Cost-effectiveness of hepatocellular carcinoma surveillance in patients with hepatitis C virus–related cirrhosis
Authors: Derek Patel, Norah A. Terrault, Francis Y. Yao, Nathan M. Bass, Uri Ladabaum
Journal: Clinical Gastroenterology and Hepatology (2005)

Background & Aims: HCV-related cirrhosis is a leading risk factor for hepatocellular carcinoma (HCC). Surveillance might detect HCC at a treatable stage. We estimated the clinical and economic consequences of a common HCC surveillance strategy in patients with HCV-related cirrhosis in the context of alternative HCC treatment strategies. Methods: With a Markov model, we examined surveillance with serum α-fetoprotein and ultrasound every 6 months in patients with compensated HCV-related cirrhosis from age 45–70 years or death, and HCC treatment with resection, cadaveric liver transplantation (CLT), or living donor liver transplantation (LDLT). Results: Compared to natural history in the base case, surveillance with resection, listing for CLT, or LDLT increased life expectancy by 0.49, 2.58, and 3.81 quality-adjusted life-years (QALYs), respectively, all at costs less than $51,000/QALY gained. The consequences of surveillance were most sensitive to the outcomes and costs of HCC treatments but not surveillance test performance characteristics or cost. Prioritizing CLT for patients with HCC over those with decompensated cirrhosis resulted in greater overall life expectancy with minimal increase in cost. Conclusions: Surveillance for HCC in patients with compensated HCV-related cirrhosis might gain QALYs at acceptable costs. The impact of surveillance depends most on the outcomes and costs of HCC treatments, rather than surveillance test characteristics. By increasing organ availability for timely definitive treatment, LDLT might achieve the greatest gain in life expectancy at acceptable costs. Prioritizing CLT for HCC might increase the population-wide benefits of CLT. Background & Aims: HCV-related cirrhosis is a leading risk factor for hepatocellular carcinoma (HCC). Surveillance might detect HCC at a treatable stage. We estimated the clinical and economic consequences of a common HCC surveillance strategy in patients with HCV-related cirrhosis in the context of alternative HCC treatment strategies. Methods: With a Markov model, we examined surveillance with serum α-fetoprotein and ultrasound every 6 months in patients with compensated HCV-related cirrhosis from age 45–70 years or death, and HCC treatment with resection, cadaveric liver transplantation (CLT), or living donor liver transplantation (LDLT). Results: Compared to natural history in the base case, surveillance with resection, listing for CLT, or LDLT increased life expectancy by 0.49, 2.58, and 3.81 quality-adjusted life-years (QALYs), respectively, all at costs less than $51,000/QALY gained. The consequences of surveillance were most sensitive to the outcomes and costs of HCC treatments but not surveillance test performance characteristics or cost. Prioritizing CLT for patients with HCC over those with decompensated cirrhosis resulted in greater overall life expectancy with minimal increase in cost. Conclusions: Surveillance for HCC in patients with compensated HCV-related cirrhosis might gain QALYs at acceptable costs. The impact of surveillance depends most on the outcomes and costs of HCC treatments, rather than surveillance test characteristics. By increasing organ availability for timely definitive treatment, LDLT might achieve the greatest gain in life expectancy at acceptable costs. Prioritizing CLT for HCC might increase the population-wide benefits of CLT. Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world.1Bosch F.X. Ribes J. Borras J. Epidemiology of primary liver cancer.Semin Liver Dis. 1999; 19: 271-285Crossref PubMed Scopus (849) Google Scholar In the United States, the incidence of and mortality from HCC have increased significantly during the past 2 decades.2El-Serag H.B. Mason A.C. Rising incidence of hepatocellular carcinoma in the United States.N Engl J Med. 1999; 340: 745-750Crossref PubMed Scopus (2713) Google Scholar HCV-related cirrhosis is the dominant risk factor for HCC in many developed countries.3Colombo M. Hepatitis C virus and hepatocellular carcinoma.Semin Liver Dis. 1999; 19: 263-269Crossref PubMed Scopus (60) Google Scholar The number of HCV-infected individuals in the United States at risk for HCC is projected to peak in the year 2015, when an estimated 1.1% of the population will have been infected for 20 or more years.4Armstrong G.L. Alter M.J. McQuillan G.M. Margolis H.S. The past incidence of hepatitis C virus infection implications for the future burden of chronic liver disease in the United States.Hepatology. 2000; 31: 777-782Crossref PubMed Scopus (461) Google Scholar The prognosis with advanced HCC is poor. In contrast, small HCC is potentially treatable by resection (partial hepatectomy), cadaveric liver transplantation (CLT), or living donor liver transplantation (LDLT).5Mor E. Kaspa R.T. Sheiner P. Schwartz M. Treatment of hepatocellular carcinoma associated with cirrhosis in the era of liver transplantation.Ann Intern Med. 1998; 129: 643-653Crossref PubMed Scopus (195) Google Scholar, 6Bismuth H. Majno P.E. Adam R. Liver transplantation for hepatocellular carcinoma.Semin Liver Dis. 1999; 19: 311-322Crossref PubMed Scopus (393) Google Scholar, 7Marcos A. Right lobe living donor liver transplantation a review.Liver Transpl. 2000; 6: 3-20PubMed Google Scholar, 8Sarasin F.P. Majno P.E. Llovet J.M. Bruix J. Mentha G. Hadengue A. Living donor liver transplantation for early hepatocellular carcinoma a life-expectancy and cost-effectiveness perspective.Hepatology. 2001; 33: 1073-1079Crossref PubMed Scopus (239) Google Scholar, 9Cheng S.J. Pratt D.S. Freeman Jr, R.B. Kaplan M.M. Wong J.B. 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Screening for hepatocellular carcinoma in patients with cirrhosis in the United States results of a national survey.Am J Gastroenterol. 1999; 94: 2224-2229Crossref PubMed Scopus (118) Google Scholar Randomized trials of surveillance in patients with HCV-related cirrhosis are unlikely to be performed because of practical and ethical considerations. In the absence of randomized trials, decision analysis provides the best means to estimate the impact of HCC surveillance. Our aims were to explore the potential clinical benefits and cost-effectiveness of the most common HCC surveillance strategy in patients with HCV-related cirrhosis. We postulated that the benefits of surveillance would depend strongly on the success rate of HCC treatment. Thus, we constructed a decision analytic model reflecting the natural history of HCV-related cirrhosis, including the risk of HCC, and evaluated the impact of surveillance with serum α-fetoprotein (AFP) and abdominal ultrasonography (US) every 6 months, with HCC treated radically by resection, listing for CLT, or LDLT. To assess recent changes in organ allocation policy, we explored the impact of prioritizing patients with HCC for CLT. MEDLINE searches from 1980–2003 were performed for English-language reports that provided data on HCV infection, cirrhosis, HCC, screening, hepatic resection, CLT, and LDLT. We created a state-transition Markov model (DATA 3.5.7, TreeAge Software Inc, Williamstown, MA; for analysis Excel 2000, Microsoft Corp, Redmond, WA and SAS 6.12, SAS Institute, Cary, NC) to simulate the natural history of HCV-related cirrhosis including the risks of decompensation, HCC, and death from liver disease or other causes. The principal health states were compensated (Child–Pugh class A) or decompensated (Child–Pugh class B or C) cirrhosis, without or with small (≤2 cm), medium (3–5 cm), or large (>5 cm or multifocal) HCC, and dead (Figure 1). Small and medium HCCs were treatable by resection (only if the patient had compensated cirrhosis), or transplantation (if the patient had either compensated or decompensated cirrhosis).15Bruix J. Sherman M. Llovet J.M. Beaugrand M. Lencioni R. Burroughs A.K. Christensen E. Clinical management of hepatocellular carcinoma conclusions of the Barcelona-2000 EASL conference—European Association for the Study of the Liver.J Hepatol. 2001; 35: 421-430Abstract Full Text Full Text PDF PubMed Scopus (3760) Google Scholar, 16Bruix J. Llovet J.M. Prognostic prediction and treatment strategy in hepatocellular carcinoma.Hepatology. 2002; 35: 519-524Crossref PubMed Scopus (995) Google Scholar Large HCC represented untreatable tumor. Only large HCC presented with symptoms. Patients entered the model at age 45 years with compensated cirrhosis and progressed until age 80 years or death, transitioning between states every 6 months on the basis of probabilities from the literature. Surveillance consisted of AFP and US during each 6-month cycle until age 70 years.15Bruix J. Sherman M. Llovet J.M. Beaugrand M. Lencioni R. Burroughs A.K. Christensen E. Clinical management of hepatocellular carcinoma conclusions of the Barcelona-2000 EASL conference—European Association for the Study of the Liver.J Hepatol. 2001; 35: 421-430Abstract Full Text Full Text PDF PubMed Scopus (3760) Google Scholar Helical triple-phase computed tomography (CT) was performed after any positive screening test (AFP > 20 μg/L17Gupta S. Bent S. Kohlwes J. Test characteristics of alpha-fetoprotein for detecting hepatocellular carcinoma in patients with hepatitis C a systematic review and critical analysis.Ann Intern Med. 2003; 139: 46-50Crossref PubMed Scopus (323) Google Scholar or mass on US). Patients with positive CT scans were considered for treatment on the basis of the state of cirrhosis and HCC size. The following strategies were superimposed on the natural history model: 1Surveillance/Resection: Surveillance followed by resection of small or medium HCC in patients with compensated cirrhosis.2Surveillance/CLT: Surveillance followed by CLT listing for small or medium HCC and compensated or decompensated cirrhosis, as well as decompensated cirrhosis without HCC.3Surveillance/LDLT: Surveillance followed by LDLT for small or medium HCC and compensated or decompensated cirrhosis, as well as decompensated cirrhosis without HCC. To distinguish the effect of surveillance for HCC from transplantation for decompensated cirrhosis only, we modeled CLT or LDLT for decompensated cirrhosis (no surveillance; CLT listing, or LDLT for decompensated cirrhosis with or without HCC). Patients with untreatable HCC received palliative care. In the base case, surveillance was performed only in potential candidates for resection or transplantation. In sensitivity analysis, we included surveillance in those who ultimately were not candidates for radical treatments. Base case inputs and the ranges tested in sensitivity analyses are shown in Table 1.Table 1Model Variables: Base-Case Values and Range Used in Sensitivity AnalysesVariableBase-case value (range)aRange in the sensitivity and Monte Carlo analyses.ReferencesClinical Age (y)45 (40–60) Mortality from compensated cirrhosis, annual %2 (1–6)18D'Amico G. Morabito A. Pagliaro L. Marubini E. 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