| OBJECTIVE:To develop Markov models reflecting the reality of hepatitis B vaccination or treatment, to simulate a variety of disease progression in the different population of hepatitis B virus(HBV) infection and to meet the need of economic evaluation for hepatitis B vaccination and antiviral treatment of prophylactic entecavir for population based-on community in C hina.To perform a cost-effectiveness analysis and to identify the cost-effectiveness acceptability levels for an antiviral therapy strategy of prophylactic entecavir for population(age between 20~59 years old) based-on community in C hina. METHODS:According to the theories and methods of Markov chain and based on related literatures in domestic and abroad, Markov models was used to describe the actuality of universal newborn hepatitis B vaccination, prevention of mother-to-child transmission and antiviral treatment for chronic hepatitis B in China through setting the states, allowable transitions and transition probabilities. The building, operation and validation of models were finished by Tree Age Pro 2015 software.The antiviral therapy strategy of prophylactic entecavir for population based-on community was put forward, that is adults are offered HBs Ag testing. Those found to be positive will be referred to visit a liver specialist for further investigation and to determine the need for antiviral therapy. If treatment is indicated, then adults will be offered treatment with entecavir. A cost-effectiveness analysis was performed to compare three strategies. These strategies comprise antiviral therapy strategy, adult hepatitis B vaccination and the status quo of no intervention. The age between 20~59 years old of the population based-on community were divided into four groups, such as 20~29, 30~39, 40~49, 50~59. The cost, quality adjusted life year(QALY) and incremental cost-effectiveness ratio(ICER) were calculated by baseline analysis and the main influencing parameters related to the optimal strategy were determined through one-way sensitivity analysis or probabilistic sensitivity analysis. RESULTS:Five types of Markov models were commonly used, including the disease progression after HBV infection in neonatal period, perinatal or adulthood, the progression after antiviral therapy for chronic hepatitis B(CHB), and the natural progression for health population. The Markov model simulating the progression after HBV infection in neonatal period comprise ten states, including susceptible to HBV, HBsAg clearance, immune tolerance, immune clearance, low replicate, HBeAg negative C HB, compensated cirrhosis, decompensated cirrhosis, Hepatocellular carcinoma(HCC) and death. States of the others Markov model adjusted from neonatal model. The Markov model of perinatal neglected the state of susceptible to HBV, and the model of adulthood take no account of immune tolerance state. The model of CHB patient does not cover state of susceptible to HBV and immune tolerance. The model of health population only incorporate states of survive and death. There are 27 transition probabilities, and all of them were divided into three kinds. These parameters remain constant over time, time dependent or follow some functions of time. The probability curve resulted from the 100,000 birth cohort analysis conform to the natural history of CHB in China, and the simulation numbers of acute infection is substantially below to early model. It manifest the Markov models of hepatitis B vaccination and treatment were corresponding to reality, and we can apply these models to economic evaluation of hepatitis B vaccination and treatment.The decision branch of decision-analytic Markov model depicting the antiviral therapy strategy of prophylactic entecavir for population based-on community consist of six chance nodes. The decision analysis model simulated the program of receiving HBs Ag test and treatment with entecavir. Various outcomes after HBV infection or receive treatment were simulated by Markov models. The results of cost-effectiveness analysis indicated the antiviral therapy strategy of prophylactic entecavir should be carry out in the population of 20~29 years old prioritly. Compared to no intervention strategy, the IC ER of antiviral therapy strategy increase with age, but less than the three times of gross domestic products per capita in C hina. Moreover, the ICER of antiviral therapy strategy also less than three times of gross domestic products per capita compared to adult hepatitis B vaccination. The results of univariate sensitivity analysis reminder that the drug cost of entecavir was the key factor affected the baseline results. In the probabilistic sensitivity analysis, the cost-effectiveness probability for the antiviral therapy strategy at ￥30,000 per QALY was 50%. At the willingness-to-pay threshold of 60,000 per QALY, the cost-effectiveness probability reached 100%. CONCLUSIONS:1、Five types of Markov models were developed to simulate the progression after infection in neonatal period, perinatal or adulthood, the progression after antiviral therapy for CHB, and the natural progression for health population, and satisfy the demanding of economic evaluation for hepatitis B vaccination and treatment in C hina.2、The Markov model of progression after infection in neonatal period was the key one among five types of models, and were consisted of ten states. There are 27 transition probabilities, and all of them were divided into three kinds. The others model derive from it. The change of models comply with the complexity of transmission in Chinese population.3、The trend of various states change with age calculated by Markov model of progression after infection in neonatal period corresponds to natural history of CHB in China, and the simulation numbers of acute infection is substantially below to early model. So there is a certain reliability for Markov models of hepatitis B vaccination and treatment to apply economic evaluation in C hina.4、 The antiviral therapy strategy of prophylactic entecavir for population based-on community is cost-effective in the age group of 20~59 years old, especially in low age group.5、The drug cost of entecavir is the key parameter of antiviral therapy strategy of prophylactic entecavir for population based-on community. |
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