An overview of diabetes and fatty liver disease

At the recent Diabetes Malaysia Conference 2025, Professor Dr Chan Wah Keong, a consultant gastroenterologist and hepatologist, gave an overview of fatty liver disease. Chan, from Universiti Malaya Medical Centre, covered topics such as nomenclature of fatty liver disease, its impact in Malaysia, management strategies and emerging treatments.

What Is fatty liver disease?

Fatty liver disease is a condition where excess fat accumulates in liver cells. It is now more accurately described as metabolic dysfunction-associated fatty liver disease (MAFLD), or metabolic dysfunction-associated steatotic liver disease (MASLD) under newer international naming systems. Both names reflect its close link to metabolic risk factors, especially type 2 diabetes, obesity, and high blood pressure.

Even those with only one metabolic risk factor can have significant liver involvement, noted Chan.

A bigger threat than expected
The National Health and Morbidity Survey 2023 found that 28.2 percent of Malaysian adults have fatty liver, based on a non-invasive index. This is likely an underestimation, and the true prevalence is probably higher. About 10 percent of these individuals may have advanced liver fibrosis.

The situation is serious as fatty liver can progress silently. In severe cases, it leads to steatohepatitis, fibrosis, cirrhosis, and subsequently liver cancer (hepatocellular carcinoma).

Patients with advanced fibrosis are most at risk of developing cancer. Long-term data show that only those with stage F3-F4 fibrosis developed liver-related complications. Cirrhosis carries the highest risk of liver failure and cancer. However, the leading cause of death in these patients is cardiovascular disease.

Clinical impact of fatty liver disease in Malaysia

Recent hospital data show fatty liver is now a leading cause of liver-related admissions and cirrhosis. The proportion of liver cancer cases linked to fatty liver is rising and, in many centres, fatty liver now surpasses hepatitis B as the cause of liver cancer. [Available at https://tinyurl.com/38pw2xte Accessed on 5 August 2025]

Management strategies

Management strategies for fatty liver disease include lifestyle Intervention and control of metabolic risk factors. The foundation of management is lifestyle change i.e., weight loss of at least 10 percent as it improves fat content, inflammation, and fibrosis. Chan noted even a 3-5 percent weight loss shows benefits as proven through magnetic resonance imaging (MRI) and liver biopsy studies.

As for control of metabolic risk factors, these include achieving LDL-cholesterol targets, maintaining blood pressure control, ensuring good glycaemic control and smoking cessation.

Identify high-risk patients for referral

Chan said not all patients with fatty liver need referral. It is better to focus on those with possible advanced fibrosis. These high-risk patients can be screened using the fibrosis-4 (FIB-4) score using age, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and platelet count. The cut-off score is 1.3 and 2.0, for patients aged <65 and ≥65, respectively. A high score suggests advanced fibrosis.

Alternatively, transient elastography (FibroScan) can also be used but cost and availability are an issue. Readings of <10 kPa suggest advanced fibrosis is unlikely. Readings of 10-15 kPa suggest possible advanced fibrosis and a reading of >15 kPa means advanced fibrosis or cirrhosis is likely. Patients with scores above the thresholds should be referred to a specialist.

Patients with type 2 diabetes mellitus are at high risk of fatty liver disease. [Diabetes Metab J 2020;44(3):382-401] Liver biopsy studies show over 70 percent have fatty liver and over 20 percent have advanced fibrosis. Additionally, diabetes is an independent risk factor for fibrosis and inflammation. Routine liver assessment including, ALT, AST, and FIB-4, should be part of diabetes care.

Some patients may already have cirrhosis but appear clinically stable. For these patients, the use of non-invasive tests can be used to identify compensated advanced chronic liver disease (cACLD) or portal hypertension (platelet <150,000 uL, FibroScan >20-25 kPa). In such patients, endoscopy may be avoided if certain non-invasive criteria are met.

Treatment options

At present, no drug has been fully approved for fatty liver in Malaysia yet, but trials are ongoing. Some promising candidates include semaglutide (glucagon-like peptide-1, GLP-1 receptor agonist), which improves inflammation and may reduce fibrosis; resmetirom, already approved by the US FDA, which has been shown to improve fibrosis and liver fat; dual agonists like tirzepatide and survodutide are demonstrating strong effects in phase 2 trials; and early data on fibroblast growth factor 21 (FGF21) analogues suggests potential fibrosis reversal even in those with cirrhosis.[J Hepatol 2024;81(3):562-576]

For now, lifestyle change remains first-line. Medications may soon offer additional options for selected patients.

Managing fatty liver in primary care
GPs can order routine liver enzyme checks for high-risk patients and use the FIB-4 to screen for fibrosis. Only those with elevated risk need referral to specialists. Others may be managed via diet, exercise, and weight loss. Additionally, it is important to optimise diabetes, cholesterol, and blood pressure control in these patients.

Key Takeaways

• Fatty liver is common and often overlooked. It carries significant risk when tied to diabetes and metabolic syndrome. Early detection and lifestyle change can prevent progression.

• Non-invasive tools allow effective screening in primary care. Only a minority need specialist referral.

• New therapies are emerging, but lifestyle remains the foundation.

• Fatty liver disease is no longer just a liver issue. It is a marker of systemic risk that must be addressed across all levels of care.