Early Treatment Consideration in Patients with Hepatitis B ‘e’ Antigen-Positive Chronic Infection: Is It Time for a Paradigm Shift?

Abstract

Chronic hepatitis B (CHB) is associated with significant morbidity and mortality, due to the adverse sequelae of cirrhosis and hepatocellular carcinoma (HCC). To date, antiviral therapy has been reserved for patients with ostensibly active liver disease, fibrosis or cirrhosis, and/or increased risk of HCC. Historically, patients with hepatitis B ‘e’ antigen (HBeAg)-positive chronic infection, were not offered antiviral therapy. Nevertheless, there has been compelling evidence emerging in recent years, demonstrating that this disease phase is in fact not characterized by immunological tolerance. HBV integration into the human genome is a frequent event found in these patients. Additionally, it may well be associated with active inflammation and fibrosis, even in the presence of persistently normal liver enzymes. Likewise, it appears that the mechanisms of hepatocarcinogenesis are already present during this early stage of the disease. This was reflected in the European Association for the Study of the Liver (EASL) guidelines, where treating patients above the age of 30 years with HBeAg-positive chronic infection was proposed. Lowering the treatment threshold to broaden treatment eligibility is likely to slow disease progression and reduce the risk of developing HCC. The current review discusses the reasons to consider early antiviral therapy in HBeAg-positive chronic infection.

Role of HBsAg levels in guiding hepatitis B virus prophylaxis in pregnancy: Insights from a multi‐ethnic cohort

“…It appears that in CHB mothers with multiple pregnancies, a one‐off measurement of HBV DNA at the index pregnancy (first antenatal visit) may be sufficient in healthcare settings with limited resources, where repeat HBV DNA measurements at subsequent pregnancies would be unnecessary as HBV DNA levels rarely cross category from low to high viremia. On the other hand, as the current HBV treatment paradigm shifts towards an earlier treatment approach, 28 NUCs are likely to be continued beyond the suggested post‐partum period of prophylaxis, especially if future pregnancies are planned.…”

IFIT3 Is Increased in Serum from Patients with Chronic Hepatitis B Virus (HBV) Infection and Promotes the Anti-HBV Effect of Interferon Alpha via JAK-STAT2 In Vitro

“…It has been reported that HBeAg plays a key role in the host-virus interplay, particularly at the stage of viral antigen presentation and recognition by CD4 + T cells ( 33 ). During the process of clinical treatment, HBeAg clearance or HBeAg seroconversion can reflect viral control by the host, which is usually considered as one of the evidence of successful antiviral response ( 34 ) and/or reduced virus replication ( 34 ) and is believed to mark the end of immune-mediated liver damage ( 35 , 36 ). Interestingly, patients who were HBeAg positive had significantly higher IFIT3 mRNA levels than did HBeAg-negative patients.…”

Enhancing interventions for prevention of mother-to-child- transmission of hepatitis B virus

“…Recommendations for antiviral treatment of women before, during and after one or more pregnancies need to be informed by wider programmatic decisions about HBV treatment in all adults, with consideration of the potential individual- and population-level benefits of lowering the DNA threshold that determines eligibility. [71] , [72] , [73] In addition to reducing the risk of long-term liver disease in the individual, future strategies that endorse ongoing maternal antiviral therapy would also reduce MTCT risk for subsequent pregnancies, tackle the risk of horizontal transmission events within households, and abrogate the risk of severe liver flares associated with NA cessation. The optimal strategy will require pre-treatment HBV DNA quantitation, and the infrastructure to provide ongoing clinical monitoring and access to treatment for the mother; achieving this in practice is currently challenging in many settings but must be scaled up.…”

“…The cost of generic TDF (frequently <50 USD/per year in many countries) or, in the future generic TAF, should not be a barrier to treatment. [71] , [72] , [73] …”