Specific Liver Function Tests (LFT’s) (see Liver Function Tests)
Transaminases (Aminotransferases) (see Serum Transaminases)
- Transaminases (Aminotransferases)
- Aspartate Aminotransferase (AST) (see Serum Transaminases)
- Formerly Called Serum Glutamate-Oxaloacetate Transaminase (SGOT)
- Alanine Aminotransferase (ALT) (see Serum Transaminases)
- Formerly Called Serum Glutamate-Pyruvate Transaminase (SGPT)
- Aspartate Aminotransferase (AST) (see Serum Transaminases)
- Origin of Transaminases (Aminotransferases)
- Liver: AST and ALT
- Cardiac and Skeletal Muscle: AST only
- Thyroid: AST only
- Sensitivity/Specificity of Transaminases (Especially ALT) for the Differentiation of Liver Disease from Other Disorders Depends on the Cutoff Value Chosen to Define an Abnormal Result
- ALT Levels Correlate with the Degree of Abdominal Adiposity Vary Between the Sexes
- AST and ALT Upper Limits of Normal Vary Between Laboratories: due to differing reference standards used
- Optimal ALT Cutoff Value (Male): 29 IU/L (Hepatology, 2012) [MEDLINE]
- Optimal ALT Cutoff Value (Female): 22 IU/L (Hepatology, 2012) [MEDLINE]
Alkaline Phosphatase (see Serum Alkaline Phosphatase)
- Origin of Alkaline Phosphatase
- Bone
- Intestine
- Kidney
- Liver
- Third Trimester Placenta
- Determination of Origin
- Elevated Alkaline Phosphatase Associated with a Normal Gamma-Glutamyl Transpeptidase or 5′-Nucleotidase Suggests a Non-Hepatic Source of the Alkaline Phosphatase
- Fractionation of Alkaline Phosphatase: may also be used to determine origin
- Heat-Labile Alkaline Phosphatase: suggests bone origin (“bone burns”)
- Heat-Stable Alkaline Phosphatase: suggests liver origin
- Alkaline Phosphatase Levels are Age-Dependent
- Alkaline Phosphatase Levels are Higher (Up to 3x Adult Levels) in Children and Adolescents: due to physiologic osteoblastic activity
- Normal Alkaline Phosphatase Level Increases from 40 to 65 y/o: especially in women
Gamma-Glutamyl Transpeptidase (GGT) (see Serum Gamma-Glutamyl Transpeptidase)
- General Comments
- Gamma-Glutamyl Transpeptidase is Elevated in Normal Neonates: levels decrease and reach adult levels by 5-7 mo of age
- Although GGT Has High Sensitivity for Liver Disease, Due to its Low Specificity, it Should Only Be Used to Evaluate Other LFT Abnormalities
- Origin of Gamma-Glutamyl Transpeptidase
- Biliary Epithelial Cells
- Brain
- Heart
- Hepatocytes
- Kidney
- Pancreas
- Seminal Vesicle
- Spleen
Bilirubin (see Serum Bilirubin)
- Bilirubin Species
- Unconjugated (Indirect) Bilirubin (see Serum Bilirubin)
- Conjugated (Direct) Bilirubin (see Serum Bilirubin)
5′-Nucleotidase (see Serum 5′-Nucleotidase)
- General Comments
- Physiologic Function of 5′-Nucleotidase is Unknown
- Origin of 5′-Nucleotidase
- Blood Vessels
- Brain
- Endocrine Pancreas
- Heart
- Liver: liver is the only organ which releases 5′-nucleotidase into the serum
Lactate Dehydrogenase (LDH) (see Serum Lactate Dehydrogenase)
- General Comments
- LDH is a Cytoplasmic Enzyme Found in Many Organs
- There are 5 LDH Isoenzymes of LDH Present in the Serum: isoenzymes can be separated by electrophoresis
- Slowest Migrating Isoenzyme is the Predominant Form Present in the Liver
- Origin of Lactate Dehydrogenase Isoenzymes
- LDH-1 (4H) Isoenzyme
- Brain
- Heart
- Red Blood Cell (RBC)
- LDH-2 (3H1M) Isoenzyme
- Reticuloendothelial System
- LDH-3 (2H2M) Isoenzyme
- Lung
- LDH-4 (1H3M) Isoenzyme
- Kidney
- Pancreas
- Placenta
- LDH-5 (4M) Isoenzyme
- Liver
- Striated Muscle
- LDH-1 (4H) Isoenzyme
Patterns of Liver Function Test Abnormalities
General Patterns
- Hepatocellular Pattern
- Disproportionate Transaminitis, Compared to Elevation of Alkaline Phosphatase
- Total Bilirubin May Be Elevated
- Tests of Hepatic Synthetic Function (Serum Albumin, Prothrombin Time/International Normalized Ratio) May Be Abnormal
- Cholestatic Pattern
- Disproportionate Elevation in Alkaline Phosphatase, as Compared to Transaminitis
- Total Bilirubin May Be Elevated
- Tests of Hepatic Synthetic Function (Serum Albumin, Prothrombin Time/International Normalized Ratio) May Be Abnormal
- Isolated Hyperbilirubinemia
- Hyperbilirubinemia with Normal Transaminases and Alkaline Phosphatase
Magnitude of AST and ALT Elevation
- General Comments: magnitude of AST and ALT elevations vary depending on the etiology of the hepatocellular injury
- Non-Alcoholic Fatty Liver Disease (NAFLD) (see Non-Alcoholic Fatty Liver Disease)
- AST: <4x upper limit of normal
- ALT: <4x upper limit of normal
- Alcoholic Fatty Liver Disease
- AST: <8x upper limit of normal
- ALT: <5x upper limit of normal
- Chronic Hepatitis B Virus Infection (see Hepatitis B Virus):
- AST: may be normal-2x upper limit of normal (may increase to >10x upper limit of normal during exacerbation)
- ALT: may be normal-2x upper limit of normal (may increase to >10x upper limit of normal during exacerbation)
- Chronic Hepatitis C Virus Infection (see Hepatitis C Virus):
- AST: wide variability, but usually <2x upper limit of normal (rarely >10x upper limit of normal)
- ALT: wide variability, but usually <2x upper limit of normal (rarely >10x upper limit of normal)
- Acute Viral/Toxic Hepatitis with Associated Hyperbilirubinemia
- AST: >25x upper limit of normal
- ALT: >25x upper limit of normal
- Ischemic Hepatitis (Hypoxic Hepatitis, Shock Liver) (see Ischemic Hepatitis)
- AST: >50x upper limit of normal
- ALT: >50x upper limit of normal
- LDH: markedly elevated (usually)
Etiology of Mildly-Moderately Elevated Transaminases (Transaminitis <15x Upper Limit of Normal)
Hepatic Disease
AST-Predominant (AST/ALT Ratio ≥1)
- Alcohol-Related Liver Disease
- General Comments
- Alcoholic Hepatitis (see Alcoholic Hepatitis)
- Alcoholic Liver Disease (see Alcoholic Liver Disease)
- Cirrhosis Due to Viral Hepatitis (see Cirrhosis)
- AST/ALT Ratio is Frequently >1 (But is Usually <2)
- Non-Alcoholic Fatty Liver Disease (NAFLD) (see Non-Alcoholic Fatty Liver Disease)
- AST/ALT Ratio May Be >1 in Some Cases
- Wilson Disease (see Wilson Disease)
- AST/ALT Ratio May Be >1
- Fuliminant Wilson Disease Cases Frequently Present with AST/ALT Ratio >2.2 and Alkaline Phosphatase/Total Bilirubin Ratio <4
ALT-Predominant (AST/ALT Ratio <1)
- General Comments: AST/ALT ratio is <1 in most cases of hepatocellular injury
- Alpha-1 Antitrypsin Deficiency (see Alpha-1 Antitrypsin Deficiency)
- Autoimmune Hepatitis (see Autoimmune Hepatitis)
- Chronic Viral Hepatitis
- Hepatitis B Virus (HBV) (see Hepatitis B Virus)
- Hepatitis C Virus (HCV) (see Hepatitis C Virus)
- Congestive Hepatopathy (see Congestive Hepatopathy)
- Drug/Toxin
- Acetaminophen Intoxication (see Acetaminophen Intoxication)
- Drug-Induced Hepatotoxicity (see Drug-Induced Hepatotoxicity)
- Toxic Mushrooms (see Toxic Mushrooms)
- Hemochromatosis (see Hemochromatosis)
- Hepatic Metastases
- Breast Cancer (see Breast Cancer)
- Lymphoma (see Lymphoma)
- Melanoma (see Melanoma)
- Multiple Myeloma (see Multiple Myeloma)
- Small Cell Lung Cancer (see Lung Cancer)
- Non-Alcoholic Fatty Liver Disease (NAFLD) (see Non-Alcoholic Fatty Liver Disease)
- Wilson Disease (see Wilson Disease)
Non-Hepatic Disease
- Adrenal Insufficiency (see Adrenal Insufficiency)
- Anorexia Nervosa (see Anorexia Nervosa)
- Celiac Disease (see Celiac Disease)
- Congestive Heart Failure (CHF) (see Congestive Heart Failure)
- Macro AST: moderate elevations in plasma AST due to the presence of AST-immunoglobulin complexes (usually IgG)
- Muscle Disorders
- Inborn Errors of Muscle Metabolism
- Polydermatomyositis (see Polydermatomyositis)
- Seizures (see Seizures)
- Heavy Exercise
- Marathon Running
- Myocardial Infarction (MI) (see Coronary Artery Disease)
- Thyroid Disease
Clinical Evaluation of Mildly-Moderately Elevated Transaminases (Transaminitis <15x Upper Limit of Normal)
- Abdominal CT (see Abdominal-Pelvic Computed Tomography)
- Abdominal CT is Useful to Diagnose Hepatic Steatosis (see Hepatic Steatosis)
- Abdominal MRI (see Abdominal-Pelvic Magnetic Resonance-Pelvic Imaging)
- Abdominal MRI is Useful to Diagnose Hepatic Steatosis (see Hepatic Steatosis)
- Autoimmune Serologies/Studies: useful to diagnose autoimmune hepatitis (see Autoimmune Hepatitis)
- Antinuclear Antibody (ANA) (see Antinuclear Antibody)
- Anti-Smooth Muscle Antibody (see Anti-Smooth Muscle Antibody)
- Anti-Liver/Kidney Microsomal Antibody Type 1 (see Anti-Liver-Kidney Microsomal-1 Antibody)
- Cosyntropin (Cortrosyn) Stimulation Test (ACTH Stimulation Test) (see Cosyntropin Stimulation Test): in appropriate patients with relevant symptoms/signs, this is useful to diagnose adrenal insufficiency (see Adrenal Insufficiency)
- Evaluation for Kaiser-Fleisher Rings: useful to diagnose Wilson disease (see Wilson Disease)
- Hepatobiliary Ultrasound with Dopplers (see Abdominal-Pelvic Ultrasound)
- Hepatic Ultrasound is Useful to Diagnose Hepatic Steatosis (see Hepatic Steatosis)
- Doppler Studies are Required to Exclude Hepatic Vein Thrombosis (Budd-Chiari Syndrome)
- Liver Biopsy (see Liver Biopsy): may be required if remaining work-up is non-diagnostic
- Utility of Liver Biopsy in the Setting of Chronic LFT Abnormalities (Am J Gastroenterol, 2000) [MEDLINE]
- Liver Biopsy May Aid in a Diagnosis, But the Results Infrequently Alter the Presumptive Pre-Biopsy Diagnosis and No Proven Therapy Exists for the Vast Majority of Patients
- Risks and Benefits of Liver Biopsy Should Be Carefully Considered, Especially in Settings Where Investigational Therapies are Not Available
- Liver Biopsy is Probably Indicated in Patients with Undiagnosed Persistent Transaminitis >2 Upper Limit of Normal
- Utility of Liver Biopsy in the Setting of Chronic LFT Abnormalities (Am J Gastroenterol, 2000) [MEDLINE]
- Serum Aldolase (see Serum Aldolase): in patients with suspected muscle disorder
- Serum Alpha-1 Antitrypsin Level (see Serum Alpha-1 Antitrypsin): useful to diagnose alpha-1 antitrypsin deficiecy
- Serum Ceruloplasmin (see Serum Ceruloplasmin): useful to diagnose Wilson disease (see Wilson Disease)
- Serum Creatine Kinase (CK) (see Serum Creatine Kinase): in patients with suspected muscle disorder
- Serum Iron and Total Iron Binding Capacity (Transferrin Saturation) (see xxxx)
- Transferrin Saturation >45% Warrants Obtaining a Serum Ferritin (see Serum Ferritin)
- Serum Ferritin Should Not Be Obtained as an Initial Test Since it is an Acute Phase Reactant and is Less Specific than the Transferrin Saturation
- Serum Ferritin >400 ng/mL (>900 pmol/L) in Male and >300 ng/mL (<675 pmol/L) in Female Supports (But Does Not Confirm) the Diagnosis of Hemochromatosis (see Hemochromatosis)
- Serum Protein Electrophoresis (SPEP) (see Serum Protein Electrophoresis)
- SPEP is Useful to Diagnose Autoimmune Hepatitis (see Autoimmune Hepatitis)
- Serum Transglutaminase Antibody (see Serum Transglutaminase Antibody): useful to diagnose celiac disease (see Celiac Disease)
- Thyroid Function Tests (TFT’s) (see Thyroid Function Tests)
- Serum Thyroid Stimulating Hormone (TSH)
- Free T4
- Free T3
- Urinary Copper Excretion: useful to diagnose Wilson disease (see Wilson Disease)
- Viral Serologies/Studies
- Hepatitis B Surface Antigen (HBsAg)
- Anti-Hepatitis B Core Antigen IgM Antibody (Anti-HBc)
- Anti-Hepatitis C Antibody
Etiology of Markedly Elevated Transaminases (Transaminitis >15x Upper Limit of Normal)
Fulminant Hepatic Failure (Acute Liver Failure) (see Fulminant Hepatic Failure)
- Physiology: acute hepatocellular injury
- Clinical
- Hepatic Encephalopathy
- Liver Function Tests >10x Upper Limit of Normal
- Prolonged Prothrombin Time (International Normalized Ratio)
Other Liver Disease (without Fulminant Hepatic Failure)
- Acute Viral Hepatitis
- Cytomegalovirus (CMV) (see Cytomegalovirus)
- Epstein-Barr Virus (EBV) (see Epstein-Barr Virus)
- Hepatitis A Virus (see Hepatitis A Virus)
- Hepatitis B Virus (HBV) (see Hepatitis B Virus)
- Hepatitis C Virus (HCV) (see Hepatitis C Virus)
- Alcoholic Hepatitis (see Alcoholic Hepatitis)
- Autoimmune Hepatitis (see Autoimmune Hepatitis)
- Heat Stroke (see Heat Stroke)
- HELLP Syndrome (see HELLP Syndrome)
- Hepatic Metastases
- Breast Cancer (see Breast Cancer)
- Lymphoma (see Lymphoma)
- Melanoma (see Melanoma)
- Multiple Myeloma (see Multiple Myeloma)
- Small Cell Lung Cancer (see Lung Cancer)
- Hepatic Vein Thrombosis (Budd-Chiari Syndrome) (see Hepatic Vein Thrombosis)
- Hepatic Veno-Occlusive Disease (VOD) (see Hepatic Veno-Occlusive Disease)
- Ischemic Hepatitis (Hypoxic Hepatitis, Shock Liver) (see Ischemic Hepatitis,)
- Drug/Toxin-Associated Hepatoxicity
- Acetaminophen Intoxication (see Acetaminophen Intoxication)
- Drug-Induced Hepatotoxicity (see Drug-Induced Hepatotoxicity)
- Toxic Mushrooms (see Toxic Mushrooms)
- Partial Hepatectomy (see Hepatectomy)
- Sepsis (see Sepsis)
- Wilson Disease (see Wilson Disease)
Other Disorders
- Muscle Disorders
- Polydermatomyositis (see Polydermatomyositis)
- Seizures (see Seizures)
- Heavy Exercise
- Marathon Running
Clinical Evaluation of Markedly Elevated Transaminases (Transaminitis >15x Upper Limit of Normal)
- Autoimmune Serologies/Studies: useful to diagnose autoimmune hepatitis (see Autoimmune Hepatitis)
- Antinuclear Antibody (ANA) (see Antinuclear Antibody)
- Anti-Smooth Muscle Antibody (see Anti-Smooth Muscle Antibody)
- Anti-Liver/Kidney Microsomal Antibody Type 1 (see Anti-Microsomal Antibody)
- Serum Immunoglobulins (see Serum Immunoglobulins)
- Evaluation for Kaiser-Fleisher Rings: useful to diagnose Wilson disease (see Wilson Disease)
- Hepatobiliary Ultrasound with Dopplers (see Abdominal-Pelvic Ultrasound)
- Doppler Studies are Required to Exclude Hepatic Vein Thrombosis (Budd-Chiari Syndrome)
- Liver Biopsy (see Liver Biopsy): may be required if remaining work-up is non-diagnostic
- Pregnancy Test (see Pregnancy Test): in women of childbearing potential
- Serum Acetaminophen Level (see Serum Acetaminophen Level)
- Serum Aldolase (see Serum Aldolase): in patients with suspected muscle disorder
- Serum Ceruloplasmin (see Serum Ceruloplasmin): useful to diagnose Wilson disease (see Wilson Disease)
- Serum Creatine Kinase (CK) (see Serum Creatine Kinase): in patients with suspected muscle disorder
- Toxicology Screen (see xxxx)
- Urinalysis (see Urinalysis): to diagnose proteinuria in pregnant patients
- Urinary Copper Excretion: useful to diagnose Wilson disease (see Wilson Disease)
- Viral Serologies/Studies
- Anti-Hepatitis A IgM Antibody
- Hepatitis B Surface Antigen (HBsAg)
- Anti-Hepatitis B Core Antigen IgM Antibody (Anti-HBc)
- Anti-Hepatitis C Antibody
- Hepatitis C Viral RNA
- Anti-Hepatitis D Antibody: in patient with acute or chronic hepatitis B (see Hepatitis B Virus)
- Anti-Hepatitis E Antibody: in patients with residence in or travel to hepatitis E endemic regions (Asia, Africa, Middle East, Central America) or in pregnant patients (due to the high rates of acute liver failure in pregnant women with hepatitis E vural infection)
- Cases of Hepatitis E Have Also Been Reported in Developed Countries without a History of Foreign Travel
- Anti-Herpes Simplex Virus (HSV) Antibody: optional
- Anti-Varicella-Zoster Antibody: optional
- Anti-CMV Antibody: optional
- CMV Antigen: optional
- Heterophile Antibody (for Epstein-Barr Virus): optional
Etiology of Moderately Elevated Alkaline Phosphatase Elevation (<4x Upper Limit of Normal) (see Serum Alkaline Phosphatase)
Hepatic
- Acute Cholangitis (see Acute Cholangitis)
- Acute Viral Hepatitis
- Cytomegalovirus (CMV) (see Cytomegalovirus)
- Epstein-Barr Virus (EBV) (see Epstein-Barr Virus)
- Hepatitis A Virus (see Hepatitis A Virus)
- Hepatitis B Virus (HBV) (see Hepatitis B Virus)
- Hepatitis C Virus (HCV) (see Hepatitis C Virus)
- Alcoholic Hepatitis (see Alcoholic Hepatitis)
- Chronic Viral Hepatitis
- Hepatitis B Virus (HBV) (see Hepatitis B Virus)
- Hepatitis C Virus (HCV) (see Hepatitis C Virus)
- Cirrhosis (see Cirrhosis)
- Congestive Heart Failure (CHF) (see Congestive Heart Failure)
- Physiology: hepatic hypoperfusion
- Hepatic Infiltration
- Amyloidosis (see Amyloidosis)
- Liver Abscess (see Pyogenic Liver Abscess)
- Lymphoma (see Lymphoma)
- Sarcoidosis (see Sarcoidosis)
- Tuberculosis (see Tuberculosis)
- Sepsis (see Sepsis)
- Physiology: hepatic hypoperfusion
Non-Hepatic
- Benign Familial Elevation of Alkaline Phosphatase
- Physiology: intestinal source
- High Bone Turnover
- Bone Metastases
- Growth
- Healing Fracture
- Hyperparathyroidism (see Hyperparathyroidism)
- Hyperthyroidism (see Hyperthyroidism)
- Osteosarcoma (see Osteosarcoma)
- Osteomalacia (see Osteomalacia)
- Paget Disease of Bone (see Paget Disease of Bone)
- Influx of Intestinal Alkaline Phosphatase After Eating a Fatty Meal
- Epidemiology: occurs in patients with blood type O or B
- Malignancy
- Gastric Cancer (see Gastric Cancer)
- Head and Neck Cancer (see Head and Neck Cancer)
- Hodgkin’s Disease (see Hodgkin’s Disease)
- Lung Cancer (see Lung Cancer)
- Osteosarcoma (see Osteosarcoma)
- Ovarian Cancer (see Ovarian Cancer)
- Renal Cell Carcinoma (see Renal Cancer)
- Uterine Cancer (see Uterine Cancer)
- Physiologic Elevation of Alkaline Phosphatase: occurs in children and adolescents
- Third Trimester of Pregnancy (see Pregnancy)
- Other
- Myeloid Metaplasia
- Peritonitis (see Peritonitis)
- Diabetes Mellitus (see Diabetes Mellitus)
- Subacute Thyroiditis (see Subacute Thyroiditis)
- Gastric Ulcer (see Peptic Ulcer Disease)
Clinical Evaluation of Elevated Alkaline Phosphatase (of Hepatic Origin) (see Serum Alkaline Phosphatase)
- Hepatobiliary Ultrasound (see Abdominal-Pelvic Ultrasound)
- Hepatic Ultrasound is Useful to Biliary Ductal Dilation (Consistent with the Diagnosis of Extrahepatic Cholestasis): however, biliary ultrasound may fail to show biliary ductal dilation in cases with partial bile duct obstruction, as well as cirrhosis and primary sclerosing cholangitis (where scarring prevents the intrahepatic ducts from dilating)
- In General, Absence of Biliary Ductal Dilation Indicates Intrahepatic Cholestasis
Etiology of Markedly Elevated Alkaline Phosphatase Elevation (≥4x Upper Limit of Normal) (see Serum Alkaline Phosphatase)
Intrahepatic Cholestasis
- Alcoholic Hepatitis (see Alcoholic Hepatitis)
- Benign Postoperative Cholestasis
- Hepatic Infiltration
- Amyloidosis (see Amyloidosis)
- Granulomatosis with Polyangiitis (GPA (Wegener’s Granulomatosis) (see Granulomatosis with Polyangiitis)
- Liver Abscess (see Pyogenic Liver Abscess)
- Lymphoma (see Lymphoma)
- Sarcoidosis (see Sarcoidosis)
- Tuberculosis (see Tuberculosis)
- Hepatic Metastases
- Breast Cancer (see Breast Cancer)
- Lymphoma (see Lymphoma)
- Melanoma (see Melanoma)
- Multiple Myeloma (see Multiple Myeloma)
- Small Cell Lung Cancer (see Lung Cancer)
- Intrahepatic Cholestasis of Pregnancy (see Pregnancy)
- Ischemic Cholangiopathy (see Ischemic Cholangiopathy)
- Liver Transplant Rejection (see Liver Transplant)
- Primary Biliary Cirrhosis (PBC) (see Primary Biliary Cirrhosis)
- Sclerosing Cholangitis
- Primary Sclerosing Cholangitis (PSC) (see Primary Sclerosing Cholangitis)
- Secondary Sclerosing Cholangitis (see Secondary Sclerosing Cholangitis)
- Sickle Cell Disease (Hepatic Crisis) (see Sickle Cell Disease)
- Drugs/Toxins
- Alkylated Steroids
- Arsenic (see Arsenic)
- Chlorpromazine (Largactil, Thorazine) (see Chlorpromazine)
- Jamaican Bush Tea (see Jamaican Bush Tea)
- Total Parenteral Nutrition (TPN) (see Total Parenteral Nutrition)
Extrahepatic Cholestasis (Biliary Obstruction)
- Acute Cholangitis (see Acute Cholangitis)
- Acute Pancreatitis (see Acute Pancreatitis)
- Biliary Infection
- AIDS Cholangiopathy (see Human Immunodeficiency Virus)
- Ascaris Lumbricoides (see Ascariasis)
- Liver Flukes (Trematodes)
- Clonorchis (see Clonorchiasis)
- Fasciola (see Fascioliasis)
- Metorchis (see Metorchiasis)
- Opisthorchis (see Opisthorchiasis)
- Biliary Stricture
- Chronic Pancreatitis with Stricture of Distal Bile Duct (see Chronic Pancreatitis)
- Post-Liver Transplant Biliary Anastomotic Stricture (see Liver Transplant)
- Post-Procedure
- Primary Sclerosing Cholangitis (PSC) with Extrahepatic Bile Duct Stricture (see Primary Sclerosing Cholangitis)
- Secondary Sclerosing Cholangitis (see Secondary Sclerosing Cholangitis)
- Choledocholithiasis (see Cholelithiasis)
- Epidemiology: most common etiology of extrahepatic biliary obstruction
- Malignant Biliary Obstruction
- Ampullary Carcinoma (see Ampullary Carcinoma)
- Cholangiocarcinoma (see Cholangiocarcinoma)
- Gallbladder Cancer (see Gallbladder Cancer)
- Pancreatic Cancer (see Pancreatic Cancer)
Non-Hepatic
- Transient Hyperphosphatemia of Infancy and Childhood
Clinical Evaluation of Elevated Alkaline Phosphatase (of Hepatic Origin) (see Serum Alkaline Phosphatase)
- Hepatobiliary Ultrasound (see Abdominal-Pelvic Ultrasound)
- Hepatic Ultrasound is Useful to Biliary Ductal Dilation (Consistent with the Diagnosis of Extrahepatic Cholestasis): however, biliary ultrasound may fail to show biliary ductal dilation in cases with partial bile duct obstruction, as well as cirrhosis and primary sclerosing cholangitis (where scarring prevents the intrahepatic ducts from dilating)
- In General, Absence of Biliary Ductal Dilation Indicates Intrahepatic Cholestasis
Etiology of Isolated Gamma-Glutamyl Transpeptidase Elevation (see Serum Gamma-Glutamyl Transpeptidase)
- Barbiturates (see Barbiturates)
- Chronic Obstructive Pulmonary Disease (COPD) (see Chronic Obstructive Pulmonary Disease)
- Diabetes Mellitus (DM) (see Diabetes Mellitus)
- Ethanol Abuse (see Ethanol)
- Hepatobiliary Disease: serum GGT is sensitive (but not specific) for the presence of hepatobiliary disease
- Acute Cholangitis (see Acute Cholangitis)
- Other Hepatobiliary Diseases
- Myocardial Infarction (M) (see Coronary Artery Disease)
- Pancreatic Disease
- Phenytoin (Dilantin) (see Phenytoin)
- Renal Failure
- Acute Kidney Injury (AKI) (see Acute Kidney Injury)
- Chronic Kidney Disease (CKD) (see Chronic Kidney Disease)
Etiology of Isolated Hyperbilirubinemia (see Hyperbilirubinemia)
Unconjugated (Indirect) Hyperbilirubinemia
Increased Bilirubin Production
- Dyserthropoiesis
- Primary Shunt Hyperbilirubinemia (Idiopathic Dyserythropoietic Jaundice)
- Hematoma
- Hemolytic Anemia (Extravascular/Intravascular) (see Hemolytic Anemia)
- Paroxysmal Nocturnal Hemoglobinuria (PNH) (see Paroxysmal Nocturnal Hemoglobinuria)
- Sickle Cell Disease (see Sickle Cell Disease)
- Wilson Disease (see Wilson Disease)
- Physiology
- Coombs-Negative Hemolytic Anemia (see Hemolytic Anemia): may occur in some cases
- Decreased Hepatic Bilirubin Uptake and Conjugation
- Physiology
Impaired Hepatic Bilirubin Uptake
- Congestive Hepatopathy (Passive Hepatic Congestion) (see Congestive Hepatopathy)
- Epidemiology: due to congestive heart failure (CHF) (see Congestive Heart Failure)
- Drugs: hyperbilirubinemia due to these drugs usually resolves within 48 hrs after discontinuation
- Bunamiodyl Cholecystographic Contrast Agent
- Flavaspidic Acid
- Probenecid (see Probenecid)
- Rifamycins (see Rifamycins)
- Rifabutin (see Rifabutin)
- Rifampin (Rifampicin, Rifadin) (see Rifampin)
- Rifapentine (Priftin) (see Rifapentine)
- Gilbert Syndrome (see Gilbert Syndrome)
- Physiology: impaired hepatic bilirubin uptake occurs in some cases
- Portosystemic Shunt
- Naturally-Occurring Portosystemic Shunt
- Transjugular Intrahepatic Portosystemic Shunt (TIPS) (see Transjugular Intrahepatic Portosystemic Shunt)
- Wilson Disease (see Wilson Disease)
- Physiology
- Coombs-Negative Hemolytic Anemia (see Hemolytic Anemia): may occur in some cases
- Decreased Hepatic Bilirubin Uptake and Conjugation
- Physiology
Impaired Bilirubin Conjugation
- Breast Milk Jaundice
- Crigler-Najjar Syndrome (Types I and II) (see Crigler-Najjar Syndrome)
- Ethinyl Estradiol (see Estrogen): found in almost all oral contraceptives (see Oral Contraceptives)
- Gilbert Syndrome (see Gilbert Syndrome): decreased hepatic bilirubin uptake and/or decreased conjugation
- Hyperthyroidism (see Hyperthyroidism)
- Hypothyroidism (see Hypothyroidism)
- Liver Disease
- Chronic Hepatitis
- Hepatitis B Virus (HBV) (see Hepatitis B Virus)
- Hepatitis C Virus (HCV) (see Hepatitis C Virus)
- Cirrhosis (see Cirrhosis)
- Wilson Disease (see Wilson Disease)
- Physiology
- Coombs-Negative Hemolytic Anemia (see Hemolytic Anemia): may occur in some cases
- Decreased Hepatic Bilirubin Uptake and Conjugation
- Physiology
- Chronic Hepatitis
- Maternal Serum Jaundice
- Neonatal Physiologic Jaundice
Conjugated (Direct) Hyperbilirubinemia
Inherited Disorders
- Rotor Syndrome (see Rotor Syndrome)
- Physiology: defective sinusoidal reuptake of conjugated bilirubin
- Dubin-Johnson Syndrome (see Dubin-Johnson Syndrome)
- Physiology: defective canalicular organic anion transport
Intrahepatic Cholestasis
- Acute Fatty Liver of Pregnancy (see Acute Fatty Liver of Pregnancy)
- Acute Viral Hepatitis
- Cytomegalovirus (CMV) (see Cytomegalovirus)
- Epstein-Barr Virus (EBV) (see Epstein-Barr Virus)
- Hepatitis A Virus (see Hepatitis A Virus)
- Hepatitis B Virus (HBV) (see Hepatitis B Virus)
- Hepatitis C Virus (HCV) (see Hepatitis C Virus)
- Alcoholic Hepatitis (see Alcoholic Hepatitis)
- Alpha-1 Antitrypsin Deficiency (see Alpha-1 Antitrypsin Deficiency)
- Autoimmune Hepatitis (see Autoimmune Hepatitis)
- Benign Postoperative Cholestasis
- Caroli Disease (see Caroli Disease)
- Chronic Viral Hepatitis
- Hepatitis B Virus (HBV) (see Hepatitis B Virus)
- Hepatitis C Virus (HCV) (see Hepatitis C Virus)
- Cirrhosis (see Cirrhosis)
- Congestive Hepatopathy (Passive Hepatic Congestion) (see Congestive Hepatopathy)
- Epidemiology: due to congestive heart failure (CHF) (see Congestive Heart Failure)
- Drugs/Toxins
- Acetaminophen (Tylenol) (see Acetaminophen)
- Alkylated Steroids
- Arsenic (see Arsenic)
- Chlorpromazine (Largactil, Thorazine) (see Chlorpromazine)
- Erythromycin (see Erythromycin)
- Jamaican Bush Tea (see Jamaican Bush Tea)
- Total Parenteral Nutrition (TPN) (see Total Parenteral Nutrition)
- Hemochromatosis (see Hemochromatosis)
- Hepatic Graft vs Host Disease (GVHD) (see Graft vs Host Disease)
- Hepatic Infiltration
- Amyloidosis (see Amyloidosis)
- Granulomatosis with Polyangiitis (GPA (Wegener’s Granulomatosis) (see Granulomatosis with Polyangiitis)
- Liver Abscess (see Pyogenic Liver Abscess)
- Liver Metastases
- Lymphoma (see Lymphoma)
- Sarcoidosis (see Sarcoidosis)
- Tuberculosis (see Tuberculosis)
- Hepatic Veno-Occlusive Disease (VOD) (see Hepatic Veno-Occlusive Disease)
- Intrahepatic Cholestasis of Pregnancy (see Pregnancy)
- Ischemic Hepatitis (Hypoxic Hepatitis, Shock Liver) (see Ischemic Hepatitis)
- Physiology: hepatic hypoperfusion
- Non-Alcoholic Fatty Liver Disease (NAFLD) (see Non-Alcoholic Fatty Liver Disease)
- Post-Liver Transplant (see Liver Transplant)
- Preeclampsia (see Preeclampsia and Eclampsia)
- Primary Biliary Cirrhosis (PBC) (see Primary Biliary Cirrhosis)
- Reye Syndrome (see Reye Syndrome)
- Sepsis (see Sepsis)
- Physiology: hepatic hypoperfusion
- Sickle Cell Disease (Hepatic Crisis) (see Sickle Cell Disease)
Extrahepatic Cholestasis (Biliary Obstruction)
- Acute Pancreatitis (see Acute Pancreatitis)
- Biliary Infection
- AIDS Cholangiopathy (see Human Immunodeficiency Virus)
- Ascaris Lumbricoides (see Ascariasis)
- Liver Flukes (Trematodes)
- Clonorchis (see Clonorchiasis)
- Fasciola (see Fascioliasis)
- Metorchis (see Metorchiasis)
- Opisthorchis (see Opisthorchiasis)
- Biliary Stricture
- Chronic Pancreatitis with Stricture of Distal Bile Duct (see Chronic Pancreatitis)
- Post-Liver Transplant Biliary Anastomotic Stricture (see Liver Transplant)
- Post-Procedure
- Primary Sclerosing Cholangitis (PSC) with Extrahepatic Bile Duct Stricture (see Primary Sclerosing Cholangitis)
- Secondary Sclerosing Cholangitis (see Secondary Sclerosing Cholangitis)
- Choledocholithiasis (see Cholelithiasis)
- Epidemiology: most common etiology of extrahepatic biliary obstruction
- Malignant Biliary Obstruction
- Ampullary Carcinoma (see Ampullary Carcinoma)
- Cholangiocarcinoma (see Cholangiocarcinoma)
- Gallbladder Cancer (see Gallbladder Cancer)
- Pancreatic Cancer (see Pancreatic Cancer)
References
- Heat stability of human serum alkaline phosphatase in bone and liver diseases. Clin Chim Acta. 1972 Oct;41:329-34 [MEDLINE]
- The SGOT/SGPT ratio–an indicator of alcoholic liver disease. Dig Dis Sci. 1979;24(11):835 [MEDLINE]
- Serum gamma-glutamyl transpeptidase and chronic alcoholism. Influence of alcohol ingestion and liver disease. Dig Dis Sci. 1985;30(3):211 [MEDLINE]
- An assessment of the role of liver biopsies in asymptomatic patients with chronic liver test abnormalities. Am J Gastroenterol. 2000;95(11):3206 [MEDLINE]
- Upper limits of normal for alanine aminotransferase activity in the United States population. Hepatology. 2012;55(2):447 [MEDLINE]
- An association of elevated levels of alkaline phosphatase and gamma-glutamyl transpeptidase with acute cholangitis. Hepatogastroenterology. 2014 Mar-Apr;61(130):291-5 [MEDLINE]