Introduction

Several factors, including increasing disease prevalence, high unmet need and growing understanding of the diverse mechanisms underlying disease pathogenesis are contributing to an increased interest in clinical research in NASH and NAFLD.

Aims & Methods

We undertook an analysis of metadata from Clinicaltrials.gov (CT.gov) to characterize trends over the last 10 years and what this may tell us about the future trajectory for treatment development. CT.gov was searched for studies containing the terms "NASH" or "Nonalcoholic Steatohepatitis" or "Nonalcoholic Fatty Liver Disease" or "NAFLD" or "NASH Cirrhosis" or "Fatty Liver Disease" or "Metabolic Steatosis" posted from 01-Jan-2013 and 31-Dec-2022. Expanded access programs were excluded as these were not considered research studies. 1095 records were returned, of which 32 were excluded as their focus was on conditions other than those of interest. 1063 studies in the analysis were divided into two equal periods: P1 - 2013 to 2017, and P2 - 2018 to 2022, and analyzed by study type, study phase, intervention type and funding.

Results

Studies increased 100% in P2 vs P1, with the most marked increase in early phase studies (108%). The majority of studies were interventional (798 [75%]), which increased by 91% in P2. Observational studies also increased markedly in P2 (131%). Drugs were the most common study intervention (39%), increasing by 98% in P2. There was also a notable increase in the number of diagnostic studies in P2 (871%), the majority of which were studies of non-invasive methods for staging liver fibrosis. 64% of studies were non-industry funded, which increased by 82% in P2. Industry funded studies increased by 140%, with the largest increase in the biotech sector (174%).

Conclusion

Our data provides evidence of a marked increase in clinical research activity in NASH and NAFLD in the last 5 years, particularly in early phase drug development and non-invasive diagnostic methods as an alternative to liver biopsy for staging fibrosis. This combined with the finding that most research has been non-industry funded suggests a growth in basic science that may translate into an increase in industry research in the future. This is supported by the finding that industry funded studies have increased more sharply than non-industry in the last 5 years.

Introduction

Pancreatic steatosis (PS) has been increasingly recognized and associated with some relevant metabolic implications. However, data on its correlation with exocrine pancreatic function remain limited. We conducted a systematic review and meta-analysis to evaluate whether PS is associated with exocrine pancreatic insufficiency (EPI).

Aims & Methods

This study aimed to investigate whether imaging-detected PS is related to exocrine pancreatic dysfunction, assessed by fecal elastase-1 (FE-1) levels. We searched PubMed, EMBASE, and Cochrane Central for studies including adults with and without PS identified on imaging, and reporting FE-1 concentrations. Data were pooled using random-effects models.

Results

Three studies evaluating a total of 1,864 patients were included. Fecal elastase levels were significantly lower in patients with PS compared to controls, indicating worse exocrine pancreatic function in this group (MD -199.78; 95% CI -303.66 to -95.91; p < 0.05; I² = 97%). Moreover, PS was associated with a significantly increased risk of exocrine pancreatic insufficiency (RR 3.13; 95% CI 1.17–8.40; p = 0.023; I² = 81%), reinforcing the link between fat accumulation in the pancreas and impaired exocrine function.

Conclusion

This meta-analysis demonstrates a significant association between PS and impaired pancreatic exocrine function, compared to individuals without known pancreas disease. These findings underscore the importance of a comprehensive metabolic assessment in patients with PS, given its potential role in pancreatic dysfunction.

Clinical Case Summary

A 71-year-old female presented to the gastroenterology clinic following a two year history of dysphagia and sensation of food sticking in the oesophagus. Her dysphagia was limited to solid foods, and symptoms were not exacerbated by positional change. Pain was mostly localised around the sternal notch where she would have the sensation of a food bolus. Over the preceding 2 years, she had experienced about 7.5kg of weight loss with no constitutional symptoms of fevers or fatigue. Her past medical history included hypertension, dyslipidaemia, lower back pain, cold agglutinin disease, monoclonal B lymphocytosis and peripheral arterial disease. On examination, there were no signs of malnourishment or palpable lymph nodes in the axilla, neck or supraclavicular region. Her abdomen was soft and non-tender. Given largely non-illuminating blood results, an oesophageal-gastroduedonoscopy was performed. However, no findings were noted, specifically no oesophageal webs, Zenker diverticulum, gastroparesis, trachealisation of the oesophagus or corrosive pathology. H. pylori was also not isolated on histopathology. A barium swallow was then performed which showed extensive external compression of the proximal third of the oesophagus at the level of the arch of the aorta, most indicative of dysphagia lusoria (Fig 1). Computed tomography angiography (CTA) showed retroesophageal aberrant right subclavian artery bifurcating from the ascending aorta independent of a brachiocephalic artery and causing external oesophageal compression (Fig 2 & 3). Given this definitive diagnosis, the patient was then seen in clinic where management of dysphagia lusoria was explained. Despite ongoing symptoms, the patient decided to continue with conservative management and lifestyle modifications, which included eating smaller bites and increase in fluid intake. Although an extensive compression typically requires surgical intervention, our patient was stable at two-year follow-up (Fig 4 A-B).

References

Figure 1: Barium swallow examination showing extrinsic compression of the proximal third of the oesophagus at the level of the aortic arch (white arrow).
Figure 2: Axial view of computed tomography angiography (CTA) showing the posterior course of the retroesophageal aberrant right subclavian artery.
Figure 3: Axial view of computed tomography angiography (CTA) showing compression of oesophagus (white arrow) by the retroesophageal aberrant right subclavian artery (white arrowhead).
Figure 4: Computed tomography angiography (CTA) multi-planar reconstruction (MPR) showing the posterior course of the right subclavian artery (white arrow), crossing the mediastinum and compressing the oesophagus. A. coronal view B. Sagittal view

Disclosure

None.