Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome: Clinical features and response to therapy

Abstract

The association of primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) is thought to be rare, and its optimal treatment is unknown. Of 130 consecutive patients with a diagnosis of PBC, we identified 12 cases (9.2%) of overlap syndrome (10 females, 2 males; median age, 50 years) strictly defined by the presence of at least two of the three recognized biochemical, serological, and histological criteria of each disease. One patient had initially pure PBC , presence of mitochondrial antibodies (n ‫؍‬ 9) or ASMA (n ‫؍‬ 9), florid bile duct lesions (n ‫؍‬ 8), and moderate or severe periportal or periseptal lymphocytic piecemeal necrosis (n ‫؍‬ 11). UDCA (13-15 mg/kg/d) given alone in 5 patients induced a significant decrease in biochemical cholestasis but not in ALT levels, and liver fibrosis progressed in 3 patients. Corticosteroids given alone in 6 patients induced a significant decrease in ALT, IgG, and AP levels, but none had a biochemical normalization. The patients with persistently abnormal liver tests under either UDCA or corticosteroids received both UDCA and corticosteroids. A further marked biochemical improvement was observed, and all patients became asymptomatic. We conclude that, in patients with PBC: 1) overlap syndrome with AIH is not rare; 2) flares of AIH may occur either spontaneously or under UDCA; and 3) combination of UDCA and corticosteroids is required in most patients to obtain a complete biochemical response.

Autoantibodies by Line Immunoassay in Patients With Primary Biliary Cirrhosis

“…The diagnosis of AIH features was based on the revised scoring system according to the International Autoimmune Hepatitis Group (IAIHG) 10) . PBC -AIH overlap was diagnosed on the basis of Paris criteria 7) proposed by Chazouilleres et al More specifically, PBC -AIH overlap was defined as meeting at least 2 of 3 criteria for PBC, that is, 1) serum ALP level ≥ 2 × upper limit of normal (ULN) or GTP level ≥ 5 × ULN, 2) positive for AMA, and 3) presence of a florid duct lesion on histology, and at least 2 of the 3 criteria for AIH, that is, 1) serum ALT level ≥ 5 × ULN, 2) serum immunoglobulin level ≥ 2 × ULN or positive for anti -smooth muscle antibody (ASMA), and 3) presence of moderate to severe interface hepatitis on histology. Serum samples were collected from these patients between March 2010 and July 2011 (i.e., on -treatment serum samples) and stored at −20°C until used for autoantibody detection.…”

“…Therefore, detection of autoantibodies other than AMA would help the diagnosis of PBC 5,6) . There is also a subset of PBC patients who have autoimmune hepatitis (AIH), referred to as PBC -AIH overlap cases 7,8) , and no detailed analysis of autoantibodies in these overlap cases has been conducted. Most of the preceding studies on autoantibodies in PBC focused on only a single type of autoantibody, and the positivity pattern of different autoantibodies in a single serum sample, as well as its clinical significance, has not been elucidated.…”

Ten–Year Survival in Ursodeoxycholic Acid-Treated Patients With Primary Biliary Cirrhosis

“…Twelve patients in whom the diagnosis of PBC-autoimmune hepatitis overlap syndrome was made were excluded from this study. 10 All patients were treated with UDCA at a dose of 13 to 15 mg/kg/d. These patients were followed from the beginning of treatment (1982 to 1996) until time of last follow-up, OLT, or death.…”

Rapid-onset Primary Biliary Cirrhosis Resembling Drug-induced Liver Injury

“…The disease is also reported to have certain characteristics regarding the reaction to treatment. Several investigators reported that the liver function test is not completely normalized without corticosteroid treatment in most cases of overlap syndrome (7,12), a fact that seems to be important.…”