Persistent or severe hepatitis followed virological relapse among patients who discontinued treatment with Baraclude for chronic hepatitis B, according to recently published data. Serum viral load at treatment cessation predicted clinical flares.
“It remains controversial whether [chronic hepatitis B] patients can safely discontinue [nucleos(t)ide analogues] before HBsAg loss. How to predict durable off-therapy remission has become the focus of intense research,” the researchers wrote. “Our study adds to current understanding about the risk and risk stratification of clinical hepatitis subsequent to virological relapse in [chronic HBV] patients who stop taking [Baraclude].”
The prospective study comprised 92 patients diagnosed with chronic HBV for more than 6 months, had been treated with Baraclude (entecavir, Bristol-Myers Squibb) for a minimum of 3 years, and were seronegative for both HBeAg and viral DNA at treatment cessation. The patients developed virological relapse over a mean follow-up of 12.6 months.
Fifty-two patients encountered clinical hepatitis with a cumulative incidence of 61% (95% CI, 49.9-72.3) at 2 years from treatment cessation and 37 patients developed persistent or severe hepatitis with a cumulative incidence of 53% (95% CI, 40.9-66.2) at 2 years.
The researchers found that serum viral load at the time of virological relapse was a significant risk factor for clinical hepatitis after adjusting for alanine aminotransferase (ALT; HR = 1.31 per log IU/mL; 95% CI, 1.07-1.6). They also observed that severity of viremia at relapse was an independent risk factor for subsequent persistent or severe hepatitis (HR = 1.63 per log IU/mL; 95% CI, 1.27-2.1), after adjusting for the effect of ALT at relapse and alpha-fetoprotein at treatment cessation.
The risk for both clinical hepatitis and persistent or severe hepatitis increased incrementally with serum viral load in a dose-dependent manner (P < .0001). Patients with HBV DNA higher than 100,000 IU/mL at virological relapse had a 2-year cumulative incidence of 89.7% (95% CI, 72.4-89.2) for clinical hepatitis compared with 51.3% (95% CI, 38.6-65.5) in those with viremia lower than 100,000 IU/mL.
Patients with viral load higher than 100,000 IU/mL similarly had a higher risk for developing persistent or severe hepatitis at a cumulative incidence of 88% (95% CI, 69.7-97.9) compared with 41.7% in those with a viral load less than 100,000 IU/mL (95% CI, 28.2-58.2).
“The major concern of stopping [nucleos(t)ide analogue] in [chronic HBV] patients is the risk of acute on chronic liver failure that may rapidly ensue after a severe bout of clinical flare,” the researchers wrote. “Based on our findings, retreatment should not be deferred in patients who relapse with a high viral load. Identification of this indicator helps to diminish the risk of persistent or severe clinical hepatitis.”
By Talitha Bennett