sCD163 in PBC Patients - Assessment of Treatment Response

Primary biliary cholangitis (PBC, previously called 'primary biliary cirrhosis') is an autoimmune cholestatic liver disease characterized by destruction of intrahepatic bile ducts and progression to liver fibrosis and cirrhosis. In the pre-cirrhotic phase, fatigue and pruritus are the dominant symptoms. These symptoms reduce PBC patients' quality of life, but the extent to which they cause the patient to leave the work force and seek disability pension is unknown. The diagnosis of PBC is based on the presence of two of three major criteria; unexplained serum alkaline phosphatase (ALP) \>1.5 times upper normal limit for more than 24 weeks, presence of anti-mitochondrial antibodies (AMA), and compatible liver histology. Multiple models have been conducted to predict prognosis in patients with PBC. The Mayo risk score is the best validated and includes information on age, bilirubin, albumin, prothrombin time and peripheral oedema. Other prognostic factors are pruritus and fatigue at diagnosis that predict the time to develop cirrhosis and its complications.

Ursodeoxycholic acid is the first line treatment for all patients with PBC. Response to treatment is assessed after 12 months of treatment using e.g. the Paris 1 criteria (ALP \<3 times upper normal limit, AST \<2 times upper normal limit, and bilirubin ≤1 mg/dL after one year of treatment). Up to 40% of patients respond inadequately to UDCA and need add-on therapies. (e.g. fibrates, budenosid or obeticholic acid).

In PBC, inflammation is attributed to an immune response to mitochondrial autoantigens followed by a serologic response of anti-mitochondrial antibodies (AMAs); and accompanied by inflammation of small bile ducts. The pathogenesis includes both CD4 and CD8 cells, which in the presence of biliary cells expressing the 2-oxo-dehydrogenase pathway (PDC-E2) activates macrophages via granulocyte macrophage colony-stimulating factor. The activated macrophages, together with AMAs, produce a proinflammatory response with subsequent liver inflammation and fibrosis. Thus, macrophages seem to be involved in PBC disease severity and progression. However, macrophage activation markers have not previously been investigated in PBC patients. The investigators in our research group have during the last years investigated the macrophage activation marker sCD163. The group have shown increased levels in relation to liver fibrosis/cirrhosis in patients with chronic viral hepatitis (HBV and HCV), non-alcoholic fatty liver disease (NAFLD/NASH) and alcoholic liver disease (alcoholic hepatitis and cirrhosis) and liver disease severity including risk of portal hypertension and development of complications and mortality. Just recently the investigators' group also demonstrated that the soluble mannose receptor (sMR) and sCD163 are associated with early and long-term prognosis of patients with cirrhosis and acute-on-chronic liver failure.

Aims:

To investigate sCD163 and sMR at diagnosis, before treatment with UDCA, as possible predictors of non-response to UDCA treatment and thus as predictors of patients needing add-on therapy.

• disease progression (blood samples, fibroscan, questionnaires) [Time frame: 3 years]