The Role of Off-Therapy Viral Kinetics in the Timing and Severity of Flares in Hepatitis B e Antigen–Negative Patients

BACKGROUND & AIMS: Hepatitis B flare occurs earlier and is more severe in patients stopping tenofovir (TDF) compared with entecavir (ETV). This study investigated relationship between hepatitis B virus (HBV) kinetics, onset timing, and the severity of flares.

METHODS: Hepatitis B e antigen-negative chronic hepatitis B patients who developed off-ETV or off-TDF hepatitis flare were recruited. Their HBV kinetics and the severity of flares were compared between patients with early (<6 months) and late (between 6 and 24 months) flares. Propensity score matching was performed at 1:1 adjusting for age, sex, cirrhosis, and end-of-treatment (EOT) hepatitis B surface antigen between off-ETV and off-TDF flares.

RESULTS: After propensity score matching, 76% and 15% of each 107 off-TDF and off-ETV patients, respectively, developed early flare. A much steeper HBV DNA upsurge (ΔHBV DNA/month) was observed in off-TDF than off-ETV flares (2.12 vs 0.73 log 10 IU/mL; P < .01). Greater ΔHBV DNA/month correlated with earlier timing and higher peak alanine aminotransferase levels of flares. ΔHBV DNA/month ≥2.5 log 10 IU/mL was an independent factor for severe off-TDF flare, and ≥1 log 10 IU/mL was a predictor for severe off-ETV flares.

CONCLUSIONS: Greater HBV DNA upsurge rate (ΔHBV DNA/month) ≥1 log 10 IU/mL is a key factor for an earlier onset and more severe flare. More frequent ΔHBV DNA/month ≥1 log 10 IU/mL in off-TDF than off-ETV flares may explain why off-TDF flare mostly occurred early and was more severe. More stringent monitoring in those with ΔHBV DNA/month ≥1 log 10 IU/mL at flare, especially ≥2.5 log 10 IU/mL in early off-TDF flares, is important for timely retreatment to prevent decompensation.