The edition · Gastroenterology & Hepatology
A framework for the two MASH drugs, and functional cure of hepatitis B turns entirely on where the antigen starts
An international panel consolidates phase 3 data and FDA labels for resmetirom and semaglutide into one care pathway for F2-F3 MASH. Separately, pooled individual data show peg-interferon add-on clears HBsAg in 37.7% below 100 IU/mL and 2.3% above 1000.
The edition in brief
Five findings and a pearl for the gastroenterology and hepatology desk. PROSPER pooled individual participant data from eight trials of peg-interferon added to nucleos(t)ide analogue therapy in 581 patients with chronic hepatitis B: HBsAg loss at end of follow-up was 8.6% overall, but 37.7% in those whose surface antigen was below 100 IU/mL at the start, 9.8% between 100 and 1000, and 2.3% above 1000, consistent across ethnicities. A meta-analysis of three studies covering 899,629 people found MASLD associated with clinically diagnosed heart failure with preserved ejection fraction at a pooled odds ratio of 1.35 (95% CI 1.26 to 1.45) - a 35% relative increase over an absolute difference of 0.35 percentage points, and the authors call it hypothesis-generating. In the ALSPAC birth cohort, 1,933 offspring assessed at 24 years had a 10.4% prevalence of MASLD; each unit of pre-pregnancy maternal BMI raised the odds by 10% and paternal BMI by 9%, with biparental overweight or obesity carrying 3.73 times the odds, two-thirds of it mediated through cumulative childhood BMI. A meta-analysis of six studies and 8,993 patients quantifies weight regain after stopping a GLP-1 receptor agonist: a 17.9% weight difference against continued treatment, larger after tirzepatide than semaglutide. The practice-changer is an international expert panel review turning the conditional FDA approvals of resmetirom and semaglutide for MASH with F2-F3 fibrosis into a single pathway - non-invasive diagnosis, agent selection by phenotype, monitoring, and definitions of response, non-response and when to switch or combine. Plus a pearl on using FIB-4 as the first gate.
Peg-interferon add-on clears HBsAg in 38% - if the starting antigen is below 100 IU/mL
Check quantitative HBsAg before offering peg-interferon add-on: below 100 IU/mL about 38% achieve functional cure, above 1000 about 2% do.
MASLD and HFpEF: a 35% relative increase over a third of a percentage point
Lower your threshold for a cardiac assessment when a MASLD patient reports breathlessness - but do not start screening echocardiography on a 0.35 percentage point difference.
Both parents' pre-pregnancy BMI predicts MASLD in offspring at 24
Ask about both parents' weight in a young adult with steatosis, and direct the intervention at childhood and adolescent adiposity, which mediated two-thirds of the risk.
Weight comes back after a GLP-1 agonist stops, and faster after tirzepatide
Tell patients at the first prescription that a GLP-1 agonist is a long-term treatment - stopping returned about 9% of body weight in these pooled data.
FIB-4 first, and know what its two thresholds actually do
Run FIB-4 on every patient with steatosis and metabolic risk, and use 1.3 to discharge, 2.67 to refer, and elastography for the zone between.
A single pathway for the two drugs now approved in MASH with F2-F3 fibrosis
Use the non-invasive staging pathway now to identify F2-F3 MASH, and define response criteria before starting either resmetirom or semaglutide.
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