From the Guidelines
Cholestasis is primarily caused by intrahepatic or extrahepatic factors, including hepatocellular cholestasis, cholangiocellular cholestasis, and extrahepatic biliary obstruction, as outlined in the EASL clinical practice guidelines 1. The causes of cholestasis can be broadly categorized into:
- Intrahepatic cholestasis, which includes hepatocellular cholestasis caused by conditions such as sepsis-, endotoxemia-induced cholestasis, cholestatic variety of viral hepatitis, alcoholic or non-alcoholic steatohepatitis, and drug- or parenteral nutrition-induced cholestasis 1.
- Cholangiocellular cholestasis, which includes primary biliary cirrhosis, primary sclerosing cholangitis, overlap syndromes of PBC and PSC with AIH, IgG4-associated cholangitis, and idiopathic adulthood ductopenia 1.
- Extrahepatic biliary obstruction, which may be caused by stones, tumors, cysts, or strictures, and can be diagnosed using imaging studies such as abdominal ultrasonography, computed tomography, magnetic resonance cholangiopancreatography (MRCP), or endoscopic ultrasound (EUS) 1. It is essential to differentiate between intrahepatic and extrahepatic cholestasis through careful patient history, physical examination, and imaging studies to guide further management and treatment 1. In cases of extrahepatic biliary obstruction, procedures like endoscopic retrograde cholangiopancreatography (ERCP) may be necessary to remove obstructions or surgery to correct structural issues, as recommended in the ACR Appropriateness Criteria for radiologic management of biliary obstruction 1.
From the Research
Causes of Cholestasis
The causes of cholestasis can be varied and depend on several factors, including the anatomical location of the defect and the acuity of presentation 2. Some of the possible causes of cholestasis include:
- Extrahepatic cholestasis, which can be caused by bile duct obstruction or other external factors 3
- Intrahepatic cholestasis, which can be caused by liver diseases such as primary biliary cirrhosis or primary sclerosing cholangitis 3, 4
- Drug-induced cholestatic disease, which can occur in the elderly 3
- Cholestatic viral hepatitis, which can occur in young people with risk factors 3
- Cholestasis of pregnancy, which can occur in the third trimester of gestation 3
- Benign recurrent intrahepatic cholestasis, which can occur in individuals with a familial history of recurrent cholestasis 3
- Alcoholic hepatitis, which can occur in individuals with a history of alcohol abuse 3
- Neonatal cholestasis syndromes, which can be caused by infections, metabolic defects, or biliary atresia 3, 5
Mechanisms of Cholestasis
The accumulation of bile acids in the liver can lead to the development of cholestasis and hepatocyte injury 6. Nuclear receptors, such as the farnesoid X receptor (FXR) and peroxisome proliferator-activated receptor alpha (PPARα), play a crucial role in controlling the synthesis and transport of bile acids in the liver 6. The activation of these receptors can reduce the amount of bile acid synthesis and decrease the bile acid content in the liver, alleviating cholestasis.
Diagnostic Approaches
The diagnostic approach to cholestasis typically involves a combination of clinical evaluation, laboratory tests, and imaging studies 3, 2. Liver ultrasound, endoscopic retrograde cholangiopancreatography (ERCP), and magnetic resonance cholangiography (MRC) can be used to evaluate the bile ducts and liver 3. Liver biopsy can also be performed to obtain a definitive diagnosis of the cause of cholestasis and to exclude potential etiologies 4.