Cholestasis is bile formation and/or bile flow impairment that manifests as fatigue, pruritus and jaundice.
It can be classified into intrahepatic or extrahepatic cholestasis.
Extrahepatic cholestasis develops from mechanical blockage in the duct system or hepatocellular defects.
Intrahepatic cholestasis may be due to functional defects hepatocellularly or from obstructive lesions of the intrahepatic biliary tract distal from the bile canaliculi.

Intrahepatic%20cholestasis Treatment


Ursodeoxycholic Acid (UDCA)

  • A hydrophilic, dihydroxy bile acid
  • Recommended treatment for ICP
    • May improve pruritus and serum liver tests 
    • Increase in the expression of bile salt export pumps and placental bile transporters occurs
    • Normalizes serum bile acid patterns in babies with minimal accumulation in amniotic fluid and cord blood
  • An effective treatment for PSC
    • Study shows that it improves serum liver tests and surrogate markers of prognosis, but does not reveal a proven benefit on survival or a delay in the need for liver transplantation
    • Thought to exert its effects in cholestatic conditions via protection of cholangiocytes against cytotoxic hydrophobic bile acids, stimulation of hepatobiliary secretion, protection of hepatocytes against bile
      acid-induced apoptosis, and induction of antioxidants
    • Some guidelines do not recommend the use of UDCA in the treatment of PSC due to inadequate proven efficacy on results such as death or liver transplantation for low- or intermediate-dose UDCA and worse outcomes described in a randomized controlled trial of high-dose UDCA
    • Although standard dose of UDCA has not been associated with adverse outcomes, UDCA cannot be recommended routinely until further data on efficacy and safety are available


  • Regarded as initial treatment of choice for IAC
    • Azathioprine at doses of up to 2 mg/kg/day should be considered in those with proximal and intrahepatic stenoses and those after relapse during/after corticosteroid therapy 
  • Have not demonstrated improvement in disease activity or outcome of PSC
  • Dexamethasone has been studied in small clinical trials for ICP but is not recommended due to adverse neurological effects in the fetus/neonate
    • Promotes fetal lung maturity, but is ineffective in reducing pruritus and aminotransferase levels in patients with ICP


  • Immunosuppressive treatment has been shown to exert a marked effect on inflammatory activity of IAC, and complete long-term remission after 3 months of treatment has been reported
    • However, the extent of disease may affect the long-term response, and a retrospective analysis showed that patients with alterations of proximal extrahepatic and intrahepatic bile ducts are prone to a higher risk of relapse after stopping of treatment than patients with distal bile duct strictures only

Other Drugs

  • Cholestyramine, antihistamines and opioid antagonists have been used to alleviate the pruritus in ICP
    • Cholestyramine is an exchange resin that binds bile acids and other anions in the intestine and increases their fecal excretion
      • It does not improve biochemical parameters or fetal outcomes in ICP
  • Ademetionine is a naturally occurring molecule found in virtually all body tissues and fluids that was found in some studies to have caused clinical improvement in patients with intrahepatic cholestasis including that associated with pregnancy
  • Phospholipids are naturally occurring lipids that some studies show have therapeutic effect for hepatic disorders although more controlled clinical trials are required to determine its benefits
  • Silymarin is a fruit extract from the plant milk thistle that is claimed to be a free radical scavenger and to have hepatoprotectant properties; it has been used in various liver disorders

Non-Pharmacological Therapy

Primary Sclerosing Cholangitis (PSC)

  • Biliary dilatation is the recommended treatment in patients with PSC that has dominant bile duct strictures with significant cholestasis
    • If there are unsatisfactory stricture dilatation and biliary drainage, biliary stent insertion should be done
  • Liver transplantation is recommended in patients with late-stage PSC and may be considered in patients with evidence of cholangiocyte dysplasia or severe recurrent bacterial cholangitis

Intrahepatic Cholestasis of Pregnancy (ICP)

  • Early delivery at 37 weeks gestation is encouraged as intrauterine death is more common in the last month of pregnancy and few deaths occur before 37 weeks of gestation
  • As the management of delivery is based on the patient’s highest total serum bile concentration at any time during the pregnancy, the risks and benefits of early delivery and the risks of ICP should be discussed with the patient

Drug-induced Cholestatic Liver Disease (DILI)

  • Withdrawal of the drug is the only effective treatment of drug-induced cholestasis
  • Prevention and early detection of abnormal serum liver tests, together with prompt withdrawal of the suspected drug, are crucial to avoid serious liver injury
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