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As the twin global epidemics of obesity and NAFLD continue to grow, it is more important than ever to develop novel therapies and effective treatment strategies to tackle NAFLD and NASH.

Promising results were reported for engineered FGF19 analogue aldafermin (NGM282) in the treatment of NASH – over 24 weeks, patients receiving aldafermin experienced significant and durable improvements in liver fat content, fibrosis and NASH histology compared with those on placebo. Another randomized, controlled phase 2b trial in 392 patients with advanced fibrosis showed that combination therapy with cilofexor 30 mg/firsocostat 20 mg for 48 weeks was well tolerated and improved both fibrosis and NASH activity.

Alcoholic liver disease (ALD) remains the major cause of liver injury in Western countries. One emerging therapy for severe alcoholic hepatitis (SAH) is early liver transplantation (eLT) but we need robust studies to provide reliable data on its effectiveness. The first prospective controlled study in this field showed that, while survival rates were high (~89%), patients with SAH not responding to medical treatment and selected for eLT were more likely to relapse than patients who received transplantation for alcohol-related cirrhosis after 6 months of abstinence (34% vs 25%). Authors of a genome-wide association study for alcohol-related cirrhosis suggest that further investigation into two novel SNPs, identified as modulating the risk of alcohol-related cirrhosis, is warranted.

Other highlights and encouraging developments reported in this session:
The Stop-NUC trial – the first large-scale randomized study of its kind – shows the potential of discontinuation of long-term nucleos(t)ide analogues for induction of durable immune control and functional cure in patients with chronic HBeAg-negative hepatitis B
The UK ATTIRE trial does not support targeted weight-based infusions of 20% human albumin solution over standard care for managing hospitalised decompensated cirrhosis
The Phase 3 APROH trial shows that proton beam radiotherapy was non-inferior for local progression-free survival in patients with recurrent hepatocellular carcinoma
Data from the INDIGO trial support the use of long-term maralixibat as a possible alternative to surgery for children with progressive familial intrahepatic cholestasis due to bile salt export pump deficiency.

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