Projected future increase in aging hepatitis C virus-infected liver transplant candidates: a potential effect of hepatocellular carcinoma.

Liver Transpl. 2012 Dec;18(12):1471-8.

Biggins SW, Bambha KM, Terrault NA, Inadomi J, Shiboski S, Dodge JL, Gralla J, Rosen HR, Roberts JP.

Division of Gastroenterology and Hepatology, University of Colorado Denver, Aurora, CO 80045, USA.


Background: In the US, the peak hepatitis C (HCV) antibody prevalence of 4% occurred in persons born in calendar years 1940 to1965. Aim: To examine observed and projected age-specific trends in the demand for liver transplantation (LTx) among patients with HCV-associated liver disease stratified by concurrent hepatocellular carcinoma (HCC). Methods: All new adult LTx candidates registered with the Organ Procurement and Transplantation Network for LTx between 1995 and 2010 were identified. Patients who had primary, secondary, or text field diagnoses of HCV with or without HCC, were identified. Results: There were 126,862 new, primary registrants for LTx, 52,540 (41%) with HCV. The number of new registrants with HCV was dramatically different by age at calendar year, suggesting a birth cohort effect. When stratified by birth year in 5-year intervals, the birth cohorts with the highest frequency of HCV in decreasing order were those born 1951-1955, 1956-1960, 1946-1950, and 1941-1945. These four birth cohorts, spanning 1941 to1960 accounted for 81% of all new registrants with HCV. A 4-fold increase in new registrants with HCV and HCC occurred between calendar years 2000 to 2010 in the 1941-1960 birth cohorts.  By 2015, we anticipate an increasing proportion of new registrants with HCV will have HCC and be over the age of 60 (born on or before 1955). Conclusions: The greatest demand for LTx due to HCV-associated liver disease is occurring among individuals born between 1941 and1960. This demand appears to be driven by the development of HCC in patients with HCV. Over the coming decade, the projected increase in demand for LTx from an aging HCV infected population will challenge the transplant community to reconsider current treatment paradigms.

Scott W. Biggins-1

Figure 1. New registration with hepatitis C virus (HCV) in the US between 1995 and 2010 by age at registration. Peak prevalence of need for HCV is in those who were 55 to 64 years old in the calendar year 2010 or born in calendar years 1946 to 1955.

Scott W. Biggins-2A

Scott W. Biggins-2B

Figure 2. Age-specific projections for new registrations for HCV related liver transplantation in the US with (2a) and without (2b) hepatocellular carcinoma, based on rates observed up to 2010. In 2015, there is a projected increase in patients who will be 55-64 years old (born in calendar years 1951-1960) needing liver transplantation who have hepatitis C related liver disease and hepatocellular carcinoma.



This study identified the 1941-1960 US birth cohort with HCV related disease as generating the greatest demand for LTx. Additionally, within this birth cohort of individuals with HCV related liver disease we found a dramatic increase in the rate of new registrants for LTx due to HCC. Interestingly, our observed and projected analyses suggest that older patients (≥60 years) with HCC will increasingly contribute to the proportion HCV infected liver transplant candidates, unless current patterns of care change dramatically.

When complications of end-stage liver disease occur in the setting of HCV there are two likely results, death or LTx. Unlike the analyses Wise et al 2 that used mortality with HCV as their measure of HCV disease burden in the US, we used listing for LTx as our HCV disease burden measure. These two HCV disease burden measures showed similar age-specific trends that we demonstrate are likely a birth cohort effect occurring in the US and previously attributed to HCV transmission due to injection drug use and unavailability of tests to adequately screen blood products for HCV during the years 1970-1990.1 In our study using listing for LTx as the HCV disease burden measure, we observed different birth cohort patterns in the rates of new registration LTx among individuals with HCV related disease depending on their HCC status.  There are at least two potential epidemiologic explanations for this: 1) HCC incidence is higher in older patients; and 2) older patients with non-HCC indications for LTx (i.e. ascites, hepatic encephalopathy or portal hypertensive bleeding) are less likely to be referred or listed for LTx.

Characterization of observed trends and projected changes in the demographics of patients seeking liver transplantation in the US may allow for proactive planning by the US liver transplant community to adapt current treatment approaches and policies to future needs. Prior epidemiologic projections of HCV-related mortality and need for LTx predicted peak event rates in the 2014 and 2015 calendar years, respectively. 8 Using more contemporary data, our analyses demonstrate a steady rise in the demand for LTx in an increasingly older population with HCV infection driven primarily by patients with HCC. Absent an abrupt reversal of our observed rate of new registrants through 2010, the peak demand stemming from the 1941-1960 birth cohort is likely to extend beyond 2015, but increasing age and other age-related comorbidities may have a significant influence on liver transplant candidacy assessments in this birth cohort who will be 60 to 79 years old in 2020.9 The Center for Disease Control10-12 and others13, 14 are currently considering expansion of HCV screening to all persons in the 1945-1965 birth cohort in the US, an approach that may increase the HCV testing rate14, 15. In the near term such a policy may increase HCV diagnosis rates and potentially HCC diagnosis rates but subsequently would be expected to reduce the occurrence of HCV-related liver disease14 and associated complications such as HCC. Additionally, advances in treatment of HCV or HCC which have the potential to alter the disease course could result in lower observed HCV related disease burden, particularly over longer time horizons and if the interventions have improved tolerability in elderly patients.


1.         Armstrong GL, Alter MJ, McQuillan GM, Margolis HS. The past incidence of hepatitis C virus infection: implications for the future burden of chronic liver disease in the United States. Hepatology 2000;31:777-82.

2.         Wise M, Bialek S, Finelli L, Bell BP, Sorvillo F. Changing trends in hepatitis C-related mortality in the United States, 1995-2004. Hepatology 2008;47:1128-35.

3.         El-Serag HB. Hepatocellular carcinoma: recent trends in the United States. Gastroenterology 2004;127:S27-34.

4.         El-Serag HB, Mason AC. Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med 1999;340:745-50.

5.         El-Serag HB, Davila JA, Petersen NJ, McGlynn KA. The continuing increase in the incidence of hepatocellular carcinoma in the United States: an update. Ann Intern Med 2003;139:817-23.

6.         Kim WR, Terrault NA, Pedersen RA, Therneau TM, Edwards E, Hindman AA, Brosgart CL. Trends in waiting list registration for liver transplantation for viral hepatitis in the United States. Gastroenterology 2009;137:1680-6.

7.         Asahina Y, Tsuchiya K, Tamaki N, Hirayama I, Tanaka T, Sato M, Yasui Y, Hosokawa T, Ueda K, Kuzuya T, Nakanishi H, Itakura J, Takahashi Y, Kurosaki M, Enomoto N, Izumi N. Effect of aging on risk for hepatocellular carcinoma in chronic hepatitis C virus infection. Hepatology 2010;52:518-27.

8.         Wong JB, McQuillan GM, McHutchison JG, Poynard T. Estimating future hepatitis C morbidity, mortality, and costs in the United States. Am J Public Health 2000;90:1562-9.

9.         Guiltinan AM, Kaidarova Z, Custer B, Orland J, Strollo A, Cyrus S, Busch MP, Murphy EL. Increased all-cause, liver, and cardiac mortality among hepatitis C virus-seropositive blood donors. Am J Epidemiol 2008;167:743-50.

10.       CDC. Testing recommendations for chronic hepatitis c virus infection Accessed 8/9/2012.

11.       Rein DB, Smith BD, Wittenborn JS, Lesesne SB, Wagner LD, Roblin DW, Patel N, Ward JW, Weinbaum CM. The cost-effectiveness of birth-cohort screening for hepatitis C antibody in U.S. primary care settings. Ann Intern Med 2012;156:263-70.

12.       Smith BD, Jorgensen C, Zibbell JE, Beckett GA. Centers for disease control and prevention initiatives to prevent hepatitis C virus infection: a selective update. Clin Infect Dis 2012;55 Suppl 1:S49-53.

13.       Tomaszewski KJ, Deniz B, Tomanovich P, Graham CS. Comparison of Current US Risk Strategy to Screen for Hepatitis C Virus With a Hypothetical Targeted Birth Cohort Strategy. Am J Public Health 2012.

14.       McGarry LJ, Pawar VS, Panchmatia HR, Rubin JL, Davis GL, Younossi ZM, Capretta JC, O’Grady MJ, Weinstein MC. Economic model of a birth cohort screening program for hepatitis C virus. Hepatology 2012;55:1344-55.

15.       Litwin AH, Smith BD, Drainoni ML, McKee D, Gifford AL, Koppelman E, Christiansen CL, Weinbaum CM, Southern WN. Primary care-based interventions are associated with increases in hepatitis C virus testing for patients at risk. Dig Liver Dis 2012;44:497-503.

16.       Aduen JF, Sujay B, Dickson RC, Heckman MG, Hewitt WR, Stapelfeldt WH, Steers JL, Harnois DM, Kramer DJ. Outcomes after liver transplant in patients aged 70 years or older compared with those younger than 60 years. Mayo Clin Proc 2009;84:973-8.

17.       Lake JR, Shorr JS, Steffen BJ, Chu AH, Gordon RD, Wiesner RH. Differential effects of donor age in liver transplant recipients infected with hepatitis B, hepatitis C and without viral hepatitis. Am J Transplant 2005;5:549-57.

18.       Thuluvath PJ, Guidinger MK, Fung JJ, Johnson LB, Rayhill SC, Pelletier SJ. Liver transplantation in the United States, 1999-2008. Am J Transplant 2010;10:1003-19.

19.       Volk ML, Reichert HA, Lok AS, Hayward RA. Variation in organ quality between liver transplant centers. Am J Transplant 2011;11:958-64.

20.       Singhal A, Sezginsoy B, Ghuloom AE, Hutchinson IV, Cho YW, Jabbour N. Orthotopic liver transplant using allografts from geriatric population in the United States: is there any age limit? Exp Clin Transplant 2010;8:196-201.

21.       Aloia TA, Knight R, Gaber AO, Ghobrial RM, Goss JA. Analysis of liver transplant outcomes for United Network for Organ Sharing recipients 60 years old or older identifies multiple model for end-stage liver disease-independent prognostic factors. Liver Transpl 2010;16:950-9.

22.       Sotiropoulos GC, Druhe N, Sgourakis G, Molmenti EP, Beckebaum S, Baba HA, Antoch G, Hilgard P, Radtke A, Saner FH, Nadalin S, Paul A, Malago M, Broelsch CE, Lang H. Liver transplantation, liver resection, and transarterial chemoembolization for hepatocellular carcinoma in cirrhosis: which is the best oncological approach? Dig Dis Sci 2009;54:2264-73.

23.       N’Kontchou G, Mahamoudi A, Aout M, Ganne-Carrie N, Grando V, Coderc E, Vicaut E, Trinchet JC, Sellier N, Beaugrand M, Seror O. Radiofrequency ablation of hepatocellular carcinoma: long-term results and prognostic factors in 235 Western patients with cirrhosis. Hepatology 2009;50:1475-83.

24.       Pietrosi G, Miraglia R, Luca A, Vizzini GB, Fili D, Riccardo V, D’Antoni A, Petridis I, Maruzzelli L, Biondo D, Gridelli B. Arterial chemoembolization/embolization and early complications after hepatocellular carcinoma treatment: a safe standardized protocol in selected patients with Child class A and B cirrhosis. J Vasc Interv Radiol 2009;20:896-902.

25.       Pelletier SJ, Fu S, Thyagarajan V, Romero-Marrero C, Batheja MJ, Punch JD, Magee JC, Lok AS, Fontana RJ, Marrero JA. An intention-to-treat analysis of liver transplantation for hepatocellular carcinoma using organ procurement transplant network data. Liver Transpl 2009;15:859-68.

26.       El-Serag HB, Mallat DB, Rabeneck L. Management of the single liver nodule in a cirrhotic patient: a decision analysis model. J Clin Gastroenterol 2005;39:152-9.

27.       Morris-Stiff G, Gomez D, de Liguori Carino N, Prasad KR. Surgical management of hepatocellular carcinoma: is the jury still out? Surg Oncol 2009;18:298-321.

28.       Cherqui D, Laurent A, Mocellin N, Tayar C, Luciani A, Van Nhieu JT, Decaens T, Hurtova M, Memeo R, Mallat A, Duvoux C. Liver resection for transplantable hepatocellular carcinoma: long-term survival and role of secondary liver transplantation. Ann Surg 2009;250:738-46.



Multiselect Ultimate Query Plugin by InoPlugs Web Design Vienna | Webdesign Wien and Juwelier SchönmannMultiselect Ultimate Query Plugin by InoPlugs Web Design Vienna | Webdesign Wien and Juwelier Schönmann