The following is a summary of “Withdrawal of Long-Term Nucleotide Analog Therapy in Chronic Hepatitis B: Outcomes From the Withdrawal Phase of the HBRN Immune Active Treatment Trial,” published in the July 2023 issue of Gastroenterology and Nutrition by Feld, et al.

The withdrawal of nucleos(t)ide analog therapy was investigated as a potential strategy to induce hepatitis B surface antigen (HBsAg) loss in chronic hepatitis B infection. The Hepatitis B Research Network Immune-Active Trial evaluated tenofovir (TDF) use for 4 years, with or without an initial 6 months of peginterferon-α (PegIFN), followed by treatment withdrawal.

Participants eligible for the study had hepatitis B e antigen (HBeAg) negative/anti-HBe positive status, hepatitis B virus (HBV) DNA levels <103 IU/mL, and no cirrhosis. After discontinuing TDF, participants were followed for at least 1 year, with the option for further follow-up. Retreatment was determined based on predefined criteria.

Out of 201 participants who received 4 years of treatment, 97 participants (45 in the TDF alone arm and 52 in the TDF + PegIFN arm, predominantly Asian) discontinued TDF. HBsAg loss was observed in 5 participants, with 2 experiencing loss within 25 weeks and 3 within 89-119 weeks post-withdrawal. The cumulative rate of HBsAg loss at 2 years was 4.3%. Alanine aminotransferase (ALT) flares (greater than 5 times the upper limit of normal) occurred after TDF withdrawal in 36 participants (37.1%), more frequently and earlier in those who were HBeAg negative at treatment initiation compared to those who were HBeAg positive. ALT flares were associated with older age, higher pretreatment HBV DNA levels, and HBV DNA levels at the visit before the flare. ALT flares were not significantly associated with HBsAg decline or loss but were associated with immune active disease at 1 year (70.6% vs. 11.9%, P < 0.0001) and 2 years (66.7% vs 25.9%, P = 0.03) post-withdrawal. Thirteen participants (13.4%) required treatment reinitiation, while 13 others remained in a sustained inactive carrier state by the end of the study follow-up. No criteria reliably predicted safe treatment withdrawal.

The results from the trial did not support the withdrawal of TDF as a therapeutic strategy. HBsAg loss was infrequent within 2 years of stopping long-term TDF treatment. If treatment withdrawal is considered, careful monitoring of HBV DNA levels is necessary, with the initiation of therapy if levels rise above 4 logIU/mL to reduce the risk of ALT flares, as they were not associated with subsequent HBsAg decline or loss.

Source: journals.lww.com/ajg/Fulltext/2023/07000/Withdrawal_of_Long_Term_Nucleotide_Analog_Therapy.23.aspx