 |
|
|
| |
HBsAg loss is higher among Caucasians compared to Asians after stopping nucleos(t)ide analogue therapy: results from a large, global, multiethnic cohort of patients with chronic hepatitis B (RETRACT-B study)
|
| |
| |
HBsAg Loss in 14% Through 4 Years After Stopping NUC
AASLD The Liver Meeting Digital Experience, November 13-16, 2020
Mark Mascolini
Four years after people with chronic HBV infection stopped a nucleos(t)ide analog (NUC) in a 1500-person global retrospective cohort, 14% had lost HBsAg, suggesting functional cure [1]. Caucasian versus Asian race favored HBsAg loss. But three quarters of the cohort had a virologic relapse through 4 years of follow-up, and one third had an alanine aminotransferase (ALT) flare.
Losing HBsAg happens only rarely during NUC therapy. Researchers have begun evaluating stopping NUCs to assess the safety and durability of that strategy, as well as its impact on HBsAg. RETRACT-B study investigators formed an international cohort of people with chronic HBV who stopped NUC therapy from 2001 to 2020 at centers in North America, Europe, and Asia, aiming to analyze the impact of stopping on HBsAg loss and other outcomes.
To be eligible for this retrospective cohort study, people had to have undetectable HBV DNA in blood and HBeAg-negative status when stopping therapy. When NUC therapy began, they could be positive or negative for HBeAg. Participants could not be coinfected with HCV, HDV, or HIV and could not have taken interferon or pegylated interferon in the 12 months before stopping NUC therapy. Researchers used Kaplan-Meier and Cox methods to determine which factors affected off-treatment HBsAg loss or retreatment.
The 1541 cohort members averaged 53 years in age at the baseline date, when they stopped NUC therapy; 73% were men, 88% Asian, and 10% Caucasian. NUC therapy lasted a median of 3 years, 60% took entecavir when they stopped, and 29% took tenofovir disoproxil fumarate (TDF). Only 5% had cirrhosis at baseline, and HBsAg level averaged 2.6 log10 IU/mL. When NUC therapy began, 77% were negative for HBeAg. Median total follow-up stood at 17 months, and participants averaged 5 visits during follow-up.
The proportion of people who lost HBsAg rose slowly but steadily over time: 3% 1 year after NUC therapy stopped, 8% after 2 years, 12% after 3 years, and 14% after 4 years. HBsAg loss proved more frequent in people 50 or older than in younger people (18% vs 9% at 4 years, P = 0.01), in Caucasians versus Asians (41% vs 11% at 4 years, P < 0.001), and in people taking TDF versus entecavir (17% vs 12% at 4 years, P = 0.001). HBeAg status when therapy began did not affect rate of HBsAg loss.
One year after stopping their NUC, 30% needed to resume therapy. That proportion rose to 43% at 2 years, 50% at 3 years, and 56% at 4 years. Retreatment proved more likely in people 50 or older (63% vs 45% at 4 years, P < 0.001). Race, type of NUC, or HBeAg status when therapy began did not affect retreatment rate.
A multivariate Cox model identified 1 factor that independently predicted HBsAg loss and 1 that predicted retreatment, at the following hazard ratios (HR) and 95% confidence intervals (CI):
HBsAg loss
-- Caucasian vs Asian: HR 5.8, 95% CI 3.6 to 9.5, P < 0.001
Retreatment
-- Age 50 or older vs younger: HR 1.6, 95% CI 1.3 to 1.9, P < 0.001
Participant sex, NUC used, or HBeAg status at the start of therapy did not affect HBsAg loss or retreatment in these analyses.
Only one quarter of participants went 4 years off therapy without virologic relapse (HBV DNA above 2000 IU/mL): 74% had such a relapse a median of 6 months after stopping therapy. More than half, 56%, had both a virologic relapse and a biochemical relapse (ALT at least 2 times the upper limit of normal) in a median of 8 months. One third of participants had an ALT flare (at least 5 times the upper limit of normal) over a median of 10 months. Fifteen people (1%) had hepatic decompensation. Among the 12 people (0.8%) who died, 9 had a liver-related cause of death reported.
Reference
1. Hirode G, Choi HSJ, Su TH, et al. HBsAg loss is higher among Caucasians compared to Asians after stopping nucleos(t)ide analogue therapy: results from a large, global, multiethnic cohort of patients with chronic hepatitis B (RETRACT-B study). AASLD The Liver Meeting Digital Experience, November 13-16, 2020. Abstract 23.
|
| |
|
|
|
|
|
