Cholestasis / obstructive jaundice

What it is

Cholestatic jaundice is conjugated hyperbilirubinemia, that is direct bilirubin above 25% of the total, together with abnormal results of other liver function tests. The pattern is put in numbers by the R value, which is serum ALT divided by its ULN, divided in turn by ALP divided by its ULN: an R value of 5 or more is hepatocellular, an R value between 2 and 5 is mixed, and an R value of 2 or less is cholestatic. Cholestasis is then split into extrahepatic cholestasis, where the bile ducts are dilated, and intrahepatic cholestasis, where they are not.

The R factor puts the same split another way. An R factor below 2 is cholestatic injury, more ALKP than ALT, suggestive of obstructive causes like biliary stones, cholangitis or primary biliary cirrhosis; an R factor above 5 is hepatocellular injury, more ALT than ALKP; and an R factor of 2 to 5 is a mixed injury pattern.

Causes and risk

Extrahepatic obstruction is typically a stone in the common bile duct, and the criteria for cholangitis are counted: 1) high ALP and bilirubin; 2) a dilated CBD with a CBD stone; 3) jaundice, fever and oily pale stool. Primary sclerosing cholangitis is a cause in a middle-aged man: cholestasis leading to progressive destruction of both intrahepatic and extrahepatic bile ducts. In the neonatal period the conjugated causes are biliary atresia, which is progressive fibrosis of the extrahepatic and intrahepatic biliary tree, choledochal cyst, which is cystic dilatation of the extrahepatic biliary system, Alagille syndrome, an autosomal dominant disorder of the JAG1 and NOTCH-2 genes, and neonatal hepatitis syndrome. Neonatal hepatitis syndrome has causes of its own: congenital infection with hepatitis A, B or C, rubella, CMV, HSV or syphilis; inborn errors of metabolism; alpha1-antitrypsin deficiency; galactosaemia; tyrosinaemia type 1; errors of bile acid synthesis; progressive familial intrahepatic cholestasis, that is PFIC; cystic fibrosis; and intestinal failure-associated liver disease, which goes with long-term parenteral nutrition. In pregnancy the cause to hold is intrahepatic cholestasis of pregnancy, also known as obstetric cholestasis, which occurs in around 1% of pregnancies, is generally seen in the third trimester, and is the most common liver disease of pregnancy.

Where the direct bilirubin is raised but the liver enzymes and the parameters of cholestasis are all normal, the fault lies in excretion or reuptake of bilirubin: Dubin Johnson syndrome and Rotor syndrome.

Once cholestasis is established the ultrasound divides the causes in two. Intrahepatic cholestasis covers liver disease, primary biliary cholangitis, drugs and toxins such as arsenic, sepsis, postoperative cholestasis and pregnancy. Biliary obstruction begins with choledocholithiasis and then covers tumors of the pancreas, bile duct or gall bladder, primary sclerosing cholangitis and pancreatitis.

Primary biliary cholangitis stands beside primary sclerosing cholangitis: an autoimmune disease of chronic cholestasis due to chronic inflammation and progressive destruction of the intrahepatic bile ducts, in a middle-aged female, associated with other autoimmune diseases such as Sjogren syndrome, rheumatoid arthritis, Hashimoto thyroiditis and scleroderma. Primary sclerosing cholangitis carries its own strong association with autoimmune diseases, particularly ulcerative colitis.