These signs and symptoms resolve on their own shortly after delivery, though they may reappar in subsequent pregnancies for 45-70% of women. In the treatment of ICP, current evidence suggests ursodeoxycholic acid (UDCA), a minor secondary bile acid in humans, is the most effective drug for reducing pruritus and improving liver function.The etiology of ICP is multifactorial and likely involves hormonal, genetic, and environmental factors. Several observations suggest estrogen plays a major role: ICP begins in the third trimester, when estrogen levels are highest, resolves after estrogen levels return to normal post-delivery, and occurs with higher incidence in multiple pregnancies, where estrogen levels are more elevated than usual. Although estrogens exact pathomechanism in ICP remains unclear, several explanations have been offered. Estrogen may induce a decrease in the fluidity of the hepatic sinusoidal membrane, leading to a decrease in the activity of basolateral Na+/K+-ATPase. A weaker Na+ gradient results in diminished sodium-dependent uptake of bile acids from venous blood into hepatocytes by the sodium/bile acid cotransporter. More recent evidence suggests that estrogen promotes cholestasis via its metabolite estradiol-17-β-D-glucuronide (E2). E2 secreted into the canaliculi by MRP2 was found to repress the transcription of bile salt export pump (BSEP), the apical ABC transporter responsible for exporting monoanionic conjugated bile acids from hepatocytes into bile canaliculi. E2 was also found to upregulate miR-148a, which represses expression of the pregnane X receptor (PXR).
In the early part of life (within the first three months), patients with Alagille syndrome exhibit conjugated hyperbilirubinemia, severe pruritus, and jaundice. Bile duct obliteration usually worsens over time, causing cirrhosis of the liver and eventual failure. Diagnosis usually occurs using the classic criteria by looking at changes associated with the five systems discussed earlier. Like FIH, the definitive treatment is a liver transplant. Almost all patients with Alagille syndrome have mutations of the genes involved in the Notch signaling pathway. Most have a mutation of the JAG1 gene, while a small minority have a mutation of the NOTCH2 gene. Sepsis
A variety of factors associated with sepsis may cause cholestasis. Typically, patients have conjugated hyperbilirubinemia and alkaline phosphatase (ALP) elevation but not to extreme levels. Sepsis-induced cholestasis may occur due to increased serum lipopolysaccharide levels. Lipopolysaccharides can inhibit and down-regulate bile salt transporters in hepatocytes, thereby leading to cholestasis. As such, in the case of sepsis, cholestasis occurs not as a result of impaired obstruction but rather the disruption of bile flow. Ischemic liver injury resulting from sepsis can also cause cholestasis. Importantly, jaundice is not indicative of cholestasis in all cases. Widespread hemolysis resulting from sepsis may release bilirubin, thereby overwhelming bilirubin reabsorption and excretion mechanism. TPN-based cholestasis
Total parenteral nutrition (TPN) is given to patients with intestinal failure or a variety of other gastrointestinal problems. Under normal settings, TPN causes a slight elevation of ALP levels. However, this does not indicate cholestasis alone.