At a Glance

Why It's Ordered
Separates hepatocellular injury from cholestasis, judges synthetic function and identifies acute liver failure in jaundice, RUQ pain, altered mentation or suspected acetaminophen or drug injury.
Check First
ALT and AST (size and pattern), INR (synthetic function), total bilirubin (jaundice) and glucose: the four values that change management in minutes.
Critical Values
INR 1.5 or more with any encephalopathy (acute liver failure) · Acetaminophen at or above 150 mcg/mL at 4 hr · Ammonia >100 µmol/L (typical; lab-specific) · ALT or AST >1,000 U/L is a marked-elevation work-up trigger, not a call-now value
Don't Miss
Acetaminophen injury with normal early AST and ALT. Start acetylcysteine without waiting if the time is unknown, history doubtful, a large ingestion (over 200 mg/kg or 10 g) will not have a level within 8 hr, or the patient is symptomatic over 24 hr; otherwise treat from the 4-hr level.
Field & Transport
No liver enzymes or bilirubin at the bedside: check glucose, mental status and POC INR if carried (confirm a high value in the lab). Send transaminases, INR, bilirubin and the APAP level with its ingestion time; repeat glucose en route.

Panel Overview

The liver panel has seven measured core analytes (total and direct bilirubin counted separately): the hepatocellular enzymes AST and ALT, the cholestatic markers ALP and bilirubin (with GGT to confirm a hepatic source), and the synthetic markers albumin and total protein. It is drawn in ED triage, ICU morning labs and before transfer when liver injury or jaundice is suspected. Its liver subset is part of the CMP (14 analytes). PT/INR and ammonia are added when synthetic failure or encephalopathy is in question.

When to Order:
  • Jaundice or pruritus: new yellow eyes or skin, dark urine, or pale stools
  • RUQ pain with fever: possible cholangitis or biliary sepsis
  • Altered mentation or bleeding: possible acute liver failure
  • Suspected overdose: any possible acetaminophen or hepatotoxic drug ingestion
  • Known liver disease: ascites, variceal bleeding or a fever with abdominal pain
  • Pre-transfer or pre-procedure: to document baseline function before transport or intervention

Hepatocellular Injury

AST (Aspartate Aminotransferase)

Normal: 10–30 U/L

Found in liver, heart, muscle and red cells. Rises in hepatocellular injury, but less liver-specific than ALT. High with normal ALT suggests muscle or hemolysis.

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ALT (Alanine Aminotransferase)

Normal: 10–40 U/L (ACG healthy ULN 33 M | 25 F)

Most liver-specific transaminase. Rises in viral, toxic, ischemic and fatty liver injury. Lower ULN in women; use the lab's reported limit.

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Cholestasis

ALP (Alkaline Phosphatase)

Normal: 30–120 U/L

Made in liver, bone, intestine and placenta. Rises with biliary obstruction and cholestasis, and with bone growth, fracture or pregnancy. Confirm the source with GGT.

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Bilirubin (Total & Direct)

Normal: total 0.3–1.2 mg/dL; direct ≤0.3 mg/dL

Hemoglobin breakdown product. Mostly direct (conjugated) with obstruction or hepatocellular injury; mostly indirect with hemolysis or Gilbert syndrome.

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GGT (Gamma-Glutamyl Transferase), add-on

Normal: 5–40 U/L

Add-on to ALP. Rises with cholestasis, alcohol and enzyme-inducing drugs; confirms a hepatic source for a high ALP.

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Synthetic Function

Albumin

Normal: 3.5–5.0 g/dL

Synthesized by the liver but a slow marker; low values mostly reflect chronic disease, inflammation or nutrition. Its half-life is about 15–20 days.

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Total Protein

Normal: 6.0–8.3 g/dL

Albumin plus globulins. Low values reflect illness or dilution; high values suggest raised globulin, including monoclonal protein.

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PT/INR, add-on

Normal: INR 0.8–1.1

Add-on for synthetic function. A prolonged INR suggests impaired synthesis, but warfarin, vitamin K deficiency and DIC also raise it.

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Common Add-Ons

Ammonia

Normal: 19–60 µg/dL (11–35 µmol/L)

Raised in acute liver failure and cirrhosis with shunting, and in urea cycle disorders. Requires an iced, promptly analyzed sample; does not grade hepatic encephalopathy.

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Acetaminophen (APAP) level

Therapeutic: 10–30 mcg/mL

Needed for any possible acetaminophen ingestion. Interpret only with the exact time since ingestion, using the revised nomogram (treatment line 150 mcg/mL at 4 hr).

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Lipase

Normal: at or below the lab ULN (U/L)

A pancreatic enzyme, not a liver test. Above 3 times the ULN with typical pain or imaging supports acute pancreatitis, and a normal value does not rule it out.

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Reference Ranges & Critical Values
TestAdult NormalSI UnitsCritical LowCritical HighNotes
AST
10–30 U/L
0.17–0.50 µkat/L
—
—
Lab- and assay-specific; women lower; >1,000 U/L is a work-up trigger
ALT
10–40 U/L
0.17–0.67 µkat/L
—
—
ACG healthy ULN 33 M | 25 F; >1,000 U/L is a work-up trigger
ALP
30–120 U/L (Critical Care Transport; lab ULNs often about 130)
0.50–2.00 µkat/L
—
—
Sex, age and pregnancy dependent; women often lower
Total bilirubin
0.3–1.2 mg/dL
5–21 µmol/L
—
—
Adults; newborns use hour-specific limits
Direct bilirubin
≤0.3 mg/dL
≤5 µmol/L
—
—
Conjugated fraction
Albumin
3.5–5.0 g/dL
35–50 g/L
—
—
Slow marker; not an acute injury test
Total protein
6.0–8.3 g/dL
60–83 g/L
—
—
Low: illness; high: globulin
GGT (add-on)
5–40 U/L
0.08–0.67 µkat/L
—
—
Confirms hepatic ALP source
PT/INR (add-on)
INR 0.8–1.1
Same
—
INR 1.5 or more with encephalopathy
Acute liver failure; lab INR critical value is typically above 5
Ammonia (add-on)
19–60 µg/dL
11–35 µmol/L
—
>100 µmol/L (>170 µg/dL), typical; lab-specific
Iced, prompt sample; see Ammonia page; >150 µmol/L is high ALF risk
Acetaminophen (add-on)
Therapeutic 10–30 mcg/mL
Same
—
150 mcg/mL at 4 hr
Treatment line; nomogram invalid if time unknown
Laboratory variation: Every lab sets its own intervals, and analyzers and assays differ too. Use your lab's reported interval and its critical-call policy. Pediatric ranges live in Special Populations.

Systematic Interpretation
  1. Pattern (R ratio): Calculate R with each enzyme's ULN from the lab report. An R above 5 points to hepatocellular injury. An R of 2 to 5 is mixed. An R below 2 is cholestasis.
  2. Severity: Express ALT and AST as multiples of ULN. Anything above 1,000 U/L is a marked elevation. It sends you to a broader work-up: viral, toxic, ischemic, autoimmune.
  3. Synthetic function: Check INR and albumin. An INR that stays high after vitamin K points to impaired synthesis. Albumin falls slowly. Low albumin mostly means chronic illness.
  4. Bilirubin fractionation: Look at the split. A high direct fraction points to obstruction or hepatocellular injury. A mostly indirect rise points to hemolysis or Gilbert syndrome.
  5. Cholestasis confirmation: Pair GGT with ALP. A rising GGT confirms a hepatic source. Bone and growth can raise ALP by themselves.
  6. Acute liver failure screen: INR of 1.5 or more with any encephalopathy is acute liver failure. This applies in a patient without known cirrhosis, with illness under 26 weeks.
  7. Toxic cause: Unexplained transaminase rise, and the ingestion is unknown or possible? Get an acetaminophen level with the exact time. Then go to the acetylcysteine decision in Critical Findings.
  8. Prognosis in known liver disease: Calculate MELD 3.0 from creatinine, bilirubin, INR, sodium, albumin and sex. That number carries the prognosis.
R ratio (pattern)
R = (ALT ÷ ALT ULN) ÷ (ALP ÷ ALP ULN)

R above 5: hepatocellular · R 2 to 5: mixed · R below 2: cholestatic.

MELD 3.0 (cirrhosis prognosis)
1.33 (if female) + 4.56 × ln(bilirubin) + 0.82 × (137 − Na) − 0.24 × (137 − Na) × ln(bilirubin) + 9.09 × ln(INR) + 11.14 × ln(creatinine) + 1.85 × (3.5 − albumin) − 1.83 × (3.5 − albumin) × ln(creatinine) + 6

Round to the nearest integer. Creatinine is bounded at 1 to 3 mg/dL. Dialysis 2 or more times in the past week sets creatinine to 3.0. Bilirubin and INR have a minimum of 1. Sodium is bounded at 125–137 mmol/L. Albumin is bounded at 1.5–3.5 g/dL. The score is capped at 40. Transplant programs rank severity with it.

Worked Example: ALT 540 U/L (ULN 33), ALP 100 U/L (ULN 129), total bilirubin 2.1 mg/dL. R = (540 ÷ 33) ÷ (100 ÷ 129) = 16.4 ÷ 0.78 ≈ 21, a hepatocellular pattern. Next, check INR and mental status. If any ingestion is possible, send an acetaminophen level.

Patterns & Differential

Start with the R ratio. Then judge synthetic function and bilirubin fractionation.

PatternKey FindingsCommon CausesNext Step
Hepatocellular
ALT and AST high, ALP near normal (R above 5)
Viral hepatitis, acetaminophen or other drug injury, autoimmune, fatty liver, alcohol
Ingestion history, serology per work-up, APAP level if relevant
Cholestatic
ALP and GGT high (R below 2); bilirubin often high
Bile duct obstruction, cholangitis, PBC, PSC, drug-induced cholestasis
Biliary imaging; ERCP-capable destination if cholangitis is suspected
Mixed
Both ALT and ALP raised (R 2 to 5)
Obstruction with hepatitis, early biliary disease, drug injury
Trend values and imaging against prior results
Ischemic hepatitis
AST and ALT above 1,000 U/L within hours of hypotension, arrest or hypoxia
Shock, cardiac arrest, respiratory failure
Treat the shock; repeat LFTs and lactate; values often fall quickly after perfusion recovers
Acetaminophen hepatotoxicity
AST and ALT may be normal early, then rise
Acetaminophen above safe dosing, repeated supratherapeutic dosing
APAP level with time; start acetylcysteine per protocol if in doubt
Acute liver failure
INR 1.5 or more with encephalopathy, no known cirrhosis
Acetaminophen, viral hepatitis, idiosyncratic drug injury, ischemia; also Wilson disease and Budd-Chiari
Glucose, APAP level, ammonia, transfer to a transplant-capable center
Alcohol-associated hepatitis
AST:ALT above 2; AST usually under 300 U/L; GGT high
Heavy alcohol use
Abstinence, nutrition, severity scoring, hepatology input
Isolated AST rise
AST high, ALT normal
Muscle injury, hemolysis, cardiac source
CK and troponin before attributing to the liver
Unconjugated hyperbilirubinemia
Indirect bilirubin high, ALT and ALP normal
Hemolysis, ineffective erythropoiesis, Gilbert syndrome
CBC and hemolysis labs; see the CBC panel
Cirrhosis synthetic failure
Low albumin, high INR, often raised bilirubin
Chronic liver disease with portal hypertension
MELD 3.0; assess ascites, encephalopathy and bleeding risk

Critical Findings & Emergency Actions

Suspected acetaminophen toxicity

Recognize: Watch for it with any intentional or unknown acetaminophen ingestion. Right upper quadrant pain, nausea, or AST or ALT above normal count too.

  1. Document the exact ingestion time and dose; draw the APAP level and AST, ALT, INR and glucose (RN, Paramedic handoff).
  2. Start acetylcysteine (RN): start without waiting if the time is unknown or the history is doubtful. Start too after a large acute ingestion (over 200 mg/kg or over 10 g) when the level will not result within 8 hr of ingestion. Start also if the patient is symptomatic and presents more than 24 hr after ingestion (2023 consensus). With a known time under 8 hr, treat from the 4-hr level. Use the three-bag label regimen: 150 mg/kg over 1 hr, then 50 mg/kg over 4 hr, then 100 mg/kg over 16 hr. That totals 300 mg/kg in 21 hr. The label also lists a two-bag option for 41 kg and up. It runs 200 mg/kg over 4 hr, then 100 mg/kg over 16 hr, for 20 hr. It is a common variant. Cap dosing weight at 100 kg. The stopping criteria decide when it ends, not the clock. Anaphylactoid reactions show up mostly in the first hour. Pause the infusion and treat per protocol. A prior reaction is not a bar to treatment in overdose. See acetylcysteine.
  3. Read the level only with a known time: The treatment line sits at 150 mcg/mL at 4 hr on the revised nomogram. It applies to levels drawn 4 to 24 hr after a single acute ingestion. Extended-release products follow the same nomogram as other acetaminophen products. To the consensus authors' knowledge, markedly delayed-absorption modified-release products are not sold in the US or Canada. Still, confirm from the history that none was taken before you rely on the nomogram. When the 4 to 12 hr level sits below the line but above 10 mcg/mL, redraw it 4 to 6 hr later. If the level is rising, activated charcoal may still help. The nomogram is off limits for unknown time, ingestions spanning more than 24 hr, or repeated supratherapeutic dosing. With repeated supratherapeutic ingestion over more than 24 hr, treat if APAP is above 20 mcg/mL or AST or ALT is abnormal, and call the poison center.
  4. Notify poison center and medical direction per local protocol.

Acute liver failure (INR 1.5 or more with encephalopathy)

Recognize: Look for an INR of 1.5 or more, any confusion or drowsiness, and no known cirrhosis.

  1. Check glucose now; if low, give dextrose D10 10 g IV (100 mL), recheck after each step and repeat per protocol (dextrose). D10 is off the ISMP high-alert list. Concentrations of 20% or more are on it.
  2. Protect the airway and manage agitation without sedatives that mask neuro status, per local protocol (Paramedic/RN/CCT).
  3. Screen for acetaminophen: Use the APAP level and acetylcysteine as above when acetaminophen is possible. In non-acetaminophen ALF, NAC is off-label and a receiving-center decision. It is sometimes considered for early-grade encephalopathy. Trial evidence is mixed.
  4. Transfer early to a transplant-capable center per medical direction (CCT).

Suspected cholangitis (fever, jaundice, right upper quadrant pain)

Recognize: Fever or rigors with jaundice and right upper quadrant pain. Add hypotension and it becomes an emergency.

  1. Sepsis care per local protocol: IV access, fluids, lactate and blood cultures.
  2. Antibiotics: ceftriaxone, in a regimen the receiving team sets from the local antibiogram. With a biliary-enteric anastomosis, add anaerobic coverage (RN/ED; ceftriaxone).
  3. Early or urgent biliary drainage by severity (Tokyo 2018 grade) at an ERCP-capable destination. Mild (Grade I) may respond to antibiotics alone. Moderate (Grade II) calls for early drainage. Severe (Grade III) calls for urgent drainage with organ support.

Cirrhosis with ascites and fever or abdominal pain

Recognize: Ascites with fever, abdominal pain, confusion or rising creatinine: Both spontaneous bacterial peritonitis and hepatorenal syndrome are possible.

  1. Antibiotics: ceftriaxone per the receiving team and local protocol (ceftriaxone), with IV albumin per cirrhosis guidance. The receiving facility does the diagnostic paracentesis.
  2. Monitor SpO₂, urine output and mental status; notify receiving facility (RN/CCT).
Pitfall: Normal AST and ALT in the first hours can still hide acetaminophen injury. Start from the history, not the enzymes.

Prehospital & Transport Considerations

Point-of-Care Testing

The field has no point-of-care test for liver enzymes, bilirubin or albumin. Use the devices below for what they can measure.

DeviceAnalytesLimitations
Glucometer
Glucose
Hypoperfusion, hematocrit and vitamin C can distort readings; treat symptoms first
Handheld lactate
Lactate
Marker of hypoperfusion; trend only, device-specific range
POC INR meter
PT/INR
Device-specific range; confirm a high value with the laboratory INR
i-STAT CHEM8+ or CG4+
Electrolytes, glucose, creatinine, lactate (no liver tests)
Does not measure AST, ALT, ALP or bilirubin

Interfacility Transfer & Handoff

  • Send with the patient: AST and ALT with trend, INR, total and direct bilirubin, albumin, and any APAP level with its ingestion time.
  • If acute liver failure is suspected: ammonia (iced, promptly analyzed), glucose trend and the time of last acetylcysteine dose.
  • Repeat en route: glucose when mental status changes; repeat INR or ammonia only per receiving-team request.
  • Pending labs: list the APAP level, cultures and any outstanding results on the handoff.

Scope Notes

  • EMS: glucose and dextrose per protocol. Medical direction sets the transport decision and the destination.
  • Hospital-administered in most systems: acetylcysteine, ceftriaxone and vitamin K (Paramedic/RN/CCT, per local protocol).
  • Before you rely on them, check your local transplant-center and poison-center referral criteria.

Special Populations

Pediatrics

AgeALP (U/L)Albumin (g/dL)
Neonate (0–14 days)
90–273
3.3–4.5
Infant (15 days–<1 year)
134–518
2.8–4.7 (to 1 year)
Child (1–<10 years)
156–369
3.8–4.7 at 1–2 years; then lab age range
Adolescent (10–<15 years)
10–<13 y: 141–460; 13–<15 y: F 62–280, M 127–517
Lab age range
Pediatric intervals: The age bands above are example values from one lab. No cited source backs them yet. Use your lab's pediatric interval.
  • ALT: Pediatric upper limits sit below adult limits and vary by age and sex. When you screen, use the age-specific limit on the E3 ALT reference page and your lab's pediatric interval. Not the adult limit.
  • Bilirubin: Read newborn bilirubin against the AAP 2022 phototherapy thresholds. Those depend on age in hours, gestational age (35 weeks or later) and risk factors. They are treatment thresholds, not reference intervals. In infants, a direct fraction above 20% of total bilirubin warrants a cholestasis evaluation. That is a commonly used rule.
  • GGT: In the neonate, GGT runs several times the adult ULN. It falls over the first months. Unlike ALP, GGT does not climb with normal childhood growth.
  • Pediatric dosing: acetylcysteine 300 mg/kg IV over 21 hr by the three-bag regimen for children 40 kg or less (150 mg/kg over 1 hr, 50 mg/kg over 4 hr, 100 mg/kg over 16 hr), with bag volumes reduced by weight per the label or poison center; labeled from 5 kg. Ceftriaxone 50–75 mg/kg/day, max 2 g/day, but do not give it to premature neonates up to 41 weeks postmenstrual age, to hyperbilirubinemic neonates, or to neonates 28 days or younger who need calcium-containing IV solutions (label contraindications); follow the neonatal protocol and medical direction. Dextrose 0.5–1 g/kg IV (max 25 g); vitamin K 1 mg IM for newborn prophylaxis of vitamin K deficiency bleeding (infants under 1.5 kg per neonatal protocol). See weight-based dosing and vital signs.

Pregnancy

  • ALP: climbs in the third trimester because the placenta makes ALP. That is expected. It does not mean liver disease on its own.
  • ALT and GGT: don't climb in a normal pregnancy. A new rise is abnormal.
  • Albumin: runs below non-pregnant values, bottoming out in the third trimester from hemodilution.
  • AST and ALT with hypertension, right upper quadrant pain or low platelets: work up HELLP or preeclampsia per the obstetric protocol.
  • Pruritus without rash in late pregnancy: consider intrahepatic cholestasis of pregnancy. Fasting serum bile acids are the key test.
  • Acute fatty liver of pregnancy: third trimester with hypoglycemia, coagulopathy (high INR), high bilirubin and high ammonia; delivery is the definitive treatment.
  • Acetylcysteine: Pregnancy is no reason to hold it back. Waiting to treat raises maternal and fetal risk.

Older Adults

  • ALT and AST: In frailty or low muscle mass, they may run lower.
  • Albumin: A low value usually means illness or inflammation. Age alone is not the reason.
  • ALP: runs mildly higher in older women. Bone turnover is often the cause.

Chronic Liver Disease

  • MELD 3.0: Use the formula in Systematic Interpretation. It compares severity between patients or over time.
  • Ascites with fever or confusion: think spontaneous bacterial peritonitis or hepatorenal syndrome. Then use Critical Findings.

Specimen Collection & Interfering Factors
  • Tube: serum gold or green-top lithium heparin plasma. The tube color and additive depend on the institution.
  • Handling: separate promptly; protect bilirubin samples from light; send ammonia iced and analyzed promptly.
  • Order of draw: blood cultures go before the serum tubes, and EDTA goes last (CLSI GP41 order). That keeps carryover out.
Error or interferentEffect on ResultsPrevention
Hemolysis
Raises AST more than ALT
Avoid traumatic draws and small needles; recollect if hemolyzed
IV-line contamination or dilution
Lowers protein, albumin and other analytes
Draw from the arm opposite the infusion, after stopping the line
Prolonged tourniquet or standing draw
Raises albumin and total protein
Limit tourniquet time; do not draw after prolonged standing
EDTA, citrate or oxalate tube
Lowers ALP
Use the correct tube; check the order of draw
Lipemia or icterus
Assay interference (colorimetric methods)
Report to the lab; use the lab's interference index
Delayed or warm ammonia sample
Falsely high ammonia
Send on ice and analyze promptly
Light exposure
Lowers bilirubin
Protect the sample from light until analyzed
Wrong-patient or mixed-up draw
Misleading trends
Two identifiers at the bedside

Clinical Pearls
Pattern first: Do the R ratio before you name a diagnosis. Hepatocellular, cholestatic and mixed patterns each send you down a different next step.
Field: In the field, glucose and mental status matter more than enzymes. Low glucose with confusion gets treated first.
Nursing: Without a documented ingestion time, an acetaminophen level has no place on the nomogram. Record the time first.
Critical care: Vitamin K fixes an INR from vitamin K deficiency or warfarin. It cannot restore synthesis in liver failure. So a trial dose goes in only when deficiency may contribute, and then the INR gets rechecked.
Normal transaminases: Normal AST or ALT does not rule out cirrhosis or late liver failure.
Ischemic hepatitis: After hypotension or arrest, a transaminase rise usually traces back to shock. Restore perfusion, and values often fall quickly.
Pitfall: A falling ALT looks like recovery. With a rising INR, bilirubin or confusion, it is liver failure.
Pitfall: A high ALP by itself is often bone, growth or pregnancy. Check GGT before you chase liver disease.

Related

References
  1. Shingina A, Mukhtar N, Wakim-Fleming J, et al. (2023). Acute liver failure guidelines (American College of Gastroenterology). Am J Gastroenterol, 118(7), 1128–1153. https://pubmed.ncbi.nlm.nih.gov/37377263/
  2. Dart RC, Mullins ME, Matoushek T, et al. (2023). Management of acetaminophen poisoning in the US and Canada: a consensus statement. JAMA Netw Open, 6(8), e2327739. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2808062
  3. Kim WR, Mannalithara A, Heimbach JK, et al. (2021). MELD 3.0: the Model for End-Stage Liver Disease updated for the modern era. Gastroenterology, 161(6), 1887–1895. https://pmc.ncbi.nlm.nih.gov/articles/PMC8608337/
  4. Newsome PN, Cramb R, Davison SM, et al. (2018). Guidelines on the management of abnormal liver blood tests. Gut, 67(1), 6–19. https://pmc.ncbi.nlm.nih.gov/articles/PMC5754852/
  5. Kwo PY, Cohen SM, Lim JK. (2017). ACG clinical guideline: evaluation of abnormal liver chemistries. Am J Gastroenterol, 112(1), 18–35. https://pubmed.ncbi.nlm.nih.gov/27995906/
  6. Miura F, Okamoto K, Takada T, et al. (2018). Tokyo Guidelines 2018: initial management of acute biliary infection and flowchart for acute cholangitis. J Hepatobiliary Pancreat Sci, 25(1), 31–40. https://pubmed.ncbi.nlm.nih.gov/28941329/

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