Cost-effectiveness of expanded antiviral treatment for chronic hepatitis B virus infection in China: an economic evaluation.

Background: China, which has the largest chronic hepatitis B virus (HBV) burden, may expand antiviral therapy to attain the World Health Organization (WHO)-2030 goal of 65% reduction in mortality. We evaluated health outcomes and cost-effectiveness of chronic HBV infection treatments based on alanine transaminase (ALT) antiviral treatment initiation thresholds and coverage in China to identify an optimal strategy. Methods: A decision-tree Markov state-transition model evaluated the cost-effectiveness of expanded antiviral treatment for chronic HBV infection by simulating 136 scenarios by ALT treatment initiation thresholds (40 U/L, 35 U/L for males and 25 U/L for females, 30 U/L for males and 19 U/L for females, and treating HBsAg+ individuals regardless of ALT values), population age groups (18-80, 30-80, and 40-80 years), implementation durations (2023, 2028, and 2033) under and treatment coverages (20%, 40%, 60%, and 80%). Deterministic and probabilistic sensitivity analyses explored model uncertainty. Findings: Besides the status quo, we finally simulated 135 treatment-expanding scenarios based on the cross combination of different thresholds of ALT, treatment coverages, population's age groups and implementation time. For the status quo, a cumulative incidence of 16,038-42,691 HBV-related complications and 3116-18,428 related deaths will happened between 2030 and 2050. When the treatment threshold is expanded to 'ALT > 35 in males & ALT > 25 in females' immediately without expanding treatment coverage, it will save 2554 HBV-related complications and 348 related deaths compared to the status quo among the whole cohort by 2030, and US$ 156 million more will be costed for gaining 2962 more QALYs. If we just expand the ALT threshold to ALT > 30 in males & ALT > 19 in females, 3247 HBV-related complications and 470 related deaths will be prevented by 2030 under the current treatment coverage of 20%, which will cost US$ 242 million, US$ 583 million or US$ 606 million more by the year of 2030, 2040 or 2050, respectively. Treatment expanded to HBsAg+ will save the largest number of HBV-related complications and death. This expanding strategy also results in large complications or death reduction when it is limited to patients older than 30 years or 40 years. Under this strategy, four scenarios (Treating HBsAg+ with coverage of 60% or 80% for patients older than 18 years or 30 years) showed the effectiveness in reaching the target before the year 2030. Among all the strategies, treatment expanded to HBsAg+ would cost the most while providing the highest total QALYs compared to other strategies with similar implementation scenarios. ALT thresholds of 30 U/L and 19 U/L for males and females, respectively, with 80% coverage for 18-80 years, can attain the goal by 2043. Interpretation: Treating HBsAg+ individuals with 80% coverage for 18-80 years is optimal; earlier implementation of expanded antiviral treatment with a modified ALT threshold could decrease HBV-related complications and deaths to support the global target of 65% reduction in viral hepatitis B deaths. Funding: This study was funded by Global Center for Infectious Disease and Policy Research (BMU2022XY030); Global Health and Infectious Diseases Group (BMU2022XY030); The Chinese Foundations for Hepatitis Control and Prevention (2021ZC032); National Science and Technology Project on Development Assistance for Technology, Developing China-ASEAN Public Health Research and Development Collaborating Center (KY202101004); in part by National Key R&D Program of China (2022YFC2505100).

How would China achieve WHO's target of eliminating HCV by 2030?

Introduction: Hepatitis C virus (HCV) infection is a major global health concern on the rise, prompting unprecedented efforts by the World Health Organization (WHO) to eliminate this epidemic by 2030. Being the country with the largest HCV-infected population in the world, China has been faced with a general lack of awareness for HCV, low treatment uptake and subpar collaborations among healthcare providers and stakeholders. Areas covered: This review discusses the epidemiological situations of HCV infection and the challenges in HCV management in China. This review also explores micro-elimination strategies in China, identifying potential sub-populations for concerted efforts in eliminating HCV. As DAAs are increasingly recognized as a more effective alternative to traditional regimens, the cost-effectiveness and budget impacts of bringing more DAAs into the reimbursement lists are also addressed. Several small-scale targeted literature searches were conducted in PubMed for various topics covered in the article, and hand searching was performed to fill any data gaps. More recent data were used wherever possible. Expert opinion: Considering the unique socioeconomical landscape of China, micro-elimination strategies might be more effective and should be targeted at high-risk populations. Varying regional needs in HCV care across the country necessitate decentralized approaches in research and policy-making.

Will Sofosbuvir/Ledipasvir (Harvoni) Be Cost-Effective and Affordable for Chinese Patients Infected with Hepatitis C Virus? An Economic Analysis Using Real-World Data.

BACKGROUND: Little is known on the cost-effectiveness of novel regimens for hepatitis C virus (HCV) compared with standard-of-care with pegylated interferon (pegIFN) and ribavirin (RBV) therapy in developing countries. We evaluated cost-effectiveness of sofosbuvir/ledipasvir for 12 weeks compared with a 48-week pegIFN-RBV regimen in Chinese patients with genotype 1b HCV infection by economic regions. METHODS: A decision analytic Markov model was developed to estimate quality-adjusted-life-years, lifetime cost of HCV infection and incremental cost-effectiveness ratios (ICERs). SVR rates and direct medical costs were obtained from real-world data. Parameter uncertainty was assessed by one-way and probabilistic sensitivity analyses. Threshold analysis was conducted to estimate the price which can make the regimen cost-effective and affordable. RESULTS: Sofosbuvir/ledipasvir was cost-effective in treatment-experienced patients with an ICER of US$21,612. It varied by economic regions. The probability of cost-effectiveness was 18% and 47% for treatment-naive and experienced patients, and it ranged from 15% in treatment-naïve patients in Central-China to 64% in treatment-experienced patients in Eastern-China. The price of 12-week sofosbuvir/ledipasvir treatment needs to be reduced by at least 81% to US$18,185 to make the regimen cost-effective in all patients at WTP of one time GDP per capita. The price has to be US$105 to make the regimen affordable in average patients in China. CONCLUSION: Sofosbuvir/ledipasvir regimen is not cost-effective in most Chinese patients with genotype 1b HCV infection. The results vary by economic regions. Drug price of sofosbuvir/ledipasvir needs to be substantially reduced when entering the market in China to ensure the widest accessibility.

Nationwide survey of specialist knowledge on current standard of care (Peg-IFN/RBV) and barriers of care in chronic hepatitis C patients in China.

BACKGROUND AND AIM: Chronic hepatitis C virus (HCV) infection is the leading cause of liver diseases including cirrhosis and hepatocellular carcinoma. In China, it is a major national health problem that demands nationwide coordinated emphasis on prevention and treatment. To inform these initiatives, a nationwide survey was conducted from January to April 2015 to evaluate the knowledge, awareness, and perceived obstacles to HCV care. METHODS: A sample of 1000 HCV specialists across mainland China were recruited. Respondents were asked a series of 30 open-ended single or multiple response and Likert-scale questions about their HCV treatment knowledge, experience, assessment of HCV care status in China, and perceptions about treatment barriers. RESULTS: Sixty percent of the respondents answered incorrectly to more than half of the questions on basic HCV treatment principles. Over half of them incorrectly believed that maintenance therapy should be prescribed for non-responders (72%) and longer treatment duration improved sustained viral response rates (62%), regardless of HCV RNA level changes. Sixty-six percent of them believed that HCV treatment would still be interferon-based therapy in the next 5 years in China. Patient-related barriers, in particular lack of disease awareness, were considered to be the most significant barriers to HCV care. Payer and medical-provider barriers included affordability issues, lack of reimbursement coverage for testing and treatments, and lack of referral to HCV specialists. CONCLUSIONS: Focused and intense patient and provider education should be carried out to increase awareness. More effective direct-acting antivirals should be made available and affordable in China.

[A preliminary assessment of the clinical utility of measuring hepatitis C virus antibody to evaluate infection status].

OBJECTIVE: To investigate the potential of hepatitis C virus (HCV) antibody measurement as a clinical approach to determine the infection status and potential for spontaneous-resolution among patients with HCV mono-infection and HCV/human immunodeficiency virus (HIV) co-infection. METHODS: A total of 340 individuals who tested positive for serum anti-HCV antibodies and/or serum anti-HW antibodies were enrolled for study in 2009 from a single village in central China. Markers of liver function (alanine aminotransferase (ALT) and aspartate aminotransferase (AST)) and infection (anti-HCV antibodies, CD4⁺ T cell counts, HCV genotype, and HCV viral load) were measured at baseline and follow-up (in July 2012). At follow-up,the subjects were grouped according to ongoing HCV mono-infection (n=129), ongoing HCV/HIV co-infection (n=98), spontaneously resolved (SR)-HCV in mono-infection (n=65), and SR-HCV in HCV/HIV co-infection (n=48) for statistical analysis. RESULTS: Almost all of the subjects in the ongoing HCV mono-infection group showed high levels of HCV antibodies (S/CO more than or equal to 10), but the majority of the subjects in the SR-HCV in mono-infection group and in the ongoing HCV/HIV co-infection group. The SR-HCV mono-infection group showed a remarkable decrease in HCV antibodies from 2009 (HIV:7.75 ± 3.8; HIV+:7.61 ± 3.47) to 2012 (HIV:5.51 ± 3.67; HIW:4.93 ± 3.35) (HIV:t =10.67, P less than 0.01; HIV+:t =9.52, P less than 0.01). The ongoing HCV/HIV co-infection group showed a positive correlation between HCV antibodies S/CO ratio and CD4⁺ T cell count (r=028, P=0.008). In the ongoing HCV mono-infection group,the levels of HCV antibodies were significantly higher in individuals infected with HCV-1b than in those with HCV-2a (14.74 ± 1.68 vs.14.08 ± 1.44, t=2.20, P=0.03). In the ongoing HCV/HIV co-infection group, the numbers of subjects with elevated (more than 40 U/L) liver function markers were significantly different according to the HCV genotype infection:HCV-1b:ALT, 25/42 vs.16/56 (x²=9.45, P=0.002); HCV2a:AST, 28/42 vs.18/56 (x²=11.49, P=0.001). The HCV RNA positive rate was significantly higher in subjects with high HCV antibody cutoff values (S/CO more than or equal to 10) than in those with low HCV antibody (S/CO less than 10) (HIV:128/151 vs.1/43, x²=102.11, P less than 0.01; HIV+:88/98 vs.10/48, x²=69.44, P less than 0.01), regardless of HIV co-infection. Significantly more subjects in the ongoing HCV mono-infection group had elevated (more than 40 U/L) ALT or AST than the subjects in the SR-HCV mono-infection group with high levels of HCV antibody (S/CO more than or equal to 10) (ALT:57/128 vs.2/23, x²=10.52, P=0.001; AST:57/128 vs.0/23, x²=16.45, P less than 0.01). CONCLUSION: Serum HCV antibody levels, in combination with other clinical information such as liver function and HIV infection status, may aid in the preliminarily evaluation of an individual's HCV infection status and likelihood for spontaneous resolution. Low levels of HCV antibody (S/CO less than 10) may indicate a better chance of SR-HCV, after ruling out the possibility of suffering from immunosuppressive diseases such as HIV infection.

Current challenges and the management of chronic hepatitis C in mainland China.

Despite decreasing prevalence, new cases of hepatitis C in China are increasing recently with growing percentage of patients who are with advanced disease, aging, or not eligible for interferon-based treatments. Hepatitis C infection represents a serious public health burden. This review was based on expert's consensus during a medical forum on hepatitis sponsored by the Beijing Wu Jie-Ping Medical Foundation. The literature searches were conducted in PubMed and critical publications in Chinese journals. Data on hepatitis C prevalence, risk factors, viral or host features, and treatment modalities were extracted and reviewed. Recent large-scale surveys reported reducing prevalence of hepatitis C to approximately 0.4% in China, partly because of regulation changes to safer medical practices and illegalizing commercial blood donations. Patient demographics evolved from being dominated by former paid blood donors to include intravenous drug users and others. Although hepatitis C genotype 1 is the most common, other genotypes are emerging in prevalence. The current standard of care is interferon-based without direct acting antivirals. However, many patients failed therapy because of high treatment costs, substantial needs to manage side effects, difficulties with treatment monitoring in the rural areas, and growing populations of elderly and cirrhotic patients. The lack of high efficacy therapies with good safety profile and low disease awareness in China resulted in increasing public burden of advanced hepatitis C disease. Despite significant reduction of hepatitis C prevalence, iatrogenic, nosocomial, and community transmissions are still significant. In addition to promoting disease awareness, interferon-free regimens are needed to reduce the public health burden.

A type-specific nested PCR assay established and applied for investigation of HBV genotype and subgenotype in Chinese patients with chronic HBV infection.

BACKGROUND: Many studies have suggested that hepatitis B virus (HBV) genotypes show not only geographical distribution and race specificity, but also are associated with disease progression and response to interferon treatment. The objective of this study was to develop a nested polymerase chain reaction (nPCR) assay for genotypes A-D and subgenotypes B1, B2, C1 and C2 of hepatitis B virus (HBV) and to investigate the distribution characteristics of HBV genotypes/subgenotype in China. METHODS: After redesigning the primers and optimizing the reaction conditions using common Taq polymerase, the sensitivity, specificity and reproducibility of the method were evaluated using plasmids and serum samples. In total, 642 serum samples from patients with chronic HBV infection were applied to investigate the distribution of HBV genotype and subgenotype in China. RESULTS: The genotype and subgenotype could be identified when the HBV DNA load of a sample was ≥10(2.3) IU/mL. For the 639 successfully genotyped samples, the sequencing results of 130 randomly selected samples (20.3%, 130/639) were consistent with those of the nPCR method. The present study showed that HBV genotype B (11.2%, 72/642), C (68.2%, 438/642) and D (7.2%, 46/642) were circulating in China, while genotype C was the dominant strain except for western region where genotype D was the prevalent strain. The main subgenotypes of genotypes B and C were B2 (87.5%, 63/72) and C2 (92.9%, 407/438), respectively. CONCLUSIONS: The low-cost nPCR method would be a useful tool for clinical and epidemiological investigation in the regions where genotypes A-D are predominant.