What treatment should be given to a patient with Non-Alcoholic Fatty Liver Disease (NAFLD) and elevated Alanine Transaminase (ALT) levels?

Treatment for NAFLD with ALT 74

Start with aggressive lifestyle modification targeting 7-10% body weight loss through Mediterranean diet and vigorous-intensity exercise, while immediately treating all metabolic comorbidities with statins for dyslipidemia and GLP-1 agonists or SGLT2 inhibitors for diabetes. 1

Immediate Risk Stratification

Before initiating treatment, calculate the FIB-4 score or obtain liver stiffness measurement to determine fibrosis risk, as this guides treatment intensity 1:

• Low risk (FIB-4 <1.3): Lifestyle modifications alone are sufficient 1
• Indeterminate risk (FIB-4 1.3-2.67): Requires hepatology referral for further evaluation 1
• High risk (FIB-4 >2.67): Needs hepatology co-management and consideration of liver biopsy and pharmacotherapy 1

With an ALT of 74, this patient likely has at least moderate inflammation and warrants thorough fibrosis assessment 2.

Core Lifestyle Interventions

Weight Loss Target

Prescribe gradual weight reduction of 7-10% total body weight over 6-12 months, with weight loss not exceeding 0.5-1 kg per week 1, 2. This magnitude of weight loss improves steatosis, inflammation, and potentially fibrosis 3. Weight loss of 3-5% improves steatosis, but 5-10% is needed to reduce hepatic inflammation 2.

Dietary Prescription

Implement a Mediterranean diet pattern emphasizing 1, 2:

• Extra virgin olive oil as the principal fat source
• Abundant vegetables, fruits, whole grains, and legumes
• Minimal red meat and processed foods
• Complete avoidance of fructose-enriched beverages and simple sugars 2
• Replace saturated fats with PUFAs (especially omega-3) and MUFAs 2

The Mediterranean diet reduces liver fat even without weight loss and is superior to other dietary patterns 3, 4.

Exercise Prescription

Prescribe vigorous-intensity exercise (≥6 METs) for at least 150 minutes per week, as moderate-intensity exercise does not improve NASH severity or fibrosis 1, 5. This can be divided into sessions of at least 30 minutes, 5 times weekly 2.

Alcohol Restriction

Restrict all alcohol consumption completely, as even low alcohol intake doubles the risk of adverse liver outcomes in metabolic fatty liver disease 1. Heavy alcohol consumption must be avoided 2.

Management of Metabolic Comorbidities

This is critical as cardiovascular disease is the main driver of mortality in NAFLD patients 6:

• Prescribe statins to treat dyslipidemia according to cardiovascular risk—they are safe in NAFLD and should not be withheld 1, 2
• For diabetes: Use GLP-1 receptor agonists (liraglutide, semaglutide) or SGLT2 inhibitors as first-line therapy, as they improve cardiometabolic profile and reverse steatosis 1
• Treat hypertension aggressively per standard guidelines 2, 6

Medication Review

Discontinue medications that worsen steatosis including corticosteroids, amiodarone, methotrexate, tamoxifen, estrogens, tetracyclines, and valproic acid 2, 6.

Liver-Directed Pharmacotherapy

Pharmacological treatments targeting the liver should be restricted to patients with biopsy-proven NASH and fibrosis, as those without steatohepatitis or fibrosis have excellent prognosis from a hepatic standpoint 1, 5.

If liver biopsy confirms NASH with fibrosis 2:

• Vitamin E 800 IU daily in non-diabetic, non-cirrhotic patients with biopsy-proven NASH 1, 6
• Pioglitazone 30 mg daily in patients with biopsy-proven NASH without cirrhosis, with or without diabetes 1, 6

Critical caveat: These medications have significant side effects. Pioglitazone causes weight gain, increased risk of congestive heart failure, bone fractures, and bladder cancer 2. High-dose vitamin E is linked to increased all-cause mortality, hemorrhagic stroke, and prostate cancer 2.

When to Consider Liver Biopsy

Consider referral for liver biopsy if 2:

• Patient has diabetes and/or metabolic syndrome (risk factors for NASH and advanced fibrosis)
• Findings concerning for cirrhosis (thrombocytopenia, AST>ALT, hypoalbuminemia)
• FIB-4 score or imaging suggests indeterminate or high fibrosis risk 1

Monitoring Protocol

• Low-risk patients: Annual follow-up with repeated non-invasive fibrosis assessment 1
• Intermediate or high-risk patients: Follow every 6 months with liver function tests and non-invasive fibrosis markers 1
• If cirrhosis develops: Right upper quadrant ultrasound every 6 months for HCC screening and EGD screening for esophageal varices 2, 5

Critical Pitfalls to Avoid

• Never pursue rapid weight loss exceeding 1 kg per week, as this can precipitate acute hepatic failure in patients with advanced disease 5
• Do not use metformin as specific treatment for NAFLD histology—it has no significant effect on liver histology despite metabolic benefits 5
• Do not prescribe liver-directed pharmacotherapy without biopsy-proven NASH and fibrosis, as no pharmacotherapy has been approved by regulatory agencies specifically for NAFLD treatment 5
• Do not avoid statins in NAFLD patients—they are safe and should be used to treat dyslipidemia 2, 1