What are the liver function test (LFT) derangements associated with steatotic liver disease?

From the Guidelines

Steatotic liver disease, also known as fatty liver disease, can lead to derangement in liver function tests (LFTs), and management involves lifestyle modifications as the primary approach, with a focus on weight loss, dietary changes, and physical exercise, as recommended by the EASL-EASD-EASO clinical practice guidelines 1. The primary goal in managing steatotic liver disease is to reduce liver fat and inflammation, thereby preventing progression to more severe forms of the disease, such as non-alcoholic steatohepatitis (NASH) and cirrhosis.

• Weight loss of 7-10% through a balanced diet and regular exercise is recommended, as it has been shown to improve liver function and reduce liver fat 1.
• Limiting alcohol consumption and avoiding hepatotoxic medications are also crucial in managing steatotic liver disease, as they can exacerbate liver damage and inflammation.
• A Mediterranean diet rich in fruits, vegetables, whole grains, and healthy fats is beneficial, as it has been shown to improve liver function and reduce liver fat 1. Some key points to consider in managing steatotic liver disease include:
• Regular monitoring of LFTs every 3-6 months to track disease progression, as recommended by the EASL-EASD-EASO clinical practice guidelines 1.
• The LFT derangement typically shows elevated ALT and AST (with AST/ALT ratio <1 in early stages), and possibly elevated GGT, which can indicate liver damage and inflammation.
• If LFTs continue to worsen despite interventions, referral to a hepatologist is warranted for further evaluation and possible liver biopsy, as recommended by the EASL-EASD-EASO clinical practice guidelines 1. It is essential to note that the management of steatotic liver disease should be individualized, taking into account the patient's underlying medical conditions, such as diabetes and obesity, and the presence of other cardiometabolic risk factors, as recommended by the EASL-EASD-EASO clinical practice guidelines 1.
• The use of incretin-based therapies, such as semaglutide and tirzepatide, may be beneficial in managing steatotic liver disease, particularly in patients with type 2 diabetes or obesity, as recommended by the EASL-EASD-EASO clinical practice guidelines 1.
• Bariatric surgery may also be considered in patients with steatotic liver disease and obesity, as it has been shown to improve liver function and reduce liver fat, as recommended by the EASL-EASD-EASO clinical practice guidelines 1.

From the Research

Steatotic Liver Disease and LFT Derangement

• Steatotic liver disease is characterized by abnormal lipid accumulation in the liver, and it encompasses various conditions, including metabolic dysfunction-associated steatotic liver disease (MASLD) and alcohol-related liver disease (ALD) 2.
• The disease affects around 30% of the global population and is mainly driven by obesity, type 2 diabetes, and alcohol intake 2.
• Liver function tests (LFTs) are often deranged in patients with steatotic liver disease, and the presence and progression of liver fibrosis led by hepatic inflammation is the main predictor of liver-related death across the entire spectrum of steatotic liver diseases 2.

Diagnosis and Management

• Early detection of liver fibrosis is crucial, and a combination of widely available biomarkers and therapeutic interventions can help reduce morbidity and mortality in patients with steatotic liver disease 2.
• Vitamin E and pioglitazone have shown beneficial effects in improving liver histology, liver markers, and lipid profile in patients with non-alcoholic fatty liver disease (NAFLD) 3.
• Vitamin E has been found to improve serum markers and histology in adults with metabolic dysfunction-associated steatotic liver disease (MASLD), including reduction of serum ALT and AST levels, steatosis, lobular inflammation, and hepatocyte ballooning 4.

Screening Guidelines and Management

• Screening for metabolic dysfunction-associated steatotic liver disease is recommended for patients at risk for significant liver fibrosis in primary care and endocrine settings 5.
• Primary care physicians should identify appropriate patients for screening, select suitable screening modalities, and determine when referral to specialty care is necessary 5.
• Management of metabolic comorbidities and changes in nomenclature should be taken into account when managing patients with steatotic liver disease 5.

Therapeutic Targets and Pipeline

• The therapeutic pipeline for MASLD is expanding rapidly, and several pharmacotherapeutics are being developed, including resmetirom, which has been recently approved by the FDA 6.
• Combination therapies and repurposing existing and approved drugs are being explored as potential treatment options for steatotic liver disease 6.
• Further research is needed to validate the efficacy of these therapeutic approaches and to develop novel therapeutic strategies for the management of steatotic liver disease 6.