OBJECTIVE: To assist with achieving these goals and to inform the development of a national strategic plan for Malaysia, we estimated the long-term burden incurred by the care and management of patients with chronic hepatitis C virus (HCV) infection. We compared cumulative healthcare costs and disease burden under different treatment cascade scenarios.

METHODS: We attached direct costs for the management/care of chronically HCV-infected patients to a previously developed clinical disease progression model. Under assumptions regarding disease stage-specific proportions of model-predicted HCV patients within care, annual numbers of patients initiated on antiviral treatment and distribution of treatments over stage, we projected the healthcare costs and disease burden [in disability-adjusted life-years (DALY)] in 2018-2040 under four treatment scenarios: (A) no treatment/baseline; (B) pre-2018 standard of care (pegylated interferon/ribavirin); (C) gradual scale-up in direct-acting antiviral (DAA) treatment uptake that does not meet the WHO 2030 treatment uptake target; (D) scale-up in DAA treatment uptake that meets the WHO 2030 target.

RESULTS: Scenario D, while achieving the WHO 2030 target and averting 253,500 DALYs compared with the pre-2018 standard of care B, incurred the highest direct patient costs over the period 2018-2030: US$890 million (95% uncertainty interval 653-1271). When including screening programme costs, the total cost was estimated at US$952 million, which was 12% higher than the estimated total cost of scenario C.

METHODS: Patients testing HBs antigen (Ag) or HCV antibody (Ab) positive within enrollment into TAHOD were considered HBV or HCV co-infected. Factors associated with HBV and/or HCV co-infection were assessed by logistic regression models. Factors associated with post-ART HIV immunological response (CD4 change after six months) and virological response (HIV RNA <400 copies/ml after 12 months) were also determined. Survival was assessed by the Kaplan-Meier method and log rank test.

RESULTS: A total of 7,455 subjects were recruited by December 2012. Of patients tested, 591/5656 (10.4%) were HBsAg positive, 794/5215 (15.2%) were HCVAb positive, and 88/4966 (1.8%) were positive for both markers. In multivariate analysis, HCV co-infection, age, route of HIV infection, baseline CD4 count, baseline HIV RNA, and HIV-1 subtype were associated with immunological recovery. Age, route of HIV infection, baseline CD4 count, baseline HIV RNA, ART regimen, prior ART and HIV-1 subtype, but not HBV or HCV co-infection, affected HIV RNA suppression. Risk factors affecting mortality included HCV co-infection, age, CDC stage, baseline CD4 count, baseline HIV RNA and prior mono/dual ART. Shortest survival was seen in subjects who were both HBV- and HCV-positive.

METHODS: An age-structured multi-state Markov model was developed to simulate the natural history of HCV infection. We tested three historical incidence scenarios that would give rise to the estimated prevalence in 2009, and calculated the incidence of cirrhosis, end-stage liver disease, and death, and disability-adjusted life-years (DALYs) under each scenario, to the year 2039. In the baseline scenario, current antiviral treatment levels were extended from 2014 to the end of the simulation period. To estimate the disease burden averted under current sustained virological response rates and treatment levels, the baseline scenario was compared to a counterfactual scenario in which no past or future treatment is assumed.

RESULTS: In the baseline scenario, the projected disease burden for the year 2039 is 94,900 DALYs/year (95% credible interval (CrI): 77,100 to 124,500), with 2,002 (95% CrI: 1340 to 3040) and 540 (95% CrI: 251 to 1,030) individuals predicted to develop decompensated cirrhosis and hepatocellular carcinoma, respectively, in that year. Although current treatment practice is estimated to avert a cumulative total of 2,200 deaths from DC or HCC, a cumulative total of 63,900 HCV-related deaths is projected by 2039.