Hepatitis B surface antigen titer is a good indicator of durable viral response after entecavir off-treatment for chronic hepatitis B

Abstract

Background/AimsClear indicators for stopping antiviral therapy in chronic hepatitis B (CHB) patients are not yet available. Since the level of hepatitis B surface antigen (HBsAg) is correlated with covalently closed circular DNA, the HBsAg titer might be a good indicator of the off-treatment response. This study aimed to determine the relationship between the HBsAg titer and the entecavir (ETV) off-treatment response.MethodsThis study analyzed 44 consecutive CHB patients (age, 44.6±11.4 years, mean±SD; men, 63.6%; positive hepatitis B envelope antigen (HBeAg) at baseline, 56.8%; HBV DNA level, 6.8±1.3 log10 IU/mL) treated with ETV for a sufficient duration and in whom treatment was discontinued after HBsAg levels were measured. A virological relapse was defined as an increase in serum HBV DNA level of >2000 IU/mL, and a clinical relapse was defined as a virological relapse with a biochemical flare, defined as an increase in the serum alanine aminotransferase level of >2 × upper limit of normal.ResultsAfter stopping ETV, virological relapse and clinical relapse were observed in 32 and 24 patients, respectively, during 20.8±19.9 months of follow-up. The cumulative incidence rates of virological relapse were 36.2% and 66.2%, respectively, at 6 and 12 months, and those of clinical relapse were 14.3% and 42.3%. The off-treatment HBsAg level was an independent factor associated with clinical relapse (hazard ratio, 2.251; 95% confidence interval, 1.076–4.706; P=0.031). When patients were grouped according to off-treatment HBsAg levels, clinical relapse did not occur in patients with an off-treatment HBsAg level of ≤2 log10 IU/mL (n=5), while the incidence rates of clinical relapse at 12 months after off-treatment were 28.4% and 55.7% in patients with off-treatment HBsAg levels of >2 and ≤3 log10 IU/mL (n=11) and >3 log10 IU/mL (n=28), respectively.ConclusionThe off-treatment HBsAg level is closely related to clinical relapse after treatment cessation. A serum HBsAg level of <2 log10 IU/mL is an excellent predictor of a sustained off-treatment response in CHB patients who have received ETV for a sufficient duration.

An expert consensus for the management of chronic hepatitis B in Asian Americans

“…Close attention for recurrent viraemia, with or without HBeAg seroreversion, ALT elevations and clinical relapse will determine if anti‐viral therapy needs to be reinstituted. Recently, in patients treated with entecavir, HBsAg titres of ≤2 to ≤2.5 log 10 IU/mL at the time of HBeAg seroconversion were predictive of a low virological relapse rate in Asian patients . Further studies quantifying HBsAg levels will be useful in confirming these findings.…”

Stopping long‐term treatment with nucleos(t)ide analogues is a favourable option for selected patients with HBeAg‐negative chronic hepatitis B

“…However, the high rate of responders in HBeAg‐negative patients was extremely important to many and resulted in further research to assess the post‐treatment response to NA. Thus, numerous, mainly non‐randomized studies have been published evaluating the response following NA treatment discontinuation . Most of these studies were retrospective analyses after a limited duration of NA treatment, as previously recommended by local guidelines.…”

“…Although the level of HBsAg has also been found to be a marker for post‐NA treatment response, results are contradictory. Certain studies have shown that HBsAg levels at the end of NA treatment could be predictive of responders to treatment withdrawal . Chen et al found that HBsAg cut‐off values of 120 and 200 IU/mL were predictive of a response to treatment .…”

“…Chen et al found that HBsAg cut‐off values of 120 and 200 IU/mL were predictive of a response to treatment . Lee et al identified serum HBsAg levels of <2 log 10 IU/mL to be a reliable predictor of a sustained off‐treatment response . In the study by Berg et al, patients who achieved a decrease in HBsAg levels after treatment withdrawal had baseline HBsAg levels <25 000 IU/mL when NA treatment was stopped .…”

“…Certain studies have shown that HBsAg levels at the end of NA treatment could be predictive of responders to treatment withdrawal. 20,23,30,36,42 Chen et al found that…”