Abnormal Liver Function Tests: MCCQE1 Preparation Guide

Introduction

Evaluating Abnormal Liver Function Tests (LFTs) is a core competency for the Medical Council of Canada Qualifying Examination Part I (MCCQE1). As a future Canadian physician, you must demonstrate the Medical Expert role by differentiating between markers of hepatocellular injury, cholestasis, and true liver function.

Understanding the Terminology

The term “Liver Function Tests” is often a misnomer. It is vital to distinguish between enzymes that indicate injury and markers that indicate function.

Classification of Liver Abnormalities

For MCCQE1, you must categorize LFT abnormalities into one of three primary patterns. This is the first step in the diagnostic algorithm.

Clinical Approach to Abnormal LFTs

Follow this step-by-step approach to handle clinical scenarios on the MCCQE1.

Differential Diagnosis by Pattern

1. Hepatocellular Pattern (Elevated AST/ALT)

Magnitude of Elevation

• Mild (< 5x ULN): Chronic viral hepatitis (B, C), MASLD, Alcohol, Hemochromatosis.
• Moderate (5–15x ULN): Acute viral hepatitis, Alcoholic hepatitis (rarely > 300-500 U/L), Autoimmune.
• Massive (> 1000 U/L): Ischemic hepatitis (“Shock liver”), Toxin/Drug-induced (Acetaminophen), Acute viral hepatitis.

The De Ritis Ratio (AST:ALT Ratio)

• AST:ALT > 2:1 → Suggestive of Alcohol-Associated Liver Disease.
  • Mnemonic: Scotch = AST.
• AST:ALT < 1 → Most other causes (Viral, MASLD).

2. Cholestatic Pattern (Elevated ALP)

Confirm liver origin by checking GGT or 5’-Nucleotidase. If GGT is normal, consider bone sources (Paget’s, malignancy, pregnancy).

Canadian Guidelines & Screening

For MCCQE1, you must be familiar with guidelines from the Canadian Association for the Study of the Liver (CASL).

MCCQE1 Study Checklist: Common Etiologies

Use this task list to ensure you have covered the high-yield topics for the exam.

• MASLD (NAFLD): Associated with metabolic syndrome. Diagnosis of exclusion + imaging. Management: Weight loss.
• Alcoholic Hepatitis: Fever, jaundice, tender hepatomegaly, AST>ALT (2:1). Maddrey’s Discriminant Function for severity.
• Autoimmune Hepatitis: Young women, other autoimmune conditions. Diagnosis: ANA, ASMA, IgG levels.
• Wilson’s Disease: Age < 40, neuropsychiatric symptoms, Kayser-Fleischer rings. Low ceruloplasmin.
• Alpha-1 Antitrypsin Deficiency: Lung (emphysema) + Liver disease. PAS-positive globules on biopsy.

Sample Question

Clinical Scenario

A 52-year-old woman presents to her family physician with a 3-month history of generalized pruritus and fatigue. She denies abdominal pain, fever, or weight loss. Her past medical history is significant for hypothyroidism. She does not drink alcohol and takes no new medications.

Physical Examination:

• Vitals: Stable.
• Skin: Excoriations on extremities, xanthelasma present on eyelids. No jaundice or spider angiomata.
• Abdomen: Soft, non-tender. Liver edge is palpable 2 cm below the costal margin, smooth. Spleen is not palpable.

Laboratory Investigations:

• Hemoglobin: 135 g/L
• ALT: 55 U/L (Normal: <35)
• AST: 48 U/L (Normal: <35)
• ALP: 340 U/L (Normal: 35–105)
• GGT: 180 U/L (Normal: <40)
• Bilirubin (Total): 18 µmol/L (Normal: <22)

Which one of the following investigations is most likely to confirm the diagnosis?

Options

• A. Endoscopic Retrograde Cholangiopancreatography (ERCP)
• B. Serum Antimitochondrial Antibody (AMA)
• C. Serum Antinuclear Antibody (ANA) and Anti-Smooth Muscle Antibody (ASMA)
• D. Serum Ferritin and Transferrin Saturation
• E. Abdominal Ultrasound

Explanation

The correct answer is:

• B. Serum Antimitochondrial Antibody (AMA)

Detailed Analysis: This clinical vignette describes a classic presentation of Primary Biliary Cholangitis (PBC).

• Epidemiology: PBC predominantly affects middle-aged women.
• Presentation: Fatigue and pruritus are the most common presenting symptoms. Xanthelasma (cholesterol deposits) occurs due to hyperlipidemia associated with cholestasis.
• Biochemistry: The lab profile shows a cholestatic pattern (significantly elevated ALP and GGT) with only mild elevation of transaminases (ALT/AST).
• Associations: There is a strong association with other autoimmune conditions, such as hypothyroidism (Hashimoto’s), as seen in this patient.

Why the other options are incorrect:

• A. ERCP: This is used for visualizing the biliary tree and treating extrahepatic obstruction (e.g., stones, strictures). While Primary Sclerosing Cholangitis (PSC) affects the large ducts and is diagnosed via imaging (MRCP/ERCP), PBC affects the small intralobular bile ducts, which are not visible on ERCP.
• C. ANA and ASMA: These are markers for Autoimmune Hepatitis. While Autoimmune Hepatitis can present with fatigue, the biochemical pattern is typically hepatocellular (elevated ALT/AST), not cholestatic.
• D. Ferritin and Transferrin Saturation: These are screening tests for Hereditary Hemochromatosis. This condition usually presents with elevated transaminases, skin hyperpigmentation (“bronze diabetes”), and arthralgia, not a cholestatic picture with pruritus.
• E. Abdominal Ultrasound: While an ultrasound is a reasonable initial test to rule out extrahepatic biliary obstruction (stones, masses), the clinical picture strongly points to an intrahepatic autoimmune cause (PBC). The confirmatory diagnostic test is AMA, which is positive in ~95% of patients with PBC.

Key Points to Remember for MCCQE1

1. Isolate the Pattern: Always determine if the injury is Hepatocellular (ALT/AST), Cholestatic (ALP/GGT), or Mixed.
2. Check Function: Remember that enzymes do not equal function. Always look at INR and Albumin to assess synthetic capacity.
3. Gilbert’s Syndrome: A very common cause of isolated unconjugated hyperbilirubinemia triggered by stress or fasting. It is benign and requires no treatment.
4. Acetaminophen Toxicity: The most common cause of acute liver failure. Nomogram use is critical.
5. Canadian Epidemiology: Keep MASLD, Alcohol, and Hepatitis C (Baby Boomers + risk factors) high on your differential.

References

1. Medical Council of Canada. MCCQE Part I Objectives: Hepatobiliary System.
2. Canadian Association for the Study of the Liver (CASL). Guidelines for the Management of Non-Alcoholic Fatty Liver Disease.
3. Burak, K. W., et al. (2018). Management of Hepatocellular Carcinoma in Canada: CASL Consensus Statement.
4. Krawczyk, M., et al. (2021). Hereditary Hemochromatosis: Origins, genetic testing, and clinical management in Canada.
5. Toronto Centre for Liver Disease. Clinical Algorithms.