Chronic hepatitis B (CHB) remains a global healthcare burden. Although the recent developments in the field have led to a reduction in incidence, the morbidity and mortality including
liver cirrhosis and
hepatocellular carcinoma (HCC) remain a formidable challenge. Advances in understanding the immunopathogenesis of CHB have led to a recent change in clinical categorization. EASL introduced the term
hepatitis B 'e' antigen (
HBeAg)-negative
chronic infection, to replace the historical term 'inactive carrier' disease phase, the commonest CHB phase. Although this disease phase is associated with a favorable prognosis, it is not a truly 'inactive' disease phase with no ostensible
liver disease, as inferred by the previous anachronistic terminology, and the risk of spontaneous reactivation and the potential risk of
disease progression and HCC development are not negligible. Likewise, the APASL also uses the term "Incidentally Detected Asymptomatic
Hepatitis B surface antigen (
HBsAg)-positive Subject (IDAHS)", comprising all
HBsAg-positive subjects who are incidentally detected during routine tests, without any previous or present symptoms of
liver disease. This entity includes HBV
infection with varied stages of
liver disease.
Antiviral treatment is generally reserved for patients with active
inflammation and/or at risk of
disease progression and HCC development.
HBsAg loss is considered an optimal treatment endpoint, and may also be achievable in
HBeAg-negative
chronic infection and IDAHS. In light of this, and the emerging novel HBV
therapies, lowering the treatment threshold and a 'Treat All' approach should now be considered. In this review, we summarize the literature and guidance on
HBeAg-negative
chronic infection, and we make a concerted effort to present the reasons why the one-dimensional term 'inactive carrier' should be abandoned.