How to Interpret Liver Function Tests (LFTs) Simplified | Clinical Guide

Cholestatic patterns require distinguishing intrahepatic from extrahepatic causes through imaging. Ultrasound is first-line (non-invasive, no radiation, good for biliary dilation). Intrahepatic causes include drug-induced (anabolic steroids, oral contraceptives), primary biliary cholangitis, intrahepatic cholestasis of pregnancy, and hereditary conditions (PFIC, BRIC). Extrahepatic causes include choledocholithiasis (most common, ~40%), malignancies (cholangiocarcinoma, pancreatic cancer), and postoperative strictures. The diagnostic algorithm progresses from ultrasound to MRCP or EUS based on findings. MRCP is preferred for initial biliary tree assessment, while EUS is better for periampullary lesions or microlithiasis. ERCP is indicated when therapeutic intervention is planned. Two clinical cases demonstrate application: a 45-year-old male with alcoholism and hepatocellular dysfunction suggesting alcoholic cirrhosis, and a 76-year-old female with acute cholangitis requiring urgent ERCP intervention.

Cholestatic liver diseases require a multidisciplinary approach between therapists and surgeons, with diagnosis based on elevated alkaline phosphatase (1.5x normal) and gamma-glutamyl transferase (>3x normal). The diagnostic algorithm includes ultrasound, anti-mitochondrial antibody testing, MRCP, and ERCP as reserved methods. Treatment primarily involves ursodeoxycholic acid and ademetionine, with emerging therapies like obeticholic acid in development. Primary biliary cholangitis is the most common classic cholestatic disease, while primary sclerosing cholangitis carries a significantly increased risk of cholangiocarcinoma requiring regular surveillance.

The diagnostic approach to jaundice follows a systematic algorithm: (1) Fractionate bilirubin to determine unconjugated vs conjugated hyperbilirubinemia; (2) Assess liver function tests to identify hepatocellular vs cholestatic patterns; (3) For cholestatic jaundice, perform ultrasound to distinguish intrahepatic from extrahepatic obstruction; (4) If extrahepatic obstruction is suspected, use MRCP or ERCP; (5) For intrahepatic cholestasis, perform serological tests for primary biliary cholangitis and primary sclerosing cholangitis; (6) If diagnosis remains unclear, liver biopsy may be necessary.

Laboratory evaluation includes CBC (infection, anemia), liver enzymes (AST, ALT, ALP, GGT), and bilirubin fractionation (conjugated vs. unconjugated). Bilirubin metabolism involves formation from heme breakdown, transport by albumin, and conjugation in the liver. Imaging follows a stepwise approach: ultrasound (first-line, shows stones and duct dilation), CT scan (if ultrasound inconclusive), MRCP (less invasive, electromagnetic imaging), and ERCP (most invasive but therapeutic). The diagnostic algorithm prioritizes less invasive tests first, with ERCP reserved for cases requiring both diagnosis and treatment.

Hepatic profile alterations affect 9-21% of the population and are primarily categorized into hepatocellular patterns (elevated aminotransferases indicating hepatocyte damage) and cholestatic patterns (elevated alkaline phosphatase and direct bilirubin indicating bile flow obstruction). Aminotransferases (ALT 13-40 U/L, AST 13-31 U/L) show mild elevation (<300 U/L) in chronic hepatitis, moderate elevation (300-800 U/L) in alcoholic liver disease, and severe elevation (>800 U/L) in viral hepatitis or toxic injury. The AST:ALT ratio helps differentiate causes: >2:1 suggests alcoholic liver disease, while ALT predominance indicates non-alcoholic fatty liver disease or viral hepatitis. Cholestatic patterns require ultrasound to assess biliary dilation, with further imaging (MRCP, ERCP) if ducts are dilated. The clinical approach involves evaluating history (alcohol, transfusions, medications), physical examination, and judicious selection of tests including albumin, prothrombin time, and bilirubin fractionation to guide diagnosis and prognosis.

The AST:ALT ratio is a valuable diagnostic tool: (1) Ratio > 2:1 suggests alcoholic liver disease, (2) Ratio > 1:1 suggests ischemic liver injury, (3) Ratio > 1:1 also seen in congestive hepatopathy (right-sided heart failure), (4) Most other liver diseases show ALT > AST. The ratio helps distinguish between different etiologies and can indicate disease severity, particularly in alcoholic liver disease where the ratio increases with disease progression.

AST (Aspartate Transaminase) and ALT (Alanine Transaminase) are essential enzymes in liver function tests, belonging to the transferase class. Normal ranges are AST 5-40 IU/L and ALT 5-35 IU/L, measured via UV kinetic enzymatic method. ALT is more liver-specific (cytosolic) and the best indicator of hepatocellular injury, while AST is less specific (found in muscle, heart, RBCs, cytosol, and mitochondria). Elevation severity grading: marked (10x normal) indicates acute viral/toxic hepatitis; moderate (2-5x) suggests chronic hepatitis; mild (<2x) indicates fatty liver or drug-induced conditions. The AST:ALT ratio (De Ritis ratio) is crucial: normal 0.8-1.2; ratio >2:1 indicates alcoholic liver disease (mitochondrial damage, vitamin B6 deficiency); ratio <1 indicates viral hepatitis or non-alcoholic fatty liver disease; ratio >3 suggests fulminant hepatic failure. Isolated AST elevation suggests extra-hepatic causes (myocardial infarction, muscle injury, hemolysis). The ratio differentiates alcoholic from non-alcoholic liver disease and assesses disease severity and prognosis.

AST interpretation requires understanding tissue-specific patterns: acute MI shows 5-6x normal rise peaking at 24 hours; viral hepatitis may reach 100x ULN; cirrhosis shows 4x ULN elevation. Increased AST originates from liver (hepatitis, cirrhosis, cholecystitis), cardiac (MI), or skeletal muscle (muscular dystrophy) injury. Decreased AST occurs in vitamin B6 deficiency or hemodialysis. The De Ritis ratio (AST/ALT ≈1.15 normal) differentiates disease etiology: ratios >2 indicate alcoholic liver disease (slower AST release), while ratios <1 suggest viral hepatitis or biliary obstruction (AST resolves before ALT). This systematic approach enables clinicians to identify underlying pathology from enzyme profiles.

The De Ritis Ratio (AST/ALT ratio) is a clinical diagnostic tool used to differentiate alcoholic liver disease from viral hepatitis; when the ratio exceeds 2:1 and AST levels are below 300 U/L, it strongly suggests alcoholic liver damage, as alcohol metabolism generates reactive oxygen species that damage mitochondria (releasing AST) while pyridoxine deficiency reduces ALT production, creating the characteristic elevated ratio.

Chronic Liver Disease (CLD) is assessed using three scoring systems: MELD (Creatinine, Bilirubin, INR) for adults, PELD (Age, Albumin, Bilirubin, Growth Failure, INR) for children under 1 year, and Child-Pugh (Albumin, Bilirubin, Coagulation, Ascites, Encephalopathy) for general CLD assessment.

Prognostic scoring systems predict outcomes and guide treatment decisions: (1) Child-Turcotte-Pugh (CTP) score - uses 5 parameters (ascites, bilirubin, albumin, INR, encephalopathy) scored 1-3 each, total 5-15: 5-6 = well-compensated, 7-9 = moderately compensated, 10-15 = decompensated; (2) MELD score (Model for End-Stage Liver Disease) - uses bilirubin, INR, and creatinine to predict 3-month mortality, used for transplant prioritization. Higher scores indicate worse prognosis. These scores help clinicians assess disease severity, predict transplant outcomes, and allocate scarce liver transplant resources.

Liver disease severity is assessed using multiple scoring systems: Child-Pugh score evaluates bilirubin, albumin, INR, ascites, and encephalopathy (scores 5-6 Class A, 7-9 Class B, 10-15 Class C with ~35% two-year survival). MELD score uses bilirubin, INR, and creatinine to predict mortality (scores 6-40). Fibrosis assessment includes liver biopsy, FibroScan (stiffness >12 kPa suggests cirrhosis), and serological markers. These tools guide treatment decisions, transplant referral, and prognosis estimation.

The MELD (Model for End-Stage Liver Disease) score is used to prioritize patients for liver transplantation and is calculated using bilirubin, INR, and creatinine. Higher scores indicate worse prognosis and higher priority for transplant. The Child-Pugh score assesses cirrhosis severity and prognosis using encephalopathy, ascites, INR, bilirubin, and albumin. Child-Pugh classes (A, B, C) indicate different levels of decompensation. The mnemonic 'BIC' (Bilirubin, INR, Creatinine) helps remember MELD components. Scores >40 indicate very poor prognosis with mortality approaching 71%. These scores are essential for clinical decision-making in cirrhotic patients.

Liver disease severity is assessed using multiple scoring systems. The MELD score (Bilirubin, INR, Creatinine) predicts transplant-free survival and guides liver transplantation prioritization. The Child-Pugh score (Bilirubin, INR, Albumin, Ascites, Encephalopathy) assesses chronic liver disease severity. These scores are essential for determining prognosis, treatment decisions, and transplant eligibility in patients with alcoholic hepatitis and other liver diseases.