Diagnostics

• Liver chemistries

  • Transaminases: ↑ ALT and AST

    • ALT > AST: present in most liver diseases (e.g., NAFLD, viral hepatitis)

    • AST > ALT: indicative of alcoholic liver disease and/or cirrhosis of any etiology

    • Massive AST and/or ALT elevation (> 15 times ULN): Consider differential diagnoses (e.g., acetaminophen toxicity, acute viral hepatitis, autoimmune hepatitis).

  • ↑ Bilirubin (may be normal initially)

  • ↑ ALP

  • ↑ Gamma‑glutamyl transferase (GGT)

• Coagulation studies: ↑ prothrombin time (↑ INR) because of decreased production of coagulation factors

• CBC

  • Thrombocytopenia: due to decreased thrombopoietin production by the liver and/or splenomegaly [13]

  • Anemia: multiple potential causes, e.g., chronic blood loss, splenic sequestration, vitamin B12 or folic acid deficiency

  • Leukopenia

• CMP

  • ↓ Albumin

  • ↓ Total protein

  • Hyponatremia

Liver chemistries may be normal in early compensated cirrhosis. [11]

Some CBC abnormalities are due to the combination of increased hepatic and splenic sequestration of thrombocytes (portal hypertension leads to splenomegaly with hypersplenism) and decreased production of hematopoietic factors by the liver.

Hepatocyte injury: ↑ AST, ALT, ALP, GGT. Synthetic dysfunction: ↑ bilirubin and PT/INR; ↓ albumin and platelets

• Viral hepatitis: especially in patients with risk factors

  • Hepatitis B and hepatitis C: HBsAg, IgM anti-HBc, anti-HCV

  • Hepatitis A and hepatitis E: IgM HAV, IgM HEV

• NASH: fasting lipid levels and HbA1c

• Hemochromatosis: serum iron, ferritin, transferrin saturation

• Autoimmune hepatitis: total IgG or serum electrophoresis (showing hypergammaglobulinemia), ANA, ASMA, anti-LKM-1 antibody, anti-soluble liver antigen antibody

• Alpha-1 antitrypsin deficiency: alpha-1 antitrypsin level and phenotype

• Wilson disease: serum ceruloplasmin, serum total and free copper, urinary copper

• Primary biliary cholangitis: antimitochondrial antibodies (AMA or AMA-M2), ALP, bilirubin

• Primary sclerosing cholangitis: cholestasis parameters (GGT, ALP, and bilirubin), pANCA, IgG

• Other tests [17][18]

  • Ammonia (not routinely indicated) [18]

  • Plasma cholinesterase

  • Serum protein electrophoresis

Abdominal ultrasound with Doppler Indications

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  • Suspected cirrhosis: best initial test

  • Established cirrhosis: for HCC screening and detecting complications

• Findings

  • Liver form and structure

    • Nodular liver surface

    • Atrophy of the right lobe

    • Loss of structural homogeneity (hyperechoic or variable increase in echogenicity) with fibrous septa

  • Liver size

    • Initially enlarged

    • Atrophies and shrinks with disease progression

    • Hypertrophy of the caudate lobe and left lobe

    • Atrophy of segment IV

  • Other possible findings

    • Changes in liver vasculature

    • Complications of portal hypertension: ascites, splenomegaly, portal vein thrombosis (PVT), increased portosystemic collateral flow

• Indication: patients in whom adequate assessment with ultrasound is not possible (e.g., because of obesity)

• Findings: similar to those on ultrasound

  • Relative hypertrophy of the left lobe and caudate lobe

  • Regenerative nodules

  • Irregular liver surface

  • Indirect findings: ascites, splenomegaly, portosystemic collaterals

• In cases of diagnostic uncertainty (gold standard)

• Grading and staging of inflammation and fibrosis

• Monitoring treatment response (e.g., in autoimmune hepatitis)

• Evaluation of focal lesions

• Screening for esophageal varices: EGD at time of diagnosis and every 1–3 years depending on the presence and size of the varices on initial screening

• HCC screening: abdominal ultrasound every 6 months