Monitoring and treatment of inactive chronic hepatitis B: Is it cost-effective?
Authors: Zobair Younossi, Linda Henry
Journal: Hepatology (2014)

In this issue of Hepatology, an interesting article by Toy et al. addresses the clinical effect and cost-effectiveness of managing inactive chronic hepatitis B (CHB) carriers.1 Current clinical practice in China for hepatitis B virus (HBV) is prevention by vaccinating all infants and children against hepatitis B. In fact, this is a common practice in most of the developing and emerging countries, especially Africa and parts of eastern Asia.2, 3 However, according to the researchers, despite a universal vaccination policy against hepatitis B in China, hepatitis B remains a major health threat to the general population. Using computer simulation and Markov modeling, the researchers assessed the cost-effectiveness of a strategy of lifelong monitoring for inactive CHB and treatment of eligible patients in Shanghai, China. In comparison with the current clinical practice in Shanghai, the strategy of "monitor and treat" was shown to be cost-effective with an incremental cost-effectiveness ratio (ICER) of $2,996 per quality-adjusted life-years (QALY) gained.1 In this analysis, ICER of monitor and treat clearly meets the threshold of <$50,000 per QALY that is the generally accepted threshold for cost-effectiveness.2 Furthermore, the result of the sensitivity analyses performed by the researchers provided additional interesting insights. In these analyses, the researchers found that by increasing the percentage of population tested and by increasing the rate of adherence to the treatment regimen, ICER will continue to improve. Moreover, the most important assumption that was identified in the sensitivity analyses was the cost of entecavir. If this cost (assumed for the base case to be $1,869) was reduced by 50% ($964), the monitor and treat strategy would actually become cost-saving.1 The researchers should be congratulated for carefully addressing an important issue in the management of inactive CHB, which could potentially have some global implications. The analytic methodology used in this study is generally sound and carried out with rigor. A few weaknesses that need to be considered are the generalizability of the transition rates, cost, and utility assumptions. For example, viral suppression was assumed to have a utility of 1.0, which defines perfect health. In reality, the extreme of utility scores (0 to 1) in the general population is hardly attainable and thus provides the reader with an overestimation of the health status associated with viral suppression. Nevertheless, this and other assumptions related to transition rates do not seem to have an important effect on the final ICER. As noted previously, of the assumptions tested in the sensitivity analyses, only the cost of entecavir was shown to significantly influence ICER. It is important to note that the cost of entecavir used in the base-case scenario or sensitivity analyses may not be generalized to the other areas of the world. Also, the researchers did not consider the cost of other important anti-HBV drugs, such as tenofovir, which are also highly effective and widely used to treat HBV. This, again, raises some potential issues with the external validity of their data. Another important limitation of this study was their goal of showing the benefit of the monitor and treat strategy at the population level. As noted by the researchers, achieving gains at the population level would require identification of more cases of CHB and appropriate treatment and management of these patients.1 Also, the ability to generalize this strategy beyond Shanghai, China, would require that the assumptions be validated using data from other parts of China and the world. Nevertheless, the rates used by Toy et al. seem to be consistent with what researchers have recently reported from other areas of the world. In one study, Ott et al., as part of the Global Burden of Diseases, Injuries and Risk Factor Study, investigated the global epidemiology of HBV and provided age-specific hepatitis B surface antigen (HBsAg) seroprevalence rates.3 A reduction in HBV prevalence rates between 1990 and 2005 was noted; however, the number of patients with HBV was influenced by their age- and gender-specific rates. The highest rate for HBsAg positivity was in East Asia, with a rate greater than 8%, and found in males over the age of 35.3 These rates were confirmed by two other studies from China with prevalence rates of 7.9%4 and 8.1%,5 respectively. Luo et al. reported a significant difference in the rates between males and females as well as an increase in the prevalence of the disease with age.4 Another estimation by Toy et al. was related to a 19% lifetime risk of developing hepatocellular carcinoma (HCC). There is some evidence that this value may actually underestimate the true risk for developing HCC in patients with CHB. In fact, Tanaka et al. recently reported that primary liver cancer in China was the second-most common cause of cancer deaths. Furthermore, most of these patients with HCC were HBV carriers.5 In another study, Gao et al. after evaluating 119 patients dying from HCC in North China reported that 82.4% of these patients were HBsAg positive.6 Finally, Ly et al. reported that patients with HBV and hepatitis C virus (HCV) die almost two decades earlier, as compared to those who were not carriers of these hepatotropic viruses. They concluded that as a result of the dramatic increase in the risk of premature death, programs need to be established for prevention, early identification, and treatment of HBV and HCV.7 These recommendations are consistent with the conclusions reached by Toy et al. in the current article.1 Toy et al. also suggest that in order for a population-based surveillance program to be effective in China, there needs to be a systematic, well-organized, and affordable surveillance system in place.1 One tool that could potentially help with the efficiency of patient education-related HBV was developed by Iloeje et al.8 As part of the Risk Evaluation of Viral Load Elevation and Associated Liver Disease/Cancer-Hepatitis B Virus study, these investigators developed nomograms that incorporated noninvasive clinical parameters into a model that then could be used to predict the development of HCC over time. If fully validated, this type of nomogram will provide a simple, efficient tool to identify the high-risk patients with HBV who may benefit from treatment. The ability to provide this type of information efficiently, accurately, and quickly can help ease the burden associated with follow-ups to inform patients of their HBV status and allow health care providers the ability to treat and educate patients about their HCC risks. One point not discussed in Toy et al.'s article, but one we consider to be relevant, is the effect of screening on patient's health-related quality of life (HRQL). Chao et al. studied the effects of an HBV intervention program on patients' HRQL in China. Using a comprehensive approach to treatment of HBV (government support, guidance from the Chinese Center for Disease Control and Prevention, standard medical care, and community involvement), patients' HRQL was measured pre- and postintervention.9 The postintervention HRQL data provided evidence that a comprehensive intervention may actually improve patients' well-being and should be considered when treating these patients.9 This is consistent with having an integrative, comprehensive approach to patients with HBV that includes not only outcomes that are important to clinicians, but also those that are important to patients.10 In summary, Toy et al. present a very interesting, thought-provoking, and clinically relevant study. Nevertheless, it will be important to further expand this model to assess cost-effectiveness of monitor and treat in other regions of the world, including the United States. Although the current estimates suggest that <0.01% of the general U.S. population are chronic HBV carriers, as high as 25% of the individuals who immigrated from endemic areas of the world for HBV, such as Asia, are chronically infected. Furthermore, less than one third of these patients actually have received treatment.11, 12 Model assumptions must be validated in other geographic locations, and country-specific strategies should be considered to fully assess the effect of CHB and its complications at the population level. Finally, thought should also be given to measuring HRQL at the time of treatment to determine its effect on patients' perceptions on their health. Zobair Younossi, M.D., M.P.H.1,2 Linda Henry, Ph.D.2 1Department of Medicine Inova Fairfax Hospital Falls Church, VA 2Betty and Guy Beatty Center for Integrated Research Inova Health System Falls Church, VA