Alkaline phosphatase primary biliary cirrhosis

Alkaline phosphatase levels and GGT are elevated in plasma with obstructive disorders that disrupt the flow of bile from hepatocytes to the bile ducts or from the biliary tree to the intestines in condition such as primary biliary cirrhosis, sclerosing cholangitis, drug-induced cholestasis, gallstone disease, and autoimmune cholestatic liver disease. 

Depending on the nature of the chronic liver disease, the biliary tract may or may not be affected, and hence bilirubin and alkaline phosphatase may be normal or raised. For example, a patient with primary biliary cirrhosis (PBC) can have an alkaline phosphatase and bilirubin raised to twice ULN. Where there is biliary involvement there is the potential for reduced fat-soluble vitamin absorption. ITence a raised alkaline phosphatase may have occurred over time owing to decreased vitamin D absorption affecting bone development, rather than being associated with the liver. Likewise, the clotting may be abnormal because of vitamin K deficiency. 

A small historical study evaluated the effect of DMPA on six patients with either chronic active viral hepatitis or primary biliary cirrhosis. The study showed that DMPA actually improved transaminase levels and the metabolic ability of the liver. The investigators suggested that the immune-modifying properties of medroxyprogesterone may make the hormone a therapeutic alternative [2]. There were limitations in that this was a very small, non-randomised study, and therefore it is difficult to make specific recommendations based on the outcome. Another study of the metabolic effects of DMPA in women who had used the method for five years or more suggested that there was a significant rise in plasma insulin, alkaline phosphatase and morning cortisol levels in the DMPA users [31]. 

Fatal liver damage was observed particularly in the UK and tended to occur in elderly subjects. The complication initially presented as jaundice or raised liver enzymes (including alkaline phosphatase). Surprisingly, biochemical and histological liver changes were not consistent with major hepatocellular damage. There were three reports of primary biliary cirrhosis, but a causal relation was not proven (SEDA-12, 84). 

SERUM ALKALINE PHOSPHATASE IN CLINICAL MEDICINE 207 7.7.3. Primary Biliary Cirrhosis... 

Patients with this disorder characteristically have high serum alkaline phosphatase activities. Only 2 of 100 patients with primary biliary cirrhosis studied by Sherlock and Scheuer (S33) had serum alkaline phosphatase values below 20 King-Armstrong units/dl, whereas 71 had values exceeding 50 King-Armstrong units/dl (Fig. 12). A reduction in serum alkaline phosphatase follows treatment with azathioprine (R30). 

Fig. 12. Serum alkaline phosphatase values in 100 patients with primary biliary cirrhosis. Male patients are shown by stippled columns. Note the presence of hyper-phosphatasemia in almost all the patients with this disorder. From Sherlock and Scheuer (S33) with permission.

---