Liver Tests: AST/ALT vs ALP/Bilirubin Patterns

Liver chemistry is a pattern-recognition game. Decide if the injury is hepatocellular(AST/ALT predominant) or cholestatic (ALP/bilirubin predominant), then chase the right causes and tests. Here’s a compact, stepwise approach.

What’s in a “Liver Panel”?

• AST, ALT: hepatocellular injury markers (not function).
• ALP: cholestasis marker; can also come from bone/placenta/intestine.
• GGT: helps confirm hepatic source of ALP.
• Total/Direct (Conjugated) Bilirubin: excretory function; cholestasis or hemolysis patterns.
• Albumin, PT/INR: true synthetic function of the liver.

First Sort: Hepatocellular vs. Cholestatic

Use the R-ratio to classify:
R = (ALT / ULN_ALT) ÷ (ALP / ULN_ALP)

• R ≥ 5: Hepatocellular pattern (ALT/AST dominate).
• R ≤ 2: Cholestatic pattern (ALP ± bilirubin dominate).
• R 2–5: Mixed injury.

Hepatocellular Pattern (High AST/ALT)

• Very high (>1000 IU/L): ischemic hepatitis (“shock liver”), acute viral hepatitis, acetaminophen or other DILI. Check acetaminophen level and INR urgently.
• AST:ALT > 2:1 suggests alcohol-associated hepatitis (with ↑GGT, ↑MCV).
• ALT > AST common in NAFLD/NASH, viral hepatitis, many DILI cases.
• Workup: hepatitis A/B/C serologies as indicated, ferritin/transferrin saturation (hemochromatosis), ANA/ASMA/IgG (autoimmune hepatitis), ceruloplasmin (young pts), ultrasound for steatosis/structural disease, med/supplement review.

Cholestatic Pattern (High ALP ± Bilirubin)

• Confirm hepatic origin: GGT elevated supports biliary source; if ALP isolated with normal GGT, think bone (check ALP isoenzymes or bone markers).
• Obstructive causes: gallstones, strictures, pancreatic/biliary malignancy.
• Intrahepatic cholestasis: PBC (check antimitochondrial antibody), PSC (MRCP; associated with IBD), drugs (e.g., amoxicillin-clavulanate), pregnancy-related cholestasis.
• Imaging first line: right upper quadrant ultrasound to look for ductal dilation; MRCP/CT if negative but suspicion persists.

Bilirubin Patterns

• Unconjugated predominance: hemolysis (check haptoglobin/LDH/retic), ineffective erythropoiesis, Gilbert syndrome (benign; fluctuates with stress/fasting).
• Conjugated predominance: cholestasis or hepatocellular dysfunction (dark urine, pale stools, pruritus more likely).

When Is It “Liver Failure”?

• Acute liver failure (ALF): INR ≥ 1.5 plus any degree of encephalopathy in a patient without cirrhosis → emergent referral to a transplant-capable center.
• Synthetic dysfunction: falling albumin over weeks/months, rising INR, ascites—think advanced chronic disease.

Common Clinical Pathways

• Asymptomatic mild AST/ALT elevation (<5× ULN): repeat in 4–12 weeks after removing alcohol/suspect drugs and optimizing weight/metabolic risk; screen viral hepatitis and metabolic causes if persistent.
• Painless jaundice with cholestasis labs: urgent imaging for obstruction (US → MRCP/CT) and surgical/GI evaluation.
• Pruritus + markedly high ALP: antimitochondrial Ab (PBC), MRCP for PSC, medication review; cholestyramine can help symptoms while evaluating cause.

Special Populations

• Pregnancy: physiologic ALP rise (placental); intrahepatic cholestasis of pregnancy presents with pruritus and ↑bile acids—obstetric management required.
• Bone disease / adolescents: high ALP from growth/osteoblast activity—normal GGT and liver enzymes.
• TPN, sepsis, heart failure: can cause cholestasis with mixed patterns.

When to Image and What

• First-line: RUQ ultrasound in cholestatic or mixed patterns.
• Escalate to: MRCP for ductal disease, CT for masses/complications. Elastography (FibroScan) for fibrosis staging in NAFLD/viral hepatitis.

Red Flags (Escalate Now)

• INR ≥ 1.5 with confusion or somnolence (possible ALF).
• ALT/AST > 1000 IU/L with systemic symptoms.
• Rapidly rising bilirubin with cholangitis signs (fever, RUQ pain, jaundice) → urgent ERCP evaluation.

Patient FAQs

“My ALT is a little high—do I have liver failure?” Not necessarily. ALT/AST indicate injury, not function; albumin and INR reflect function.

“Can supplements cause this?” Yes—bodybuilding and “detox” products are common culprits. Always list all supplements and teas.

References & Notes

This overview reflects common hepatology pathways: pattern recognition (R-ratio), targeted serologies, judicious imaging, and early escalation for red flags. Local protocols vary—use institutional guidance. Educational only.