Durability of Hepatitis B e Antigen Seroconversion in Chronic Hepatitis B Patients Treated with Entecavir or Tenofovir

Abstract

Introduction Loss of HBeAg and development of anti-HBe (seroconversion) is seen as a milestone and endpoint in the treatment of HBeAg-positive patients with chronic hepatitis B (CHB). Among patients treated with nucleos (t)ide analogs (NA), recurrent viremia is common after discontinuation of therapy. Entecavir (ETV) and tenofovir (TDF) are highly potent NA. The durability of virological response and HBeAg seroconversion in patients treated with these agents is not well studied. Methods We retrospectively studied the outcomes of 54 HBeAg-positive CHB patients who were treated with either ETV (n = 30) or TDF (23) or both (n = 1) that achieved virological response and underwent seroconversion and consolidation therapy before cessation of treatment. Results Only 4 (7 %) patients had sustained virological, serological, and biochemical remission. Thirteen patients (24 %) continued to have HBV DNA levels below 2000 IU/mL and normal alanine aminotransferase activity (ALT). Thirty-seven patients (69 %) developed HBV DNA >2000 IU/mL, with 20 having elevated ALT. Among these 37 patients, 23 (62 %) remained HBeAg negative/anti-HBe positive, 12 (32 %) became HBeAg positive, and 2 (5 %) were HBeAg and anti-HBe negative. Duration of consolidation therapy did not correlate with low versus high level of virological relapse. Conclusions Durability of HBeAg seroconversion associated with ETV or TDF was not superior to that reported in patients treated with less potent NA. Our results, aggregated with others, suggest HBeAg seroconversion should not be considered as a treatment endpoint for most HBeAg-positive patients treated with NA. Future updates of treatment guidelines should reconsider HBeAg seroconversion as an endpoint to therapy.

TDF Monotherapy Is Effective Regardless of Prior Nucleos(t)ide Analogue Treatment in Chronic Hepatitis B Patients in China

“…HBeAg seroconversion is closely associated with a sustained reduction in HBV DNA levels during therapy [21]. From this study, we showed that HBeAg seroconversion in NA-naïve and NA-experienced group was 27.8% (5/18) and 11.4% (4/35), respectively.…”

5-year efficacy of entecavir in Indian patients with chronic hepatitis B

“…This indicates its ineffectiveness in clearing the cccDNA which is regarded as the hallmark of complete viral [5,7,16,19]. In such studies, a HBV DNA cutoff level of 20 to 2000 IU/mL was considered for stopping or restarting therapy.…”

“…It became popular for its ease of use and generally high patient tolerance. Both short and long-term studies have shown its high efficiency in viral suppression [3,4], preventing liver disease progression in the form of cirrhosis, decompensation and hepatocellular carcinoma (HCC), but also its inefficiency in complete viral eradication [5][6][7]. Reports on its long-term use in Indian patients are scarce [8][9][10].…”

“…Thus, in spite of its efficacy in preventing disease progression, it falls short of being the panacea. Though other studies report higher rate of e antigen seroconversion (23 % to 42.6 %)[3,5,7,10,18] after prolonged therapy, there is high rate of seroreversion and relapse (i.e. development of e negative hepatitis) after stopping the drug…”

The HBV Drugs Work: Now What?

“…Why aft er 3 years of viral suppression and substantial reduction in antigen exposure, the immune response has not re-established a state that will prevent the virus from replicating? Th is is a repetitive fi nding with other studies demonstrating that over 80% of the individuals with chronic HBV will relapse aft er stopping eff ective anti-HBV therapy ( 6,7 ). Part of the issue resides in the defi nition of response to therapy for chronic viral infection.…”