An earlier valve, a liver test without biopsy, a fixed gene: a 4-story digest

Replacing a narrowed aortic valve before it became severe cut heart failure events in a randomised trial

On 2 November 2026 the New England Journal of Medicine published PROGRESS, an international open-label trial in 744 people with moderate aortic stenosis — a narrowed aortic valve that current guidelines manage with an echocardiogram every one to two years until it becomes severe. Everyone also had at least one at-risk feature, such as a symptom or a structural or functional change in the heart linked to faster progression. Their mean age was 78, 39.1% were women and 45.6% were at low surgical risk. Half were assigned to transcatheter aortic valve replacement (TAVR) with a balloon-expandable valve threaded in through the groin artery, half to standard surveillance.

At two years, death from any cause or a heart failure event had occurred in 16.7% of the TAVR group and 23.9% of the surveillance group, a difference of 7.2 percentage points (95% CI −13.1 to −1.3). The gap came from heart failure events, 10.8% versus 19.0%; deaths were 8.4% and 7.3%. Complications linked to the procedure were similar to those in surveillance patients who later had their valve replaced.

The trial was not blinded, and heart failure events counted with or without a hospital stay, which leaves room for judgement in a softer outcome. It was funded by Edwards Lifesciences. The result applies to people with moderate stenosis plus a risk feature, not to everyone with a narrowed valve, and it does not show that early replacement helps people live longer.

In 1,590 biopsied patients, panels of blood markers came closest to replacing liver biopsy in fatty liver disease

The Lancet print issue of 31 October 2026 carried LITMUS, a prospective diagnostic study from 13 countries in Europe and the USA. It compared 12 single markers and 18 multi-marker panels against centrally read liver biopsies in 1,590 adults with metabolic dysfunction-associated steatotic liver disease (MASLD)). The authors counted a test as a potential replacement for biopsy if its area under the curve (AUC), the study's accuracy measure, was above 0.80.

For at-risk steatohepatitis, inflammation plus significant scarring, only one test cleared that bar: SomaSignal, a panel built from blood protein measurements, with an AUC of 0.83. For advanced scarring it reached 0.92, ahead of FibroMeter-VCTE at 0.87, which combines blood tests with liver stiffness. For cirrhosis FibroMeter-VCTE led with 0.94. Single markers performed variably and mostly fell short, while a two-step approach starting with the liver enzyme gamma-glutamyl transferase met the threshold for both advanced fibrosis and at-risk disease.

Everyone in the study already had biopsy-confirmed MASLD and 37% had advanced scarring, and the study did not assess how the tests perform in primary care. The study measured how well tests match the biopsy, not whether using them improves outcomes. It was funded by the Innovative Medicines Initiative 2 Joint Undertaking.

A liver biopsy confirmed that in-body base editing corrected the faulty gene in about half the cells of a man with alpha-1 antitrypsin deficiency

In early November 2026 the Journal of Hepatology published, ahead of print, a case report from the YOLT-202 phase I/Ia trial. A 66-year-old man had alpha-1 antitrypsin deficiency with the PI*ZZ genotype: a single-letter error in the SERPINA1 gene makes the liver produce a misfolded protein that builds up in the liver and leaves too little in the blood to protect the lungs. He was treated with in vivo base editing, which corrects a single DNA letter inside the body's own cells without cutting both strands of DNA.

Ten weeks later a liver biopsy showed the faulty variant corrected in 54% of gene copies by one sequencing method and 57% by another, with no detectable edits at off-target sites. The tissue showed no inflammation. Liver enzymes rose for a while after treatment and then returned to baseline, and monthly blood tests showed sustained levels of the protein that still blocked elastase, the enzyme it is meant to restrain.

This is one patient in an early trial, with ten weeks to biopsy and limited follow-up, so it shows the edit can happen in a human liver, not that it prevents lung or liver disease over the years. Several authors sit on the trial's safety committee. The registry entry lists an estimated 18 participants at a hospital in China, and the approach is far from approval.

An experimental JAK1 tablet restored facial skin colour in about one in five adults with vitiligo in two phase 3 trials

On 2 November 2026 Nature Medicine published STOP-V1 and STOP-V2, two parallel double-blind phase 3 trials of povorcitinib, an investigational tablet that blocks the JAK1 signalling enzyme, against placebo in adults with moderate to severe nonsegmental vitiligo, in which patches of skin lose their pigment. The trials enrolled 467 and 449 people.

The main goal was at least 75% repigmentation of the face after 52 weeks. It was reached by 18.9% on povorcitinib versus 6.8% on placebo in the first trial and 18.9% versus 3.1% in the second. Side effects of any kind were reported in 68.7% and 66.7% of those on the drug and in 63.7% and 62.7% on placebo; acne was more common on the drug, about 11% versus 2–3%. Serious side effects were mostly single events, and the problems typical of the JAK inhibitor class were absent or rare.

Four in five people on the drug did not reach the main goal within a year, and these primary results cover 52 weeks only. The trials were sponsored by the developer, Incyte, and the paper reports results, not a regulatory decision. In the USA a cream with a different JAK inhibitor, ruxolitinib, has been approved for this form of vitiligo since 2022.

This article is for information only and does not replace a consultation with a doctor. Nothing in it is a recommendation to start, stop or change treatment.

Sources

• Généreux P, Makkar RR, Pibarot P, et al. TAVR in Patients with Moderate Aortic Stenosis with At-Risk Features. N Engl J Med. 2026. PMID 42970708, doi:10.1056/NEJMoa2607326, NCT04889872

• Vali Y, Wonders K, Lee J, et al. Non-invasive tests in metabolic dysfunction-associated steatotic liver disease: the LITMUS prospective multicentre diagnostic accuracy study. Lancet. 2026;408:1850-1865. PMID 42956772, doi:10.1016/S0140-6736(26)01145-1

• Krooss SA, Yang T, Yuan Q, et al. Liver biopsy confirms precise and efficient correction of SERPINA1 after in vivo Base Editing in a Patient with Alpha-1 Antitrypsin Deficiency. J Hepatol. 2026. PMID 42971508, doi:10.1016/j.jhep.2026.09.028, NCT07193615

• Ezzedine K, Lui H, Eleftheriadou V, et al. Povorcitinib for nonsegmental vitiligo: two randomized, controlled, phase 3 STOP-V trials. Nat Med. 2026. PMID 42972109, doi:10.1038/s41591-026-04739-2, NCT06113445, NCT06113471