Pocket Medicine

GASTROENTEROLOGY

ABNORMAL LIVER TESTS

Tests of hepatocellular injury or cholestasis

•  Aminotransferases (AST, ALT): intracellular enzymes released 2° necrosis/inflammation

ALT more specific for liver than is AST (heart, skeletal muscle, kidney, brain, RBC/WBC)

ALT > AST → viral hepatitis or fatty liver/nonalcoholic steatohepatitis (precirrhotic)

AST: ALT >2:1 → alcoholic hepatitis, cirrhosis; nonhepatic source

ALT/AST >15× ULN → etiologies of acute liver failure (↑↑↑ LDH → ischemia/toxic)

•  Alkaline phosphatase (AΦ): enzyme bound in hepatic canicular membrane

besides liver, also found in bone, intestines, kidney and placenta

confirm liver origin with: ↑ 5′-NT, ↑ GGT or AΦ heat fractionation

↑ levels seen with biliary obstruction or intrahepatic cholestasis (eg, hepatic infiltration)

Tests of hepatic function

•  Albumin: marker for liver protein synthesis, ↓ slowly in liver failure (t1/2 ~20 d)

•  Prothrombin time (PT): depends on synthesis of coag factors by liver (except FVIII); b/c t1/2 of some factors (eg, V, VII) is short, ↑ PT can occur w/in hrs of liver dysfxn

•  Bilirubin: product of heme metab (unconjugated, “indirect”) carried by alb to liver where taken up for conjugation (“direct”) to make soluble, then excreted into bile; most sensitive test to detect parenchymal disease; in those w/ normal LFTs, high nl Tbili (? marker of ↑ heme oxygenase) a/w ↓ resp disease & death (JAMA 2011;305:691)

Patterns of liver injury

•  Hepatocellular: ↑↑ aminotransferases, ± ↑ bilirubin or AΦ

↑↑↑ ALT & AST (>1000): severe viral hepatitis, drugs, ischemia, Wilson’s, AIH

•  Cholestasis: ↑↑ AΦ and bilirubin, ± ↑ aminotransferases

•  Isolated hyperbilirubinemia: ↑↑ bilirubin (direct or indirect), nl AΦ and aminotransferases

•  Infiltrative: ↑ AΦ, ± ↑ bilirubin or aminotransferases

•  Jaundice is a clinical sign seen when bilirubin >2.5 mg/dL (esp. in sclera or under

tongue); if hyperbilirubinemia conjugated → ↑ urine bilirubin

Figure 3-3 Approach to abnormal liver tests with hepatocellular pattern

•  Acute workuptoxins (EtOH, acetaminophen); vascular abnl (U/S w/ Doppler); viral tests: IgM anti-HAV, HBsAg, IgM anti-HBc, HBV DNA, HCV RNA, anti-HEV, ± EBV, CMV, HSV, VZV;autoimmune (ANA, ASMA, ALKM); ceruloplasmin

•  Chronic workup: HBsAg, anti-HCV; Fe, TIBC; glc, HbA1c, TG; ANA, ASMA, ALKM; anti-tissue transglutaminase; ceruloplasmin & ɑ1-AT; TSH; vascular abnl (U/S w/ Doppler)

Figure 3-4 Approach to abnormal liver tests with cholestatic pattern

Figure 3-5 Approach to abnormal liver tests with isolated hyperbilirubinemia

Figure 3-6 Approach to abnormal liver tests with infiltrative pattern

Abnormal liver tests in asymptomatic patients (Clin Liver Dis 2009;13:167)

•  Careful review of history (meds, EtOH/drug use, exposures, risk factors for liver disease) and physical exam. Evaluate for any clues to etiology 1st (eg, d/c med and repeat LFTs).

•  Confirm hepatic source: if primarily ↑ AΦ (✓ GGT) or AST > ALT (✓ CK, aldolase, TFT)

•  Hepatocellular

Evaluate for most common causes: hepatitis A/B/C, hemochromatosis; screen for evidence of chronic liver disease (platelets, PT/INR, albumin)

If  evaluation → lifestyle modification (wt loss, DM control) + repeat test 6 mo

If evidence of chronic liver disease or persistent lab abnl, screen for less common causes: AIH, Wilson’s, celiac, ɑ1-AT; ✓ U/S & consider liver bx

If still  → liver bx if ALT or AST >2× ULN for >6 mo; o/w observe

•  Cholestatic: ✓ RUQ U/S, AMA

if biliary dilatation or obstruction → MRCP

if AMA  and U/S , or AMA  and U/S w/ abnl parenchyma → liver bx

if AMA & U/S :  AΦ >1.5× ULN → consider bx;  AΦ <1.5× ULN → observe

•  Isolated hyperbilirubinemia: ✓ conjugated vs. unconjugated

conjugated → perform abdominal U/S → MRCP if dilatation or obstruction; if nl ultrasound ✓ AMA and consider MRCP or liver bx

unconjugated → ✓ Hct, retic count, smear, LDH, haptoglobin

Common medications that cause abnormal liver tests (http://livertox.nlm.nih.gov)