Presentation given by Chris Byrne, Professor Endocrinology & Metabolism, University of Southampton & Southampton NIHR BRC, University Hospital Southampton

The 6th Global NASH Congress in London witnessed an enlightening presentation by Professor Chris Byrne, a distinguished metabolic physician and endocrinologist. His comprehensive exploration of non-alcoholic fatty liver disease (NAFLD) unveiled its intricate nature as a multisystem disorder. This blog post aims to delve deeper into the key insights shared by Professor Byrne, elaborating on the relationship between NAFLD and type 2 diabetes, the significance of diagnosing NAFLD in patients living with diabetes, the potential benefits of PPAR gamma agonists, and the amplified risk of extrahepatic complications in NAFLD when people have type 2 diabetes.

NAFLD and Type 2 Diabetes: A Vicious Spiral

A pivotal aspect of Professor Byrne’s presentation revolved around the intricate relationship between NAFLD and type 2 diabetes. NAFLD increases the risk of developing type 2 diabetes, and conversely, the presence of type 2 diabetes exacerbates the progression of liver fibrosis in NAFLD patients. This vicious spiral calls for early detection and comprehensive management strategies for NAFLD in patients with type 2 diabetes. Accurate identification of liver fibrosis in these patients is crucial, given its substantial implications, including an increased risk of hepatocellular carcinoma.

NAFLD as a Silent Multisystem Disease

Professor Byrne’s extensive body of work has revealed that NAFLD extends beyond its impact on liver health and affects various systems throughout the body. Patients with NAFLD and type 2 diabetes often exhibit metabolic abnormalities associated with the metabolic syndrome, such as dyslipidaemia, elevated blood pressure, and insulin resistance. These factors significantly contribute to the heightened risk of adverse outcomes beyond liver health. Consequently, diagnosing and managing NAFLD in patients with type 2 diabetes becomes imperative for mitigating the risks associated with this silent multisystem disease.

Amplified Risk of Extrahepatic Complications in NAFLD

Professor Byrne’s research, supported by robust meta-analyses and fruitful collaborations, consistently demonstrates that NAFLD amplifies the risk of several extrahepatic complications. Over 10 years ago, Prof Byrne showed with colleagues in Korea that NAFLD is an independent risk factor for developing new onset type 2 diabetes. Recently, with the team in Korea, he has shown effect modification of this relationship by sex and menopausal status. Importantly, in this work, the team showed for the first time that a diagnosis of NAFLD improved risk prediction for developing type 2 diabetes, over and above more traditional diabetes risk factors.

In addition to an increased likelihood of developing type 2 diabetes, NAFLD is associated with a higher incidence of chronic kidney disease (CKD), cardiovascular disease (CVD) and certain types of extra-hepatic cancers. Moreover, the presence of concurrent type 2 diabetes further exacerbates the risk of cardiovascular events. These findings underscore the need for healthcare professionals to consider the broader implications of NAFLD and implement appropriate preventive measures and interventions beyond liver health.

The Potential Role of PPAR Gamma Agonists

During his presentation, Professor Byrne dedicated a significant portion of his discussion to the potential benefits of PPAR gamma agonists in the treatment of NAFLD. Specifically, he highlighted the efficacy of pioglitazone, a PPAR gamma agonist, as a promising therapeutic option.

Pioglitazone, a PPAR gamma agonist, has demonstrated notable effects in lowering glucose levels and improving insulin sensitivity. It has also shown favourable outcomes beyond the liver, including a decrease in the incidence of myocardial infarction and stroke. Despite concerns about potential side effects such as weight gain and cardiac failure, when used in carefully selected patients, pioglitazone proves to be an effective and cost-effective cardioprotective drug. Professor Byrne emphasized the importance of considering pioglitazone as a valuable treatment option for NAFLD, particularly in patients without contraindications.

Future Directions and Conclusion

Professor Chris Byrne’s presentation at the Global NASH Congress provided valuable insights into the complexities of NAFLD as a multisystem disease. The interrelationship between NAFLD and type 2 diabetes, the amplified risks of extrahepatic complications, and the potential benefits of PPAR gamma agonists highlighted the need for comprehensive management strategies and early detection in patients with NAFLD, particularly those with concomitant type 2 diabetes. Professor Byrne emphasised the potential for combination therapy with pioglitazone and GLP-1 receptor agonists that already exist as licensed treatments for people with type 2 diabetes. He stressed the potential of future treatments combining incretin receptor agonists with glucagon receptor agonists, that may hold promise in the management of NAFLD.

He mentioned that further research is warranted to unravel the intricacies of the gut-liver axis and to determine the true potential of microbiota modulation in NAFLD treatment. Professor Byrne’s team have investigated the interplay between NAFLD and gut microbiota and whether it is possible to ameliorate liver disease with a synbiotic treatment, designed to change the gut microbiota to have more favourable profile. Abnormal gut microbiota profiles have been observed in individuals with NAFLD, leading to a growing interest in the potential of improving gut microbiota to improve the disease. However, concrete evidence supporting this notion is still lacking. Professor Byrne highlighted a significant 14-month study undertaken by his team (the INSYTE trial) that investigated the effects of synbiotic treatment, a combination of prebiotics and probiotics, on NAFLD. Although the study successfully induced changes in the gut microbiota profile as expected, these alterations did not result in substantial improvements in measures of liver disease in NAFLD. This underscores the complexity of the gut-liver axis and the challenges associated with leveraging microbiota modulation for effective NAFLD treatments.

In conclusion, Professor Byrne stated it is crucial for healthcare professionals to recognize the silent nature of NAFLD and the significant impact it has on various systems and organs within the body. By identifying and addressing NAFLD early in patients with type 2 diabetes, we can mitigate the risks and improve patient outcomes. With continued research, collaboration, and an interdisciplinary approach, we can pave the way for more effective strategies in combating NAFLD and its associated complications.

This article was written by Nick Noakes summarising the presentation given by Chris Byrne, Professor Endocrinology & Metabolism, University of Southampton & Southampton NIHR BRC, University Hospital Southampton