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Liver Function Tests and Anaesthetic Implications

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1. Overview of the Liver - Anaesthetic Relevance

• Portal vein: 75% of hepatic blood flow (nutrient-rich, relatively deoxygenated)
• Hepatic artery: 25% of blood flow - each vessel contributes ~50% of oxygen delivery

• Synthesis of all clotting factors (except Factor VIII) and albumin
• Drug metabolism (Phase I - cytochrome P450; Phase II - conjugation)
• Glucose homeostasis, ammonia detoxification (urea cycle)
• Bile production for fat-soluble vitamin absorption

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2. Liver Function Tests: Classification and Interpretation

2.1 Hepatocellular Injury Markers

• AST:ALT ratio >2:1 - strongly suggests alcoholic liver disease
• Mild elevation (<3x ULN): NAFLD, chronic viral hepatitis, medication-induced
• Moderate elevation (3-20x ULN): Acute viral hepatitis
• Markedly elevated (>1000 U/L): Ischaemic hepatitis, acetaminophen toxicity, fulminant hepatitis

2.2 Cholestatic (Canalicular) Markers

2.3 Hepatic Synthetic Function Tests

2.4 Six Major Diagnostic Patterns (Henry's Laboratory Medicine)

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3. Perioperative Risk Stratification in Liver Disease

3.1 Child-Turcotte-Pugh (CTP) Score

• Child's A: Perioperative mortality ~10% (acceptable surgical risk)
• Child's B: Perioperative mortality ~30-50% (significant risk; optimise first)
• Child's C: Perioperative mortality ~82% (elective surgery contraindicated)

3.2 MELD Score (Model for End-Stage Liver Disease)

MELD = 3.78 × ln[bilirubin mg/dL] + 11.2 × ln[INR] + 9.57 × ln[creatinine mg/dL] + 6.43

• Score range: 6-40
• MELD < 11: Low postoperative mortality - acceptable surgical risk
• MELD 12-20: Intermediate risk; consider optimisation
• MELD ≥ 20 (or Child's C): High mortality risk; elective procedures contraindicated until after liver transplantation

Key point from Barash's Clinical Anesthesia: "The perioperative risk of patients with end-stage liver disease depends more on the operative site and the degree of liver impairment than the anesthetic technique."

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4. Anaesthetic Implications of Abnormal LFTs

4.1 Drug Pharmacokinetics in Liver Disease

• Hypoalbuminaemia increases free fraction of highly protein-bound drugs (e.g., thiopentone, diazepam, propofol)
• This increases pharmacodynamic effect for a given dose

• Ascites and peripheral oedema increase Vd for hydrophilic drugs
• Leads to reduced plasma concentrations but prolonged duration of action

• Reduced biotransformation of drugs dependent on hepatic enzymes
• Prolongs action of opioids (fentanyl, morphine), benzodiazepines, local anaesthetics
• Halothane hepatitis: trifluoroacetylated liver proteins formed from halothane, enflurane, isoflurane, and desflurane can trigger immune-mediated hepatic injury

• Bypasses hepatic first-pass metabolism
• Oral bioavailability of drugs (e.g., propranolol, midazolam) is markedly increased
• Nitrogenous waste enters systemic circulation - precipitates encephalopathy

4.2 Specific Drug Considerations

4.3 Coagulopathy: Assessment and Management

• Elevated von Willebrand factor compensates for low platelet count
• Thrombin generation may be normal or even elevated in cirrhosis
• Increased FVIII (not produced by hepatocytes)

• Reduced Factors II, V, VII, IX, X, XI
• Reduced Protein C and Antithrombin III (actually pro-thrombotic)
• Thrombocytopenia (30-64% of cirrhotics): primarily from splenic sequestration in portal hypertension
• Dysfibrinogenaemia in 70-80% of cirrhotics

• Standard PT/INR overestimates bleeding risk in cirrhosis
• Thromboelastography (TEG) or ROTEM better guide transfusion in bleeding cirrhotic patients
• Vitamin K infusion can correct coagulopathy of cholestatic disease (fat-soluble vitamin malabsorption), but NOT hepatocellular dysfunction
• Platelet transfusion indicated for active bleeding with count <56,000/mm³ (minimum needed for near-normal thrombin generation); not for prophylaxis alone
• In cholestatic disease with cholestasis: parenteral vitamin K corrects deficiency in Factors II, VII, IX, X, Protein C, and S

4.4 Cardiovascular Implications

• Decreased systemic vascular resistance (SVR)
• Increased cardiac output (CO)
• Relative hypotension
• Mechanism: excess nitric oxide and splanchnic vasodilation

• Hypotension during induction is common and exaggerated
• Volatile agents and neuraxial blockade worsen SVR reduction
• "Cirrhotic cardiomyopathy" - systolic dysfunction may be unmasked by TIPS (transjugular intrahepatic portosystemic shunt) which increases preload

4.5 Respiratory Implications

• Hepatopulmonary syndrome: intrapulmonary shunting causing hypoxaemia; V/Q mismatch; platypnoea (dyspnoea worse when upright)
• Portopulmonary hypertension: elevated PVR; significant perioperative risk
• Ascites: impairs respiratory mechanics; increased aspiration risk; patient may not tolerate supine position
• Requires modified rapid sequence induction consideration

4.6 Renal Implications

• Hepatorenal syndrome (HRS): intense renal vasoconstriction in setting of portal hypertension; functional renal failure
• Oliguria and rising creatinine in a cirrhotic are a medical emergency
• Avoid nephrotoxic agents: aminoglycosides, NSAIDs, contrast agents
• Albumin is indicated for HRS-AKI in conjunction with splanchnic vasoconstrictors (terlipressin)
• Bilirubin >4 mg/dL or creatinine >1 mg/dL + spontaneous bacterial peritonitis: albumin infusion prevents renal impairment

4.7 Hepatic Encephalopathy

• Precipitated by sedatives, opioids, benzodiazepines, constipation, GI bleeding, infection
• All CNS depressants dramatically worsen encephalopathy
• Grade III-IV encephalopathy: cerebral oedema risk 25-75%
• Avoid N2O (increases intracranial pressure in encephalopathy)

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5. Preoperative Optimisation in the Patient with Liver Disease

1. Treat active infection (SBP, etc.) before elective surgery
2. Minimise vasoactive infusions - allow baseline haemodynamics to stabilise
3. Optimise central blood volume and renal status - correct dehydration or volume overload
4. Minimise ascites - therapeutic paracentesis; administer albumin 6-8 g per litre drained
5. Improve encephalopathy - lactulose, rifaximin; restrict precipitants
6. Correct coagulopathy - use TEG/ROTEM to guide targeted therapy; avoid blanket FFP prophylaxis
7. Avoid oesophageal instrumentation if varices present or suspected

• Acute alcoholic hepatitis (high perioperative mortality)
• Acute liver failure
• Acute viral hepatitis
• MELD ≥ 20 or Child's C (unless surgery is life-saving)

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6. Halothane Hepatitis and Anaesthetic Agent Hepatotoxicity

• Type I (mild, transient): Subclinical AST/ALT elevation after any halogenated volatile agent; due to Zone 3 hepatocyte hypoxia; self-limiting
• Type II (immune-mediated halothane hepatitis): Rare (1:35,000 exposures); occurs after repeated halothane exposure; trifluoroacetyl (TFA) protein adducts act as neoantigens; massive hepatocellular necrosis; mortality 50-75%
• All halogenated agents (halothane, enflurane, isoflurane, desflurane) form TFA protein adducts, but to differing degrees
• Halothane highest risk; desflurane and isoflurane very low risk
• Prior volatile agent hepatitis is a contraindication to future halogenated agents

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7. Acute Liver Failure (ALF) - Anaesthetic Management

• Cerebral oedema is the leading cause of death (75% incidence in Grade IV encephalopathy)
• Targets: control ICP; maintain CPP; osmotherapy (hypertonic saline/mannitol); avoid hypercapnia
• Coagulopathy management: FFP and platelets as needed but guided by TEG/ROTEM
• Renal support: haemofiltration often required
• Haemodynamic instability: vasopressor support; avoid hypotension (reduces hepatic perfusion further)

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8. Summary Table: LFT Abnormality and Anaesthetic Concerns

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• Barash, Cullen, and Stoelting's Clinical Anesthesia, 9th Edition - Chapter 46 (Hepatic Function)
• Henry's Clinical Diagnosis and Management by Laboratory Methods - Chapter 9 (LFTs)
• Schwartz's Principles of Surgery, 11th Edition - Liver Function Tests
• Sleisenger and Fordtran's Gastrointestinal and Liver Disease - Surgical Candidacy
• Recent review: Espinosa et al., "Anaesthesia evaluation and perioperative strategies in liver disease patients with cardiohepatic syndrome," Rev Esp Anestesiol Reanim, 2025 [PMID: 40147631]