II. Epidemiology

  1. Mild asymptomatic transaminase elevations (<5x normal) are common
    1. U.S. Prevalence may be as high as 10%
    2. However, serious liver disease is found in only 5% of these cases

III. Approach: Focus of evaluation

  1. Iatrogenic or Treatable disease
  2. Communicable or Inheritable disease
  3. True abnormality versus False Positive testing

V. Symptoms (mild elevations are usually asymptomatic)

  1. Constitutional Symptoms
    1. Fever
    2. Weight loss
    3. Fatigue
    4. Malaise
    5. Nausea or Vomiting
  2. Pruritus
  3. Arthralgias

VI. Signs

  1. Weight loss
  2. Stigmata of Chronic Liver Disease or Cirrhosis
    1. Gynecomastia
    2. Testicular atrophy
    3. Spider nevi
    4. Finger nail Clubbing
    5. Asterixis
  3. Abdominal exam
    1. Hepatomegaly
    2. Splenomegaly
    3. Ascites

VII. Differential Diagnosis (Transaminase elevation)

  1. Common hepatic causes
    1. Alcoholic Liver Disease (27%)
      1. AST/ALT ration >2
      2. GGT increased
    2. Nonalcoholic Fatty Liver Disease (25-51%)
      1. Metabolic Syndrome
      2. Increased Serum Triglycerides and Serum Glucose and low HDL Cholesterol
  2. Uncommon hepatic causes
    1. Hepatitis B or Hepatitis C (18%)
    2. Hemochromatosis (3%)
      1. Serum Iron and Ferritin levels increased
    3. Hepatotoxins (medications)
  3. Rare hepatic causes
    1. Autoimmune Hepatitis (1%)
      1. More common in young women with autoimmune disorders
      2. Evaluation includes SPEP, ANA, SMA, LKM-1
    2. Alpha-1 antitrypsin deficiency (1%)
      1. Associated with premature COPD
    3. Primary biliary Cirrhosis (0.3%)
    4. Wilson Disease
      1. Consider in liver disease at a young age (e.g. <30 years old)
      2. Serum ceruplasmin abnormal
  4. Extrahepatic causes
    1. Celiac Disease
    2. Hemolysis
      1. Causes include G6PD, Sickle Cell Anemia, infection
    3. Muscular disorders (e.g. Polymyositis)
      1. Increased CPK and aldolase
    4. Hypothyroidism or Hyperthyroidism

VIII. Labs

  1. See Liver Function Test
  2. Markers of hepatocyte injury
    1. Precautions
      1. Liver transaminases (ALT, AST) true normal ranges are <25 IU/L in women, <33 IU/L in men
      2. For those with liver disease risk factors, the lab cut-offs (50-60 IU/L) are abnormal (not simply borderline)
      3. Transaminase elevations are considered mild if <5 times normal
      4. Elevations >5 times normal require extensive evaluation for cause
    2. Alanine transaminase (ALT)
      1. Most specific for hepatocyte injury
    3. Aspartate transaminase (AST)
      1. Less specific than ALT (present outside liver)
      2. Non-liver causes include Celiac Sprue, Hemolysis, Dermatomyositis, tissue infarction, Hyperthyroidism
    4. AST to ALT Ratio
      1. AST/ALT ratio <1 in Non-Alcoholic Fatty Liver Disease (LR+ 80, LR- 0.2)
        1. Sorbi (1999) Am J Gastroenterol 94(4): 1018-22 [PubMed]
      2. AST/ALT ratio >2 in Alcoholism (LR+ 17, LR- 0.49)
      3. AST/ALT ratio >4 in Wilson's Disease
    5. Lactate Dehydrogenase (LDH)
      1. Least specific for hepatocyte injury
      2. Dramatically increased in ischemic hepatitis
      3. Increased with alk phos in liver metastases
  3. Markers of cholestasis
    1. Serum Alkaline Phosphatase
    2. Gamma glutamyl transferase (GGT)
    3. Serum Bilirubin
  4. Marker of liver function and Protein synthesis
    1. Serum Albumin
    2. Prothrombin Time
  5. Markers of advanced fibrosis
    1. Platelet Count (Thrombocytopenia)

IX. Imaging

  1. Abdominal Ultrasound right upper quadrant
    1. Preferred cost-effective evaluation
  2. Abdominal CT
    1. Consider if Ultrasound is non-diagnostic

X. Management: Increased serum transaminases (ALT, AST)

  1. Criteria
    1. Indicated in mild, asymptomatic liver transaminase (ALT, AST) elevations <5 times normal
    2. Symptomatic or elevations >5 times normal should prompt more urgent, thorough evaluation
    3. See Alkaline Phosphatase for cholestasis causes
  2. Step 0: History and Physical
    1. Lab and diagnostic evaluation as directed by history and physical
    2. Avoid Hepatotoxins including Alcohol
    3. Consider Fasting lipid profile and Serum Glucose (or complete in step 1)
    4. Plan repeat evaluation and labs in 2-4 weeks (see Step 2)
  3. Step 1: Obtain initial lab work
    1. Hepatic panel (as above)
    2. Prothrombin Time (INR)
    3. Serum Albumin
    4. Complete Blood Count with Platelet Count
    5. Viral Hepatitis Serology
      1. Consider Hepatitis A Serology
      2. Hepatitis B Serology (HBsAg)
      3. Hepatitis C Serology
      4. Consider Monospot
    6. Serum Ferritin, Serum Iron and TIBC (Hemochromatosis)
    7. Fasting lipid profile and Fasting Glucose (or Hemoglobin A1C)
  4. Step 2: Evaluate labs, history and examination
    1. Treat specific causes
    2. Consider Non-Alcoholic Fatty Liver disease (NAFLD) - most common
  5. Step 3: General measures if no cause identified
    1. Avoid Hepatotoxins
      1. Withdraw suspected medications
      2. Abstain from Alcohol use
    2. Reduce hepatic Steatosis risks
      1. Weight loss if Overweight
      2. Improve Blood Sugar control in Diabetes Mellitus
      3. Treat Hyperlipidemia (esp. Serum Triglycerides)
    3. Repeat Liver Function Tests in 2-6 months
      1. Obtain imaging as above if elevations persist
      2. Liver Function Tests often remain elevated on follow-up for longer than 2 years
      3. Lilford (2013) Health Technol Assess 17(28): 1-307 [PubMed]
  6. Step 4: Abnormal transaminases persist on recheck
    1. Obtain Ultrasound of right upper quadrant
    2. Obtain disease specific markers
      1. Complete initial labs in Step 1 if not done
      2. Ceruloplasmin (Wilson's Disease)
      3. Antinuclear Antibody
      4. Anti-Smooth Muscle Antibody
      5. Alpha-1-antitrypsin
      6. Anti-tissue transglutaminase Antibody: Celiac Sprue
    3. Consider non-hepatic transaminase elevations
      1. Peripheral Smear, Coombs test (Hemolysis)
      2. Rhabdomyolysis or Polymyositis (Creatine Kinase, aldolase)
    4. If testing as above is negative for specific cause
      1. Obese patient: See Steatosis
      2. Non-obese Patient
        1. Aminotransferases exceed twice normal
          1. Refer to Gastroenterology for biopsy
        2. Aminotransferases mildly elevated
          1. Follow serial Aminotransferases (AST, ALT)

XI. Management: Increased Alkaline Phosphatase (marked) with normal transaminases

  1. Confirm increase is due to gastrointestinal cause (e.g. as opposed to bone) with a fractionated Alkaline Phosphatase
  2. Cholestatic Liver Disease
    1. Primary Sclerosing Cholangitis
    2. Primary Biliary Cirrhosis
  3. Infiltrative Conditions
    1. Malignancy
    2. Amyloidosis
    3. Sarcoidosis
    4. Infectious disease
  4. References
    1. Loftus (2012) Mayo POIM Conference, Rochester

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Related Studies

Ontology: Liver function tests abnormal finding (C0151766)

Concepts Finding (T033)
ICD9 794.8
ICD10 R94.5
SnomedCT 207471009, 207474001, 158662000, 143922007, 158664004, 274882007, 166603001
English Nonspecific abnormal results of function study of liver, LIVER FUNCTION TESTS ABNORMAL NOS, Abnorm.liver funct.test NOS, Abnorm.liver function test, Abnormal liver function test, Abnormal liver function test NOS, LFT's abnormal, [D]Abnormal liver function test (context-dependent category), [D]Abnormal liver function test NOS (context-dependent category), [D]Abnorm.liver funct.test NOS, [D]Abnorm.liver function test, [D]Abnormal liver function test, [D]Abnormal liver function test NOS, [D]LFT's abnormal, Abn result liver funct studies, Abnormal liver function tests, Liver function test abnormal, Liver function tests NOS abnormal, Liver function tests abnormal NOS, Disturbance of liver function tests, Abn liver function study, abnormal liver function test (diagnosis), abnormal liver function test, Abnormal;liver function test, abnormal function liver tests, abnormal lft, liver function test abnormal, abnormal liver function tests, [D]Abnormal liver function test (situation), [D]Abnormal liver function test NOS (situation), Abnormal results of liver function studies (finding), Liver function tests abnormal, Liver function tests abnormal (finding), function studies; liver abnormal, abnormal; function studies, liver, liver; function studies abnormal, Abnormal results of liver function studies, Liver function tests abnormal finding, Abnormal LFTs
Italian Prova di funzione epatica anormale, Alterazione delle prove di funzionalità epatica, Prove della funzione epatica anormali, Prove di funzionalità epatica anormali NAS, Risultati anormali non specificati di altre prove funzionali del fegato, Prove di funzionalità epatica anormali, Prove di funzionalità epatica NAS anormali
Dutch abnormale leverfunctietests, leverfunctietests NAO abnormaal, verstoring van leverfunctietests, leverfunctietests abnormaal NAO, niet-specifieke abnormale resultaten van functieonderzoek van lever, abnormaal; functie-onderzoek, lever, functie-onderzoek; lever afwijkend, lever; functie-onderzoek afwijkend, Afwijkende uitslagen van leverfunctie-onderzoeken, leverfunctietests abnormaal
French Dérèglement des tests de fonction hépatique, Tests de la fonction hépatique anormaux, Tests de la fonction hépatique anormaux SAI, TFH anormaux, Tests des fonctions hépatiques SAI anormaux, Tests de fonction hépatique anormaux, Résultats de l'étude de la fonction hépatique anormaux non spécifiques, ANOM EPREUVES FONCT HEPAT SAI, Test de la fonction hépatique anormal
German nichtspezifische anomale Ergebnisse einer Funktionsstudie der Leber, Entgleisung der Leberwerte, anomale Leberfunktionstests, Leberfunktionstests anomal NNB, Leberfunktionstests anomal, Leberfunktionstests NNB anomal, anomale LFTs, Abnorme Ergebnisse von Leberfunktionspruefungen, LEBERFUNKTIONSTESTS PATHOLOGISCH, Leberfunktionstest anomal
Portuguese Provas funcionais do fígado anormais NE, Provas da função hepática NE anormais, Provas funcionais do fígado anormais, Alteração das provas funcionais do fígado, Resultados anormais inespecíficos de estudo funcional do fígado, PROVAS DE FUNCAO HEPATICA ANORMAI, Prova da função hepática anormal
Spanish Alteración de las pruebas de función hepática, Pruebas funcionales hepáticas NEOM anormales, Pruebas de función hepática anormales, PFH anormales, Resultados anormales no específicos del estudio de la función del hígado, Pruebas anormales de función hepática NEOM, [D]prueba de función hepática anormal (categoría dependiente del contexto), [D]prueba de función hepática anormal, SAI (categoría dependiente del contexto), HIGADO, PRUEBAS DE FUNCION ANORMA, [D]prueba de función hepática anormal (situación), [D]prueba de función hepática anormal, resultados anormales de estudios de función hepática (hallazgo), resultados anormales de estudios de función hepática, [D]prueba de función hepática anormal, SAI (situación), [D]prueba de función hepática anormal, SAI, pruebas de función hepática anormales (hallazgo), pruebas de función hepática anormales, Prueba anormal de función hepática
Japanese 肝機能検査異常, 肝機能検査の非特異性異常所見, 肝機能検査異常NOS, 肝機能検査NOS異常, カンキノウケンサイジョウNOS, カンキノウケンサノヒトクイセイイジョウショケン, カンキノウケンサイジョウ, カンキノウケンサNOSイジョウ
Czech Abnormální funkční jaterní testy, Porucha funkčních jaterních testů, Abnormální funkční jaterní testy NOS, Funkční jaterní test abnormální, Nespecifické abnormální výsledky funkce jater
Korean 간 기능 연구상 이상 결과
Hungarian Májfunkciós vizsgálatok zavara, Kóros LFT vizsgálat, Kóros májfunkciós vizsgálat, Májfunkciós vizsgálat kóros, Májfunkciós vizsgálatok kóros, Májfunkciós vizsgálatok kóros k.m.n., Nem specifikus kóros májfunkciós vizsgálati eredmények, Májfunkciós vizsgálatok k.m.n. kóros