Diabetes and non‐alcoholic fatty liver disease: a bittersweet symphony

The prevalence of non‐alcoholic fatty liver disease (NAFLD) and its more progressive form non‐alcoholic steatohepatitis (NASH)1,2 has increased markedly, both in Australia and overseas, over the past two decades, as has the prevalence of frequently associated conditions such as type 2 diabetes mellitus3 and obesity.4 Further, as the most common condition affecting the liver, NAFLD is rapidly becoming the most frequent indication for liver transplantation and a major risk factor for liver cancer. Nevertheless, few strategies to combat NAFLD or NASH have been developed in Australia or overseas.5 Only limited local data are available regarding the risk factors for progressive liver disease in people with NAFLD and the roles that frequently associated conditions play in its progression.

In this issue of the MJA, O'Beirne and colleagues report a comprehensive and robust data linkage study of factors associated with the progression to decompensated cirrhosis in more than 8000 Queenslanders followed for a median of 4.6 years after index hospitalisations with NAFLD/NASH during 2009–18.6 Their most important finding was that the rate of progression from compensated to decompensated cirrhosis was considerable, a mean of 5.5% per year. The significance of this result cannot be overstated, especially given that the prevalence of NAFLD in Australia has been projected to increase by 25% between 2019 and 2030.1 Moreover, the risk of progression was greater for older people (over 50 years of age); given our ageing population,7 the impact on individual health and the public health system will consequently continue to grow. Decompensated cirrhosis is associated in Australia with higher health care costs and hospital re‐admission rates,8 and moderating the projected increase in its incidence should be an important objective for our health care system.

Another important finding of the study by O'Beirne and colleagues concerned the impact of diabetes mellitus on the progression of NAFLD/NASH. In people without cirrhosis at their index admission, diabetes mellitus was associated with a 2.8‐fold increase in the risk of progression, and the mean rate of progression to decompensated cirrhosis was relatively high at 1.0% per year. The impact of diabetes mellitus was even greater for people with cirrhosis at baseline; the rate of progression to decompensation was 7.1% per year (1.5‐fold greater risk).6 These important local findings not only point to the relative contribution of diabetes mellitus to progression from uncomplicated NAFLD/NASH to decompensated cirrhosis, but also the high risk of disease progression over the coming decades for an increasingly older population.

The study by O'Beirne and colleagues had several limitations associated with retrospective data linkage studies, particularly those based on International Classification of Diseases coding, including possible diagnostic misclassification, as well as incomplete capture of data for factors and other medical conditions that may influence disease progression. However, the authors appropriately attenuated these risks in their detailed analyses. Moreover, the contribution of poor diabetes control to the results could not be established in this type of study, but it is recognised that poorer glycaemic control is associated with increased risk of deteriorating liver histology in people with NAFLD.9

The findings by O'Beirne and his colleagues make clear the importance of both adequately screening for and monitoring diabetes mellitus in people with NAFLD/NASH, as well as proactively managing the disorder. From a public health perspective, their findings highlight the need for a national guideline or approach to NAFLD/NASH screening and management that focuses on identifying people at greatest risk of poor outcomes. The study provides a timely background to the multidisciplinary Australian consensus guidelines for the identification and risk stratification in primary care of people with NAFLD (including those with diabetes mellitus), to be published in 2024, as well as additional information about the potential multiple system impacts of preventive health in the burgeoning group of people at risk of or living with diabetes mellitus.3

Finally, the study by O'Beirne and colleagues indicate that further national data are needed, particularly at the primary care level with regard to the ability to mitigate the identified modifiable risks of progression in people with NAFLD, as well as the need for updated economic modelling of the projected impact of NAFLD/NASH on the health system that includes both liver and non‐liver conditions, such as cardio‐metabolic diseases.