Tenofovir withdrawal should not be recommended for patients with chronic hepatitis B virus (HBV) infection, according to study results published in the American Journal of Gastroenterology.
The Hepatitis B Research Network (HBRN) trial was conducted at 21 sites in the United States and Canada. Patients with chronic HBV infection were enrolled in 1 of 3 studies between 2012 and 2017, in which they received 300 mg daily tenofovir for 192 weeks with or without 24 weeks of weekly 180 mg subcutaneous peginterferon-α. In this withdrawal study, patients (N=97) who had HBV DNA less than 1000 IU/mL between weeks 168 and 192 and were free from cirrhosis at baseline were withdrawn from tenofovir treatment at week 192. Patients were evaluated for HBV DNA every 4 weeks after withdrawal through week 216, every 12 weeks through week 240, and were offered continued follow-up every 24 weeks thereafter.
At baseline, the participants were aged median 44.0 (IQR, 37.1-54.2) years, 66.0% were men, 82.3% were Asian, 45.4% had HBV genotype B, 29.9% had HBV genotype C, 25.8% were hepatitis B e antigen (HBeAg)-positive, 2.1% had quantitative hepatitis B surface antigen (qHBsAg) levels less than 100 IU/mL, they had an HBV DNA level of 5.7 (IQR, 4.7-6.6) log10IU/mL, and alanine aminotransferase (ALT) of 2.9 (IQR, 2.0-4.5) upper limit of normal (ULN). At treatment withdrawal, 9.3% were HBeAg-positive, 19.6% had qHBsAg levels less than 100 IU/mL, they had an HBV DNA level of 0.8 (IQR, 0.6-1.1) log10IU/mL, and ALT was 1.1 (IQR, 0.8-1.3) ULN.
The patients either received tenofovir alone (n=45) or with peginterferon-α (n=52). No significant cohort differences were observed at baseline or at tenofovir withdrawal.
After treatment withdrawal, 5 patients lost hepatitis B surface antigen (HBsAg) status at 25-119 weeks postwithdrawal. Three of these patients had received tenofovir alone, 3 were HBeAg-negative at baseline, 4 had any ALT elevation, 1 had an ALT flare, and the maximum observed ALT level was 12.27 ULN. The individuals had HBV genotypes A2 (n=2), B2 (n=1), C5 (n=1), and E (n=1).
The change in mean qHBsAg levels among all individuals who withdrew tenofovir (n=97), among only the subset who did not restart tenofovir (n=84), and those who did not withdraw tenofovir treatment (n=77) did not differ significantly between any groups (all P ³.053).
Predictors of ALT flare after tenofovir withdrawal included HBV DNA greater than 5 compared with less than or equal to 5 log10IU/mL (odds ratio [OR], 35.30; P <.0001) or HBV DNA greater than 4 compared with less than or equal to 4 log10IU/mL (OR, 32.72; P <.0001) at the visit prior to flare, for every log10IU/mL in qHBsAg (OR, 5.97; P =.003) and HBV DNA (OR, 2.74; P <.0001) at the ALT flare visit, for every log10IU/mL in HBV DNA at baseline (OR, 1.40; P =.02), and age at baseline (OR, 1.05; P =.01).
Sustaining an inactive carrier status through week 240 associated with qHBsAg less than 100 compared with at least 100 log10IU/mL at tenofovir withdrawal (adjusted risk ratio [aRR], 7.37; P =.0002) and HBeAg status at baseline (aRR, 2.39; P =.04).
This study was limited by the low event rate of losing HBsAg status.
[T]his prospective study showed that withdrawal of TDF [tenofovir] after 4 years of therapy was associated with a low rate of HBsAg decline or loss,” the study authors noted. “ALT elevations after treatment withdrawal were frequent but did not lead to HBsAg decline or loss and were associated with more active future disease.”
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
This article originally appeared on Gastroenterology Advisor
Feld JJ, Wahed AS, Fried M, et al. Withdrawal of long-term nucleotide analogue therapy in chronic hepatitis B: Outcomes from the withdrawal phase of the HBRN immune active treatment trial. Am J Gastroenterol. Published online January 13, 2023. doi:10.14309/ajg.0000000000002176