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1860
4-year outcomes after cessation of tenofovir in
immune-tolerant chronic hepatitis B patient
Vincent W. Wong1,2, Aric Josun Hui3, Grace L.H. Wong1,2, Rosita
S. Chan3, Angel ML Chim1,2, Angeline Oi-Shan Lo1, Henry Lik-
Yuen Chan1,2; 1Department of Medicine and Therapeutics, The
Chinese University of Hong Kong, Hong Kong, China; 2Institute
of Digestive Disease, The Chinese University of Hong Kong, Hong
Kong, Hong Kong; 3Department of Medicine, Alice Ho Miu Ling
Nethersole Hospital, Hong Kong, Hong Kong
Background: With emerging efficacy and safety data, some
patients with immune-tolerant chronic hepatitis B may receive
temporary antiviral therapy (e.g. to prevent vertical transmission
of hepatitis B virus [HBV]). The long-term outcome after
cessation of antiviral therapy in such patients is unknown.
Methods: This was a follow-up study of a phase 2 trial at 2
Hong Kong centers (NCT00507507). Immune-tolerant patients
were randomized to receive tenofovir disoproxil fumarate (TDF)
or TDF plus emtricitabine (FTC) for 4 years. Patients who discontinued
TDF±FTC were followed for another 4 years. Virological
relapse was defined as HBV DNA >2000 IU/ml; clinical
relapse was defined as HBV DNA >2000 IU/ml and alanine
aminotransferase (ALT) >2 times the upper limit of normal
(ULN). Results: 20 patients stopped treatment (age 36±9; 65%
females; 10 treated with TDF and 10 with TDF+FTC; 10 genotype
B and 10 genotype C) and were followed for 206±14
weeks. All patients developed virological relapse at post-treatment
Week 4 (HBV DNA 7.07±1.45 log IU/ml). 10 (50%)
patients developed clinical relapse at 15±11 weeks, among
whom 6 had ALT >5 times ULN and 3 had ALT >10 times ULN
(highest 1149 U/l). All patients with clinical relapse had the
first ALT elevation at or before Week 24. No patient developed
liver decompensation or hepatocellular carcinoma. 11 (55%)
patients were restarted on antiviral therapy (7 on entecavir and
4 on TDF); 4 achieved complete HBV DNA suppression, 10
had ALT normalization, and 1 achieved hepatitis B e antigen
(HBeAg) seroconversion. Among the 9 patients not restarted
on therapy, 2 patients had HBeAg seroconversion at week 45
and month 33, with normal ALT and HBV DNA of 7.12 log IU/
ml and 1.62 IU/ml, respectively. The remaining 7 untreated
patients continued to have positive HBeAg, high HBV DNA
(8.50±0.34 log IU/ml) and normal ALT for 196±18 weeks
post-treatment. Conclusions: Rapid virological relapse is universal
and clinical relapse is common after stopping antiviral
therapy in patients with immune-tolerant chronic hepatitis B.
Treatment initiation and cessation do not enhance HBeAg seroconversion.
Therefore, immune-tolerant patients should only be
treated when there are strong indications. If temporary antiviral
therapy is needed, a drug with high genetic barrier to resistance
should be used, and liver biochemistry should be monitored
closely for at least 6 months after treatment cessation.
Disclosures:
Vincent W. Wong - Advisory Committees or Review Panels: AbbVie, Gilead,
Janssen, Tobira; Consulting: Merck, NovaMedica; Speaking and Teaching: Gilead,
Echosens
Grace L.H. Wong - Speaking and Teaching: Echosens, Echosens, Echosens,
Echosens
Henry Lik-Yuen Chan - Advisory Committees or Review Panels: Gilead, Janssen,
Bristol-Myers Squibb, Roche, Novartis Pharmaceutical, Abbvie; Speaking and
Teaching: Echosens
The following people have nothing to disclose: Aric Josun Hui, Rosita S. Chan,
Angel ML Chim, Angeline Oi-Shan Lo
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发表于 2016-10-6 19:09