Ending NUC Treatment May Induce Functional Cure in Patients With Chronic Hepatitis B

Termination of long-term nucleoside/nucleotide analogues (NUCs) treatment in patients with HBeAg-negative chronic hepatitis B was associated with functional cure among some patients, a recent study found.

The study, published in Journal of Hepatology, included 158 HBeAg-negative patients with chronic hepatitis B and HBV DNA under 172 IU/ml for at least four years. Patients were divided into two groups, with one group stopping NUC treatment and the other continuing treatment.

After a 96-week observation period, 10.1% (95% CI 4.8%–19.5%) of patients in the group that stopped treatment met the primary endpoint of sustained HBsAg loss. None of the patients who continued treatment achieved the primary endpoint. Many patients also saw reduction in HBV DNA.

“We were able to show that in some patients discontinuing long-term therapy with nucleoside or nucleotide analogues after at least four years is more effective than continuing it, and that many patients no longer require antiviral therapy at all after discontinuation,” lead author Florian van Bömmel, senior physician in the Department of Hepatology at Leipzig University Hospital, said in a statement. “In particular, patients who show low HBsAg levels when they discontinue treatment have a high chance of functional cure.”

Among those who’s baseline HBsAg levels were less than 1,000 IU/ml, 28% achieved the primary endpoint of HBsAg loss. Sustained remission was achieved among 40.5% of patients who stopped treatment. Treatment was resumed among 13.9% of patients.

The study reported no serious adverse events related to stopping treatment.

“However, in other studies, severe cases of hepatic inflammation were observed in a few cases after antiviral therapy was discontinued,”van Bömmel said. “Stopping NUC treatment should therefore only be carried out under the supervision of an experienced physician.”

The study also showed that 77% of patients no longer had elevated liver inflammation.

Six patients (7.6%) in the arm that stopped treatment achieved HBsAg seroconversion to anti-HBs.

NUC treatment is mostly lifelong for chronic hepatitis B patients, which can lead to bone density loss and deterioration of kidney function along with drug-related adverse events, drug resistance and high costs.

The Stop-NUC study is a prospective, multicenter, randomized, controlled trial inspired by a European study that showed promising evidence that HBeAg-negative patients who discontinued NUC treatment could achieve a sustained response.

“We expect that in the future international guidelines for the treatment of hepatitis B will refer to this study,” van Bömmel and Thomas Berg, MD, of Leipzig University Hospital, said in a news release. “By the middle of this year, results from the extension of the study will be evaluated and will show whether the number of patients with immune control continues to increase in the long term after discontinuation of antiviral treatment.”