Hepatocellular cancer care: Cost is important but only one factor of disease burden
Authors: Fasiha Kanwal, Hashem B. El-Serag
Journal: Journal of Hepatology (2008)

“Burden of disease” is an all encompassing term that captures not only the frequency (such as the incidence and prevalence) of the disease but also reflects how the disease impacts other aspects of the health of a population (Table 1). These include negative impact of disease on longevity (such as pre-mature death and years of lost life), morbidity (pain and impaired health related quality of life), and economic consequences of the disease (such as direct health care expenditures in caring for the disease and indirect costs related to lost income from premature death or disability). Therefore, one needs to take all these aspects into account to understand the true magnitude of a disease’s burden. Such understanding is also essential in formulating health care policies to prioritize health interventions and to allocate scarce resources across a range of medical diseases. For example expensive interventions (e.g., screening to detect early disease, treatment) will add cost and therefore may increase the overall disease burden, however these interventions may actually reduce the overall disease burden by prolonging life, and improving quality of life.Table 1Burden of diseaseFrequency –Prevalence (pool of existing cases) –incidence (occurence of new cases)Impact on –Longevity (premature death) –Morbidity (in- and outpatient care, quality of life) –Finance (direct and indirect costs to society) Open table in a new tab Hepatocellular cancer (HCC) is the fifth most common solid tumor in the world. The incidence and prevalence of HCC is rising in the United States, several parts of Europe, and until recently Japan [[1]El-Serag H.B. Hepatocellular carcinoma: recent trends in the United States.Gastroenterology. 2004; 127: S27-S34Abstract Full Text Full Text PDF PubMed Scopus (899) Google Scholar]. In the United States, this rise is mainly due to an increase in hepatitis C related HCC and it is likely that this upward trend will continue with the aging of the hepatitis C Lang cohort [[2]Davila J.A. Morgan R.O. Shaib Y. McGlynn K.A. El-Serag H.B. Hepatitis C infection and the increasing incidence of hepatocellular carcinoma: a population-based study.Gastroenterology. 2004; 127: 1372-1380Abstract Full Text Full Text PDF PubMed Scopus (433) Google Scholar]. HCC is highly fatal and significantly impairs health-related quality of life [3Greenlee R. Hill-Harmon M. Murray T. Thun M. Cancer statistics, 2001.Cancer J Clin. 2001; 51: 15-36Crossref PubMed Scopus (3355) Google Scholar, 4Steel J.L. Chopra K. Olek M.C. Carr B.I. Health-related quality of life: hepatocellular carcinoma, chronic liver disease, and the general population.Qual Life Res. 2007; 16: 203-215Crossref PubMed Scopus (56) Google Scholar]. Thus, the burden of illness related to the rising frequency of HCC is multiplied by this negative impact on patients’ survival and health-related quality of life. However until now, data on the economic burden of HCC are limited. In this issue of the Journal, Lang and colleagues estimate the annual direct as well as indirect costs associated with HCC in the United States [[5]Lang K. Danchenko N. Gondek K. Shah S. Thompson D. The burden of illness associated with hepatocellular carcinoma in the United States.J Hepatol. 2009; 50: 89-99Abstract Full Text Full Text PDF PubMed Scopus (112) Google Scholar]. This study, therefore, fills an important gap in our understanding of the overall disease burden in HCC. Lang et al. used the linked Surveillance, Epidemiology and End Results (SEER) and Medicare dataset to derive their cost data. SEER is a premier source for cancer statistics in the United States and collects information on incidence, survival, and prevalence from specific geographic areas representing 26 percent of the US population [[6]SEER-Medicare linked database. Available from: http://healthservices.cancer.gov/seermedicare/. Accessed October 20, 2008.Google Scholar]. Medicare is the US government health insurance plan that provides hospital, medical, and surgical benefits for all persons age 65 and older and for people with certain disabilities. The SEER-Medicare data reflect the linkage of these two large population-based sources of data that provide detailed clinical, demographic, healthcare utilization, and cause of death information for Medicare enrollees with cancer [[6]SEER-Medicare linked database. Available from: http://healthservices.cancer.gov/seermedicare/. Accessed October 20, 2008.Google Scholar]. Although the linkage of these two data sources results in a unique population-based source of information that can be used for epidemiological and health services research, the SEER-Medicare database has its own limitations. First, the data are mostly limited to patients 65 and older and cannot be easily generalized to younger patients. Second, Medicare data have the disadvantages inherent in any administrative database, such as unreliability due to coding problems and lack of information on non-users. Third, Medicare data does not include claims for persons who are simultaneously enrolled in other insurance plans, such as an HMO plans or the Veterans Administration, and it does not include information on oral prescriptions [[6]SEER-Medicare linked database. Available from: http://healthservices.cancer.gov/seermedicare/. Accessed October 20, 2008.Google Scholar]. Despite these limitations, the SEER-Medicare database provides a unique data source that makes it possible to derive incidence and prevalence based estimates of cancer-related medical care costs by site and stage of disease and by age and gender strata for individuals older than 65 years. Using HCC incidence rates and median survival estimates from the SEER component of the linked database, Lang et al. first estimated the annual prevalence of HCC in the United States for 2005 [[5]Lang K. Danchenko N. Gondek K. Shah S. Thompson D. The burden of illness associated with hepatocellular carcinoma in the United States.J Hepatol. 2009; 50: 89-99Abstract Full Text Full Text PDF PubMed Scopus (112) Google Scholar]. The authors estimated annual health care costs in HCC by tracking a subgroup of patients who had continuous enrollment in the Medicare plan for the entire study year (1999). Given the limitations of data (as stated above), they excluded patients who had any supplementary insurance during the study year and estimated the frequency of oral prescription drug use based on previous published literature. Due to a lack of healthcare utilization for patients younger than 65, they assumed that the resource use and accompanying costs for this age group to be equivalent to those observed for the youngest patients in the SEER-Medicare database (i.e., aged 65–69 years), and tested this assumption is several sensitivity analyses. After accounting for inflation, the study estimated that caring for a patient with HCC cost an average $32,907 in 2005. With the estimated prevalence of approximately 14,000 patients with HCC in 2005, the total economic burden of HCC was estimated to be $454.5 million. What does this cost dollar amount mean? First of all, this cost estimate is likely a conservative one. The direct costs in this study are based on the frequency of HCC specific healthcare utilization in 1999. The treatment repertoire in HCC has changed significantly since 1999. The proven efficacy of local ablative (such as ethanol ablation, radiofrequency ablation) as well as the palliative treatments (such as transarterial chemoembolization and sorafenib) has changed the treatment algorithms in HCC[[7]El-Serag H.B. Marrero J.A. Rudolph L. Reddy K.R. Diagnosis and treatment of hepatocellular carcinoma.Gastroenterology. 2008; 134: 1752-1763Abstract Full Text Full Text PDF PubMed Scopus (931) Google Scholar]. As one would expect, these treatment modalities were only sparsely used in 1999, and sorafenib was introduced only in 2007 [5Lang K. Danchenko N. Gondek K. Shah S. Thompson D. The burden of illness associated with hepatocellular carcinoma in the United States.J Hepatol. 2009; 50: 89-99Abstract Full Text Full Text PDF PubMed Scopus (112) Google Scholar, 8Llovet J.M. Ricci S. Mazzaferro V. Hilgard P. Gane E. Blanc J.F. et al.Sorafenib in advanced hepatocellular carcinoma.N Engl J Med. 2008; 359: 378-390Crossref PubMed Scopus (9764) Google Scholar]. Moreover, because patients with HCC receive a higher priority in the current Model for End Stage Liver Disease (MELD) based liver donor allocation system, liver transplantation has become more widely available for patients with HCC since 2002.[[9]Ioannou G.N. Perkins J.D. Carithers Jr., R.L. Liver transplantation for hepatocellular carcinoma: impact of the MELD allocation system and predictors of survival.Gastroenterology. 2008; 134: 1342-1351Abstract Full Text Full Text PDF PubMed Scopus (220) Google Scholar] For example, over the last 6 years, on average, 1000 patients with HCC received liver transplantation in the US each year [[9]Ioannou G.N. Perkins J.D. Carithers Jr., R.L. Liver transplantation for hepatocellular carcinoma: impact of the MELD allocation system and predictors of survival.Gastroenterology. 2008; 134: 1342-1351Abstract Full Text Full Text PDF PubMed Scopus (220) Google Scholar]. This number is significantly higher than that used by Lang and colleagues in their analysis. Lastly, HCC incidence and prevalence is expected to increase considerably over the next decade. Combined together, these recent changes in the healthcare utilization as well as epidemiology of HCC will likely inflate the $454.5 million estimate presented in this paper. Second, the healthcare cost estimates may be meaningless in the absence of simultaneous data on healthcare effectiveness. Specifically, this high (and likely rising) cost of HCC care may be acceptable to the society if this expense results in prolonging patients’ life or improving their health related quality of life. For example, Lang et al. found that the healthcare costs were highest for patients with localized HCC. Similarly, younger patients incurred higher costs than older patients [[5]Lang K. Danchenko N. Gondek K. Shah S. Thompson D. The burden of illness associated with hepatocellular carcinoma in the United States.J Hepatol. 2009; 50: 89-99Abstract Full Text Full Text PDF PubMed Scopus (112) Google Scholar]. With the implementation of HCC surveillance programs, more patients are likely to get diagnosed at a younger age and with earlier stage tumors. Given that these factors appear to be the major drivers of cost in HCC, the total cost of HCC may soar in the coming years. However, because patients diagnosed through the surveillance programs are more likely to receive effective treatments [10Zhang B.H. Yang B.H. Tang Z.Y. Randomized controlled trial of screening for hepatocellular carcinoma.J Cancer Res Clin Oncol. 2004; 130: 417-422Crossref PubMed Scopus (19) Google Scholar, 11McMahon B.J. Alberts S.R. Wainwright R.B. Bulkow L. Lanier A.P. Hepatitis B-related sequelae. Prospective study in 1400 hepatitis B surface antigen-positive Alaska native carriers.Arch Intern Med. 1990; 150: 1051-1054Crossref PubMed Google Scholar], the accrued costs may still be acceptable. Third, although the cost estimates in the present study cannot be anchored to the effectiveness of available healthcare services in HCC, these data will be extremely useful as inputs in future cost-effectiveness studies. Such studies may, in turn, guide medical decision analysts and health care policymakers to determine whether or not these costs are acceptable and below their willingness-to-pay thresholds. As the incidence of HCC increases and the repertoire of screening, diagnosis, and treatment grows with the availability of more effective yet more expensive treatments, cost of care in HCC will continue to rise. These treatments will cost additional money and require additional resources. However, this rising cost of care may still be acceptable or justifiable if it results in an accompanying improvement in the quality adjusted life years (i.e., cost-effective). On the other hand, the true cost saving alternative may actually be prevention of HCC by channeling resources to patients with earlier stages of liver disease. Primary prevention includes HBV vaccination, cessation of heavy alcohol and tobacco consumption, reducing the spread of HCV, and possibly maintaining optimum body weight. Secondary prevention includes targeted screening and subsequent treatment of high-risk groups (e.g., HCV, HBV, NASH) may be the only way to decelerate this increasing economic burden of HCC.