• Patients with obstructive jaundice that can be treated surgically or endoscopically should be promptly identified. Abdominal imaging, usually in specialized care, should be performed urgently on acutely icteric patients.
• Jaundice from biliary obstruction lasting more than 3 weeks can cause permanent liver damage.
• Investigations are performed to disclose whether jaundice due to hepatic cell damage is associated with acute or chronic liver disease.
• Haemolysis (Haemolytic anaemia) should be diagnosed.
• True icterus should be differentiated from Gilbert's syndrome (Gilbert's syndrome).

• Jaundice is observed in the skin or sclerae, or plasma bilirubin is > 40 .

Haemolysis or Gilbert's syndrome

• The bilirubin is unconjugated (total bilirubin is increased, conjugated bilirubin is not). Results of other liver function tests (ALT, ALP) are normal.

Parenchymal jaundice

• The concentration of conjugated bilirubin is increased.
• Acute jaundice
  • Acute viral hepatitis
  • Drug-induced hepatitis or by herbal products
  • Right-sided heart failure
  • Sepsis
  • Intravenous nutrition
• Chronic jaundice
  • Alcoholic hepatitis
  • Cirrhosis of the liver
  • Autoimmune hepatitis
  • Chronic viral hepatitis (HBV, HCV)
  • Hepatocellular carcinoma
  • Intrahepatic cholangiocarcinoma
  • Cancer that has metastasized to the liver

Obstructive jaundice

• Common bile duct stone (Cholelithiasis)
• Cholangitis
• Acute (Acute pancreatitis) or chronic (Chronic pancreatitis) pancreatitis
• Primary sclerosing cholangitis (Primary sclerosing cholangitis)
• Autoimmune cholangitis, autoimmune pancreatitis (IgG4-associated diseases)
• Carcinoma of the pancreas (Carcinoma of the pancreas)
• Cholangiocarcinoma of the extrahepatic bile ducts (Cancer of the liver and the biliary tract)
• Postoperative stricture of the biliary ducts

• Duration of the jaundice
• Itch (suggestive of obstruction or intrahepatic cholestasis)
• Abdominal pain (common in obstruction but may also occur in alcoholic hepatitis)
• Upper abdominal operations
• Loss of appetite (viral hepatitis)
• Loss of weight (malignancies)
• Travel abroad, contact with an icteric patient, transfusions
• Used drugs, including natural organic products
• Consumption of alcohol (it is worth asking the patient's family or friends, too)
• Sex history (risk-taking behavior?)
• Intravenous narcotics

• Tenderness (cholecystitis)
• Liver size (enlarged liver – alcoholic fatty liver, hepatitis, tumour)
• Consistency of the liver
• Signs of portal hypertension: spider naevi, palmar erythema, gynaecomastia, splenomegaly, ascites
• Palpable, untender gallbladder (carcinoma of the pancreas)
• Signs of intravenous narcotic use, such as injection scars
• Surgical scars on the upper abdomen

• Yellowing of the skin caused by hypercarotenemia occurs in people who eat a lot of carrots.
• The sclerae are usually not icteric. Liver function tests are normal, but usually a history and normal physical findings are sufficient for making the diagnosis.

Basic investigations

• Basic blood count with platelets, CRP, bilirubin, conjugated bilirubin, ALT, AST, alkaline phosphatase, GGT, plasma or urine amylase, plasma albumin, prothrombin time or INR
• Upper abdominal ultrasonography
  • In the case of mild chronic jaundice, only a mildly increased bilirubin concentration and patient in good condition, an urgent ultrasonography can be performed in primary health care.
• An acutely jaundiced patient, whose icterus has been confirmed by laboratory tests, should be referred to hospital for the following morning for diagnosis and treatment. If obstructive icterus lasts for more than three weeks a permanent liver damage results. The obstruction should be relieved before that.
• Ultrasonography can differentiate obstructive jaundice from parenchymal jaundice: the intrahepatic bile ducts are usually dilated in obstructive jaundice, although they may be normal during the first few days. Gallbladder stones, cholecystitis, and often also hepatic metastases can be visualized.

Further laboratory investigations

• If the infrahepatic bile ducts are not dilated and the cause of jaundice is not clear after the aforementioned basic investigations, examine the following:
  • to disclose alcoholic aetiology (Recognition of alcohol and drug abuse): blood PEth
  • to disclose haemolysis (Haemolytic anaemia): blood reticulocyte count, plasma lactate dehydrogenase and haptoglobin concentrations, Coombs’ test
    • Especially when other liver function tests are normal
  • to disclose autoimmune liver diseases (Autoimmune hepatitis): plasma IgG, IgA, IgM, antinuclear antibodies (ANA), anti-smooth muscle antibodies, antimitochondrial antibodies
  • to disclose viral hepatitis (Viral hepatitis): HAV-IgM antibodies, HBV surface antigen (HBsAg), HCV antibodies, CMV nucleic acid, EBV nucleic acid and, if necessary, HEV antibodies.
• Other aetiology (rarer reasons of chronic icterus, investigations based on consideration)
  • Haemochromatosis (Haemochromatosis): ferritin, transferrin saturation
  • Wilson’s disease https://www.orpha.net/en/disease/detail/905: 24-hour urine copper, caeruloplasmin
  • Alpha-1-antitrypsin deficiency: alpha-1-antitrypsin
• Interpretation
  • Alkaline phosphatase > 150 U/l suggests obstructive jaundice.
  • Increased MCV, increased GGT/alkaline phosphatase ratio, increased AST/ALT ratio, increased IgA or blood PEth or positive plasma ethanol suggest alcoholic liver disease.
  • Decreased plasma albumin or increased INR suggest parenchymal disease.

Other further investigations

• Abdominal computed tomography (CT) is not enough to exclude gallstones, but is more sensitive than ultrasonography in detecting bile duct enlargement, hepatic metastases and a possible tumour obstructing the biliary duct.
• If necessary, the cause of the obstruction can be further investigated by MRI cholangiography (MRI of the upper abdomen and MRCP).
• Endoscopic retrograde cholangiography (ERCP) is the best investigation for finding out the location and type of obstruction. If needed, the obstruction can be alleviated by extraction of stone or by stenting the malignant stricture.
• Doppler ultrasonography (changes or obstruction of flow in the portal vein and hepatic veins)
• Liver biopsy is the best method to investigate the aetiology, severity and prognosis of chronic liver disease (liver enzyme concentrations increased > 6 months).

• Based on laboratory tests according to suspected aetiology
• Acute icterus requires urgent abdominal imaging, which is usually performed in specialized care. Jaundice due to bile duct obstruction lasting more than 3 weeks can cause permanent liver damage, so efforts should be made to find and clear the obstruction promptly.