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Metabolic Dysfunction–Associated Steatotic Liver Disease

Metabolic dysfunction–associated steatotic liver disease (MASLD), formerly non-alcoholic fatty liver disease (NAFLD), is a chronic liver condition characterised by excessive fat buildup in the liver along with at least one metabolic risk factor. It is distinguished from alcohol-related liver disease by the absence or minimal presence of alcohol intake.

Stages of metabolic dysfunction–associated steatotic liver disease, progressing from healthy, to steatosis (fat accumulation), inflammation, fibrosis and cirrhosis.
Stages of metabolic dysfunction–associated steatotic liver disease, progressing from healthy, to steatosis (fat accumulation), inflammation, fibrosis and cirrhosis.

Signs and Symptoms

MASLD is often asymptomatic in its early stages, making early diagnosis challenging. As the disease progresses, symptoms may include fatigue, digestive issues, and deposits of cholesterol on the eyelids. Advanced stages may lead to liver cirrhosis, liver failure, and cardiovascular diseases.

Comorbidities

MASLD is strongly associated with type 2 diabetes, insulin resistance, and metabolic syndrome. Other associated conditions include hormonal disorders, persistently elevated transaminases, and obstructive sleep apnoea. Individuals with lean MASLD tend to have impaired insulin sensitivity and increased cardiovascular disease risk.

Risk Factors

Genetics

Genetic predispositions play a significant role in MASLD, with variations in genes like PNPLA3 and TM6SF2 being associated with the disease. Familial history of diabetes type 2 often correlates with MASLD, particularly among Asian and Hispanic populations.

Diet and Lifestyle

Overnutrition, particularly diets high in omega-6 fatty acids and fructose, increases the risk of MASLD. Habitual snoring, indicating possible obstructive sleep apnoea, can also be a contributing factor.

Pathophysiology

MASLD is characterised by the accumulation of triglycerides in the liver, leading to steatosis. Possible mechanisms include oxidative stress, hormonal imbalances, and mitochondrial abnormalities. Insulin resistance exacerbates the condition by promoting free fatty acid release and de novo lipogenesis. Dysbiosis, or disruptions in the gut microbiota, is also implicated in MASLD progression.

Mallory-Denk body
Mallory-Denk body
Ballooning degeneration
Ballooning degeneration

Diagnosis

Blood Tests

Blood tests like liver function tests, erythrocyte sedimentation rate, serum glucose, and albumin levels can indicate MASLD. However, these are often complemented by imaging techniques for a more accurate diagnosis.

Imaging

Ultrasound and MRI are commonly used to diagnose steatosis. Transient elastography and magnetic resonance elastography are effective for staging liver fibrosis.

MRI of a healthy liver (top row) and one with severe steatosis (bottom row)
MRI of a healthy liver (top row) and one with severe steatosis (bottom row)

Liver Biopsy

Liver biopsy remains the gold standard for diagnosing MASLD and assessing the stage of fibrosis and inflammation.

A small quantity of tissue is sampled from the liver when doing a biopsy, which is then examined under a microscope
A small quantity of tissue is sampled from the liver when doing a biopsy, which is then examined under a microscope
Micrograph of non-alcoholic fatty liver disease, demonstrating marked steatosis (fat in liver cells appears white; connective tissue, blue). Trichrome stain
Micrograph of non-alcoholic fatty liver disease, demonstrating marked steatosis (fat in liver cells appears white; connective tissue, blue). Trichrome stain

Management

Lifestyle

Weight loss through diet and exercise is the most effective treatment for MASLD. A structured weight loss programme shows significant improvements in liver health. A Mediterranean diet and avoiding fructose-rich foods are recommended.

Medication

Medications like pioglitazone, GLP-1 agonists, and SGLT-2 inhibitors have shown promise in treating MASLD. Statins are recommended for cardiovascular protection. Omega-3 fatty acids may improve blood lipid profiles but are not conclusive in improving liver histology.

Surgery

Bariatric surgery is effective for severely obese individuals with MASLD, improving or resolving the liver condition in many cases. Preoperative weight loss is recommended to reduce liver volume and operative risks.

For severely obese individuals with MASLD or NASH, bariatric surgery improves or cures the liver disease if there is no cirrhosis nor liver cancer.
For severely obese individuals with MASLD or NASH, bariatric surgery improves or cures the liver disease if there is no cirrhosis nor liver cancer.

Screening

Regular cardiovascular screening is essential due to the high risk of cardiovascular complications. For those with cirrhotic NASH, screening for gastric and esophageal varices and liver cancer is recommended. Liver biopsies may be necessary for monitoring disease progression post-transplantation.

Prognosis

The progression rate of MASLD varies, with fibrosis and obesity being significant predictors of poorer outcomes. Cardiovascular diseases remain the leading cause of death among MASLD patients.

Non-alcoholic fatty liver disease prevalence in 2019
Non-alcoholic fatty liver disease prevalence in 2019

Epidemiology

MASLD is the most common liver disorder globally, with prevalence rates varying from 9% to 36.9% across different regions. It is particularly prevalent in developed countries and among obese and diabetic individuals. The incidence is rising, making it a significant public health concern.


Self-assessment MCQs (single best answer)

What characterises metabolic dysfunction–associated steatotic liver disease (MASLD)?



Which of the following is NOT a common symptom of MASLD in its early stages?



Which gene variation is associated with the development of MASLD?



What is considered the "gold standard" for diagnosing MASLD and assessing the stage of fibrosis and inflammation?



Which lifestyle modification is recommended as the most effective treatment for MASLD?



Which medication has shown promise in treating MASLD?



Which factor is NOT a significant predictor of poorer outcomes in MASLD?



In which population is MASLD particularly prevalent?



Which dietary component is recommended to be avoided to manage MASLD?



What type of surgery is effective for severely obese individuals with MASLD?



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