SUMMARY: 

37% of American adults have NAFLD and as many as 70% with T2DM have NAFLD. While usually asymptomatic, NAFLD significantly increases the risk of cardiovascular disease, diabetes and liver disease including cirrhosis and liver cancer. Findings of fatty liver on imaging and/or elevated liver function tests require evaluation for NAFLD. Obese patients, especially those with metabolic issues (hypertension, (pre) diabetes, cardiovascular disease) should all be evaluated for NAFLD.  Evaluation of NAFLD starts with non-invasive blood test monitoring and measuring liver stiffness.  Treatments of NAFLD is multidisciplinary, including weight loss, alcohol evaluation, medications, evaluation and control of metabolic issues, and often referral to hepatologists, cardiologists, endocrinologists, dieticians, and sometimes bariatric surgeons.   

Definitions 

• Nonalcoholic Fatty Liver Disease (NAFLD): General term for anyone with fatty liver 
• Nonalcoholic Steatohepatitis (NASH): Aggressive form of NAFLD, usually fatty liver and elevated liver enzymes
  • Liver biopsy may be needed to confirm this diagnosis 
  • Diagnosis implies minimal alcohol
    • <14 drinks week for women 
    • <21 drinks per week in men 
  • Often NASH may be combined with alcoholic liver disease 
• Liver fibrosis (i.e., liver scarring)
  • Fibrosis correlates with increased risk of cirrhosis 
  • Mild to moderate fibrosis may be reversible 
  • Four stages, from minimal F1 to cirrhosis F4 
• Cirrhosis
  • Liver is scarred  
  • Scarring is rarely reversible 
• Decompensated cirrhosis
  • cirrhosis with any of the following
    • Hepatic encephalopathy 
    • Ascites 
    • Variceal bleeding 
    • Hepatocellular carcinoma 
    • Hepatorenal syndrome 
  • Failing liver may require transplant  

Clinical Presentation 

• Fatty liver found incidentally on liver imaging done for nonliver causes 
• Abnormal LFT’s found on routine lab testing 
• Low platelet count may be first sign of cirrhosis 
• Usually asymptomatic unless evidence of decompensated cirrhosis  
• Physical exam regarding liver is usually normal unless decompensated cirrhosis 

Risk Factors 

• Type 2 diabetes or prediabetes requires screening for NAFLD 
• Patients with at least 2 manifestations of metabolic syndrome
  • Hypertension 
  • dyslipidemia especially high triglycerides and low HDL 
  • central obesity 
  • 2 or more factors require screening for NAFLD 

Evaluation 

History and Physical  

• Examine for signs of cirrhosis 
  • Jaundice 
  • Spider angiomata 
  • Gynecomastia 
  • Hepatosplenomegaly 
  • Caput medusae;  dilated abdominal vein
  • Testicular atrophy
  • Clubbing
  • Dupuytren’s contracture
  • Asterixis with  hepatic encephalopathy 

Labs 

• Routine Labs
  • CBC, complete metabolic profile, lipid profile, TSH, INR, HbA1C  
  • Cardiovascular disease screening  such as stress echo or cardiac ct 
  • Diabetes screening – HgB A1C 
• Screen for other liver diseases
  • HCV antibody | HCV RNA
  • HbsAg, HBsAb, HBcAb
  • Autoimmune panel: Antinuclear antibody, Antimitochondrial antibodies (AMA), immunoglobulin IGG 
  • Ferritin | Alpha 1 antitrypsin 
  • CRP, CRP, Anti smooth muscle Ab, Anti mitochondrial antibodies 
• FIB-4: Estimate amount of liver scarring fibrosis
  • Most popular noninvasive blood test for liver fibrosis 
  • Requires age, AST, ALT, platelet count 

Imaging 

• Routine: Liver ultrasound 
• Liver stiffness measurement (LSM) via transient elastography (FibroScan)
  • Best screening imaging test for fibrosis | Based on FIB-4 Score
    • Fib-4 <1.3: Not needed  
    • FIB-4 of 1.3 to 2.67: Needed  
    • Fib-4 >2.67: Consider FibroScan  
  • LSM risk assessment
    • <8 kPa: Low risk for liver fibrosis 
    • 8 to 12 kPa: Indeterminate risk for significant liver fibrosis 
    • >12 kPa: High risk for advanced fibrosis/cirrhosis 

Additional Studies  

• Typically ordered by hepatologist
  • Liver biopsy 
  • Magnetic Resonance Elastography (MRE) may be needed  

Screen for Alcohol Use and Abuse  

• The Alcohol Use Disorders Identification Test (AUDIT) 10-item screening tool developed by WHO (see ‘Learn More – Primary Sources’ below)  

or 

• CAGE Screening Tool    

Treatment 

Lifestyle Guidance 

• Exercise  
• Mediterranean diet 
• Avoid all alcohol if indeterminant to high-risk fibrosis 
• If overweight
  • Advise structured weight loss plan 
  • Consider anti-obesity medication 
  • Consider bariatric surgery 

Medications  

• There are no FDA approved medications for NAFLD | Consider medication for indeterminant or significant fibrosis 
  • NASH w/o T2D and no cirrhosis: Vitamin E 800 IU daily 
  • Diabetics and NASH: Consider Semaglutide
    • Once a week 0.25 mg weekly subQ for 1 month, then increase to 0.5 mg subQ once a week (Ozempic) 
    • 3 mg po once a day for 1 month, then increase to 7 mg po once a day (Rybelsus) 
  • NASH with or without diabetes consider Pioglitazone (Actos) 15 to 30 mg po once daily 
  • Obesity and NASH: Consider Liraglutide (Saxenda) or Semaglutide (Wegovy), both FDA approved for weight loss (not FDA approved for liver disease) 
  • Liraglutide (Saxenda) is given subQ daily, Semaglutide (Wegovy) is given Subq weekly, both require starting at low dose and increasing slowly to therapeutic dose | Both very expensive with potential side effects especially nausea, vomiting, diarrhea 
• Do NOT combine liraglutide with semaglutide 

KEY POINTS:  

• Liver fibrosis is the most important determination of the significance of NAFLD 
• NAFLD significantly increases risk of cardiovascular disease 
• 11% of patients with fatty liver are at risk for advanced liver fibrosis 
• Elevated LFTs + fatty liver = higher risk of liver fibrosis 
• Statins
  • If indicated, should be given  
  • No contraindication if LFTs are abnormal from NAFLD 
  • Soluble statins (simvastatin, atorvastatin) reduce risk of liver decompensation 
  • Contraindicated in decompensated cirrhosis 
• Specialist Referrals 
  • Hepatologist if indeterminant or advanced fibrosis 
  • Endocrinologist may be indicated for (pre)diabetes control 
  • Cardiologist for screening for cardiovascular disease 
  • Bariatric surgery consultation if indicated 
  • Liver cancer screening every 6 months if advanced fibrosis/cirrhosis

Quick Links 

FIB-4 Calculator 

CAGE Screening Tool Calculator 

LEARN MORE – Primary sources 

Clinical Care Pathway for the Risk Stratification and Management of Patients with Nonalcoholic Fatty Liver Disease

The Alcohol Use Disorders Identification Test (AUDIT) is a 10-item screening tool developed by the World Health Organization