Nonalcoholic fatty liver disease (NAFLD)
Definition
Hepatic steatosis - Excessive fat accumulation in liver (intracellular fat in >5% hepatocytes)
Nonalcoholic fatty liver disease (NAFLD) – Hepatic steatosis present in the absence of other causes of steatosis (eg. alcohol)
Nonalcoholic steatohepatitis (NASH)- Hepatic steatosis with hepatic injury/inflammation on biopsy
Cirrhosis develops when simple steatosis -> steatohepatitis -> fibrosis
Hepatocellular carcinoma (HCC) is associated with cirrhosis due to NAFLD (2.4-12.8% over three years)
Risk factors for progression
Obesity
DM2
Dyslipidemia
Metabolic syndrome (BP, fasting glucose, HDL, TG, waist circumference)
ALT and AST > 2 ULN
Note: Coffee consumption associated with lower risk of progression
DDx of secondary hepatic steatosis
Macrovesicular steatosis
Alcohol consumption
Hepatitis C
Wilson’s disease
Lipodystrophy
Starvation
Parenteral nutrition
Abetalipoproteinemia
Medications (e.g., amiodarone, methotrexate, tamoxifen, corticosteroids)
Microvesicular steatosis
Reye’s syndrome
Medications (valproate, anti-retroviral medicines)
Acute fatty liver of pregnancy
HELLP syndrome
Inborn errors of metabolism (e.g., LCAT deficiency, cholesterol ester storage disease, Wolman disease)
Investigations
Alcohol intake
Medication review and history of steatosis-associated drugs
Person and family history of diabetes, hypertension, cardiovascular disease, cirrhosis
BMI, waist circumference, body weight change
Labs
CBC (platelets)
AST, ALT, Alk phos, Bilirubin
Albumin
HBsAg, Anti-HCV Ab
Ferritin, iron
Fasting glucose, A1C
Lipid panel
INR
Consider additional testing in patients with abnormal liver tests or family history of cirrhosis
ANA, anti-SM, anti-LKM
Other: a-1 antitrypsin, ceruloplasmin, anti-TTG/IgA, TSH
Imaging
Ultrasound first-line
May consider MRI/CT
Management
Exercise and Weight loss
Avoid alcohol consumption
Diet - Calorie-restricted (aim 1kg/week)
Consider referral to dietician
May consider Orlistat if fail lifestyle intervention and BMI>30, only continue if >5% weight loss in 3 months (max one year to avoid risk of Vitamin deficiency)
Benefit of bariatric surgery in NASH unclear
Hepatitis A and B vaccination if no serologic evidence of immunity
Pneumoccocal vaccine and age-appropriate vaccine
Treat comorbid conditions, such as diabetes, hyperlipidemia, hypertension, or sleep apnea
Statins are not contraindicated (not at increased risk of hepatotoxicity)
Calculate risk score
If FIB-4>1.30 (or Fibrosis Score ≥ F2), consider referral for fibroscan
If low, consider recalculate score q2-5 years
Indications for additional investigation (Biopsy vs. Fibroscan)
Peripheral stigmata of chronic liver disease (suggestive of cirrhosis)
Splenomegaly (suggestive of cirrhosis)
Cytopenias (suggestive of cirrhosis)
Serum ferritin >1.5 times the upper limit of normal (suggestive of NASH and advanced fibrosis)
>45 years of age with associated obesity or diabetes (increased risk of advanced fibrosis)
Other:
ALT:AST >1
ALT/AST elevated > 6 months
Management of Biopsy-Proven NASH
Medications if biopsy-proven pre-cirrhotic NASH who failed lifestyle
May consider Vitamin E 800 units/day in non-diabetic
Risk of hemorrhagic stroke, prostate cancer
Thiazolidinediones: Pioglitazone 30mg/day
Risk of weight gain, CHF, bladder CA, osteoporosis
NASH Cirrhosis should undergo HCC screening with serial ultrasound q6 months and endoscopy for varices screening
References:
Obes Facts 2016. https://www.karger.com/Article/Fulltext/443344
BMJ 2014. http://fg.bmj.com/content/flgastro/5/4/277.full.pdf
AAFP 2013. https://www.aafp.org/afp/2013/0701/p35.html
AASLD/ACG/AGA 2012. https://www.nature.com/articles/ajg2012128.pdf