Should We Treat Immune Tolerant Chronic Hepatitis B? Lessons from Asia

• Published in: Journal of clinical and experimental hepatology Vol. 12; no. 1; pp. 144 - 154
• Main Authors: Premkumar, Madhumita, Chawla, Yogesh K.
• Format: Journal Article
• Language: English
• Published: India Elsevier B.V 01.01.2022; Elsevier
• Subjects: cccDNA; chronic hepatitis B; HBV Elimination in India; HBV RNA; hepatocellular carcinoma; immune tolerant phase; Review; chronic hepatitis B; cccDNA; PWID; ALT; HCC; HBV Elimination in India; IT; HBV RNA; NA; IA; HCV; CHB; MTCT; immune tolerant phase; HBV; hepatocellular carcinoma; WHO; HBV, hepatitis B virus; NA, nucleos(t)ide analogs; IT, immune tolerant; HCV, hepatitis C virus; IA, immune active; MTCT, mother-to-child transmission; CHB, chronic hepatitis B; ALT, alanine transaminase; PWID, persons who inject drugs; HCC, hepatocellular carcinoma; WHO, World Health Organization
• ISSN: 0973-6883; 2213-3453
• DOI: 10.1016/j.jceh.2021.08.023

Chronic hepatitis B (CHB) remains a public health burden, with more than 257 million persons living with hepatitis B virus globally. Despite the availability of a safe and efficacious vaccine, access to immunization remains poor. As per current estimates, if Asian countries rely only on immunization to reduce the burden of disease, the timelines for HBV elimination will be extended to 2060–2090, a far cry from the World Health Organization’s clarion call for viral hepatitis elimination by 2030. Currently, all practice guidelines lay stress on immunization, prevention of mother-to-child transmission and treatment of immune active disease or cirrhosis. In this review, we critically examine the data from the Asian cohorts, clinical and public health rationale of early treatment, risk of HCC, and assess the need for revision of guidelines. Patients in the immune tolerant phase (IT) remain untreated till they meet variable age, transaminase, or fibrosis criteria, are often lost to follow up and continue transmitting the infection. With global migration patterns, immunization programmes alone cannot prevent the complications of HBV like cirrhosis, end-stage liver disease, and hepatocellular carcinoma (HCC). In addition, data from Asian cohorts from Taiwan and Korea suggest that HBV DNA levels are directly associated with increased risk of HCC. Histological evidence of advanced fibrosis or immune reactive T cell subsets in the IT phase also raises doubts about the viability of current guidelines that focus on age, alanine transaminase levels, and liver stiffness as markers of risk of inflammation and fibrosis. Current practice does not take into account the histological subsets with minimal inflammation, HBV genome integration or risk of HCC with high viral loads. New data from Asian cohorts argue the case of expanding access to care to IT-CHB from public health and clinical perspective.