Antimitochondrial Antibody-Negative Primary Biliary Cirrhosis
Antimitochondrial Antibody-Negative Primary Biliary Cirrhosis
Objective: Antimitochondrial antibodies (AMA) are the hallmark in primary biliary cirrhosis (PBC); nevertheless, it has long been recognized that 5-10% patients with typical features compatible with PBC do not have detectable AMA, and they were referred to as "AMA-negative PBC". This study aimed to evaluate whether AMA-negative/positive PBC represents different clinical entities.
Methods: We compared the clinical, laboratory, percentage of regulatory T cells (Tregs) in peripheral blood, liver biopsy features and response to treatment of the two groups of patients. The first group was comprised of 12 patients with "AMA-negative PBC". The second was made up of another 12 PBC patients with positive AMA.
Results: Antimitochondrial antibodies-negative/positive patients were remarkably similar in terms of clinical manifestations, liver biochemistries and histological findings. The frequency of anti-nuclear antibodies, anti-smooth-muscle antibody, anti-gp210 and anti-sp100 antibody showed no significant difference between the two groups. A significantly lower mean percentage of CD4CD25 T cells was observed in peripheral blood mononuclear cells of AMA-negative/positive PBC patients compared with that of the 12 control subjects (5.8±1.8 and 5.4±1.4% vs. 7.6±1.7% respectively; P = 0.014 and 0.004). However, no difference could be found between AMA-negative and AMA-positive PBC patients (P = 0.599). After 1 year treatment with ursodeoxycholic acid, the two groups showed similar response.
Conclusion: Antimitochondrial antibody-negative/positive PBC patients are similar in clinical, laboratory, percentage of Treg in peripheral blood, liver biopsy features and response to treatment. This suggests that AMA-negative PBC may be a variant of AMA-positive PBC rather than a separate clinical entity.
Primary biliary cirrhosis (PBC) is a chronic cholestatic disorder characterized by progressive, non-suppurative inflammation and destruction of intrahepatic small bile ducts. The presence of antimitochondrial antibodies (AMA) in the sera is a very important finding for the diagnosis of PBC. The sensitivity and specificity of AMA for PBC are both >90-95%; therefore, AMA is the major hallmark of PBC. However, it has been reported that 5-10% patients with clinical, biochemical and histological features compatible with PBC do not have detectable AMA. These AMA-negative PBC patients have been noted to differ from positive ones with respect to production of other antibodies, manifesting higher titres of anti-nuclear antibodies (ANA) and lower total levels of IgM.
It is important to distinguish AMA-negative/positive PBC for a better understanding of this condition. This issue could not be addressed by previous studies in view of the small number of patients described in most series and the cross-sectional design used. Specifically, no prospective studies have compared the clinical and immunological features of these two groups of patients. Furthermore, although some evidence supported the hypothesis that the clinical features of autoimmune chronic liver disease might vary in different geographical areas, available data on AMA-negative PBC had been obtained only from patients living in northern Europe and North America.
For these reasons, the present study was conducted to compare the clinical, biochemical, immunological and histological features and the response to ursodeoxycholic acid (UDCA) treatment of AMA-negative/positive PBC patients. We have explored whether patients with features of PBC and AMA negativity are specific enough to be an independent entity.
Abstract and Introduction
Abstract
Objective: Antimitochondrial antibodies (AMA) are the hallmark in primary biliary cirrhosis (PBC); nevertheless, it has long been recognized that 5-10% patients with typical features compatible with PBC do not have detectable AMA, and they were referred to as "AMA-negative PBC". This study aimed to evaluate whether AMA-negative/positive PBC represents different clinical entities.
Methods: We compared the clinical, laboratory, percentage of regulatory T cells (Tregs) in peripheral blood, liver biopsy features and response to treatment of the two groups of patients. The first group was comprised of 12 patients with "AMA-negative PBC". The second was made up of another 12 PBC patients with positive AMA.
Results: Antimitochondrial antibodies-negative/positive patients were remarkably similar in terms of clinical manifestations, liver biochemistries and histological findings. The frequency of anti-nuclear antibodies, anti-smooth-muscle antibody, anti-gp210 and anti-sp100 antibody showed no significant difference between the two groups. A significantly lower mean percentage of CD4CD25 T cells was observed in peripheral blood mononuclear cells of AMA-negative/positive PBC patients compared with that of the 12 control subjects (5.8±1.8 and 5.4±1.4% vs. 7.6±1.7% respectively; P = 0.014 and 0.004). However, no difference could be found between AMA-negative and AMA-positive PBC patients (P = 0.599). After 1 year treatment with ursodeoxycholic acid, the two groups showed similar response.
Conclusion: Antimitochondrial antibody-negative/positive PBC patients are similar in clinical, laboratory, percentage of Treg in peripheral blood, liver biopsy features and response to treatment. This suggests that AMA-negative PBC may be a variant of AMA-positive PBC rather than a separate clinical entity.
Introduction
Primary biliary cirrhosis (PBC) is a chronic cholestatic disorder characterized by progressive, non-suppurative inflammation and destruction of intrahepatic small bile ducts. The presence of antimitochondrial antibodies (AMA) in the sera is a very important finding for the diagnosis of PBC. The sensitivity and specificity of AMA for PBC are both >90-95%; therefore, AMA is the major hallmark of PBC. However, it has been reported that 5-10% patients with clinical, biochemical and histological features compatible with PBC do not have detectable AMA. These AMA-negative PBC patients have been noted to differ from positive ones with respect to production of other antibodies, manifesting higher titres of anti-nuclear antibodies (ANA) and lower total levels of IgM.
It is important to distinguish AMA-negative/positive PBC for a better understanding of this condition. This issue could not be addressed by previous studies in view of the small number of patients described in most series and the cross-sectional design used. Specifically, no prospective studies have compared the clinical and immunological features of these two groups of patients. Furthermore, although some evidence supported the hypothesis that the clinical features of autoimmune chronic liver disease might vary in different geographical areas, available data on AMA-negative PBC had been obtained only from patients living in northern Europe and North America.
For these reasons, the present study was conducted to compare the clinical, biochemical, immunological and histological features and the response to ursodeoxycholic acid (UDCA) treatment of AMA-negative/positive PBC patients. We have explored whether patients with features of PBC and AMA negativity are specific enough to be an independent entity.