Evaluation of Liver Function¶
Chapter 348 | Part 10: Disorders of the Gastrointestinal System
KEY CLINICAL POINTS¶
- Child-Pugh and MELD scores are critical for staging cirrhosis and prioritizing liver transplantation.
- Liver function tests (LFTs) include serum enzymes (AST, ALT), bilirubin, albumin, and coagulation factors (INR).
- Non-invasive fibrosis tests (FibroTest, FIB4, TE/MRE) and imaging (ultrasound, MRI) are essential for diagnosing liver disease.
- Isolated hyperbilirubinemia requires differentiation between conjugated (liver/biliary disease) and unconjugated (hemolysis, genetic disorders).
- Liver biopsy remains the gold standard for confirming diagnoses and staging fibrosis in focal liver lesions.
1. DEFINITION & OVERVIEW¶
Liver function evaluation encompasses biochemical, radiologic, and histologic tests to assess hepatic synthetic, metabolic, and excretory functions. Key tests include serum enzymes (AST, ALT), bilirubin, albumin, coagulation factors, and imaging modalities. The Child-Pugh and MELD scores are used to predict prognosis and prioritize liver transplantation.
Table 347-6 Child-Pugh Classification of Cirrhosis¶
| FACTOR | POINTS TOWARD TOTAL SCORE | UNITS | 1 | 2 | 3 |
|---|---|---|---|---|---|
| Serum bilirubin | mmol/L | <34 | 34–53 | >51 | |
| Serum bilirubin | mg/dL | <2.0 | 2.0–3.0 | >3.0 | |
| Serum bilirubin | g/L | >35 | 30–35 | <30 | |
| Serum bilirubin | g/dL | >3.5 | 3.0–3.5 | <3.0 | |
| Prothrombin time | Seconds prolonged | <4 | 4–6 | >6 | |
| Prothrombin time | INRa | <1.7 | 1.7–2.3 | >2.3 | |
| Ascites | None | Easily controlled | Poorly controlled | ||
| Hepatic encephalopathy | None | Minimal | Advanced |
1.1 Liver Function Tests¶
Serum biochemical tests (aminotransferases, bilirubin, albumin, INR) detect liver disease, differentiate etiologies (hepatocellular vs. cholestatic), and monitor treatment response. However, they lack specificity and cannot confirm diagnoses alone.
1.2 Non-Invasive Fibrosis Assessment¶
Multiparameter blood tests (FibroTest, ELF) and imaging (TE/MRE) provide non-invasive staging of hepatic fibrosis. These are increasingly used as alternatives to liver biopsy for fibrosis assessment.
2. EPIDEMIOLOGY¶
Liver disease affects 10–15% of the global population. Risk factors include viral hepatitis (B/C), alcohol abuse, non-alcoholic fatty liver disease (NAFLD), and metabolic syndrome. Cirrhosis prevalence is 0.5–1.5% in developed countries, with higher rates in populations with chronic hepatitis or alcohol use.
2.1 Demographics¶
Cirrhosis is more common in males, individuals over 50 years, and those with a history of heavy alcohol consumption. Hepatitis B and C are leading causes in endemic regions.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
Liver dysfunction arises from hepatocellular injury (viral hepatitis, alcohol), cholestasis (biliary obstruction, drugs), or systemic conditions (cirrhosis, metabolic disorders). The MELD score reflects hepatic synthetic function via INR, bilirubin, and creatinine.
3.1 Hepatocellular Injury¶
Damage to hepatocytes disrupts protein synthesis (albumin, clotting factors) and enzyme release (AST, ALT). Viral hepatitis, alcohol, and toxins cause necrosis, leading to elevated transaminases.
3.2 Cholestasis¶
Impaired bile flow results in conjugated hyperbilirubinemia, elevated alkaline phosphatase, and pruritus. Causes include intrahepatic (primary biliary cholangitis) or extrahepatic (stones, tumors) obstruction.
4. CLINICAL FEATURES¶
Symptoms include jaundice, fatigue, ascites, and hepatic encephalopathy. Signs may involve spider angiomas, palmar erythema, and splenomegaly. Complications include variceal hemorrhage, spontaneous bacterial peritonitis, and hepatocellular carcinoma (HCC).
4.1 Jaundice¶
Conjugated hyperbilirubinemia (direct) indicates biliary obstruction or hepatocellular damage. Unconjugated hyperbilirubinemia (indirect) suggests hemolysis or genetic disorders (e.g., Gilbert’s syndrome).
5. DIFFERENTIAL DIAGNOSIS¶
Distinguish between hepatocellular (elevated AST/ALT), cholestatic (elevated alkaline phosphatase), and non-hepatic causes (hemolysis, muscle disease). Consider viral hepatitis, autoimmune liver disease, and drug-induced injury.
5.1 Alkaline Phosphatase Elevation¶
Liver origin (cholestasis, cirrhosis) vs. bone/biliary isoenzymes. Elevated GGT may indicate alcohol use or biliary disease.
6. INVESTIGATIONS & DIAGNOSIS¶
Diagnostic workup includes serum bilirubin, aminotransferases, INR, and imaging (ultrasound, MRI). Liver biopsy is reserved for focal lesions or uncertain diagnoses. The algorithm in Figure 348-1 guides evaluation of abnormal LFTs.
Table 348-1 Liver Test Patterns¶
| Test Pattern | Etiology |
|---|---|
| Isolated elevation of bilirubin | Hemolysis, Gilbert’s syndrome |
| Isolated elevation of alkaline phosphatase | Cholestasis, bone disease |
| Elevated AST/ALT | Hepatocellular injury (hepatitis, drug toxicity) |
| Elevated INR | Impaired synthetic function (cirrhosis) |
6.1 Liver Function Tests¶
AST/ALT ratios help differentiate etiologies: AST/ALT >1 suggests alcohol or cirrhosis; AST/ALT <1 indicates viral hepatitis or NAFLD.
6.2 Imaging¶
Ultrasound detects biliary obstruction, gallstones, and space-occupying lesions. MRCP/ERCP evaluates biliary tree anatomy. TE/MRE assesses hepatic stiffness for fibrosis.
7. MANAGEMENT & TREATMENT¶
Management includes avoiding hepatotoxic drugs, treating underlying causes (e.g., antivirals for hepatitis), and monitoring for complications. Cirrhosis requires beta-blockers for varices and HCC surveillance. Liver transplantation is indicated for end-stage disease.
7.1 Cirrhosis Management¶
Beta-blockers (e.g., propranolol) prevent variceal bleeding. Surveillance for HCC via ultrasound every 6 months. Avoid NSAIDs and alcohol.
7.2 Non-Invasive Fibrosis Testing¶
FibroTest, FIB4, and TE/MRE guide treatment decisions without biopsy. These tests are preferred for patients with chronic hepatitis or MASLD.
8. PROGNOSIS & COMPLICATIONS¶
Child-Pugh class C (score ≥ 10) and MELD score >30 predict poor outcomes. Complications include variceal hemorrhage, HCC, and hepatic encephalopathy. Prognosis is worse with advanced fibrosis or cirrhosis.
8.1 MELD Score¶
MELD 3.0 incorporates INR, bilirubin, creatinine, and sodium. Higher scores indicate greater mortality risk and prioritize liver transplantation.
9. SPECIAL CONSIDERATIONS¶
Pregnancy: Avoid hepatotoxic drugs; monitor for hepatic dysfunction. Pediatrics: Use PELD score for liver transplantation. Elderly: Consider drug interactions and reduced hepatic clearance. Monitor for drug-induced liver injury (DILI).
9.1 Drug Use¶
Avoid NSAIDs, acetaminophen, and anabolic steroids in cirrhosis. Use paracetamol cautiously in patients with chronic alcohol use.
10. KEY POINTS & CLINICAL PEARLS¶
- Use Child-Pugh and MELD scores to stage cirrhosis and prioritize transplants. 2. Isolated hyperbilirubinemia requires fractionation to distinguish etiologies. 3. Aminotransferase ratios (AST/ALT) help differentiate liver disease types. 4. Non-invasive fibrosis tests reduce the need for liver biopsy in many cases. 5. Monitor for complications (varices, HCC) in cirrhosis with regular imaging and endoscopy.