Hepatocellular carcinoma (HCC) is the fifth most prevalent cancer worldwide and the third most frequent cause of cancer-related mortality.[1, 2] More than 700,000 cases were diagnosed in 2008. At least 80% of cases are diagnosed in areas with poor healthcare infrastructures, leaving the vast majority of patients without proper treatment. In Western countries the incidence and prevalence of HCC are also increasing. In the U.S. the age-adjusted incidence is around 4.2 per 100,000, accounting for about 20,000 new cases diagnosed each year.[1, 2] Several treatment options are available to patients with early to intermediate stage HCC with similar short-term results. Liver transplantation is curative for both HCC and the accompanying liver cirrhosis; however, it can be offered only to a minority of patients.
HCC imposes a severe human and economic burden on patients, their families, and society. The assessment of the burden of disease is an area of growing interest and is used to establish public health objectives, to inform decisions on the allocation of healthcare resources across disease categories, and to evaluate the costs and benefits of health interventions in specific fields.[3, 5] Core measures of disease burden include incidence, prevalence, mortality, and the cost of illness (COI). The COI includes direct costs, morbidity costs (i.e., the lost income due to work disability and absenteeism), and the mortality costs (i.e., the loss of income associated with premature death).
Thein et al. in the current issue of Hepatology present a population-based study reporting the healthcare costs associated with HCC. The study, based on the Ontario Cancer Registry and linked administrative data, enrolled 2,341 cases of HCC identified in Ontario, Canada, between 2002 and 2008. The authors measured the “direct costs” of care, i.e., the expenditures for medical procedures and services used for the care of the disease. The main limitations of the study are the lack of tumor stage classification and the lack of etiological stratification. Furthermore, it is worth noting that due to differences in epidemiology, medical practice, physicians attitude and culture, patterns of treatment, patients' preferences, and financial incentives these results cannot be transferred from one healthcare system to another without proper adjustments. Despite these limitations, this important study provides us with innovative cost analyses, including:
- Estimates of the 5-year average net cost of a patient with HCC. As shown in Thein et al.'s article, the per-patient 5-year net cost of care for HCC is higher than other cancers (about $77,000, range: $60,000 to $94,000). This is not surprising, because HCC usually occurs as a complication of liver cirrhosis. The presence of a chronic disease and of reduced liver function restricts therapeutic approaches and aggravates the costs of the disease. As discussed by the authors, these costs are also higher than those calculated in prior studies reporting HCC costs in the U.S. and Taiwan.[7, 8] Clearly, several factors come into play, including types of data collected and local regulatory and reimbursement issues. Nevertheless, the methodology described in this article should be useful for further studies evaluating costs for specific healthcare systems.
- Estimates of the aggregate 5-year net costs of treating all patients with HCC from the perspective of a universal coverage healthcare system based on a whole population, and not on a sample. Thein et al.'s article does not provide estimates of the burden based on a more or less representative sample, but rather on the aggregate economic value of the care provided to the entire population. Should these figures be transferable to the U.S., the cost of managing the 20,000 new U.S. cases per year, not including morbidity and mortality costs, would be around one billion U.S. dollars.
- Phase-specific estimates of the direct costs of HCC. In Western countries, HCC is most often diagnosed in patients with liver cirrhosis undergoing an ultrasound (US) / alpha-fetoprotein (αFP)-based protocol of oncologic surveillance. The primary tumor is treated following a stage-based approach defined by the American Association for the Study of Liver Diseases (AASLD) guidelines. Patients showing a complete response undergo an intensive follow-up protocol. The length of this intermediate phase is mostly dependent on the HCC stage at the time of diagnosis. Treatments are usually applied sequentially, as in most cases HCC recurs. Ultimately, the recurrent tumor(s) will lead to vascular invasion and/or distant metastases. To capture the economic impact of this natural history, detailed phase-specific estimates of direct medical costs derived from patient-level longitudinal expenditures are needed. Unfortunately, the few studies available on costs of care in HCC were designed to consider costs as they come across specific treatment episodes. Instead, Thein et al., using an approach designed along the full cycle of care, were able to capture the specific costs for the initial, continuing, and terminal phases of HCC care. By showing the evolution of costs incurred by third-party payers as the patient progresses along the natural history of disease, this innovative study is able to transform clinical perceptions into monetary values. It is worth noting that the more costly stage of disease is the terminal phase, providing further indirect evidence of the value of early diagnosis, and of the importance of maintaining patients in stable, less costly phases. This information will be fundamental to assess the efficiency of competing or alternative treatments and disease management programs.
A word of caution is needed when analyzing cost data without reference to the outcomes. Cost data are useful for budgetary reasons, but the real goal should be to understand the value of the care for a given condition, and this depends on both costs and outcomes, i.e., on the ability to achieve the best possible outcome using the appropriate amount of resources. Both dimensions of the value of care must be taken into account in decision making.
Thein et al.'s study makes a strong economic case for HCC prevention. This is very important because the development of HCC is associated with a number of preventable risk factors. Some of them, including alcohol, obesity/overweight, and exposure to hepatitis viruses, could be modified by lifestyle interventions. Vaccination against hepatitis B virus (HBV) has proved to be an effective measure to reduce the incidence of HCC in the countries that have adopted it. Life-long treatment with antivirals to suppress HBV replication reduces the incidence of liver cirrhosis, hepatic decompensation, and liver cancer. Successful eradication of hepatitis C virus (HCV) also reduces the incidence of liver decompensation and HCC. Newer and more active drugs able to achieve very high rates of HCV clearance, even in previous nonresponders to peg-interferon and ribavirin are now available, and interferon-free antiviral regimens are around the corner. The successful implementation of these complex preventive and therapeutic interventions requires specialized care and Hepatology services able to recognize and prevent risk factors and to manage chronic liver disease across the continuum of disease stages. It also requires adequate vision and funding from policy-makers.
The value of these services is reciprocal to the burden of disease and can be expressed in terms of reduction in the incidence (i.e., cases avoided), reduction in mortality (i.e., live years saved and quality-adjusted life years saved), and reduction in cost of illnesses. Often policy-makers tend to think that prevention is costly, as it needs funding here and now. Articles like Thein et al.'s provide evidence that failure to prevent can be even more costly: here, now, and in the future.
Lorenzo G. Mantovani1Mario Strazzabosco2
1Department of Clinical Medicine and Surgery di Medicina Clinica e Chirurgia, University of Napoli Federico II, Napoli, Italy
2Digestive Disease Section, Department of Surgical and Medical Transplational Sciences, University of Milan-Bicocca, Milan, Italy, and Yale University Liver Center, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT