What is the management for elevated liver function tests (LFTs)?

Management of Elevated Liver Function Tests

For elevated LFTs, immediately obtain a complete panel (ALT, AST, ALP, GGT, bilirubin, albumin, PT/INR) to classify the injury pattern as hepatocellular, cholestatic, or mixed, then stratify severity and manage based on the degree of elevation. 1

Initial Laboratory Assessment

• Measure both aminotransferases (ALT, AST) and cholestatic markers (ALP, GGT, total/direct bilirubin, albumin, PT/INR) to determine the pattern of liver injury 1, 2
• Check serum creatine kinase (CK) to exclude muscle injury as a cause of elevated AST 2
• Review all previous LFT results before ordering additional investigations, as this is often overlooked in practice 3

Pattern Classification

Hepatocellular Pattern (Predominant ALT/AST Elevation)

• Test for viral hepatitis: anti-HAV IgM, HBsAg, anti-HBc IgM, and anti-HCV 1
• Screen for NAFLD risk factors: obesity, type 2 diabetes, dyslipidemia, hypertension 1
• For patients with NAFLD risk factors, perform risk stratification using FIB-4 or NAFLD Fibrosis Score 1
• Consider autoimmune hepatitis markers (ANA, ASMA, ANCA) if clinical suspicion is high 1
• Common causes include NAFLD, alcohol-induced liver disease, viral hepatitis, and drug-induced liver injury 2

Cholestatic Pattern (Predominant ALP/GGT Elevation)

• Confirm hepatic origin of elevated ALP by checking GGT 1
• Perform abdominal ultrasound to evaluate for biliary obstruction, assess liver parenchyma, exclude masses, and evaluate the biliary system 1, 2
• Check anti-mitochondrial antibody if cholestatic pattern is present 4

Severity Stratification and Monitoring

Mild Elevations (<5× ULN)

• Monitor liver enzymes weekly until normalization 1, 4
• Discontinue all potentially hepatotoxic medications and alcohol 1, 4
• If initial workup is unrevealing and LFTs remain mildly elevated, observe for 3-6 months with repeat testing before proceeding to liver biopsy, during which time eliminate potential hepatotoxins and address metabolic risk factors 2

Moderate Elevations (5-10× ULN)

• Monitor liver enzymes every 2-3 days until stable or improving 1, 4
• For patients on immune checkpoint inhibitors with Grade 2 hepatotoxicity (AST/ALT >3.0 to ≤5.0× ULN), hold treatment temporarily and consider steroids (0.5-1 mg/kg/day prednisone) if no improvement after 3-5 days 1

Severe Elevations (>10× ULN)

• Monitor liver enzymes every 1-2 days 1, 4
• For patients on immune checkpoint inhibitors with Grade 3 hepatotoxicity (AST/ALT 5-20× ULN), consider permanently discontinuing treatment and immediately start steroids (1-2 mg/kg methylprednisolone) 1

Life-Threatening Elevations (>20× ULN)

• Immediate hospitalization for intensive monitoring and supportive care 1, 2
• For patients on immune checkpoint inhibitors with Grade 4 hepatotoxicity, permanently discontinue treatment 1

Critical History Elements

• Review all medications including prescription drugs, over-the-counter medications, herbal supplements, and illicit drugs 4, 1
• Quantify alcohol intake using the AUDIT-C scoring tool 4, 3
• Assess metabolic syndrome features: central obesity, hypertension, diabetes, dyslipidemia 4
• Identify viral hepatitis risk factors: country of birth, injecting drug use, travel history, parental exposure 4, 3

Medication Management Based on Severity

Stop all potentially hepatotoxic medications if ALT/AST exceeds 5× ULN, or if any elevation occurs with jaundice or elevated bilirubin, regardless of the absolute enzyme level. 4

Drug-Specific Considerations

For patients on methotrexate 3:

• Minor elevations are common
• If elevation exceeds 2× normal, check more frequently
• If exceeds 3× normal, consider dose reduction
• If exceeds 5× normal, discontinue

For patients on TNF inhibitors, monitor CBC and LFTs annually at minimum 3

For patients on tocilizumab 3:

• If LFTs 1-3× ULN: decrease dosage or increase interval between doses
• If >3× ULN: withhold administration
• If >5× ULN: discontinue treatment

Special Population Considerations

Harmful Alcohol Drinkers

• For those consuming >50 units/week (men) or >35 units/week (women), perform risk stratification with FibroScan/ARFI elastography 1, 4
• Refer to hepatology if ARFI >7.8 kPa 4
• Refer to alcohol services for adults with AUDIT score >19 indicating alcohol dependency 1

Pediatric Patients

• Maintain a low threshold for pediatric referral 4
• Urgently assess neonatal cholestasis 4

Referral Indications to Hepatology

Refer for 4, 1:

• Hepatitis B or C infection
• Autoimmune hepatitis
• Primary biliary cholangitis or primary sclerosing cholangitis
• Hemochromatosis
• Persistent unexplained elevations after initial workup
• Evidence of advanced fibrosis on non-invasive testing
• ALT >5× ULN

Common Pitfalls to Avoid

• Context matters critically: A patient on statins with ALT 80 U/L who is well differs vastly from a patient with end-stage alcohol-related liver disease with ALT 30 U/L (within normal range) who may have weeks to live 3
• The magnitude of LFT elevation does not always correlate with prognosis—diagnosis and clinical context are more important (e.g., acute hepatitis A with ALT >1000 U/L has excellent prognosis, while hepatitis C with normal ALT can progress to cirrhosis) 3
• Liver enzymes are a poor guide to progressive liver fibrosis in alcohol-related liver disease, though GGT is the best predictor of mortality 3
• Consider liver biopsy only if steroid-refractory or if differential diagnoses would alter management 1, 4