Long-term surveillance strategies after hepatitis B cure

Abstract

Consider a patient who, after years of antiviral therapy, achieves what hepatologists call a functional cure of hepatitis B: sustained loss of hepatitis B surface antigen (HBsAg), with or without the development of protective anti-HBs antibodies, and undetectable HBV DNA off treatment. The question that follows how long and how intensively should this patient be monitored?—has no consensus answer. Current guidelines range from cautious lifelong surveillance to optimistic suggestions that monitoring can be relaxed, and the evidence base for either position is thin, particularly in high-prevalence regions where healthcare resources are constrained. This research examined the long-term outcomes of 68 patients who achieved functional cure of chronic hepatitis B at the Cairo Institute of Public Health Sciences between January 2012 and December 2017, with a minimum five-year post-cure follow-up extending through December 2022. All patients had documented HBsAg loss sustained for at least 12 months off nucleos(t)ide analogue therapy. The primary outcomes were serological relapse (reappearance of HBsAg), virological relapse (redetection of HBV DNA above 20 IU/mL), and hepatocellular carcinoma development during the surveillance period. A three-phase surveillance protocol was implemented: intensive monitoring (quarterly testing in year one), consolidation (biannual testing in years two and three), and maintenance (annual testing from year four onward). At a median follow-up of 6.3 years post-cure, 49 patients (72.1%) maintained sustained functional cure with no evidence of relapse or HCC. Serological relapse occurred in 10 patients (14.7%), all within the first 36 months; eight of these were re-treated successfully and re-achieved HBsAg loss. Virological relapse without serological relapse occurred in 6 patients (8.8%), all at low-level viraemia below 200 IU/mL. Three patients (4.4%) developed hepatocellular carcinoma during follow-up, all of whom had pre-existing cirrhosis at the time of functional cure. Pre-cure cirrhosis (hazard ratio 4.72, p = 0.003) and absence of anti-HBs seroconversion (HR 2.86, p = 0.018) were the only independent predictors of any adverse outcome. Surveillance adherence was full in 58.8% of patients, partial in 26.5%, and 14.7% were lost to follow-up. HBsAg decline rate prior to functional cure correlated strongly with the probability of sustained cure (rho = -0.67, p