A 25-year-old man with very high alkaline phosphatase
WHAT TEST NEXT FOR OUR PATIENT?
1. What is the next most appropriate diagnostic step for our patient?
- Liver biopsy
- Ultrasonography of the liver
- Computed tomography (CT) of the liver
- Observation
Our patient has an elevated GGT level, which suggests that his elevated alkaline phosphatase is of hepatic rather than bony origin. Moreover, a serum alkaline phosphatase level that is elevated out of proportion to the aminotransferase levels reflects cholestatic liver injury.
CASE CONTINUED: ULTRASONOGRAPHY IS MOSTLY NORMAL
Ultrasonography of the right upper quadrant revealed that the liver had normal echogenicity and was mildly enlarged. There was no focal hepatic lesion. The gallbladder appeared normal, with no stones or sludge. No dilated intrahepatic or extrahepatic biliary ducts were seen. The common bile duct measured 4 mm. A small amount of ascites not amenable to paracentesis was present.
Thus, in the absence of biliary dilation on ultrasonography, we are dealing with an intrahepatic cholestatic process.
CAUSES OF CHOLESTATIC LIVER DISEASE
Viral hepatitis
Viral hepatitis most often produces a hepatocellular pattern of injury (ie, AST and ALT elevations predominate). However, in rare cases it can cause a cholestatic pattern of injury.
Our patient subsequently had serologic tests for viral hepatitis, including hepatitis A, B, and C, and the results were negative.
Autoimmune liver disease
The three most common forms of autoimmune liver disease are autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis.
Autoimmune hepatitis is characterized by high serum ALT and AST levels, whereas primary biliary cirrhosis and primary sclerosing cholangitis are associated with predominant elevations of alkaline phosphatase, since they are cholestatic disorders.
Our patient’s alkaline phosphatase level was much higher than his ALT and AST levels, making the latter two diseases more likely.
Primary biliary cirrhosis (and autoimmune hepatitis) are associated with autoantibodies in the serum, such as antinuclear antibody, smooth muscle antibody, and antimitochondrial antibody.
Our patient subsequently was tested for these antibodies, and the results were negative.
Primary sclerosing cholangitis usually affects the extrahepatic biliary system. Thus, if it is present, abnormalities should be seen on imaging.
As mentioned previously, no dilated intrahepatic or extrahepatic biliary ducts were seen on ultrasonography in our patient. Moreover, primary sclerosing cholangitis is associated with inflammatory bowel disease, particularly ulcerative colitis, which our patient did not have.
Drug-induced liver injury
Drug-induced liver injury is a common cause of cholestatic liver disease. However, our patient was not taking any prescribed, over-the-counter, or herbal medications. Additionally, he denied heavy alcohol use.
Infiltrative disorders
Infiltrative disorders such as amyloidosis, sarcoidosis, or lymphoma should be considered in the differential diagnosis of cholestatic liver disease. A clue to a possible infiltrative process is a markedly elevated level of alkaline phosphatase with a mildly increased serum bilirubin concentration, both of which our patient had.
