Chinese Medical Journal review highlights advances in the treatment of metabolic dysfunction-associated fatty liver disease

The worldwide prevalence of lifestyle disorders has increased significantly over the past few decades owing to modern fast-paced lives. This frequently affects the liver and given the organ’s central role in biosynthesis and detoxification, liver dysfunction is associated with a broader spectrum of long-term disorders. The liver plays a key role in fat metabolism. Build-up of excess fat is therefore a frequent cause of liver damage and associated complications. Insulin resistance—a condition in which the body’s cells are less sensitive to insulin, which subsequently results in hyperglycemia, diabetes mellitus, and further metabolic problems—adds to the woes.

For the longest time, “non-alcoholic fatty liver disease (NAFLD)” has been used as an umbrella term encompassing a range of conditions caused by excess fat accumulation in the liver in the absence of alcohol consumption. However, mounting evidence now suggests that NAFLD is strongly associated with certain comorbidities like diabetes, obesity, metabolic dysfunction, and cardiovascular diseases. Lifestyle factors, environmental insults, and genetic predisposition also contribute to disease progression. Given the multi-factorial etiology of NAFLD, the novel comprehensive term “metabolic dysfunction-associated fatty liver disease (MAFLD),” was recently proposed to account for the heterogeneity of liver diseases as well as their association with other metabolic disorders. While this definition helps with a more precise and accurate diagnosis, a specific treatment strategy for MAFLD is lacking. Currently, studies suggest that only 20% to 40% of patients with the condition respond to pharmacological treatment; effective management of MAFLD, thus, continues to remain a challenge.

A review article made available online on 28 February 2022, and published in Volume 135 Issue 9 of the Chinese Medical Journal on 5 May 2022 has attempted to shed light on the current advances and future perspectives in the treatment of MAFLD. Prof. Jiangao Fan of the Shanghai Jiao Tong University School of Medicine, China, the corresponding author of the article, says, “In terms of health burden management, screening patients with a high risk of MAFLD and providing them with individual comprehensive treatment is critical. Although there are numerous agents entering clinical trials for MAFLD treatment every year, there is still no effective approved drug, especially for those with steatohepatitis,” In this context, the article certainly seems timely.

And the insights it offers on MAFLD are valuable. It argues that a multi-pronged treatment approach combining lifestyle modifications and pharmaceutical therapeutics is favorable to treat the condition since patients with MAFLD are diagnosed with a fatty liver along with type-2 diabetes, obesity, or cardio-metabolic risk factors. Lifestyle interventions can help slow down disease progression and decrease the risk of multi-organ dysfunction. For example, losing weight and giving up smoking and alcohol consumption have been shown to improve liver fibrosis, a condition that develops after fat accumulation in the liver, as FLD progresses to end-stage liver disease or cirrhosis. To this end, obese individuals can benefit from a calorie-restricted diet with lesser saturated fats along with adequate physical activity. In morbidly obese individuals, bariatric surgery, which helps people reduce weight by modifying the volume of their stomach, food intake capacity, and eating behavior, may be another promising alternative to achieve weight loss, thereby improving MAFLD symptoms.

Apart from obesity, in patients with MAFLD, diabetes increases the risk of adverse hepatic and cardiovascular outcomes. Medicines that control blood sugar levels have been shown to improve certain MAFLD features and may therefore be worth pursuing as a potential treatment strategy. In patients with MAFLD and diabetes, hypertension is also a frequent manifestation. Statins and other anti-hypertensive agents may help reduce the overall risk of complications in such cases.

Apart from underscoring the benefits of treatments targeting obesity and diabetes for patients with MAFLD, the review also highlights the use of metabolic regulators as biomarkers and therapeutic targets. It suggests, besides controlling the dietary intake of fat, exercising pharmacological control over lipid metabolism can also serve as an effective treatment strategy for improving liver damage.

Overall, given how diverse the pathogenesis and clinical presentation of MAFLD could be, the article strongly suggests adopting a comprehensive approach is crucial for accurate and patient-specific diagnosis and treatment of this condition. Prof. Fan concludes by saying, “Given the paucity of direct therapies, combining lifestyle modifications and pharmaceutical interventions, as discussed in our review, may serve as a more effective means of decreasing the risk of disease progression in patients with MAFLD.”

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Reference

DOI: https://doi.org/10.1097/CM9.0000000000002091