Role of biochemical markers and autoantibodies in diagnosis of early-stage primary biliary cholangitis

Abstract

Background: Primary biliary cholangitis (PBC) is a chronic progressive autoimmune cholestatic disease. The main target organ of PBC is the liver, and nonsuppurative inflammation of the small intrahepatic bile ducts may eventually develop into cirrhosis or liver fibrosis.

Aim: To explore the clinical characteristics of early-stage PBC, identify PBC in the early clinical stage, and promptly treat and monitor PBC.

Methods: The data of 82 patients with PBC confirmed by pathology at Tianjin Second People's Hospital from January 2013 to November 2021 were collected, and the patients were divided into stage I, stage II, stage III, and stage IV according to the pathological stage. The general data, serum biochemistry, immunoglobulins, and autoimmune antibodies of patients in each stage were retrospectively analyzed.

Results: In early-stage (stages I + II) PBC patients, 50.0% of patients had normal alanine aminotransferase (ALT) levels, and 37.5% had normal aspartate aminotransferase (AST) levels. For the remaining patients, the ALT and AST levels were mildly elevated; all of these patients had levels of < 3 times the upper limit of normal values. The AST levels were significantly different among the three groups (stages I + II vs stage III vs stage IV, P < 0.05). In the early stage, 29.2% of patients had normal alkaline phosphatase (ALP) levels. The remaining patients had different degrees of ALP elevation; 6.3% had ALP levels > 5 times the upper limit of normal value. Moreover, γ-glutamyl transferase (GGT) was more robustly elevated, as 29.2% of patients had GGT levels of > 10 times the upper limit of normal value. The ALP values among the three groups were significantly different (P < 0.05). In early stage, the jaundice index did not increase significantly, but it gradually increased with disease progression. However, the above indicators were significantly different (P < 0.05) between the early-stage group and the stage IV group. With the progression of the disease, the levels of albumin and albumin/globulin ratio tended to decrease, and the difference among the three groups was statistically significant (P < 0.05). In early-stage patients, IgM and IgG levels as well as cholesterol levels were mildly elevated, but there were no significant differences among the three groups. Triglyceride levels were normal in the early-stage group, and the differences among the three groups were statistically significant (P < 0.05). The early detection rates of anti-mitochondria antibody (AMA) and AMA-M2 were 66.7% and 45.8%, respectively. The positive rate of anti-sp100 antibodies was significantly higher in patients with stage IV PBC. When AMA and AMA-M2 were negative, in the early stage, the highest autoantibody was anti-nuclear antibody (ANA) (92.3%), and in all ANA patterns, the highest was ANA centromere (38.5%).

Conclusion: In early-stage PBC patients, ALT and AST levels are normal or mildly elevated, GGT and ALP levels are not elevated in parallel, GGT levels are more robustly elevated, and ALP levels are normal in some patients. When AMA and AMA-M2 are negative, ANA especially ANA centromere positivity suggests the possibility of early PBC. Therefore, in the clinic, significantly elevated GGT levels with or without normal ALP levels and with ANA (particularly ANA centromere) positivity (when AMA and AMA-M2 are negative) may indicate the possibility of early PBC.

Keywords: Autoantibodies; Biochemical makers; Early stage; Pathology; Primary biliary cholangitis.