Long-term outcomes after nucleos(t)ide analogue cessation in chronic hepatitis B - follow-up from the RETRACT-B cohort.

BACKGROUND & AIMS: Stopping nucleos(t)ide analogues (NAs) in patients with chronic hepatitis B can increase hepatitis B surface antigen (HBsAg) loss rates. However, long-term follow-up (FU) data after NA cessation in a multiethnic population are lacking. This study aimed to assess long-term outcomes after NA cessation in a large global cohort.

METHODS

Extended FU data were collected from patients enrolled in the RETRACT-B cohort. New patients were added if they met the inclusion criteria (virally suppressed, HBeAg negative, and HBsAg positive at end of therapy [EOT]). The primary outcome was the 10-year off-treatment HBsAg loss rate. Secondary outcomes were retreatment and adverse events.

RESULTS

In total, 2,029 patients were included. At EOT, mean age was 52 years; 81% were Asian, 15% White, and 4% Black/Other. Mean HBsAg at EOT was 2.7 log10 IU/ml (<100/100-1,000/≥1,000 IU/ml: 16/46/38%). Median FU was 65 [range 35-99] months. The 10-year off-treatment HBsAg loss rate was 17% (<100/100-1,000/≥1,000: 52/13/6%, p <0.001) and 59% were retreated (<100/100-1,000/≥1,000: 28/62/71%). HBsAg seroreversion was observed in 9 out of 171 (5.3%) patients, of whom 6 re-lost HBsAg. The 10-year risks of flares, hepatocellular carcinoma and decompensation were 30%, 3.9%, and 3.3%, respectively. A history of cirrhosis was associated with a higher risk of decompensation (10-year: 5.7% vs. 3.0%) and hepatocellular carcinoma (10-year: 12% vs. 2.4%), both p <0.001.

CONCLUSION

At 10 years, 17% of patients achieved off-treatment HBsAg loss, whereas more than half were retreated. Patients with HBsAg levels <100 IU/ml benefit the most from NA cessation with a HBsAg loss rate of 52%. Based on our data, finite NA therapy is not recommended if HBsAg is ≥1,000 IU/ml or in patients with cirrhosis.

IMPACT AND IMPLICATIONS: Based on our study, we can conclude that finite nucleos(t)ide analogue therapy can be considered in patients with hepatitis B surface antigen (HBsAg) levels <100 IU/ml when aiming for HBsAg loss, since they have the highest likelihood of achieving this endpoint (52%) and the lowest need for retreatment (28%) during long-term follow-up, but only when strict monitoring can be guaranteed. In contrast, finite therapy is not recommended in patients with HBsAg levels ≥1,000 IU/ml or those with a history of cirrhosis, especially as cirrhosis is a known risk factor for hepatic decompensation and hepatocellular carcinoma. In addition, our data can be used to further improve patient monitoring after finite nucleos(t)ide analogue therapy, especially in those who successfully remain off-therapy for 5 to 10 years.