Blood2009;114:630-7
|
| [20] |
Schrem H,Kaltenborn A.Incidence and long-term risk of de novo malignancies after liver transplantation with implications for prevention and detection.Liver Transpl2013;19:1252-61
|
| [21] |
Rompianesi G,Jose S.Incidence and outcome of colorectal cancer in liver transplant recipients: a national, multicentre analysis on 8115 patients.Liver Int2019;39:353-60
|
| [22] |
Safaeian M,Berndt SI,Fraumeni JF Jr.Risk of colorectal cancer after solid organ transplantation in the United States.Am J Transplant2016;16:960-7 PMCID:PMC5218822
|
| [23] |
D'Arcy ME,Lynch CF.Risk of rare cancers among solid organ transplant recipients.J Natl Cancer Inst2021;113:199-207 PMCID:PMC7850530
|
| [24] |
Lee KF,Lin CY.Cancer Incidence among heart, kidney, and liver transplant recipients in Taiwan.PLoS One2016;11:e0155602 PMCID:PMC4873185
|
| [25] |
Park B,Choi D.De novo cancer incidence after kidney and liver transplantation: Results from a nationwide population based data.Sci Rep2019;9:17202 PMCID:PMC6868238
|
| [26] |
Tsai HI,Kuo CF.De novo malignancy in organ transplant recipients in Taiwan: a nationwide cohort population study.Oncotarget2017;8:36685-95 PMCID:PMC5482688
|
| [27] |
Heo J,Oh YT,Kim L.Second primary cancer after liver transplantation in hepatocellular carcinoma: a nationwide population-based study.Hepatol Int2017;11:523-8
|
| [28] |
Bhat M,Dierkhising R.Gender, Race and disease etiology predict de novo malignancy risk after liver transplantation: insights for future individualized cancer screening guidance.Transplantation2019;103:91-100
|
| [29] |
Rademacher S,Eurich D.The 28-year incidence of de novo malignancies after liver transplantation: a single-center analysis of risk factors and mortality in 1616 patients.Liver Transpl2017;23:1404-14
|
| [30] |
Wimmer CD,Schwarz B.Impact of cyclosporine versus tacrolimus on the incidence of de novo malignancy following liver transplantation: a single center experience with 609 patients.Transpl Int2013;26:999-1006
|
| [31] |
Noone AM,Dorgan JF.Cancer-attributable mortality among solid organ transplant recipients in the United States: 1987 through 2014.Cancer2019;125:2647-55 PMCID:PMC6625902
|
| [32] |
Watt KD,Kremers WK,Charlton MR.Evolution of causes and risk factors for mortality post-liver transplant: results of the NIDDK long-term follow-up study.Am J Transplant2010;10:1420-7 PMCID:PMC2891375
|
| [33] |
Na R,Meagher NS,Keogh AM.De novo cancer-related death in Australian liver and cardiothoracic transplant recipients.Am J Transplant2013;13:1296-304
|
| [34] |
Acuna SA,Daly C.Cancer mortality among recipients of solid-organ transplantation in Ontario, Canada.JAMA Oncol2016;2:463-9
|
| [35] |
D'Arcy ME,Lynch CF.Survival after a cancer diagnosis among solid organ transplant recipients in the United States.Cancer2019;125:933-42 PMCID:PMC6403005
|
| [36] |
Miao Y,Gross TG.De novo cancers arising in organ transplant recipients are associated with adverse outcomes compared with the general population.Transplantation2009;87:1347-59
|
| [37] |
Vajdic CM,Kelly PJ.Survival after cutaneous melanoma in kidney transplant recipients: a population-based matched cohort study.Am J Transplant2014;14:1368-75
|
| [38] |
Benoni H,Ekbom A,Smedby KE.Survival among solid organ transplant recipients diagnosed with cancer compared to nontransplanted cancer patients-a nationwide study.Int J Cancer2020;146:682-91
|
| [39] |
Younossi ZM,Saab S.The impact of viral hepatitis-related hepatocellular carcinoma to post-transplant outcomes.J Viral Hepat2016;23:53-61
|
| [40] |
Zamoiski RD,Gibson TM.Risk of second malignancies in solid organ transplant recipients who develop keratinocyte cancers.Cancer Res2017;77:4196-203 PMCID:PMC5540772
|
| [41] |
Mangus RS,Kubal CA.Worse long-term patient survival and higher cancer rates in liver transplant recipients with a history of smoking.Transplantation2015;99:1862-8
|
| [42] |
Herrero JI,D'Avola D.Risk factors of lung, head and neck, esophageal, and kidney and urinary tract carcinomas after liver transplantation: the effect of smoking withdrawal.Liver Transpl2011;17:402-8
|
| [43] |
Desai R,Watson CJ,Moss P.Impact of cytomegalovirus on long-term mortality and cancer risk after organ transplantation.Transplantation2015;99:1989-94
|
| [44] |
Leblond V,Charlotte F.Posttransplant lymphoproliferative disorders not associated with Epstein-Barr virus: a distinct entity?.J Clin Oncol1998;16:2052-9 PMCID:PMC387363
|
| [45] |
Dotti G,Motta T.Epstein-Barr virus-negative lymphoproliferate disorders in long-term survivors after heart, kidney, and liver transplant.Transplantation2000;69:827-33
|
| [46] |
Yanik EL,Shiels MS.Cancer Risk After Pediatric Solid Organ Transplantation.Pediatrics2017;139:e20163893 PMCID:PMC5404730
|
| [47] |
Piselli P,Lauro A.Italian Transplant and Cancer Cohort StudyHead and neck and esophageal cancers after liver transplant: results from a multicenter cohort study. Italy, 1997-2010.Transpl Int2015;28:841-8
|
| [48] |
Krynitz B,Lundh Rozell B,Edgren G.Risk of basal cell carcinoma in Swedish organ transplant recipients: a population-based study.Br J Dermatol2016;174:95-103
|
| [49] |
Park CK,Austin PC.Incidence and risk factors of keratinocyte carcinoma after first solid organ transplant in Ontario, Canada.JAMA Dermatol2019:1041 PMCID:PMC6537781
|
| [50] |
Harwood CA,McGregor JM.A surveillance model for skin cancer in organ transplant recipients: a 22-year prospective study in an ethnically diverse population.Am J Transplant2013;13:119-29
|
| [51] |
Ducroux E,Ocampo MA.Skin cancers after liver transplantation: retrospective single-center study on 371 recipients.Transplantation2014;98:335-40
|
| [52] |
Kim YJ,Park GH.Twenty-eight-year incidence and characteristics of post-transplant skin cancers: Comparative analysis of past and recent 10-year experience.J Dermatol2020;47:1131-40
|
| [53] |
Funk-Debleds P,Guillaud O.Subsequent nonmelanoma skin cancers and impact of immunosuppression in liver transplant recipients.J Am Acad Dermatol2018;79:84-91
|
| [54] |
Murray SL,O'Kelly P.The impact of switching to mTOR inhibitor-based immunosuppression on long-term non-melanoma skin cancer incidence and renal function in kidney and liver transplant recipients.Ren Fail2020;42:607-12 PMCID:PMC7946013
|
| [55] |
Phan K,Hogarty DT,McColl D.Mammalian target of rapamycin (mTOR) inhibitors and skin cancer risk in nonrenal solid organ transplant recipients: systematic review and meta-analysis.Int J Dermatol2019:91-8
|
| [56] |
Knoll GA,Mallick R.Effect of sirolimus on malignancy and survival after kidney transplantation: systematic review and meta-analysis of individual patient data.BMJ2014;349:g6679 PMCID:PMC4241732
|
| [57] |
Yanik EL,Gustafson SK.Effects of maintenance immunosuppression with sirolimus after liver transplant for hepatocellular carcinoma.Liver Transpl2016;22:627-34 PMCID:PMC4846564
|
| [58] |
Eccher A,Marletta S.Donor-transmitted cancers in transplanted livers: analysis of clinical outcomes.Liver Transpl2021;27:55-66
|
| [59] |
Roemhild A,Moll G.Regulatory T cells for minimising immune suppression in kidney transplantation: phase I/IIa clinical trial.BMJ2020;371:m3734 PMCID:PMC7576328
|
| [60] |
Clavien P,de Oliveira ML,Sanchez-fueyo A.Can immunosuppression be stopped after liver transplantation?.Lancet Gastroenterol Hepatol2017;2:531-7
|
| [61] |
Moscicki AB,Huchko MJ.Guidelines for cervical cancer screening in immunosuppressed women without HIV infection.J Low Genit Tract Dis2019;23:87-101
|
| [62] |
Krynitz B,Lyth J,Lindelöf B.Cutaneous malignant melanoma in the Swedish organ transplantation cohort: a study of clinicopathological characteristics and mortality.J Am Acad Dermatol2015;73:106-113.e2
|
| [63] |
Maor D,Cumming S.Melanoma in a cohort of organ transplant recipients: experience from a dedicated transplant dermatology clinic in Victoria, Australia.J Am Acad Dermatol2020;83:773-9
|
| [64] |
Chan AW,Austin PC.Improved keratinocyte carcinoma outcomes with annual dermatology assessment after solid organ transplantation: Population-based cohort study.Am J Transplant2019;19:522-31
|
| [65] |
Stapleton CP,McKnight AJ.Polygenic risk score as a determinant of risk of non-melanoma skin cancer in a European-descent renal transplant cohort.Am J Transplant2019;19:801-10 PMCID:PMC6367067
|
| [66] |
Stapleton CP,Keating BJ,Cavalleri GL.Polygenic risk score of non-melanoma skin cancer predicts post-transplant skin cancer across multiple organ types.Clin Transplant2020;34:e13904
|
| [67] |
de Koning HJ,de Jong PA.Reduced lung-cancer mortality with volume CT screening in a randomized trial.N Engl J Med2020;382:503-13
|
| [68] |
Aberle DR,Berg CD.National Lung Screening Trial Research TeamReduced lung-cancer mortality with low-dose computed tomographic screening.N Engl J Med2011;365:395-409 PMCID:PMC4356534
|
| [69] |
Renaud L,Thimonier E.De novo malignancies screening after liver transplantation for alcoholic liver disease: a comparative opportunistic study.Liver Transpl2018;24:1690-8
|
| [70] |
Gong CS,Kim BS.De novo gastric cancer after liver transplantation.Ann Transplant2016;21:386-91
|
| [71] |
Miura K,Jiyad Z.Omega-3 fatty acid intake and decreased risk of skin cancer in organ transplant recipients.Eur J Nutr2020;
|
| [72] |
Jamieson NJ,Josephson MA.Motivations, challenges, and attitudes to self-management in kidney transplant recipients: a systematic review of qualitative studies.Am J Kidney Dis2016;67:461-78
|
| [73] |
Donovan JC.Compliance with sun protection following organ transplantation.Arch Dermatol2006;142:1232-3
|
| [74] |
Watt KD.Keys to long-term care of the liver transplant recipient.Nat Rev Gastroenterol Hepatol2015;12:639-48
|
| [75] |
Harwood CA,Leigh IM.Low-dose retinoids in the prevention of cutaneous squamous cell carcinomas in organ transplant recipients: a 16-year retrospective study.Arch Dermatol2005;141:456-64
|