Cholestasis

Cholestasis commonly presents with jaundice, pale stools and dark urine. There may be abdominal pain and fever in case of infection or cholecystitis. A common feature of cholestasis is pruritus, which may be disabling or significantly affecting the daily life of the patient. Children may show failure to thrive, hormonal disturbances, and attention deficits. Sometimes, xanthomas may be observed on the trunk and diaper area and in skin folds [8].

• Blood analysis: Elevated serum bilirubin levels, total serum bile salt concentration levels and total serum cholesterol level are found. Serum lipoprotein-X levels are elevated in conditions leading to obstructive cholestasis. Increased levels of of serum alkaline phosphatase, serum 5'-nucleotidase, and serum gamma-glutamyl transferase (GGT) are observed. Hematology screen may show anemia in case of malignancy. Leukocytosis is present in case of infection. Cholestasis often leads to abnormally shaped cells. In case of prehepatic jaundice, reticulocytosis may be seen and prothrombin time should be checked.
• Abdominal ultrasound and CT: Anatomic causes of obstructive cholestasis can be detected with ultrasonography and CT scan of liver and bile ducts. 
• Hepatoiminodiacetic acid [HIDA] scanning is used to identify anatomic causes of obstructive cholestasis and to differentiate between hepatocellular and obstructive cholestasis. 
• Endoscopic retrograde cholangiography or endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangiography are useful to identify anatomic causes of obstructive cholestasis. Operative cholangiography, when done is definitive in detecting the cause. 
• Liver biopsy when possible, can lead to definitive diagnosis. 
• Urea, electrolytes and creatinine derangement signifies acute renal damage may be present. 

Medical therapy is largely ineffective in cholestasis. However, ursodeoxycholic acid (20-30 mg/kg/d) has been used in children to increase bile formation and antagonize the effect of hydrophobic bile acids on biological membranes. Children with chronic cholestasis may be given phenobarbital (5 mg/kg/d). Dietary substitution for treatment of fat malabsorption is recommended. Vitamin supplementation in chronic cholestasis, oral absorbable, fat-soluble vitamin formulation A, D, E, and K are given to children. Osteopenia, if present, is treated with bisphosphonates. Pruritus is treated with phototherapy, ursodeoxycholic acid, colestyramine, rifampicin and external biliary drainage. Surgical treatment is indicated for underlying causes that are amenable to surgery [9] [10].

Cholestasis can give rise to secondary liver disease like hepatic fibrosis, metabolic bone disease like osteopenia and osteoporosis, and life threatening bleeding tendencies in children. Prognosis depends on the underlying condition giving rise to cholestasis. Although cholestasis itself does not result in death, it causes significant morbidity due to the widespread systemic effects.

Cholestasis is classified as acute or chronic, and based on the localization of the interference of bile flow or formation, as extrahepatic (obstructive) and intrahepatic (hepatocellular) cholestasis.

Acute extrahepatic cholestasis is caused by obstruction to the bile ducts due to malignancy, benign bile duct stricture, bile duct compression, bile duct stones, gallstones and infectious cholangitis.

Drugs, viral infections, sepsis and cholestatic conditions can lead to acute intrahepatic cholestasis. Acute cholestasis may also occur as a part of paraneoplastic syndrome due to the release of inflammatory mediators from cancer cells. Other obstructive causes are Alagille syndrome and nonsyndromic ductal paucity.

Primary biliary cirrhosis and primary sclerosing cholangitis are considered causes of chronic cholestasis. Some other causes of hepatocellular cholestasis are drug-induced, alpha-1-antitrypsin deficiency, inborn errors of bile acid synthesis and cholestasis associated with total parenteral nutrition. Drugs that can cause cholestasis are antibiotics, contraceptive pills, anabolic steroids, cimetidine, chlorpromazine, imipramine, prochlorperazine, terbinafine, and tolbutamide. Intrahepatic cholestasis of pregnancy is reversible, influenced by hormones and develops in late pregnancy in women with genetic predisposition [2] [3] [4].

More than 70% of all cholestasis cases have extrahepatic causes. Although there is not differences between men and women in the incidence of cholestasis induced by genetic diseases, overall women are more affected due to cholestasis in pregnancy. Biliary atresia and drug-induced cholestasis also occur more in women. Pediatric cholestasis is also more common as newborns and infants have an immature liver [5] [6].

In hepatocellular cholestasis bile is present within hepatocytes and canalicular spaces leading to hepatocellular injury. Bile plugging of the interlobular bile ducts, bile duct proliferation in association with centrilobular cholate injury and portal expansion is found in obstructive cholestasis.

There is increased cholesterol content of membranes leading to imapirment of the functioning of integral membrane proteins. Retention of bile salts results in injury to biological membranes throughout the body, with most damage to the liver. Bile salts may be a mediator of hepatic fibrosis as well. Injury to red blood cells can result in spur-cell hemolytic anemia [7].

There is no definitive way to prevent cholestasis, but timely diagnosis and treatment can prevent debilitating and serious complications. The possibility of cholestasis should be borne in mind in patients undergoing total parenteral nutrition, or who are pregnant or have any of the known associated genetic conditions. Vaccination against viral hepatitis can prevent the related cases of cholestasis.

As the bile flow from the gallbladder into the duodenum is hindered, cholestasis leads to retention of bile and regurgitation of unconjugated bilirubin and bile salts into the serum, leading to major effects on all organ systems. Jaundice, pruritus, nausea, vomiting, and pain are frequent symptoms. Management consists of treatment of underlying cause and treatment of pruritus [1].

• Definition: Cholestasis is the term used when the flow of bile from the gall bladder into the small intestine is slowed or blocked.
• Cause: The liver related causes can be infections, pregnancy, alcoholic liver disease, cancers, and primary biliary cirrhosis. The causes that are outside liver are commonly bile duct tumors, stones, pancreatic diseases, and cysts. 
• Symptoms: The white of your eyes may look yellowish. There may be yellow tinge to the skin and dark colored urine. Commonly the stool may be clay colored or white and you may have digestion problems. There can be nausea and vomiting and pain in the upper part of the abdomen. You may have itching. 
• Diagnosis: Some blood tests will be done to see the level of contents of bile in the blood and other enzymes that show the functioning of the liver. Ultrasound and CT scan of the abdomen may be done. A test called endoscopic retrograde cholangiopancreatography (ERCP) may be useful. 
• Treatment and follow-up: Treatment involves treating the cause of the bile flow obstruction like removal of stones and treatment of infection. Although completely resolved bile duct stones and such acute problems may not cause require frequent follow-ups, you must continue regular follow up for chronic diseases according to your physician’s recommendation, and consult a doctor for any recurrence of symptoms. 

1. Sellinger M, Boyer JL. Physiology of bile secretion and cholestasis. Prog Liver Dis. 1990;9:237-59.
2. Karlsen TH, Vesterhus M, Boberg KM. Review article: controversies in the management of primary biliary cirrhosis and primary sclerosing cholangitis. Aliment Pharmacol Ther. 2014;39(3):282-301.
3. Kimmings AN, Van deventer SJ, Obertop H, Rauws EA, Gouma DJ. Inflammatory and immunologic effects of obstructive jaundice: pathogenesis and treatment. J Am Coll Surg. 1995;181(6):567-81.
4. Williamson C, Geenes V. Intrahepatic cholestasis of pregnancy. Obstet Gynecol. 2014;124(1):120-33.
5. James OF, Myszor M. Epidemiology and genetics of primary biliary cirrhosis. Prog Liver Dis. 1990;9:523-36.
6. Mathias A, Wax JR, Pinette MG, Cartin A, Blackstone J. Progressive familial intrahepatic cholestasis complicating pregnancy. J Matern Fetal Neonatal Med. Jun 1 2009;1-3.
7. Elferink RP, Groen AK. The mechanism of biliary lipid secretion and its defects. Gastroenterol Clin North Am. Mar 1999; 28(1):59-74, vi.
8. Gossard AA, Talwalkar JA. Cholestatic liver disease. Med Clin North Am. 2014; 98(1):73-85.
9. Beuers U, Kremer AE, Bolier R, Elferink RP. Pruritus in cholestasis: facts and fiction. Hepatology. 2014;60(1):399-407.
10. Festi D, Montagnani M, Azzaroli F, et al. Clinical efficacy and effectiveness of ursodeoxycholic acid in cholestatic liver diseases. Curr Clin Pharmacol. May 2007; 2(2):155-77.

• Cholestasis
  Guest, 2019-01-04 15:09
• Previous gallbladder/bileduct
  Guest, 2018-10-02 16:17