Treatment Endpoints for Chronic Hepatitis B

Hierarchy of Treatment Endpoints

The American Association for the Study of Liver Diseases recommends that sustained off-therapy HBsAg loss is the ideal treatment endpoint for chronic hepatitis B, representing a functional cure and improved long-term outcomes, including reduced mortality and hepatocellular carcinoma risk 1, 2
The European Association for the Study of the Liver suggests that HBsAg loss is the ultimate goal for all patients with chronic hepatitis B, associated with complete and definitive remission of chronic hepatitis B activity and improved long-term outcomes, including survival and reduced HCC risk 1, 2, 3
The achievement of HBsAg loss is infrequently achievable with currently available antiviral agents, occurring in only 0-4% of patients at one year, depending on the agent used 1, 4

For HBeAg-positive patients, the American Gastroenterological Association recommends sustained off-therapy HBeAg seroconversion, combined with HBV DNA <2000 IU/mL and ALT normalization, as a satisfactory endpoint, associated with improved prognosis and consideration of treatment discontinuation 1, 5, 6
For HBeAg-negative patients, the American Association for the Study of Liver Diseases suggests that sustained off-therapy virological response, with HBV DNA <2000 IU/mL, ideally undetectable, and ALT normalization, is the satisfactory endpoint 1, 2

The European Association for the Study of the Liver recommends maintained virological remission, with undetectable HBV DNA by sensitive PCR assay, under long-term antiviral therapy, as the next most desirable endpoint when off-therapy endpoints cannot be achieved 1, 2

The American Association for the Study of Liver Diseases defines virological response as undetectable HBV DNA by sensitive PCR assay, typically <10-15 IU/mL detection limit, for nucleoside/nucleotide analogue therapy 1, 4
The European Association for the Study of the Liver suggests that HBV DNA levels should be as low as possible, ideally undetectable, to ensure full prevention of liver disease progression and emergence of resistance 5, 6

The American Gastroenterological Association defines biochemical response as normalization of ALT levels, confirmed with determinations at least every 3 months for a minimum of 1 year post-treatment 1, 2
The American Association for the Study of Liver Diseases suggests that histological improvement should accompany virological suppression, lessening the risk of cirrhosis and decreasing HCC risk, particularly in non-cirrhotic patients 1, 2

The American Association for the Study of Liver Diseases recommends that even after HBsAg loss, patients with significant fibrosis or cirrhosis at baseline require lifelong HCC screening 7
The American Gastroenterological Association suggests that for HBeAg-negative patients on nucleoside analogues, guidelines for treatment discontinuation have not been clearly defined 5, 6

The European Association for the Study of the Liver recommends that if treatment is stopped, healthcare providers must check patient health often, and perform blood tests regularly to monitor for HBV reactivation is not clearly defined, however, transient ALT elevations may occur within the first year after treatment discontinuation before long-term biochemical remission 1, 2