Hepatitis C virus in India: Challenges and Successes

Abstract

Answer questions and earn CME Content available: Audio Recording The past decade has seen a paradigm shift in the management of hepatitis C virus (HCV) infection with the development of direct-acting antiviral (DAA) drugs. In 2016, the World Health Organization laid out the Global Health Sector Strategy on viral hepatitis, which endorsed the elimination of viral hepatitis by 2030. In a country like India with a large population and diverse socioeconomic status and cultural practices, the path to HCV elimination has indeed thrown up both challenges and success stories. According to global estimates, the prevalence rate of HCV viremia in India in 2015 was 0.5%, affecting about 4.7 to 10.9 million people.1 In a meta-analysis of 327 studies, the prevalence rate of HCV in India, as estimated by the seropositive rates of anti-HCV antibody, was 0.85% in community studies, 0.44% in asymptomatic blood donors, and 0.88% in pregnant women.2 The community-based prevalence results were available from only three states in the country and were associated with marked heterogeneity; therefore, they may not truly reflect the nationwide prevalence. Similarly, the prevalence rates of anti-HCV positivity among blood donors varied between 0.11% and 1.24% across different states (Fig. 1). Notwithstanding the limitations, in a country with more than 1.3 billion individuals, this suggests a huge burden of disease. In contrast with the community prevalence, high-risk individuals, including patients with human immunodeficiency virus (HIV) infection, patients receiving hemodialysis, intravenous drug users, patients requiring multiple blood transfusion, individuals with high-risk sexual behavior, and attendees of sexually transmitted disease clinics, have a high prevalence of HCV ranging from 3.5% to 44.7%. In a meta-analysis of 30 studies, the pooled prevalence rate of HCV and hepatitis B virus (HBV) coinfection was 1.89% in India.3 The prevalence rate of antibodies to HCV ranged between 7.2% and 76.6% in patients with HIV. Integration of HCV testing into existing programs catering to those at high risk (e.g., those with HIV) has shown an increase in the identification and treatment of such patients.4 Hence it is imperative to implement HCV infection screening in these diverse high-risk groups and integrate HCV testing in patients with HIV or HBV infections. Data on modes of transmission are also scarce, but policies regarding the safe use of blood products and safe injection practices have been implemented to break the transmission chain. Testing all blood donors for HCV was made mandatory by the Government of India in June 2001. Nucleic acid amplification tests (NATs) are highly sensitive and specific for the detection of HCV among blood donors, albeit costly. Until 2017, barely 2% of the blood banks in India had facilities for NATs, and limited results showed HCV positivity rates of 1 in about 5400 seronegative samples.5 It is indeed warranted to expand this testing facility and ensure more widespread application across the country. In India, HCV genotype 3 is the predominant genotype as compared with genotype 1 in the West.6 All-cause mortality, progression to cirrhosis, and development of hepatocellular cancer are highest in patients with genotype 3.7 Of all available DAAs, only four are available in India: sofosbuvir (SOF), velpatasvir (VEL), ledipasvir (LDV), and daclatasvir (DCV). This limits our armamentarium for treating those with prior DAA failure, cirrhosis and genotype 3, or resistance-associated substitutions. The availability of pangenotypic drugs has obviated the need for genotype testing outside research settings. However, the total cost of HCV-RNA testing and 12-week therapy costs about $250 to $300, which is still prohibitive for many patients. Widespread, rapid, and cheap availability of HCV-RNA testing and a cost-effective mechanism to provide uninterrupted free drugs are essential if we aim to reach the elimination target by 2030. Past experience from other national programs, such as the National Tuberculosis Elimination Program, has shown that about 15% of patients default despite free treatment.8 A proportion of patients with HCV infection may be asymptomatic and incidentally detected on screening. Ensuring compliance to therapy, therefore, becomes challenging. Patients with HCV-related cirrhosis need a more comprehensive evaluation than just DAA therapy. In addition to providing free medications, we also need effective mechanisms for monitoring adherence, testing for treatment response, management of cirrhosis and its complications, and hepatocellular cancer screening at the community level. The coronavirus disease 2019 (COVID-19) pandemic affected health care services worldwide. It is estimated that 1-year delay in HCV treatment programs would result in more than 72,000 deaths.9 Despite the lack of published data from India, it is reasonable to assume that strict lockdown, travel restrictions, and diversion of hospital services to patients with COVID infections would have impacted the treatment of patients with HCV infection. The Government of India launched the National Viral Hepatitis Control Program (NVHCP) in 2018 with the aim to prevent and treat viral hepatitis (hepatitis A, B, C, and E) and provide screening, diagnosis, treatment, and counseling services free of cost to all. The NVHCP synergizes with other national programs, such as the National AIDS Control Program, to promote safe blood and blood products, preventive services for the high-risk population, and injection safety practices. Therefore, an integrated approach will lead to better utilization of resources, promote screening and early treatment, and prevent attrition. The availability of generic DAAs has reduced the cost of therapy and has shown excellent results with 12-week posttreatment virological suppression rates (Table 1).6 Treatment with generic DAAs increases life expectancy by about 8 years, and the treatment becomes cost-effective within 2 years.10 Extension for health care outcomes is a novel model for collaboration between specialists and primary care physicians in rural areas. A decentralized care hub-and-spoke model was implemented in Punjab, the state with the highest seroprevalence of HCV in India. Using an algorithm-based treatment with generic DAA combined with fortnightly supervision by telehealth clinics, more than 48,000 patients with HCV received medication, of which 91.2% of patients achieved sustained virological response (SVR) at 12 weeks posttherapy (SVR-12).11 These results are comparable with those from academic centers and other real-world cohorts (Tables 1 and 2). In a meta-analysis of studies estimating treatment outcomes of decentralized HCV care, the pooled SVR-12 was 81% on intention-to-treat (ITT) analysis.12 It further affirms this model’s utility in providing the standard of care using a decentralized model with the existing public health infrastructure. HCV elimination in India by 2030 is difficult but possible. Contributions from multiple stakeholders are warranted. In addition to the government policies and financial allocation for drug availability, testing kits, and operational expenditures, we also require media support for creating awareness among the common public regarding preventive and treatment options for HCV. The success of the decentralized model has shown that it can be applied in other areas of the country. Although the entire focus of the country is presently diverted to management of the COVID-19 pandemic, it is imperative that HCV treatment not be ignored. Continuing services through the NVHCP and teleconsultation-based regular patient follow-up are measures that can enable uninterrupted care. We still have a long way to go, but we have taken small steps in the right direction.

Topics & Concepts