Elevated Liver Enzymes

Mild bumps in liver enzymes are common in primary care. The trick for new nurse practitioners is knowing how to quickly sort hepatocellular vs cholestatic patterns, rule out dangerous causes, and decide when to refer. Here’s a practical, real-world NP workflow you can use in clinic.

What the Numbers Mean (Quick Refresher)

• ALT: More liver-specific; inside hepatocytes.

  • ULN: ~20–40 IU/L (lab-specific).

• AST: Found in liver, muscle, heart, RBCs. Exercise/muscle injury can elevate.

  • ULN: ~15–40 IU/L.

• ALP: From bile ducts, bone, placenta.

  • ULN: ~40–120 IU/L (varies).

• Tip: If ALP is up, confirm hepatic source with GGT or 5′-nucleotidase.

Rule of Thumb Patterns

• ALT > AST → viral hepatitis, NAFLD/NASH, drug-induced.

• AST > ALT (≥2:1) → alcohol-associated liver disease, cirrhosis/advanced fibrosis.

• ALP predominant → cholestasis (bile duct), infiltrative disease, or bone.

Severity:

• Mild = <5× ULN

• Moderate = 5–15× ULN

• Severe = >15× ULN (or AST/ALT >1000 → think ischemic, toxic, or acute viral).

First Questions (Your 2-Minute History)

• Red flags? Jaundice, RUQ pain, pruritus, fever, confusion, bleeding, weight loss.

• Alcohol & meds/supplements? (acetaminophen, statins, amiodarone, methotrexate, TB meds, herbals, bodybuilding steroids).

• Metabolic risks? Obesity, T2DM, dyslipidemia (NAFLD/NASH).

• Viral risks? Hep B/C exposures, tattoos, transfusions.

• Muscle injury/exertion? (AST from muscle).

• Pregnancy? (ALP can rise; cholestasis of pregnancy).

Classify the Pattern

• Hepatocellular: ALT/AST disproportionately high vs ALP.

• Cholestatic: ALP disproportionately high vs ALT/AST.

• Mixed: Both up (use R-ratio: ≥5 hepatocellular, ≤2 cholestatic, 2–5 mixed).

Initial Workup (Baseline Panel)

• ALT, AST, ALP, total & direct bilirubin

• Albumin, PT/INR

• CBC

• GGT (if ALP up)

• CK (if muscle source suspected)

Targeted tests:

• Viral: HBsAg, anti-HBc, anti-HCV (with reflex HCV RNA)

• Metabolic: fasting lipids, A1c; iron studies + ferritin

• Autoimmune: ANA, ASMA, IgG

• Cholestatic AI: AMA (PBC); MRCP if PSC suspected (IBD)

• Wilson (<40 y): ceruloplasmin ± 24-h urine copper

• α-1 antitrypsin phenotype

• TSH, celiac serologies if unexplained

• Pregnancy test when relevant

Imaging:

• RUQ ultrasound for most persistent or significant abnormalities

• MRCP/ERCP if cholestasis suspected

• Document steatosis if fatty liver; consider FibroScan if available

Common Causes by Pattern

Hepatocellular (ALT/AST predominant):

• NAFLD/NASH

• Viral hepatitis (A, B, C)

• Alcohol use (AST>ALT)

• DILI (acetaminophen, meds)

• Autoimmune hepatitis

• Ischemic hepatitis (AST/ALT >1000)

• Wilson, hemochromatosis, α-1 antitrypsin deficiency

Cholestatic (ALP predominant):

• Gallstones/choledocholithiasis

• Malignancy (pancreas, cholangiocarcinoma)

• PBC (↑AMA), PSC (IBD history)

• Drug-induced cholestasis (Augmentin, estrogen, steroids)

• Infiltrative disease (sarcoid, malignancy)

• Bone disease (if GGT normal → bone source)

When to Refer/Urgent Action

• Jaundice, elevated INR, low albumin, low platelets, or high bilirubin

• AST/ALT >5× ULN or >1000

• Persistent elevation >6 months

• Suspected autoimmune hepatitis, PSC/PBC, Wilson, hemochromatosis, mass, or biliary obstruction

Management Pearls

• Stop alcohol; limit acetaminophen ≤2 g/day until clarified.

• Weight loss 7–10% may normalize enzymes in NAFLD/NASH.

• Vaccinate nonimmune patients for Hep A & B.

• Recheck labs in 6–12 weeks after med/lifestyle changes.

Quick Pattern Table

Takeaway for New Nurse Practitioners

Mild enzyme bumps are common in primary care, and most aren’t dangerous. The key is recognizing patterns, red flags, and when to refer. With a structured approach, you’ll save time, feel more confident, and deliver safe, evidence-based care.

✉️ Questions or tricky cases? Email me at [email protected]  or DM me on social.
📌 Need plug-and-play templates like this across your clinic? Check out my NP mentorship program for practical, no-fluff resources designed for new nurse practitioners in primary care.