Intended for healthcare professionals


Ann Robinson’s research reviews—15 February 2024

51app 2024; 384 doi: (Published 15 February 2024) Cite this as: 51app 2024;384:q366
  1. Ann Robinson, NHS GP and health writer and broadcaster

Resmetirom for non-alcoholic steatohepatitis

The global incidence of non-alcoholic fatty liver disease is estimated to be one in 20. About a fifth of cases will cause liver cell inflammation and damage known as non-alcoholic steatohepatitis (NASH). As NASH progresses to severe fibrosis and on to cirrhosis, the risk of death from liver disease increases. Lifestyle changes help early stage NASH, but there’s no approved drug treatment as yet.

This phase 3 trial is encouraging. Among 966 patients with NASH, resmetirom (80 mg and 100 mg doses)—an oral, liver-directed, thyroid hormone receptor agonist that reduces fibrosis—was more effective than placebo in resolution of NASH with no worsening of fibrosis (26% v 30% v 10%) and improving liver fibrosis (24% v 26% v 14%) over one year. Lipid profiles improved too, which is helpful as most of these patients with NASH also had diabetes and are at increased risk of cardiovascular disease.

N Engl J Med doi:10.1056/NEJMoa2309000

Scaling the heights

Psoriasis treatment has come a long way. It’s 20 years since the first game-changing monoclonal antibodies and proteins that target inflammatory cytokines such as interleukin 23 were involved in treating this multisystem inflammatory condition. One downside of most biologics is that they have to be injected, which limits their use in children or the many adults who hate needles.

This short and small phase 2 trial of an oral interleukin 23 antagonist (JNJ-77242113) suggested that, at doses ranging from 25 mg once daily to 100 mg twice daily, it offers a safe and effective alternative to injectables in adults with moderate to severe psoriasis compared with placebo. Head-to-head phase 3 trials against other oral treatments (such as apremilast) are needed to compare efficacy and tease out any rare adverse events.

N Engl J Med doi:10.1056/NEJMoa2308713

Covid vaccination in pregnancy

When covid vaccination became available, some pregnant women expressed disquiet about whether it could damage their unborn baby. This was despite data that 98% of pregnant women admitted to hospital with severe covid were unvaccinated and that the vaccination was likely to be safe and effective.

This population based cohort study compared over 94 000 infants in Sweden and Norway whose mothers had had a covid vaccination while pregnant with over 100 000 matched controls born when covid was a threat but no vaccination was available yet. The results are encouraging, with no increased risk of neonatal adverse events in infants born to mums who had the vaccination. In fact, there were lower odds of neonatal intracranial haemorrhage and neonatal mortality. There was also no increase in miscarriage, stillbirths, or neonatal myocarditis, which have all been areas of concern. There’s always scope for confounding, but this huge and well conducted study offers reassurance both now and for the next time.

JAMA doi:10.1001/jama.2023.26945

Curiouser and curiouser

Around a third of US adults have prediabetes, which puts them at increased risk of diabetes, heart and kidney disease, and premature death. At the same time, many men—especially those with prediabetes or established diabetes—have low testosterone levels (hypogonadism), which is associated with fat accumulation, insulin resistance, and diabetes. Testosterone replacement therapy (TRT) helps; more muscle, less fat, and better insulin sensitivity. Logically, giving TRT to men with low testosterone should mean they’re less likely to progress from prediabetes to diabetes.

But this nested substudy within a major trial found that it didn’t. In men aged over 45 years with low testosterone and prediabetes, testosterone gel was no more effective than placebo in preventing progression to diabetes (13.4% v 15.7% at 48 months) or improving glycaemic control. This is on the back of another substudy of the same trial that found TRT didn’t reduce clinical fractures in hypogonadal men despite the known positive effect of testosterone on skeletal mass.

JAMA Intern Med doi:10.1001/jamainternmed.2023.7862

The quest to avoid neonatal deaths and damage

Cerebro-placental ratio (CPR) has been around for about 10 years and is an additional tool in assessing fetal growth and hypoxia. It’s calculated by dividing middle cerebral artery Doppler flow by umbilical artery Doppler flow, and the aim is to identify the highest risk pregnancies to allow elective delivery in time to prevent perinatal deaths and brain injury.

In this study of over 11 000 pregnant women with low risk pregnancies, everyone had CPR measured in addition to routine care, which included ultrasound with growth assessment and Doppler evaluation after 36 weeks. Planned delivery was recommended for all pregnancies if the fetal weight was below the 10th centile. Women were randomised to a revealed group, in which clinicians knew the results of the CPR and recommended planned delivery after 37 weeks if the CPR was below the fifth centile, or to a concealed group in which the women and clinicians didn’t know the CPR result. There was no significant difference in perinatal mortality rates from 24 weeks’ gestation to the time the baby went home between the two groups (0.3%), but there was a significant reduction in severe neonatal morbidity in the revealed group compared with the concealed group (0.38% v 0.73%). The addition of CPR to standard current fetal growth assessment in low risk pregnancies needs further study.

Lancet doi:10.1016/S0140-6736(23)02228-6


  • Competing interests: None declared

  • Provenance and peer review: Not commissioned; not peer reviewed