Projected Future Increase in Aging Hepatitis C
Virus–Infected Liver Transplant Candidates: A
Potential Effect of Hepatocellular Carcinoma
Scott W. Biggins,1Kiran M. Bambha,1Norah A. Terrault,4John Inadomi,7Stephen Shiboski,5
Jennifer L. Dodge,6Jane Gralla,2,3Hugo R. Rosen,1and John P. Roberts6
1Division of Gastroenterology and Hepatology,2Department of Pediatrics, and3Department of Biostatistics
and Informatics, University of Colorado Denver, Aurora, CO;4Division of Gastroenterology and
Hepatology,5Department of Epidemiology and Biostatistics, and6Department of Surgery, University of
California San Francisco, San Francisco, CA; and7Division of Gastroenterology and Hepatology,
University of Washington, Seattle, WA
In the United States, the peak hepatitis C virus (HCV) antibody prevalence of 4% occurred in persons born in the calendar
years 1940-1965. The goal of this study was to examine observed and projected age-specific trends in the demand for liver
transplantation (LT) among patients with HCV-associated liver disease stratified by concurrent hepatocellular carcinoma
(HCC). All new adult LT candidates registered with the Organ Procurement and Transplantation Network for LT between
1995 and 2010 were identified. Patients who had primary, secondary, or text field diagnoses of HCV with or without HCC
were identified. There were 126,862 new primary registrants for LT, and 52,540 (41%) had HCV. The number of new regis-
trants with HCV dramatically differed by the age at calendar year, and this suggested a birth cohort effect. When the candi-
dates were stratified by birth year in 5-year intervals, the birth cohorts with the highest frequency of HCV were as follows
(in decreasing order): 1951-1955, 1956-1960, 1946-1950, and 1941-1945. These 4 birth cohorts, spanning from 1941 to
1960, accounted for 81% of all new registrants with HCV. A 4-fold increase in new registrants with HCV and HCC occurred
between the calendar years 2000 and 2010 in the 1941-1960 birth cohorts. By 2015, we anticipate that an increasing pro-
portion of new registrants with HCV will have HCC and be ?60 years old (born in or before 1955). In conclusion, the great-
est demand for LT due to HCV-associated liver disease is occurring among individuals born between 1941 and 1960. This
demand appears to be driven by the development of HCC in patients with HCV. During the coming decade, the projected
increase in the demand for LT from an aging HCV-infected population will challenge the transplant community to reconsider
current treatment paradigms. Liver Transpl 18:1471-1478, 2012. V
C 2012 AASLD.
Received May 23, 2012; accepted August 30, 2012.
Hepatitis C virus (HCV) is the most common blood-
borne infection and is a leading cause of liver disease
in the United States.1An estimated 1.3% of the total
US population is chronically infected with HCV.1
Among individuals who have been infected with
chronic HCV for 20 to 30 years, 10% to 20% will
develop cirrhosis, and 1% to 5% will develop hepatocel-
lular cancer.2This high burden of HCV disease in the
United States has made HCV the leading indication for
liver transplantation (LT) in the United States.3
Several studies have characterized the epidemiology
and estimated the future burden of HCV disease in
Abbreviations: HCC, hepatocellular carcinoma; HCV, hepatitis C virus; LT, liver transplantation.
This work was funded in part by grants from the National Center for Research Resources (KL2 RR024130), the National Institute
of Diabetes and Digestive and Kidney Diseases (DK076565), and the Agency for Healthcare Research and Quality (DK076565).
Address reprint requests to Scott W. Biggins, M.D., M.A.S., Division of Gastroenterology and Hepatology, University of Colorado Denver,
Anschutz Outpatient Pavilion, 7th Floor, 1635 Aurora Court, Mail Stop B-154, Aurora, CO 80045. Telephone: 720-848-2293; FAX:
303-724-1891; E-mail: email@example.com
View this article online at wileyonlinelibrary.com.
LIVER TRANSPLANTATION.DOI 10.1002/lt. Published on behalf of the American Association for the Study of Liver Diseases
LIVER TRANSPLANTATION 18:1471-1478, 2012
C 2012 American Association for the Study of Liver Diseases.
hepatitis C virus with a hypothetical targeted birth
cohort strategy. AmJ Public Health;
19. McGarry LJ, Pawar VS, Panchmatia HR, Rubin JL, Davis
GL, Younossi ZM, et al. Economic model of a birth cohort
screening program for hepatitis C virus. Hepatology
20. Litwin AH, Smith BD, Drainoni ML, McKee D, Gifford AL,
Koppelman E, et al. Primary care-based interventions
are associated with increases in hepatitis C virus testing
for patients at risk. Dig Liver Dis 2012;44:497-503.
21. Aduen JF, Sujay B, Dickson RC, Heckman MG, Hewitt
WR, Stapelfeldt WH, et al. Outcomes after liver trans-
plant in patients aged 70 years or older compared with
those younger than 60 years. Mayo Clin Proc 2009;84:
22. 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:
23. 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(pt
24. Volk ML, Reichert HA, Lok AS, Hayward RA. Variation in
organ quality between liver transplant centers. Am J
25. Singhal A, Sezginsoy B, Ghuloom AE, Hutchinson IV, Cho
YW, Jabbour N. Orthotopic liver transplant using allo-
grafts from geriatric population in the United States: is
there any age limit? Exp Clin Transplant 2010;8:196-201.
26. 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 identi-
fies multiple Model for End-Stage Liver Disease-inde-
27. Sotiropoulos GC, Dru ¨he N, Sgourakis G, Molmenti EP,
Beckebaum S, Baba HA, et al. Liver transplantation,
liver resection, and transarterial chemoembolization for
hepatocellular carcinoma in cirrhosis: which is the best
oncological approach? Dig Dis Sci 2009;54:2264-2273.
28. N’Kontchou G, Mahamoudi A, Aout M, Ganne-Carri? e N,
Grando V, Coderc E, et al. Radiofrequency ablation of
hepatocellular carcinoma: long-term results and prog-
nostic factors in 235 Western patients with cirrhosis. He-
29. Pietrosi G, Miraglia R, Luca A, Vizzini GB, Fili’ D, Ric-
cardo V, et al. 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
30. Pelletier SJ, Fu S, Thyagarajan V, Romero-Marrero C,
Batheja MJ, Punch JD, et al. An intention-to-treat analy-
sis of liver transplantation for hepatocellular carcinoma
using Organ Procurement Transplant Network data.
Liver Transpl 2009;15:859-868.
31. El-Serag HB, Mallat DB, Rabeneck L. Management of the
single liver nodule in a cirrhotic patient: a decision anal-
ysis model. J Clin Gastroenterol 2005;39:152-159.
32. 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.
33. Cherqui D, Laurent A, Mocellin N, Tayar C, Luciani A,
Van Nhieu JT, et al. Liver resection for transplantable
hepatocellular carcinoma: long-term survival and role of
secondary liver transplantation. Ann Surg 2009;250:
Liver Transpl 2010;16:
1478 BIGGINS ET AL. LIVER TRANSPLANTATION, December 2012