How should I interpret elevated alkaline phosphatase levels in the context of suspected PBC?

Elevated alkaline phosphatase (ALP) levels in the context of suspected primary biliary cholangitis (PBC) should be interpreted as a key biochemical marker indicating cholestatic liver injury, reflecting damage to the intrahepatic bile ducts. In PBC, ALP elevation is typically persistent and disproportionate compared to other liver enzymes, and it is one of the earliest and most sensitive indicators of the disease process ⁴.

ALP elevation in PBC results from immune-mediated destruction of small intrahepatic bile ducts, leading to cholestasis and subsequent release of ALP into the bloodstream (Moreno-Otero et al., 1989). This pattern of cholestatic liver enzyme abnormality, especially when accompanied by positive antimitochondrial antibodies (AMA), strongly supports the diagnosis of PBC ⁴.

While elevated ALP is not specific to PBC and can be seen in other cholestatic or infiltrative liver diseases, in the appropriate clinical context—such as middle-aged women with fatigue or pruritus—persistent ALP elevation should prompt further investigation for PBC, including serological testing and possibly liver biopsy ⁴.

Therefore, in general practice, an elevated ALP level should be viewed as a critical biochemical clue that warrants further diagnostic evaluation for PBC, especially when other causes of cholestasis have been excluded. Early recognition and diagnosis based on ALP elevation allow timely initiation of treatment to slow disease progression (Moreno-Otero et al., 1989) ⁴.