Clinical Trial Details
— Status: Recruiting
Administrative data
NCT number |
NCT02931513 |
Other study ID # |
PBC AU 2 |
Secondary ID |
|
Status |
Recruiting |
Phase |
|
First received |
|
Last updated |
|
Start date |
September 2016 |
Est. completion date |
September 2031 |
Study information
Verified date |
August 2022 |
Source |
University of Aarhus |
Contact |
Lars Bossen, PhD-student |
Phone |
+4522800676 |
Email |
larsbossen[@]clin.au.dk |
Is FDA regulated |
No |
Health authority |
|
Study type |
Observational
|
Clinical Trial Summary
Primary biliary cholangitis (PBC) is an autoimmune chronic liver disease, characterised by
destruction of the small intrahepatic bile ducts. Ursodeoxycholic acid (UDCA) is the first
line treatment for patients with PBC. However, up to 40% of patients respond inadequate to
this treatment.
sCD163 is a macrophage activation marker shedded into plasma by macrophages in the liver. sMR
is a soluble mannose receptor. The investigators want to investigate whether sCD163 and sMR
can predict response to treatment with UDCA in newly diagnosed patients with PBC.
Description:
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.