Bulevirtide holds hepatitis D for three years, and most patients relapse when it stops

Design

phase III randomised trial, 144 weeks of treatment with 96 weeks of post-treatment follow-up (MYR301)

Population

150 patients with compensated chronic hepatitis D, randomised to bulevirtide 2 mg/day, 10 mg/day, or 48-week delayed start then 10 mg/day

Primary outcome

virologic response (undetectable HDV RNA or 2 log10 IU/mL decline), ALT normalisation and combined response

Effect

virologic response 73%, 76% and 92% at end of treatment, falling to 33%, 30% and 32% at 96 weeks off treatment; sustained undetectability in 23/64 (36%)

MYR301 randomised 150 patients with compensated chronic hepatitis D to bulevirtide 2 mg or 10 mg daily for 144 weeks, or to a 48-week delay followed by 96 weeks of 10 mg, and then followed everyone for a further 96 weeks off treatment. The question was not whether bulevirtide works during treatment, which was already established, but what happens afterwards.

At the end of treatment, virologic response, defined as undetectable HDV RNA or a fall of at least 2 log10 IU/mL, was reached by 73%, 76% and 92% of the three groups, with alanine aminotransferase normalising in around 60% and HDV RNA undetectable in 29% to 52%. Two years after stopping, virologic response had fallen to roughly a third in every group and undetectability to about a fifth. Of 64 patients with undetectable HDV RNA at the end of treatment, 23 (36%) were still undetectable at the end of follow-up, and the strongest predictor was simply how many weeks they had been continuously undetectable before stopping. Hepatic serious adverse events after stopping occurred in 14% and resolved in 85% of those affected.

The honest reading is that bulevirtide is suppressive therapy for most patients, in the way nucleoside analogues are for hepatitis B, with a minority able to stop. That reframes the counselling: the question at the outset is not how long a course will be, but whether long-term treatment is available and affordable.

For Indian practice the constraint is access. Bulevirtide is approved in the European Economic Area, the United Kingdom, Switzerland, the Russian Federation, Australia, Canada and the United States, according to the trial report; it names no Indian approval, and the CDSCO position is not something this record establishes. Hepatitis D remains under-tested here, and the more actionable step for most clinicians is to test for it at all: anti-HDV should be checked in every HBsAg-positive patient, particularly those with disproportionate liver injury.

• Test every HBsAg-positive patient for anti-HDV at least once, especially with raised ALT or unexplained progression
• Counsel bulevirtide as long-term suppression, not a defined course, unless HDV RNA has been undetectable for a prolonged period
• Where stopping is considered, use duration of continuous undetectability as the main argument, not a single undetectable result
• Monitor ALT and HDV RNA closely after any planned discontinuation: hepatic serious adverse events occurred in 14% off treatment
• Confirm local availability before raising bulevirtide with a patient; the trial reports approvals elsewhere and none in India

The statistics, in plain English

The gap between end-of-treatment and post-treatment figures is the whole finding: a response rate of 73% to 92% on treatment falling to about 30% off it means the drug controls the virus rather than clearing it in most people. The 36% sustained undetectability figure comes from a subgroup of 64 patients defined after the fact by their response, so it describes who did well rather than predicting who will; the association with duration of undetectability is plausible but not a validated stopping rule. With 150 patients split across four groups, differences between the dose arms are too small to act on.

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