Are We Prepared for the Fatty Liver Epidemic?

Non-alcoholic fatty liver disease (NAFLD) is a silent epidemic, affecting nearly a quarter of the global population. The high prevalence is likely due to unhealthy Western dietary habits, rising obesity, and sedentary lifestyles, which are key risk factors associated with disease development.

Because NAFLD is heavily influenced by lifestyle, patients who are diagnosed early are often advised to lose weight and adopt a healthy lifestyle to control or even reverse their symptoms. If left untreated, NAFLD can progress to non-alcoholic steatohepatitis (NASH), fibrosis, and then cirrhosis, which in some cases will lead to hepatocellular carcinoma (HCC).

NASH is usually discovered incidentally, and early detection is one of the greatest challenges related to diagnosis. This is because individuals typically present with few signs or symptoms in the early stages, only showing symptoms when the liver is severely damaged.  At this point, the damage is often irreversible and no treatments for NAFLD and NASH have currently been approved.

The incidence of NASH is projected to increase by up to 56% in the next 10 years,¹ providing further evidence that early diagnosis and treatment is urgently needed to curb epidemic.

NASH Diagnosis: Where Are We Now?

The gold standard for NASH diagnosis is an expensive and invasive liver biopsy. Currently, non-invasive diagnostic methods such as blood biomarkers or imaging-based techniques lack sufficient accuracy. “To diagnose NASH easily and quickly we need to establish a novel non-invasive preclinical in vivo imaging protocol to visualize and quantify disease progression,” said Jérémy Sadoine, and In Vivo Pharmacology Scientist at Galapagos NV.

The team at Galapagos have been exploring innovative strategies to aid in the development of NASH diagnostic tools. One method they have tested is to study NASH diagnostic parameters non-invasively using a combination of microCT and optical imaging to quantify both liver steatosis and fibrosis. “All our in vivo data correlate with ex vivo measurements allowing us to conclude that microCT and optical imaging associated with appropriate probes are convenient for NASH in vivo staging,” said Jérémy Sadoine. This approach could also be used to investigate the efficacy of liver fibrosis-preventing drugs on NAFLD progression in order to reduce the need for liver transplantation.

Therapeutic Pipeline

The first-line therapy for NASH patients is making lifestyle changes to reduce fat build up in the liver. Bariatric surgery remains an effective treatment for obesity, offering an opportunity to reduce the likelihood of progression to cirrhosis and the need for liver transplant. However, there is still a lack of approved drugs to treat the condition and often transplant is the only option.

Last year, three potential therapeutics were terminated in Phase III clinical trials: Cenicriviroc (Allergan), Elafibranor (GENFIT), and Selonsertib (Gilead). But there are still many therapies in late-stage clinical trials, which could offer hope for affected patients if successful. “With more pharmacologic candidates, such as Resmetirom (agonist for thyroid hormone β-receptor), Semaglutide (GLP-1 analogue), or Lanifibranor (pan-PPAR agonist) in phase III trials and many others in the pipeline, it is anticipated that a novel treatment for NASH will be available in the near feature.” said Professor Jian Wu, who is based at Fudan University Shanghai Medical College in China. “A combination of therapeutics may be needed to address multiple hits better than a single drug candidate.”

Webinar: Non-invasive Imaging Approach to Quantify NASH and Assessing Emerging Therapeutics

NASH disease pathology, early diagnosis, and emerging therapeutic development were the main topics of conversation in a recent webinar presented by Jérémy Sadoine and Prof. Wu.

Jérémy Sadoine showcased his lab’s multimodal imaging approach to tracking in vivo liver steatosis, inflammation, and apoptosis in a NASH mouse model, and Dr. Jian Wu discussed emerging pharmacotherapeutics targeting different key pathogenic pathways for treatment of NASH and interprets current phase II and III trial data.

References

1. https://pubmed.ncbi.nlm.nih.gov/33349658/