Jaundice

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

Jaundice is yellowish discoloration of the skin, conjunctiva (a clear covering over the sclera, or whites of the eyes) and mucous membranes caused by hyperbilirubinemia (increased levels of bilirubin in red blooded animals). Usually the concentration of bilirubin in the blood must exceed 2–3 mg/dL for the coloration to be easily visible.

Jaundice comes from the French word jaune, meaning yellow. It was once believed persons suffering from the medical condition jaundice saw everything as yellow, but this is not true. In 1885, Luhrman noted jaundice as an adverse effect of vaccination. In 1935, A. O. Whipple, an American surgeon first described obstructive jaundice. Many viruses that cause hepatitis and jaundice was discovered in 1950-2000.

Jaundice is classified in two categories including unconjugated hyperbilirubinemia and conjugated hyperbilirubinema. Unconjugated hypebilirubinemia can be caused by either increased production, reduced reuptake or defects in conjugation of bilirubin. While conjugated hyperbilirubinemia is further classified into obstruction of biliary tract, interahepatic cholestasis, injury to hepatocellular parenchyma, and defects of hepatocellular canalicular excretion or re-uptake in sinusoids.

Bilirubin is the catabolic product of the heme which is the main component of the red blood cells. Bilirubin is formed in the liver and spleen then it passes through several process in order to be metabolized. Metabolism processes include hepatic uptake, conjugation, clearance and excretion of the bilirubin in the bile. Jaundice develops due to increase the level of bilirubin and deposition under the skin and cause the yellow discoloration of the skin. Pathogenesis of neonatal jaundice includes physiologic process of bilirubin accumulation or pathological mechanism. The pathological jaundice may be acquired or inherited. Acquired neonatal jaundice include Rh hemolytic disease, ABO incompatibility disease, and hemolytic disease due to G6PD enzyme deficiency. Inherited neonatal jaundice is due to defect of one of the processes of bilirubin metabolism and it concludes some inherited syndromes. Inherited neonatal jaundice include Gilbert’s syndrome, Crigler-Najjar syndrome type I and II, Lucey-Driscoll syndrome, Dubin-Johnson syndrome, and Rotor syndrome. 

Common causes of jaundice are classified under conjugated and unconjugated hyperbilirubinemia. Unconjugated hyperbilirubinemia is caused by either increased bilirubin production in the body, impaired hepatic bilirubin uptake in the liver or impaired bilirubin uptake in the liver, all of which causes pooling of unconjugated bilirubin in the body leading to unconjugated hyperbilirubinemia. On the other hand, intra or extra hepatic cholestasis lead to accumulation of conjugated bilirubin causing conjugated hyperbilirubinemia. 

Jaundice is yellowish discoloration of the skin, conjunctiva, and mucous membranes caused by hyperbilirubinemia. Usually, the concentration of bilirubin in the blood must exceed 2–3 mg/dL for the coloration to be easily visible.

The incidence of jaundice is approximately 40,000 per 100,000 individuals of intensive care unit patients. Neonatal jaundice is more common among Asian and mixed Asian/white infants than white infants. Hepatocellular jaundice mainly from viral hepatitis commonly affects young patients. Cholestatic jaundice mainly from liver cancer, hepatitis, and liver cirrhosis commonly affects older patients. Male are more commonly affected by hepatocellular jaundice and liver cancer than female. Female are more commonly affected by hemolytic jaundice mainly from cholangiocarcinoma than male.

Common risk factors in the development of jaundice are classified under conjugated and unconjugated hyperbilirubinemia. The most common risk factors for unconjugated hyperbilirubinemia includes neonatal period, drugs like rifampin and probenecid, syndromes like Gilbert and Crigler-Najjar syndrome types I and II, steroids and chronic liver diseases. The most common risk factors for conjugated hyperbilirubinemia includes viral hepatitis, alcohol, non-alcoholic fatty liver disease, chronic hepatitis, primary biliary cirrhosis, drugs, and toxins (eg, alkylated steroids, chlorpromazine, herbal medications, arsenic), sepsis and hypoperfusion states, infiltrative diseases (eg, amyloidosis, lymphoma, sarcoidosis, and tuberculosis), pregnancy, cirrhosis, choledocholithiasis, intrinsic and extrinsic tumors of biliary tracts, primary sclerosing cholangitis, acute and chronic pancreatitis.

There is insufficient evidence to recommend routine screening for jaundice.

Natural history of jaundice varies greatly and symptoms can manifest at any age of life depending on the underlying cause. The type and the severity of complications depends on the underlying cause leading to jaundice. Certain individuals may not suffer any long-term complications and recovers fully, while for others the appearance of jaundice may be the first indication of a life-threatening situation.

Bilirubin plasma level is the gold standard test for the diagnosis of jaundice. Usually the concentration of bilirubin in the blood must exceed 2–3 mg/dL for the coloration to be easily visible.

Common symptoms of jaundice that the patient will notice, is yellowing of the skin, nausea, and vomiting. Specific symptoms will depend on the underlying factor that caused jaundice to occur. Patients may present with fever, anorexia, dark urine, fatigue, pruritis, right upper quadrant pain. A detailed history of alcohol use, blood transfusions, history of viral hepatitis and family history of liver disease must be taken in all patients.

Jaundice is a yellowish discoloration of the skin and sclerae that is an important symptom of elevated serum bilirubin. Physical examination of patients with jaundice is based on underlying disease, include Cervical lymphadenopathy, hepatomegaly, splenomegaly, and peripheral edema. 

An elevated concentration of serum total bilirubin is diagnostic for jaundice. The upper limit of normal is >1 mg/dL or >1.3 mg/d in some laboratories. Hyperbilirubinemia can be further categorized as conjugated or unconjugated. Serum conjugated bilirubin concentration >0.4 mg/dL (6.8 micromol/L) revealed conjugated hyperbilirubinemia. In unconjugated hyperbilirubinemia conjugated bilirubin is <1 mg/dL (17 micromol/L) if the total bilirubin is <5 mg/dL, or less than 20 percent of the total bilirubin if the total bilirubin is >5 mg/dL (85 micromol/L).

There are no ECG findings associated with jaundice.

There are no x-ray findings associated with jaundice.

Abdominal CT scan may be helpful in the diagnosis of cirrhosis in patient with jaundice. Findings on CT scan suggestive of cirrhosis include cirrhotic liver, as shrinkage and atrophy in liver, dilated portal vein and/or splanchnic veins, esophageal varices, collaterals in any abdominal organ, splenomegaly, and ascites.

Abdominal MRI may be helpful in the diagnosis of jaundice caused by cirrhosis. Findings on MRI suggestive of cirrhosis include re-canalized umbilical vein, dilated portal vein and/or splanchnic veins, esophageal varices, collaterals in any abdominal organ, splenomegaly, and ascites.

Ultrasonography may be helpful in the diagnosis of jaundice due to cirrhosis. Findings on an abdominal ultrasonography suggestive of cirrhosis include splenomegaly, ascites, re-canalization of umbilical vein — pathognomonic of portal hypertension, and porto-systemic collaterals.

Endoscopic retrograde cholangiopancreatography (ERCP) is an alternative imaging modality for diagnosing the cause of cholestasis in patients with jaundice.

The gold standard diagnostic test for jaundice caused by cirrhosis is liver biopsy, although it is rarely necessary for diagnosis or treatment. Sample of the liver is obtained bypercutaneous approach, transjugular approach, and laparoscopic radiographically- guided fine-needle approach. A biopsy is not necessary if the clinical, laboratory, and radiologic data suggest cirrhosis. There is a small but significant risk associated with liver biopsy, and cirrhosis itself predisposes to the complications of liver biopsy.

The mainstay of treatment for jaundice is to conjugate the unconjugated bilirubin or excretion and clearance of bilirubin from the circulation. Jaundice is treated mainly through treating underlying diseases, such as viral hepatitis, alcoholic hepatitis, or cirrhosis.

Surgery is not the first-line treatment option for patients with jaundice. Surgery is usually reserved for patients with either cirrhosis, cholestasis, and liver failure. The surgical procedures which are used to treat jaundice include transjugular intrahepatic portosystemic shunting (TIPS), cholecystectomy, and liver transplantation.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Farnaz Khalighinejad, MD [2]

Jaundice comes from the French word jaune, meaning yellow. It was once believed persons suffering from the medical condition jaundice saw everything as yellow, but this is not true. In 1885, Luhrman noted jaundice as an adverse effect of vaccination. In 1935, A. O. Whipple, an American surgeon first described obstructive jaundice. Many viruses that cause hepatitis and jaundice was discovered in 1950-2000.

• Jaundice comes from the French word jaune in circa 1300 AD, meaning yellow. And the word ‘jaunis’ itself is derived from an earlier French word ‘jalnice’.^[1]
• In 1885, Luhrman noted jaundice as an adverse effect of vaccination.^[2]

• In 1908, McDonald suggested that jaundice may be caused by an agent much smaller than a bacterium.^[3]
• In 1935, A. O. Whipple, an American surgeon first described obstructive jaundice.^[4]
• During WWII, approximately 16 million people died as a consequence of hepatitis. This led to a lot of research on vaccines and different type of hepatitis.^[5][6]
• In 1947, Clinicians divided hepatitis into two types including epidemic/infectious hepatitis and serum hepatitis (SH). Epidemic hepatitis had a short incubation period, serum hepatitis had long incubation period.^[6]
• In 1953, World Health Organization (WHO) suggested usage of the terms hepatitis A for infectious hepatitis and hepatitis B for serum hepatitis.^[6]
• During 1950-1970, an epidemic of viral hepatitis took place in China, India and the adjoining region. This led to the discovery of hepatitis E virus.^[2]
• In 1974, a third virus was discovered that causes infectious hepatitis, other than hepatitis A virus (HAV) and hepatitis B virus (HBV). It was named non-A, non-B hepatitis (NANBH).^[7]
• In 1977, hepatitis D virus was discovered.^[2]
• In 1995, the GB virus-C was discovered that targets liver.^[8]
• In 1997, transfusion-transmitted virus (TTV) was discovered in patient with non A-B-C-G hepatitis.^[9]

• In 1935, A. O. Whipple invented the concept of preoperative biliary drainage by the procedure of staged pancreatoduodenectomy.^[4]
• Since 1982, a vaccine against hepatitis B has been available.^[10]
• In 1992, the Global Advisory Group to the World Health Organization (WHO) recommended that hepatitis B vaccine be incorporated into national immunization programs in all countries by 1997.^[11]
• In 1986 first effort to develop interferon-alpha (IFN-a) treatment against HCV was initiated by Jay Houston Hoofnagle.^[12]
• The drug was finally approved by the Food and Drug Administration (FDA) for HCV treatment in 1991.^[13]
• In 1997 was first used to treat HCV.^[13]
• In 1998 The FDA approved the use of combination therapy of interferon alpha and ribavirin.^[13]
• Newer HCV protease inhibitors, such as telepravir, were developed in 2007.^[13]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Fatima Shaukat, MD [2]

Jaundice is classified in two categories including unconjugated hyperbilirubinemia and conjugated hyperbilirubinema. Unconjugated hypebilirubinemia can be caused by either increased production, reduced reuptake or defects in conjugation of bilirubin. While conjugated hyperbilirubinemia is further classified into obstruction of biliary tract, interahepatic cholestasis, injury to hepatocellular parenchyma, and defects of hepatocellular canalicular excretion or re-uptake in sinusoids.

Jaundice is classified into two subtypes:^[1][2][3][4]

• Conjugated hyperbilirubinemia
• Unconjugated hyperbilirubinemia

Jaundice classification

Predominately conjugated hyperbilirubenemia

Mixed conjugated and unconjugated hyperbilirubinemia

Predominately unconjugated hyperbilirubinemia

Obstruction of biliary tract

Intra-hepatic cholestasis

Injury to hepatocellular parenchyma

Defects of hepatocellular canalicular excretion or re-uptake in sinusoids

Increased production

Reduced uptake

Defects in conjugation

Acquired

Inherited

• Cholangiocarcinoma • Pancreatic cancer • Gallbladder cancer • Ampullary cancer • Choledocholithiasis  • Choledocholithiasis •Postoperative biliary strictures •Primary sclerosing cholangitis • Chronic pancreatitis • AIDS cholangiopathy • Parasitic disease ascariasis

• Primary biliary cholangitis •Primary sclerosing cholangitis • Viral hepatitis (ocassionally) • Progressive familial intrahepatic cholestasis • Intrahepatic Cholestasis of Pregnancy •Corticosteroids

Infiltrative liver disorders like • Hemochromatosis •Amyloidosis

• Dubin-Johnson syndrome • Rotor syndrome

• Wilson’s disease •Viral hepatitis •Alcoholic hepatitis • Drug toxicity • Autoimmune hepatitis

• Hemolysis • Hereditary spherocytosis • G6PD deficiency • Thalassemia • Paroxysmal nocturnal hemoglobinuria • Immune hemolysis • Extravasation • Shunt hyperbilirubinemia

• Portosystemic shunts • Drugs • Gilbert syndrome (some cases)

• Neonatal • Maternal milk • Lucy-Driscoll •Hyperthyroidism • Chronic persitent hepatitis • Advanced cirrhosis

• Crigler-Najjar syndrome l • Crigler-Najjar syndrome II • Gilbert syndrome

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Eiman Ghaffarpasand, M.D. [2], Ahmed Elsaiey, MBBCH [3]

Bilirubin is the catabolic product of the heme which is the main component of the red blood cells. Bilirubin is formed in the liver and spleen then it passes through several process in order to be metabolized. Metabolism processes include hepatic uptake, conjugation, clearance and excretion of the bilirubin in the bile. Jaundice develops due to increase the level of bilirubin and deposition under the skin and cause the yellow discoloration of the skin. Pathogenesis of neonatal jaundice includes physiologic process of bilirubin accumulation or pathological mechanism. The pathological jaundice may be acquired or inherited. Acquired neonatal jaundice include Rh hemolytic disease, ABO incompatibility disease, and hemolytic disease due to G6PD enzyme deficiency. Inherited neonatal jaundice is due to defect of one of the processes of bilirubin metabolism and it concludes some inherited syndromes. Inherited neonatal jaundice include Gilbert’s syndrome, Crigler-Najjar syndrome type I and II, Lucey-Driscoll syndrome, Dubin-Johnson syndrome, and Rotor syndrome.

• Bilirubin is the final catabolic product of the heme. The heme is a component of various biological molecules and enzymes but, it is mainly incorporated in the hemoglobin which is the primary component of the red blood cells.^[1][2]
• Bilirubin is formed mainly in the liver and spleen through two steps which include:^[3][4]
  • Heme oxygenase enzyme degrades the porphyrin ring of the heme and breaks it down. A green compound called biliverdin is then formed as a result of the previous reaction. Carbon monoxide is released as a result of the reaction.
  • Biliverdin reductase enzyme catalyzes the formation of bilirubin from biliverdin.
• Bilirubin is a toxic metabolite so, the body has physiologic processes to eliminate the bilirubin. Bilirubin elimination process includes:^[5]
  • Hepatic uptake^[6]
    • After the formation of the bilirubin and its secretion into the bloodstream, bilirubin becomes bound to the albumin to facilitate its transportation to the liver.
    • The hepatocytes then reuptake the bilirubin and prepare it for excretion.
  • Conjugation^[7][8]
    • Bilirubin is then conjugated with glucuronic acid producing bilirubin diglucuronide which is water soluble.
    • Being water soluble, hence, the conjugated bilirubin can be excreted into bile.
    • The conjugation process occurs by the glucuronosyltransferase enzyme in the liver cells.
  • Clearance and excretion^[9]
    • After conjugation of the bilirubin in the liver, it is secreted into the bile then into the gastrointestinal tract.
    • In the GIT, the conjugated bilirubin is metabolized by the gut enzymes into urobilinogen which is oxidized into urobilin.
    • Metabolism of the conjugated bilirubin occurs properly in the adults. However, the newborns have sterile gastrointestinal canal which impedes the catalyzation of the conjugated bilirubin.
    • The sterile tract ends up with a small amount of excreted bile.
    • The remaining conjugated bilirubin is unconjugated by the beta-glucuronidase enzyme in the neonatal intestine.
    • The unconjugated bilirubin is reabsorbed back into the blood and to the liver through the enterohepatic circulation of bilirubin.
    • A small amount of bilirubin is cleared into the urine as urobilinogen.

• Jaundice in adult patients classified into two major types:
  • Unconjugated hyperbilirubinemia
  • Conjugated hyperbilirubinemia

The primary pathophysiology of unconjugated hyperbilirubinemia include:^[10]

• Overproduction of bilirubin
• Reduced bilirubin uptake
• Impaired bilirubin conjugation
  • The combination of progestational and estrogenic steroids may result in increased UDP-glucuronyl transferase activity

• Biliary tract obstruction leads to both conjugated and unconjugated bilirubinemia.
• Bilirubin is transported back to the plasma by ATP-consuming pumps.
• The markers are serum concentrations of bilirubin and alkaline phosphatase.
• Biliary retention secondary to obstruction may reverse the glucuronidation.
• Produced unconjugated bilirubin will diffuse or be transported back into the plasma.
• Mirizzi syndrome^[12]
  • Extrahepatic bile ducts compression by a distended gallbladder due to cholelithiasis.
• Primary sclerosing cholangitis and cholangiocarcinoma
  • Intrahepatic and extrahepatic portions of the bile ducts are affected.
• Parasites
  • Adult Ascaris lumbricoides
  • Eggs of certain liver flukes (e.g., Clonorchis sinensis, Fasciola hepatica)
• AIDS cholangiopathy^[13]
  • Cryptosporidium species
  • Cytomegalovirus
  • HIV
    • Viral hepatitis (hepatitis viruses, herpes simplex virus, Epstein-Barr virus)
    • Mycobacterium tuberculosis and atypical mycobacteria (especially Mycobacterium avium intracellulare)
    • Fungal infections (Cryptococcus neoformans, Histoplasma capsulatum, Candida albicans, Coccidioides immitis)
    • Parasites (Pneumocystis carinii)
    • Tumor infiltration (lymphoma, Kaposi sarcoma)
    • Drug-induced liver disease

• Viral hepatitis: For more information about viral hepatitis click here
• Alcoholic hepatitis: For more information about viral hepatitis click here
• Nonalcoholic steatohepatitis: For more information about viral hepatitis click here
• Primary biliary cholangitis: For more information about viral hepatitis click here
• Toxicity^[14]
  • Dose-related fashion (e.g., alkylated steroids such as methyltestosterone and ethinyl estradiol)
  • Idiosyncratic or allergic reaction (e.g., chlorpromazine, halothane).
  • Pyrrolizidine alkaloids which may cause veno-occlusive disease of the liver (e.g., Jamaican bush tea)
• Sepsis and low perfusion states^[15]
  • Hypotension
  • Drugs
  • Bacterial endotoxins
• Paraneoplastic syndromes
  • Renal cell carcinoma
  • Malignant lymphoproliferative diseases
  • Gynecologic malignancies
  • Prostate cancer
• Infiltrative diseases of the liver
  • Amyloidosis
  • Lymphoma
  • Sarcoidosis
  • Tuberculosis
• Total parenteral nutrition (TPN)^[16]
  • At least two to three weeks of TPN may lead to development of cholestasis.
    • Intestinal endotoxins transfer into the portal system
    • Bacterial sepsis
    • Formation of secondary bile acids (e.g., lithocholic acid)
    • Biliary sludge after six weeks of TPN
    • Hepatotoxic factors, such as tryptophan degradation metabolites and aluminum contaminants
    • Bacterial overgrowth in the small intestine
• Sickle cell disease^[17]
  • Hemolysis
  • Mild hepatic dysfunction
  • Both unconjugated and conjugated bilirubin accumulate in the plasma
• Intrahepatic cholestasis of pregnancy^[18]
  • Usually in the third trimester but sometimes earlier
  • Heralds cholestasis and then frank jaundice
  • May be associated with increased stillbirths and prematurity
  • All the pathologic changes would disappear after delivery

• Different presentations simulate cholestatic syndromes.
• Intracellular proteins and small molecules are released into the plasma.
• Increased transaminases, such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT).

Sepsis

Paraneoplastic syndrome

Infiltrative hepatic diseases

Total parenteral nutrition

Sickle cell disease

Pregnancy

Extravascular hemolysis

Intravascular hemolysis

Extravasation

Dyserythropoiesis

• Cholelithiasis • Tumor • Primary biliary cholangitis • Parasites • Pancreatitis • Stricture

• Choledochal cyst • Cholelithiasis • Tumor

• Biliary atresia • Choledochal cyst

• Decreased hepatic blood flow • Decreased delivery of bilirubin

• Capillarization of the sinusoidal endothelial cells (loss of fenestrae)

• Impaired bilirubin uptake at the sinusoidal surface of hepatocytes

• Rifamycin antibiotics • Probenecid • Flavaspidic acid • Bunamiodyl (a cholecystographic agent)

• Type I and II Crigler Najjar syndrome

• Hyperthyroidism • Ethinyl estradiol

• Novobiocin • Gentamicin

• Chronic persistent hepatitis • Advanced cirrhosis • Wilson’s disease

Adult

Children

Neonates and infants

Heart failure Portosystemic shunt

Cirrhosis

Gilbert’s Syndrome

Drug-induced defect

↓ or NoUGT activity

Inhibit UGT

Hepatocellular Disease

Biliary obstruction

Intrahepatic cholestasis

Reduced bilirubin uptake

Overproduction of bilirubin

Impaired bilirubin conjugation

Conjugated hyperbilirubinemia

Unconjugated hyperbilirubinemia

Jaundice

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Fatima Shaukat, MD [2]

Common causes of jaundice are classified under conjugated and unconjugated hyperbilirubinemia. Unconjugated hyperbilirubinemia is caused by either increased bilirubin production in the body, impaired hepatic bilirubin uptake in the liver or impaired bilirubin uptake in the liver, all of which causes pooling of unconjugated bilirubin in the body leading to unconjugated hyperbilirubinemia. On the other hand, intra or extra hepatic cholestasis lead to accumulation of conjugated bilirubin causing conjugated hyperbilirubinemia.

Jaundice may be caused by:^[1][2][3]

Causes of unconjugated hyperbilirubenemia includes:^[4][5]

• Increased bilirubin production:
  • Extravascular hemolysis
  • Extravasation of blood into tissues
  • Intravascular hemolysis
  • Wilson’s disease
• Impaired hepatic bilirubin uptake:
  • Heart failure
  • Portosystemic shunts
  • Drugs – Rifampin, Probenecid
• Impaired bilirubin conjugation:^[6]
  • Crigler-Najjar syndrome types I and II
  • Gilbert syndrome
  • Ethinyl estradiol
  • Liver diseases – chronic hepatitis, advanced cirrhosis

• Increased bilirubin production:
  • Dyserythropoiesis
• Impaired hepatic bilirubin uptake:
  • Some patients with Gilbert syndrome
  • Drugs – Flavaspadic acid, Bunamiodyl
• Impaired bilirubin conjugation:
  • Neonates
  • Hyperthyroidism

Causes of conjugated hyperbilirubinimia includes: ^[7]

• Intrahepatic cholestasis:
  • Viral hepatitis^[3]
  • Alcoholic hepatitis^[8]
  • Non-alcoholic fatty liver disease
  • Chronic hepatitis
  • Primary biliary cirrhosis^[8]
  • Drugs and toxins (eg, alkylated steroids, chlorpromazine, herbal medications [eg, Jamaican bush tea], arsenic)
  • Sepsis and hypoperfusion states
  • Infiltrative diseases (eg, amyloidosis, lymphoma, sarcoidosis, tuberculosis)
  • Pregnancy
  • Cirrhosis
• Extrahepatic cholestasis (biliary obstruction):
  • Choledocholithiasis
  • Intrinsic and extrinsic tumors (eg, cholangiocarcinoma)
  • Primary sclerosing cholangitis
  • Acute and chronic pancreatitis

• Intrahepatic cholestasis:
  • Total parenteral nutrition
  • Postoperative cholestasis
  • Following organ transplantation
  • Hepatic crisis in sickle-cell disease
• Extrahepatic cholestasis (biliary obstruction):
  • AIDS cholangiopathy
  • Certain parasitic infections (eg, Ascaris lumbricoides, liver flukes)
  • Strictures after invasive procedures
• Defect of canalicular organic anion transport:
  • Dubin-Johnson syndrome
• Defect of sinusoidal re uptake of conjugated bilirubin:
  • Rotor syndrome

Cardiovascular	Eclampsia, Alagille syndrome, Infective endocarditis, Lupus, Trisomy 18, Heart failure
Chemical / poisoning	1,2-Dibromoethane, 2-acetylamino-fluorene, 2-Nitropropane, 3,3-Dichlorobenzidine, 4-Dimethylaminoazobenzene, 8-Hydroxyquinolone, Acer rubrum, Acetates, Acetonitrile, Acetylene Tetrabromide, Acrylonitrile, Aflatoxin, Albitocin, Alicyclic Hydrocarbons, Aliphatic Amines, Aliphatic Hydrocarbons, Aliphatic hydrogenated hydrocarbons, Allyl alcohol, Amanita phalloides, Aromatic amines, Aromatic halogenated hydrocarbons, Aromatic Hydrocarbons, Arsenic, Arsine, Benzene, Benzyl chloride, Beryllium, Bipyridyl pesticides, Black nightshade poisoning, Boron, Cadmium, Capecitabine, Carbarsone, Carbolic Acids and Anhydrides, Carbon Disulfide, Carbon Tetrachloride, caspofungin acetate, Chloramphenicol, Chlorate salts, Chlordane, Chlorinated benzenes, Chlorinated naphthalene, Chlorodiphenyls and derivatives, Chloroform, Chloromethane, Chloroprene, Chromium, Comfrey, Copper, Cresol, Cycasin, Cyclochlorotine,Dapsone, Dibromochloropropane, Diethylene Glycol, Dimethyl sulfate, Dimethylnitrosamine, Dinitrobenzene, Dinitrocresol, Dinitrophenol, Dinitrotoluene, Eltrombopag, Ethanolamines, Ethyl Acetate, Ethyl alcohol, Ethyl benzene, Ethyl Ether, Ethyl Salicylate, Ethylene chlorohydrin, Ethylene Dibromide, Ethylene dichloride, Ethylene oxide, Ethylenediamine, Fluoxymesterone, Germander, Germanium, Gold, Hafnium, Horse nettle , Hydrochlorothiazide ,Icterogenin, Hydrogen bromides, Hydrogen Cyanide, Indospicine, Isopropyl acetate, Kepone pesticides, Lanthanides, Lead, Mercaptans, Mercury, Meropenem, Methoxyflurane, Methyl acetate, Methyl Bromide, Methyl Chloride, Methylene chloride, Methylene Dianiline, Metolachlor, miltefosine, Monomethylhydrazine,Nabumetone, N,N-Dimethylformamide, N-butyl acetate, N-N-Dimethylacetamide, N-Nitrosodimethylamine, N-propyl acetate, Naphthalene, Naphthol, Ngaione, Nickel, Niobium, Nitriles, Nitrobenzene, Nitromethane, Nitroparaffins, Ochratoxin, Para-Dichlorobenzene, Phosphine, Phosphorus, Phthalic Anhydride, Picric Acid, Polybrominated biphenyls, Polychlorinated biphenyls, Polygonum multiflorum, Probenecid, Propylene dichloride, Psoralea Corylifolia, Pyrogallol, Pyrrolidizine, Ragwort, Rubratoxin, Safrole, Solanine, Solder, Sterigmatocystin, Stibine,, Tellurium, Tetrachloroethane, Tetrachloroethylene, Tetramethylthiuram disulfide, Thallium, Thioxanthene, Thorium dioxide, Thorotrast , Toluene, Trichloroethylene, Trinitrotoluene, Uranium, Vicia faba, Vinyl Chloride, White Phosphorus, Xylene, alkylated steroids, chlorpromazine, Jamaican bush tea
Dermatologic	Griscelli disease, NISCH syndrome, Hashimoto-Pritzker syndrome, Kawasaki disease, Deal-Barratt-Dillon syndrome, Lupus, Hemochromatosis
Drug Side Effect	5-Fluorocytosine, Acetaminophen and Oxycodone, Aldesleukin, Allopurinol, Alprazolam, Amineptine, Amiodarone, Amlodipine, Amodiaquine, Amphotericin, Anabolic C-17, Aztreonam, Bicalutamide, Bromazepam, Buprenorphine, Butyrophenones, Bunamiodyl, Cabozantinib, Cefaclor, Cefotaxime sodium, Ceftazidime, Ceftibuten, Cephalosporins, Chlordiazepoxide, Chlorpromazine, Cidofovir, Cimetidine, Clarithromycin, Clavulanic acid, Clindamycin, Co-amoxiclav, Cobicistat, Colchicine,crofelemer, Cyclopropane, Cycloserine, Cytarabine, Dantrolene, Dapsone, Daptomycin, Deracoxib, Diazepam, Diflunisal, Diphenoxylate and Atropine, Disulfiram, Docetaxel, Doxepine, Duloxetine, Dydrogesterone, Erythromycin estolate, Erythromycin Ethyl succinate, Estrogen and Progestin, Ethionamide, Fenoprofen, Flavaspadic acid, Flucloxacillin, Flurbiprofen, Framycetin, Fusidic acid, Griseofulvin, Halothane, Hycanthone, Hydroxyzine, Ibuprofen, ibuprofen lysine, Idoxuridine, Imipramine, Indinavir, Indomethacin, Isoniazid, Itraconazole, Ixabepilone, Ketoconazole, Loprazolam, Loratadine, Lorazepam, Lormetazepam, Meloxicam, Mepacrine, Mephenytoin, Mercaptopurinr, Metaxalone, Methocarbamol, Methimazole, Methyldopa, Metronidazole, Minocycline, Mirtazapine, Monoamine oxidase inhibitors, Naproxen, Niacin, Nitrofurantoin, Nitrous Oxide, Nizatidine, Novobiocin, Olanzapine, Oxandrolone, Oxaprozin, Oxycodone, p-aminosalicylic acid, Papaverine, Paroxetine, Pegaspargase, Penicillin, Pergolide, Phenol, Phenothiazine, Phenylbutazone, Phenytoin, Piperacillin/tazobactam, pomalidomide, Promethazine, Pyridine, Rifampin, Quinupristin dalfopristin, Quinidine-induced Immune Hemolytic Anemia, Quinolone, Ranitidine, Repaglinide, Rifampicin, Salicylate, sodium sulfate, potassium sulfate and magnesium sulfate Sibutramine, Sorafenib, Spectinomycin, Sulindac, Sulfasalazine, Sulphonamides, Tamoxifen, Tegaserod, Telithromycin, Tetracycline, Thalidomide, Thiabendazole, Trazodone, Triazolam, Trovafloxacin mesylate, Valproic acid, Vidarabine, Zoxazolamine, zileuton
Ear Nose Throat	Arthrogryposis — renal dysfunction — cholestasis syndrome
Endocrine	Gestational diabetes, Growth hormone deficiency, Hyperthyroidism, Hypopituitarism, Hypothyroidism, Thyroid agenesis
Environmental	No underlying causes
Gastroenterologic	Accessory pancreas, Acinic cell carcinoma, Acral dysostosis — dyserythropoiesis , Acute Cholecystitis, Acute fatty liver of pregnancy, Acute hepatitis, Acute liver failure, Addison-Gull syndrome, Alagille syndrome, Alcoholic Hepatitis, Alcoholic liver disease, Angiosarcoma of the liver, Arthrogryposis — renal dysfunction — cholestasis syndrome, Ascending cholangitis, Autoimmune Hepatitis, Baber’s syndrome, Banti’s syndrome, Bile duct cancer, Bile duct paucity, non syndromic form, Bile plug syndrome, Biliary atresia, Biliary cirrhosis, Biliary colic, Budd-Chiari syndrome, Byler Disease, Caroli’s Disease, Chlorpropamide, Cholangiocarcinoma, Cholangitis, Choledochal cyst, hand malformation, Choledochal cysts, Choledocholithiasis, Cholestasis, Cholestasis — pigmentary retinopathy — cleft palate, Chronic cholecystitis, Chronic Hepatitis, Cirrhosis of liver, Colorectal cancer, Crigler-Najjar syndrome, Eosinophilic gastroenteritis, Esophageal cancer, Gallbladder cancer, Gallstones, Gilbert’s syndrome, Hemosuccus pancreaticus, Hepatic amyloidosis with intrahepatic cholestasis, Hepatic encephalopathy syndrome, Hepatoma, Hyperemesis gravidarum, Idiopathic liver cirrhosis, Intrahepatic cholangiocarcinoma, Intrahepatic cholestasis of pregnancy, Islet Cell adenoma, Liver cancer, Mirizzi’s syndrome, Mosse syndrome, Neonatal hepatitis, Neuroma biliary tract, Non-alcoholic fatty liver disease, Obliterative portal venopathy, Pancreatic adenoma, Pancreatic cancer, Pancreatitis, Pancreatoblastoma, Papillary stenosis, Peliosis hepatis, Portal hypertension, Portosystemic shunts, Primary biliary cirrhosis, Primary sclerosing cholangitis, Sarcoma botryoides of common bile duct, Secondary Biliary Cirrhosis, Xanthogranulomatous cholecystitis, Xanthomatous biliary cirrhosis, Zieve’s syndrome, NISCH syndrome, Benign intrahepatic cholestasis , Dubin-Johnson syndrome, Familial Selective Vitamin B12 Malabsorption, Hemochromatosis, Imerslund-Najman-Grasbeck Syndrome, Progressive familial intrahepatic cholestasis (PFIC) , Summerskill-Walshe-Tygstrup syndrome, HELLP syndrome, Heptaosplenic T-cell Lymphoma, Pernicious anemia, Alpha 1-Antitrypsin Deficiency , Viral Hepatitis A, Viral Hepatitis B, Viral Hepatitis C, Viral Hepatitis D, Viral Hepatitis E, Viral hepatitis X (non-A,-B,-C,-D,-E), Reynolds syndrome, Deal-Barratt-Dillon syndrome, Aagenaes syndrome , Infectious mononucleosis, Fanconi-ichthyosis-dysmorphism, Wilson’s Disease, Cholesteryl ester storage disease, Chediak-Higashi syndrome, Weil’s disease, Exocrine Pancreatic Insufficiency, Dyserythropoietic Anemia, And Calvarial Hyperostosis, Zellweger syndrome, Trisomy 18
Genetic	Aagenaes syndrome , Aldolase A deficiency , Arthrogryposis — renal dysfunction — cholestasis syndrome, Benign intrahepatic cholestasis , Chediak-Higashi syndrome, Cholesteryl ester storage disease, Dubin-Johnson syndrome, Exocrine Pancreatic Insufficiency, Dyserythropoietic Anemia, And Calvarial Hyperostosis, Familial Selective Vitamin B12 Malabsorption, Galactosemia, Glucose-6-phosphate dehydrogenase deficiency, Glutaric aciduria , Hemochromatosis, Hereditary elliptocytosis, Hereditary fructose intolerance, Hereditary xerocytosis, Imerslund-Najman-Grasbeck Syndrome, Lucey-Driscoll syndrome, Lymphoproliferative syndrome, EBV-Associated, Autosomal, Niemann-Pick disease, Porphyria, Progressive familial intrahepatic cholestasis (PFIC) , Pseudo-torch syndrome, Rotor syndrome, Sotos syndrome, Summerskill-Walshe-Tygstrup syndrome, Tyrosinemia, Wilson’s Disease, Wolman disease, X-linked alpha thalassemia mental retardation syndrome (ATR-X), X-linked lymphoproliferative syndrome, X-linked sideroblastic anaemia, Zellweger syndrome, Griscelli disease, Hemoglobin C homozygous (CC), Hereditary spherocytosis, Thalassemia, Fructose intolerance, Alpha 1-Antitrypsin Deficiency , Acral dysostosis — dyserythropoiesis , Pyruvate kinase deficiency, Arthrogryposis — renal dysfunction — cholestasis syndrome, Alagille syndrome, Trisomy 18
Hematologic	Achrestic anemia, Autoimmune hemolytic anemia, Evans syndrome, Fanconi-ichthyosis-dysmorphism, Favism, Hashimoto-Pritzker syndrome, HELLP syndrome, Hemoglobin C homozygous (CC), Hemolytic anemia, Hemolytic disease of the newborn, Hemophagocytic lymphohistiocytosis familial ,Hepatic veno-occlusive disease with immunodeficiency , Heptaosplenic T-cell Lymphoma, Hereditary spherocytosis, HLH (Hemophagocytic lymphohistiocytosis), Hodgkin’s Disease, Kawasaki disease, Langerhans Cell Histiocytosis, Lymphoma, Myelofibrosis-osteosclerosis ,Pernicious anemia, Rh deficiency syndrome, Thalassemia, Thrombotic thrombocytopenic purpura, Acral dysostosis — dyserythropoiesis , Mosse syndrome, Zieve’s syndrome, Aagenaes syndrome , Exocrine Pancreatic Insufficiency, Dyserythropoietic Anemia, And Calvarial Hyperostosis, Glucose-6-phosphate dehydrogenase deficiency, Sickle-cell disease, Hereditary elliptocytosis, Hereditary xerocytosis, Porphyria, X-linked lymphoproliferative syndrome, X-linked sideroblastic anaemia, Pyruvate kinase deficiency, Kaposiform hemangio-endothelioma, Goldstein-Hutt syndrome, Infectious mononucleosis, Rh disease, Kawasaki disease, Sickle-cell disease, Griscelli disease, Lymphoproliferative syndrome, EBV-Associated, Autosomal, Aldolase A deficiency , X-linked alpha thalassemia mental retardation syndrome (ATR-X), Lupus
Iatrogenic	Post operative jaundice, Strictures after invasive procedures
Infectious Disease	Alveolar Hydatid Disease ., Aspergillosis, Congenital TORCH infections, Fascioliasis, Infective endocarditis, Malignant boutonneuse fever, Nanukayami, Neonatal sepsis, Omphalitis, Pneumonia, Sepsis, Tuberculosis, Q fever, Relapsing fever, Syphilis, Weil’s disease, Histoplasmosis, Malaria, Cytomegalovirus, Hepadnaviruses, Herpes, Infectious mononucleosis, Lábrea fever, Marburg virus, Viral Hepatitis A, Viral Hepatitis B, Viral Hepatitis C, Viral Hepatitis D, Viral Hepatitis E, Viral hepatitis X (non-A,-B,-C,-D,-E), Ascending cholangitis, Lymphoproliferative syndrome, EBV-Associated, Autosomal, Acute meningitis, AIDS,  Ascaris lumbricoides, liver flukes
Musculoskeletal / Ortho	Deal-Barratt-Dillon syndrome, Choledochal cyst, hand malformation, X-linked alpha thalassemia mental retardation syndrome (ATR-X), Fanconi-ichthyosis-dysmorphism, Myelofibrosis-osteosclerosis, Lupus, Exocrine Pancreatic Insufficiency, Dyserythropoietic Anemia, And Calvarial Hyperostosis, Sotos syndrome, Cholestasis — pigmentary retinopathy — cleft palate, Alagille syndrome, Hemochromatosis, Aldolase A deficiency , Lupus, Trisomy 18, Arthrogryposis — renal dysfunction — cholestasis syndrome
Neurologic	Absence of septum pellucidum and septo-optic dysplasia , Acute meningitis, Eclampsia, Hepatic encephalopathy syndrome, Pseudo-torch syndrome, Sotos syndrome, Wilson’s Disease, Zellweger syndrome, Lissencephalic syndromes, Chediak-Higashi syndrome, Alagille syndrome, Arthrogryposis — renal dysfunction — cholestasis syndrome, Trisomy 18
Nutritional / Metabolic	Breast feeding jaundice, Breast milk jaundice, Congenital disorders of glycosylation, Fructose intolerance, Manganese deficiency, Molybdenum deficiency, Organic acidemia, Pyruvate kinase deficiency, Selenium deficiency, Vitamin A overdose, Vitamin B12 Deficiency, Crigler-Najjar syndrome, Gilbert’s syndrome, Cholesteryl ester storage disease, Galactosemia, Glutaric aciduria , Hereditary fructose intolerance, Lucey-Driscoll syndrome, Niemann-Pick disease, Tyrosinemia, Wolman disease, Acute fatty liver of pregnancy, Aldolase A deficiency, Total parenteral nutrition
Obstetric/Gynecologic	HELLP syndrome, Acute fatty liver of pregnancy, Eclampsia
Oncologic	Breast cancer, Embryonal rhabdomyosarcoma, Kaposiform hemangio-endothelioma, Acinic cell carcinoma, Angiosarcoma of the liver, Bile duct cancer, Cholangiocarcinoma, Colorectal cancer, Esophageal cancer, Gallbladder cancer, Hepatoma, Intrahepatic cholangiocarcinoma, Islet Cell adenoma, Liver cancer, Neuroma biliary tract, Pancreatic adenoma, Pancreatic cancer, Pancreatoblastoma, Lymphoma, Zellweger syndrome, Mesothelioma
Opthalmologic	Goldstein-Hutt syndrome, Cholestasis — pigmentary retinopathy — cleft palate, Chediak-Higashi syndrome, Absence of septum pellucidum and septo-optic dysplasia , Wilson’s Disease, Alagille syndrome
Overdose / Toxicity	Acetaminophen, Iron, Vitamin C , Vitamin A
Psychiatric	No underlying causes
Pulmonary	Alpha 1-Antitrypsin Deficiency , Mesothelioma, Sarcoidosis, Pneumonia, Tuberculosis
Renal / Electrolyte	Arthrogryposis — renal dysfunction — cholestasis syndrome, Weil’s disease, Alagille syndrome, Deal-Barratt-Dillon syndrome, Lupus
Rheum / Immune / Allergy	Autoimmune Hepatitis, Primary biliary cirrhosis, Primary sclerosing cholangitis, Autoimmune hemolytic anemia, Evans syndrome, Hemolytic disease of the newborn, Hepatic veno-occlusive disease with immunodeficiency , Sarcoidosis, Lupus, Transfusion reaction
Sexual	X-linked alpha thalassemia mental retardation syndrome (ATR-X), Lupus, Hemochromatosis
Trauma	Cephalhematoma, Hepatic trauma
Urologic	No underlying causes
Dental	No underlying causes
Miscellaneous	Brown Recluse spider bite , Neonatal adrenal hemorrhage, Neonatal physiological jaundice, Premature birth, Reye’s syndrome,  organ transplantation

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mehrian Jafarizade, M.D [2]

Jaundice is yellowish discoloration of the skin, conjunctiva, and mucous membranes caused by hyperbilirubinemia. Usually, the concentration of bilirubin in the blood must exceed 2–3 mg/dL for the coloration to be easily visible.

For the differential diagnosis for jaundice and RUQ pain, click here.

For the differential diagnosis for jaundice and pruritis, click here.

For the differential diagnosis for jaundice and fever, click here.

For the differential diagnosis for jaundice, fever, and RUQ pain, click here.

For the differential diagnosis for jaundice, pruritis and RUQ pain, click here.

Differential diagnosis of jaundice are: ^{[1][2][3][4][5]}

Classification of jaundice based on etiology Disease History and clinical manifestations Diagnosis Lab Findings Other blood tests Other diagnostic Family history Fever RUQ Pain Pruritis AST ALT ALP BLR Indirect BLR Direct Viral serology Jaundice Hepatocellular Jaundice Infiltrative liver disorders: Hemochromatosis, amyloidosis + – -/+ – ↑ ↑ ↑/N ↑/N N – Ferritin ↑ (hemochromatosis) Liver biopsy Wilson’s disease + – -/+ – ↑ ↑ N ↑/N N – ↑ Serum ceruloplasmin Liver biopsy Viral hepatitis – -/+ – – ↑ ↑ N ↑/N N + Specific viral antibody for each type – Alcoholic hepatitis – -/+ -/+ – ↑↑ ↑ N ↑/N N – – – Drug induced hepatitis – -/+ – – ↑ ↑ N ↑/N N – – – Autoimmune hepatitis -/+ – – -/+ ↑ ↑ N ↑/N N – Anti-LKM antibody Liver biopsy Cirrhosis -/+ -/+ -/+ – ↑ ↑ ↑/N ↑/N ↑/N -/+ Low platate Small liver on ultrasond Nonalcoholic steatohepatitis -/+ – – – ↑ ↑ N ↑/N N – Dyslipidemia liver biopsy Ischemic hepatopathy -/+ – -/+ – ↑ ↑ N ↑/N N – Cardiovascular risk factors – Cholestatic Jaundice Common bile duct stone -/+ – + + N N ↑ N ↑ – Dilated ducts on ultrasound CT/ERCP Cholangitis – + + +/- N N ↑ N ↑ – Dilated ducts on ultrasound CT/ERCP Hepatitis A (cholestatic type) – -/+ + + N/↑ N/↑ ↑ N ↑ + HAV- Ab Abdominal ultrasound EBV / CMV hepatitis – -/+ + + N N ↑ N ↑ + Positive serology – Primary biliary cirrhosis -/+ + -/+ + N/↑ N/↑ ↑ N ↑ – AMA positive Liver biopsy Primary sclerosing cholangitis -/+ – -/+ + N/↑ N/↑ ↑ N ↑ – ↑Autoantibodies (P-ANCA), hypergammaglobulinemia MRCP, Liver biopsy Sickle cell disease + – – +/- N/↑ N/↑ ↑ N ↑ – Genetic testing periampullary cancer (Pancreatic carcinoma, cholangiocarcinoma) + – -/+ -/+ N/↑ N/↑ ↑ N ↑ – – CT scan for diagnosis AIDS cholangiopathy – – -/+ -/+ N/↑ N/↑ ↑ N ↑ – HIV Ab Ultrasound or ERCP Parasites induces cholestasis – – -/+ -/+ N/↑ N/↑ ↑ N ↑ – Serology Ultrasound or ERCP Intrahepatic cholestasis of pregnancy -/+ – -/+ + ↑ ↑ ↑ N ↑ – Thrombocytopenia Diagnosed clinically Isolated Jaundice Crigler-Najjar type 2 + – – – N N N ↑ ↑ – Genetic testing Gilbert + – – – N N N ↑ ↑ – Genetic testing Rotor syndrome + – – – N N N N ↑ – Genetic testing Liver biopsy Dubin-Johnson syndrome + – – – N N N N ↑ – Genetic testing Liver biopsy Hereditary spherocytosis + – -/+ – N N N ↑ N – Genetic testing Osmotic fragility G6PD deficiency + – – – N N N ↑ N – Genetic testing Thalassemia + – – – N N N ↑ N – Genetic testing Paroxysmal nocturnal hemoglobinuria – – – – N N N ↑ N – Flocytometery Immune hemolysis – -/+ – – N N N ↑ N – Autoantibodies Hematoma – -/+ – – N N N ↑ N – Anemia Truma or surgery in history

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Farnaz Khalighinejad, MD [2]

The incidence of jaundice is approximately 40,000 per 100,000 individuals of intensive care unit patients. Neonatal jaundice is more common among Asian and mixed Asian/white infants than white infants. Hepatocellular jaundice mainly from viral hepatitis commonly affects young patients. Cholestatic jaundice mainly from liver cancer, hepatitis, and liver cirrhosis commonly affects older patients. Male are more commonly affected by hepatocellular jaundice and liver cancer than female. Female are more commonly affected by hemolytic jaundice mainly from cholangiocarcinoma than male.

• The incidence of jaundice is approximately 40,000 per 100,000 individuals of intensive care unit patients.^[1]

• In 2015, the prevalence of cirrhosis was approximately 270 per 100,000 individuals in the United States.^[2]
  • Currently, approximately seventy percent of cirrhotic individuals are unaware of having liver disease and go undiagnosed.
  • The prevalence of cirrhosis is higher in areas with high illiteracy rates.
  • Chronic and heavy alcohol use is responsible for more than half of the cases of cirrhosis in the United States.

• The 10 year-mortality rate of cirrhosis is approximately 34- 66 percent, largely dependent on the cause of cirrhosis.^[3]

• In 2001, cirrhosis was the tenth leading cause of death among men and the twelfth leading cause of death among women in the United States.

• In 2006, cirrhosis was the twelfth leading cause of overall deaths in United States.

• Neonatal jaundice is more common among Asian and mixed Asian/white infants compared to white infants.^[4].
• The prevalence of cirrhosis is higher in:^[5]
  • Non-Hispanic blacks
  • Mexican Americans
  • Hispanics with hepatitis C infection

• Hepatocellular jaundice, particularly from viral hepatitis, commonly affects young patients.^[6]

• Cholestatic jaundice, particularly from liver cancer, hepatitis, and liver cirrhosis, commonly affects older patients.^[6]
• Cirrhosis is infrequently seen in young adults.^[6]
• The incidence of cirrhosis increases with age; the median age for the diagnosis of cirrhosis due to alcoholic liver disease is 52 years.^[7]

• Male are more commonly affected by hepatocellular jaundice and liver cancer than female.^[6]

• Female are more commonly affected by hemolytic jaundice.^[6]

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