Selected patients with chronic HBV may be able to discontinue antiviral treatment and maintain virological control

A substantial proportion of people receiving oral antiviral treatment for hepatitis B virus (HBV) may be able to achieve durable virological remission after the withdrawal of therapy, investigators report in Hepatology. Researchers conducted a systematic review of studies examining rates and predictors of virological control after the withdrawal of oral antiviral therapy for chronic HBV infection. Overall, 51% were in virological remission twelve months after discontinuation of therapy, with hepatitis B e antigen (HBeAg)-positive people more likely to achieve this outcome than HBeAg-negative people. Longer duration of therapy was associated with increased chances of virological remission for HBeAg-negative people.

“The pooled overall rate of durable VR [virological remission] was approximately 46%, with most of the relapses occurring within the first or second year after NA [nucleoside/nucleotide analogue] discontinuation,” comment the authors. “Additional studies are required to identify predictors of durable VR.”

Oral nucleoside/nucleotide therapy can have major health benefits for people with chronic HBV. However, it is currently unclear if virological control of HBV can be maintained after the withdrawal of this treatment.

An international team of investigators therefore conducted a meta-analysis and systematic review of virological and biomedical outcomes in people with chronic HBV who discontinued oral nucleoside/nucleotide therapy. Participants were required to have received at least twelve months of treatment and to have been followed for a minimum of twelve months after stopping treatment. Viral control was defined as HBV levels below 20,000 IU/ml.

The investigators identified 25 studies conducted between 2002 and 2014; all but one were cohort studies, the remaining study being a randomised control trial. One study was evaluated as high quality, 14 as acceptable and ten as low quality. A total of 1726 people discontinued oral antiviral therapy and post-therapy follow-up data were available for 1716 of these individuals. Of these, 43% were HBeAg-positive and 56% were HBeAg-negative – HBeAg status was unclear in the remaining 1% of participants. Cirrhosis was present in 18% of participants with reported histological data at the time treatment was stopped.

Durable virological remission was reported in 46% of participants. The rate was higher in people who were HBeAg-positive than in people who were HBeAg-negative (50 vs 38%, p < 0.001).

Overall rates of remission at 6, 12, 24 and 36 months were 68, 51, 39 and 38%, respectively. Rates of remission at all follow-up points were higher among HbeAg-positive people than HBeAg-negative people.

Durable biological remission – good liver function – was observed in 65% of participants overall. The rate was higher – but not statistically so – among HBeAg-positive people compared to HBeAg-negative people (76 vs 57%).

HBsAg loss was observed in 2% of patients, with no difference in the rate of this outcome between initially HBeAg-positive and HBeAg-negative people (1 vs 1.7%).

Duration of therapy was not associated with virological remission rates overall. However, for HBeAg-negative people, the twelve-month remission rate was 35% for people who received less than 24 months of treatment, compared to a remission rate of 75% for people who received over 24 months of oral antiviral treatment.

Factors associated with virological remission in individual studies included lower baseline ALT, lower baseline HBV DNA, younger age, female gender and absence of cirrhosis. The researchers call for more studies to identify factors associated with post-treatment outcomes.

A deterioration in liver function post-treatment discontinuation was reported in 39% of patients with cirrhosis. Liver decompensation occurred in 1% of patients and 2.5% developed jaundice. Retreatment was effective in all but one person who died because of liver failure.

“Discontinuation of long-term NA therapy may be attempted if close follow-up can be guaranteed in patients without advanced liver disease,” conclude the authors. “NA discontinuation may be considered not only in HBeAg-positive patients without cirrhosis who achieve stable HBeAg seroconversion for at least 12 months but also in HBeAg-negative patients without cirrhosis who remain in biological remission and virological remission under NAs for a few years.”