Epidemiology & Risk Factors
- #1 cause of chronic liver disease in the US.
- Core driver: Insulin resistance (causes ↑ peripheral lipolysis → hepatic FFA accumulation).
- Key associations (Metabolic Syndrome): c
- Obesity (central/visceral).
- DM2 / Impaired fasting glucose.
- Dyslipidemia (high TGs, low HDL).
- HTN.
Clinical Features
- History:
- Asymptomatic (> 90%); detected via incidental lab/imaging abnormalities.
- Vague fatigue or dull RUQ fullness.
- Physical Examination:
- Hepatomegaly (smooth, non-tender).
- Acanthosis nigricans (marker of insulin resistance).
- Stigmata of cirrhosis if advanced (spider angiomas, palmar erythema, ascites).
Diagnosis
- Initial Test: Abdominal US (diffusely hyperechoic / “bright” liver).
- Key Labs:
- Transaminases: Mild ↑, ALT > AST (AST/ALT ratio < 1; ratio flips to > 1 if cirrhosis develops). c
- Exclusion of secondary causes (Mandatory): Negative viral serologies (HBV/HCV), negligible EtOH intake (< 20–30 g/day), normal transferrin saturation (< 45%).
- Fibrosis Risk Stratification:
- Non-invasive: FIB-4 score → follow with Transient Elastography (FibroScan) to assess stiffness.
- Gold Standard:
- Liver Biopsy: Differentiates steatosis from steatohepatitis (MASH).
- Reserved for diagnostic uncertainty or indeterminate fibrosis risk.
- Histology: Macrovesicular steatosis, hepatocyte ballooning, Mallory-Denk bodies.
Mnemonic
There is more ALT than AST (AST/ALT < 1) if the Liver is infiltrated with Lipids.
Differential Diagnostics
- Alcohol-Associated Liver Disease (ALD):
- Diff by significant EtOH history and AST:ALT ratio ≥ 2:1.
- Autoimmune Hepatitis (AIH):
- Diff by female predominance, hypergammaglobulinemia, and (+) ANA / ASMA.
- Hereditary Hemochromatosis:
- Diff by transferrin sat > 45%, ferritin > 1000 ng/mL, HFE mutation, and bronze hyperpigmentation.
- Chronic Viral Hepatitis (HBV/HCV):
- Diff by (+) HBsAg or (+) anti-HCV / HCV RNA.
- Wilson Disease:
- Diff by age < 40, neuropsychiatric signs, Kayser-Fleischer rings, and low ceruloplasmin.
Management
- First-Line (Lifestyle & Risk Factors):
- Weight loss (7–10%) via hypocaloric diet + aerobic exercise (reverses steatosis/fibrosis).
- Aggressive CV risk control: Statins are safe and indicated for dyslipidemia; strict glycemic control.
- Second-Line (Pharmacotherapy for MASH / Fibrosis):
- GLP-1 RAs (e.g., semaglutide) or Pioglitazone (preferred if concurrent DM2/obesity).
- Vitamin E: Improves histology in non-diabetic pts with biopsy-proven MASH.
- Resmetirom: Approved for non-cirrhotic MASH with moderate-to-advanced fibrosis (F2–F3).
- Refractory / End-Stage:
- Bariatric surgery: For refractory obesity (BMI ≥ 35 kg/m²).
- Liver Transplantation: Indicated for decompensated cirrhosis.
Complications
- Cardiovascular Disease (CVD): #1 cause of death in MASLD pts (not liver failure).
- Cirrhosis & Portal HTN: Ascites, varices, hepatic encephalopathy.
- Hepatocellular Carcinoma (HCC):
- Risk is elevated and can occur without cirrhosis.
- Cirrhotic pts require screening: RUQ US ± AFP every 6 months.