What is the next step in managing elevated Liver Function Tests (LFTs)?

Management of Elevated Liver Function Tests

When you encounter elevated LFTs, immediately determine the pattern of elevation (hepatocellular vs. cholestatic) and obtain a comprehensive clinical history with targeted laboratory workup rather than simply repeating the same tests. 1

Initial Pattern Recognition and Severity Assessment

Determine the specific pattern of liver enzyme elevation:

• Hepatocellular pattern: Predominant ALT/AST elevation with ALT:AST ratio >1 suggesting non-alcoholic causes, or AST:ALT ratio >1 indicating alcoholic liver disease 2, 3
• Cholestatic pattern: Predominant alkaline phosphatase (ALP) elevation; confirm hepatic origin by checking GGT 3, 4
• Mixed pattern: Both hepatocellular and cholestatic features present 2

Categorize severity of elevation: 2, 3

• Mild to moderate: <3× upper limit of normal (ULN)
• Severe: >3× ULN
• Marked elevation: >1000 U/L suggests acute viral hepatitis 2

Critical History Elements to Obtain

Medication review is essential - document all prescribed medications, over-the-counter drugs, herbal supplements, and illicit substances as these commonly cause hepatotoxicity 1, 2

Obtain detailed alcohol history: 1

• Current and past intake in average units per week
• Consider AUDIT-C screening tool

Assess metabolic syndrome features: 1

• Central obesity
• Hypertension
• Diabetes/insulin resistance
• Dyslipidemia

Additional history elements: 1, 2

• Viral hepatitis risk factors (country of birth, injection drug use, high-risk sexual behavior)
• Symptoms: jaundice, abdominal pain, weight loss, pruritus, fever
• Family history of liver disease or autoimmune conditions
• Travel history and occupational exposures
• History of inflammatory bowel disease (raises concern for PSC if cholestatic pattern)

Physical Examination Findings

Calculate body mass index and perform abdominal examination looking for: 1, 2

• Hepatosplenomegaly
• Ascites
• Signs of chronic liver disease (spider angiomata, palmar erythema)

Core Laboratory Panel

Order a comprehensive "liver aetiology screen" rather than simply repeating LFTs: 1, 2, 3

• Complete blood count with platelets
• Comprehensive metabolic panel including creatinine
• Additional liver function tests: total and direct bilirubin, albumin, INR
• Viral hepatitis screen: Hepatitis B surface antigen, Hepatitis C antibody
• Autoimmune markers: IgG, ANA, anti-smooth muscle antibody
• Anti-mitochondrial antibody (if cholestatic pattern for primary biliary cholangitis)
• Iron studies: serum iron, total iron-binding capacity, ferritin, transferrin saturation
• For marked ALT elevations (>1000 U/L): Consider Hepatitis A, E, and cytomegalovirus testing 1, 2

Imaging Studies

Abdominal ultrasound should be obtained to assess: 1, 2

• Liver parenchyma
• Biliary tract for dilated ducts
• Signs of cirrhosis or focal lesions

MRI/MRCP should be considered if: 1, 2

• Cholestatic pattern with history of inflammatory bowel disease or autoimmune disease (to evaluate for primary sclerosing cholangitis)
• Ultrasound shows dilated bile ducts

When NOT to Simply Repeat Tests

Do not simply repeat the same panel of tests unless there is high clinical suspicion of a transient finding. 1 The evidence shows that 84% of abnormal LFTs remain abnormal on retesting after 1 month, and 75% remain abnormal at 2 years 1. Simply repeating tests without investigating the cause delays diagnosis and wastes resources 1.

Exception for repeat testing: Only if there is clear evidence of an acute insult (e.g., intercurrent illness, vascular disease) where LFTs are expected to normalize within 2 days 5

Immediate Referral Criteria

Refer immediately to hepatology or hospital if: 1, 2, 3

• Unexplained clinical jaundice
• Suspicion of hepatic or biliary malignancy
• Evidence of synthetic dysfunction (elevated INR, low albumin)
• Dilated bile ducts on imaging
• Imaging suggests advanced fibrosis, cirrhosis, or focal lesions

Urgent referral criteria: 2, 3

• ALT >8× ULN or >5× baseline in those with elevated baseline
• ALT >3× ULN with total bilirubin >2× ULN (meets Hy's Law criteria)
• Persistent elevation >2× ULN after 3 months despite addressing modifiable factors

Management Based on Identified Cause

For suspected NAFLD (most common cause in primary care): 1, 2, 3

• Calculate non-invasive fibrosis scores (FIB-4 or NAFLD Fibrosis Score)
• FIB-4 <1.3 or NAFLD Fibrosis Score ≤-1.455 indicates low risk of advanced fibrosis
• For patients >65 years, use higher cut-offs: FIB-4 <2.0
• Implement lifestyle modifications (weight loss, exercise)

For medication-related elevations: 2, 3

• Consider modification or discontinuation of suspected hepatotoxic medications
• Stop unnecessary medications and known hepatotoxic drugs

For alcohol-related disease: 2, 3

• Recommend alcohol cessation
• AST:ALT ratio >2 supports alcoholic etiology

For specific diagnoses requiring specialist referral: 1

• Hepatitis B (HBsAg positive) or Hepatitis C (antibody positive, then PCR positive)
• Autoimmune hepatitis (raised IgG ± positive autoantibodies)
• Primary biliary cholangitis (cholestatic enzymes + positive anti-mitochondrial antibody)
• Primary sclerosing cholangitis (cholestatic enzymes ± inflammatory bowel disease history)
• Hemochromatosis (raised ferritin and transferrin saturation >45%)

Monitoring Strategy

For mild elevations (<3× ULN) without clear cause: 2, 3

• Repeat testing in 2-5 days to establish trend
• If persistent, proceed with full etiological workup rather than continued monitoring

For identified chronic liver disease: 2

• Monitor liver enzymes every 3-6 months initially
• Annual monitoring for complications

Common Pitfalls to Avoid

Critical errors to avoid: 1, 2, 3

• Don't ignore mild elevations assuming they will resolve - 84% remain abnormal after 1 month 1
• Don't miss hepatitis B or C infection, which may be asymptomatic but require treatment 3
• Don't assume the extent of LFT abnormality correlates with clinical significance - patients with significant fibrosis may have normal or minimally elevated enzymes 1
• Don't forget that isolated elevated ferritin is commonly seen in dysmetabolic iron overload syndrome (NAFLD, alcohol excess) and does not necessarily reflect hemochromatosis 1
• In children, maintain a low threshold for referral to pediatrics as the differential diagnosis is wider and common adult causes are less frequent 1