| New cases of liver cancer accounted for 45.3% and deaths accounted for 47.1%of the total global cases of liver cancer in China.The burden of liver cancer in China,especially the economic burden,is still heavy.Liver cancer screening targets high-risk population carry out reasonable early intervention,reduce liver cancer mortality and improve the quality of life of patients.More than 80% of liver cancer are co-infected with hepatitis B virus(HBV)in China,that is,chronic hepatitits B(CHB)related liver cancer,of which liver cirrhosis when they are diagnosed with liver cirrhosis.The incidence of hepatocellular carcinoma(HCC)in liver cirrhosis patients is as high as 3%-8%,which is the leading cause of HCC in China.Therefore,formulating effective screening strategies for liver cirrhosis patients is a key means to reduce the burden of liver cancer in China.In addition to the commonly used imaging tests for HCC screening,such as ultrasound,computerized tomography(CT),magnetic resonance imaging(MRI),and alpha fetoprotein(AFP),our research group has been evaluating the application value of anti-tumor associated antigen autoantibody(TAAb)for HCC screening and diagnosis for a long time.For evaluation of HCC screening strategies,in addition to the accuracy of screening measures,population acceptance,costs and other key factors,the cost-effectiveness analysis(CEA)of screening strategies is also crucial.The purpose of economic evaluation of HCC screening is to provide a scientific basis for the allocation of limited medical resources and financial resources,as well as to provide a basis for clinical screening for HCC in liver cirrhosis patients.When evaluating the cost-effectiveness value of liver cancer screening for liver cirrhosis,not only the benefits of antiviral therapy as a method to prevent cancer should be paid attention to,but also the economic value of antiviral therapy can not be ignored.The medical and health-related cost-effectiveness analysis guidelines recommend that the quality adjusted life years(QALYs)should be the final effect evaluation indicators,while the existing health utility value data for patients with CHB-related diseases cannot meet the needs of CEA in this study.Therefore,it is also necessary to measure the health utility value of patients with CHB-related diseases before evaluating the economic value of HCC screening strategies.ObjectivesThe purpose of this study was to conduct a questionnaire survey of CHB-related diseases patients in multiple clinical centers,and to calculate the health utility value based on the Short Form-Six Dimension(SF-6D)health utiliy value points system preferred by the Chineses population.Another purpose was constructed Markov model for HCC screening in patients with liver cirrhosis that meets our national conditions and to explore the optimal strategy for CHB liver cancer screening from an economic perspective,The third aim of this study was to evaluate the impact of antiviral therapy on the economic value of liver cancer screening strategies and to explore the economic value of TAAb for HCC screening in China.Methods1.The method of measuring the health utility value of CHB-related disease patients.We conducted a questionnaire survey on the patients with CHB-related diseases(including CHB,compensated cirrhosis,decompensated cirrhosis,HCC)by using time-phase cluster sampling and the Chinese version of SF-36v2 and the personal information questionnaire in quality of life in three liver disease clinical centers in Beijing and Zhengzhou,Henan Province.We calculated the quality of life of patients with each diagnostic classification based on Chinese norm data,to convert life quality into health utility value via SF-6D and used non-parametric test Kruskal-Wallis rank sum test for comparison of differences between groups.Multivariate linear regression analysis was used to conduct a multivariate analysis of factors affecting the quality of life of patients with CHB-related diseases.2.Construction of Markov model for CHB-related HCC screeningThe Markov model for HCC screening was constructed according to the basic principles of the Markov chain,the natural outcome history of CHB-related diseases and the Barcelona Staging(Barcelona Clinic Liver Cancer,BCLC)system.The model parameters were collected through the formulation of operating conditions of the model in combination with the literature analysis method,expert consultation method,special survey method and so on.Some of the regression rate parameters were converted by the life decline index approximation method.3.Cost-effectiveness analysis methods and strategy optimization methods for liver cancer screeningTaking 40-year-old patients with liver cirrhosis as the simulation object,three screening cohorts of patients with liver cirrhosis were constructed according to the different antiviral treatments of patients in the simulation cohort,and a Markov model was construct by Tree Age Pro 2020 software for decision analysis of HCC screening.Screeing methods were ultrasound,ultrasound combined with AFP,CT,and MRI.Screening frequency were once every six months or once a year.Totally,there were 8screening strategies.The optimal strategy for liver cancer screening was determined.Taking 3 times of China per capita GDP in 2019 as the baseline analysis result of willingness to pay.And one-way sensitivity analysis,probability sensitivity analysis,and plotting of payable curve were performed to evaluate the influence of main parameters on the stability of the model.4.Cost-effectiveness analysis method of TAAb for HCC screeningA Markov model of decision analysis for early screening of HCC was constructed taking 40-year-old patients with liver cirrhosis as a simulation object.This study used liver ultrasound combined with AFP.recommended by the guidelines as the control strategy,TAAb screening alone or TAAb combined with AFP two screenings were used as the research strategy.Three termination conditions were set up for the model to run for 10 years,30 years and run to death of 99.9% of the population deaths.,the cost-effective value of TAAb for HCC screening under different model termination conditions was determined by taking 3 times per capita GDP of China in 2019 and the commonly used threshold in developed countries($50,000)as willingness to pay to evaluate the results of the baseline analysis One-way sensitivity analysis,probability sensitivity analysis were also performed to evaluate the influence of main parameters on the stability of the model.Results1.Results of the health related quality of life(HRQoL)and health utility value of CHB-related diseases patients.A total of 1071 valid questionnaires were collected included 639 CHB patients,125 CC patients,85 DC patients and 222 HCC patients with an average age of patients at 42.49.The health utility values of chronic hepatitis B,compensated cirrhosis,decompensated cirrhosis and HCC were 0.796(0.132),0.752(0.189),0.664(0.203)and 0.562(0.258),respectively.The health utility values of BCLC(0/A),BCLC(B)and BCLC(C/D)were 0.580(0.267),0.555(0.247)and 0.513(0.262),respectively.In the CHB stage,the patients’ physiologically related HRQoL did not decrease,while the psychologically related HRQoL decreased significantly.As the disease progresses,the overall physiological score of patients has a greater decline than the psychological related HRQoL.2.Results of Markov model construction of HCC screening.There were 4 Markov models constructed in this study for HCC screening in patients with liver cirrhosis,namely: Markov model for liver cirrhosis patients not receiving either antiviral therapy or liver cancer screening,Markov model for liver cirrhosis patients not receiving antiviral therapy but undergoing cancer screening,Markov model for liver cirrhosis patients receiving antiviral therapy without liver cancer screening,and Markov model for liver cirrhosis patients with both antiviral therapy and liver cancer screening.The goodness of fit between the actual and predicted values of the cumulative incidence of liver cancer in patients with liver cirrhosis treated with antiviral therapy were 0.994 and 0.969,respectively.3.Cost-effectiveness analysis and strategy optimization results of HCC screening.For the 40-year-old antiviral treatment cohort in China,the ultrasound with AFP screening strategy every half yeaf was the most cost-effective,and its cost-effectiveness ratio was 33683 yuan/QALY.When the cohort of patients with liver cirrhosis not receiving antiviral treatment was screened for HCC,the cost-effectiveness ratio of the half-year CT screening strategy was 25524 yuan/QALY,which has the most cost-effective value.For a cohort in which 80% of the patients receive the antiviral treatment,the ultrasound with AFP screening strategy every six months was the optimal strategy,and the cost-effectiveness ratio was 32339 yuan/QALY.The sensitivity analysis results show that the economic evaluation results were reliable.When the willingness to pay was 3 times per capita GDP,the probability that the above three optimal strategies have cost-effective value is 96.6%,69.9% and 89.1%,respectively.4.Results of cost-effectiveness analysis of TAAb for HCC screening.For HCC screening in 40-year-old patients with liver cirrhosis in China,if the model runed for 10 years,compared with ultrasound with AFP strategy,ICER adopting TAAb with AFP strategy was 13568548 yuan/QALY,which has no cost-effective value.If the model runed for 30 years or when 99.9% of the population die,ICER was 203207 yuan/QALY and 144548 yuan/QALY,which has cost-effective value.Sensitivity analysis results showed that the economic evaluation results of TAAb+AFP strategy were reliable.When the willingness to pay threshold is 3 times the per capita GDP,the probability of this strategy being cost-effective is47.5%,72.7% and 78.5%.Conclusion1.The results of the health utility value not only provide parameters for this study,but also provide important data support for the cost-effectiveness analysis of CHB-related diseases or liver cancer.CHB-related patients maintain a better quality of life by slowing down the progression of chronic hepatitis B-related diseases and providing psychological support for patients in the early stages of the disease.2.The Markov models constructed in this study for HCC screening in liver cirrhosis patients are credible and can meet the needs of economic evaluation of HCC screening strategies for patients with liver cirrhosis in China.3.For cirrhosis patients over 40 years old who do not receive antiviral therapy,the CT screening every six months strategy is the optimal strategy.Improving the adherence of antiviral therapy in patients with liver cirrhosis will increase the costeffectiveness value of ultrasound combined with AFP screening strategy.Antiviral therapy is one of the means to prevent HCC,and its impact on the cost-effectiveness value of HCC screening strategies cannot be ignored.4.The TAAb with AFP strategy as an early screening method for HCC in40-year-old patients with liver cirrhosis in China has cost-effective value.This strategy is compatible with the current level of economic and social development in our country and can be clinically promoted. |
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