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Background Autoimmune hepatitis ( AIH) is historically classified into type 1 and type 2 on the basis of the autoantibody profile, anti-nuclear and/or anti-smooth muscle antibodies being the serological markers of type 1 AIH, whereas anti-liver/kidney microsomal antibody type 1 and/or anti-liver cytosol antibody type 1 characterise type 2 AIH. Aim To evaluate whether such a distinction is justified on the basis of different expression of the disease in adults. Methods Twenty-six adult patients with type 2 AIH and 52 age- and sex-matched patients with type 1 AIH, representative of the entire cohort of adults with type 1 AIH, were compared at onset and during follow-up. Results At diagnosis, median age was 26 years (range 17-53), female sex 86%, acute presentation 43%, severe liver histology 54%, cirrhosis 14%, complete response to treatment 52%, progression of the disease 17%, and median disease duration 72 months (range 12-280). HLA- DRB1*0301 was present in 26%, HLA- DRB1*0401 in 23% and HLA- DRB1*0701 in 25%. Clinical presentation, biochemical parameters, severe liver histology, genetic profile, response rate and progression of the disease were identical between type 1 and type 2 AIH. Conclusion There is not enough clinical, biochemical, histological or genetic reason to subdivide adults with autoimmune hepatitis into type 1 and type 2 on the basis of the autoantibody profile, and the term 'autoimmune hepatitis' without qualification should be preferred. [ABSTRACT FROM AUTHOR]

Background Primary biliary cirrhosis (PBC) may be associated with various rheumatological disorders. Aim To investigate the frequency and significance of ‘rheumatological’ antinuclear antibodies in the field of autoimmune chronic liver disease, with special regard to PBC. Methods We studied 105 patients with PBC, 162 autoimmune liver disease controls (type 1 and 2 autoimmune hepatitis, primary sclerosing cholangitis), 30 systemic lupus erythematosus and 50 blood donors. Sera were tested for the presence of antibodies to extractable nuclear antigens (anti-ENA) by counterimmunoelectrophoresis, enzyme-linked and immunoblot (IB) assay, and for the presence of anti-centromere antibodies (ACA) by indirect immunofluorescence on HEp-2 cells and IB. Results The overall prevalence of IB-detected anti-ENA in PBC (30%) was higher than in type 1 autoimmune hepatitis (2.5%, P < 0.0001), type 2 autoimmune hepatitis (0%, P < 0.0001) and primary sclerosing cholangitis (11.5%, P = 0.006) and lower than in systemic lupus erythematosus (53%, P = 0.03). The most frequent anti-ENA reactivity in PBC was anti-SSA/Ro-52kD (28%). ACA were detected by IB in 21% PBC patients and never in the other subjects ( P < 0.0001). Anti-SS-A/Ro/52kD positive PBC patients had at the time of diagnosis a more advanced histological stage ( P = 0.01) and higher serum levels of bilirubin ( P = 0.01) and IgM ( P = 0.03) compared with negative ones. Conclusions In the autoimmune liver disease setting, anti-SS-A/Ro-52kD and ACA have a high specificity for PBC and can thus be of diagnostic relevance in anti-mitochondrial antibodies negative cases. If confirmed in further studies with adequate follow-up, anti-SS-A/Ro-52kD antibodies might identify PBC patients with a more advanced and active disease. [ABSTRACT FROM AUTHOR]

Background Serum antinuclear antibodies giving the ‘multiple nuclear dots’ or the ‘rim-like/membranous’ patterns are frequently detected by indirect immunofluorescence on HEp-2 cells in patients with primary biliary cirrhosis. Aim To assess the accuracy of multiple nuclear dot and rim-like/membranous antinuclear antibodies for the diagnosis of primary biliary cirrhosis. Methods Sera from 4371 consecutive patients referred to our laboratory were analysed under code for antinuclear antibodies testing by indirect immunofluorescence on HEp-2 cells. Results Review of the clinical records of the 4371 patients allowed identification of 101 patients with antimitochondrial antibody-positive primary biliary cirrhosis and 22 with antimitochondrial antibody-negative variant. Multiple nuclear dot and/or rim-like/membranous patterns were found in 59 (1.3%) of the 4371 patients: 31 antimitochondrial antibody-positive primary biliary cirrhosis, 17 antimitochondrial antibody-negative primary biliary cirrhosis and 11 non-primary biliary cirrhosis. The specificity for primary biliary cirrhosis of both the antinuclear antibodies pattern was 99%. Positive predictive value and likelihood ratio for a positive test were 86% (95% CI: 72.7–94) and 221 (95% CI: 91.7–544) for multiple nuclear dot, 79% (95% CI: 62.2–90.1) and 132 (95% CI: 56.8–312.7) for rim-like/membranous, respectively. Conclusions Multiple nuclear dot and rim-like/membranous antinuclear antibodies are rare findings. Their positivity strongly suggests the diagnosis of primary biliary cirrhosis, irrespective of antimitochondrial antibody status. The high specificity for primary biliary cirrhosis makes them a useful diagnostic tool especially in antimitochondrial antibody-negative patients. [ABSTRACT FROM AUTHOR]

Background : Besides the autoantibodies included in the diagnostic criteria of type 1 autoimmune hepatitis, many other autoantibodies have been described in this condition. Recently, antibodies against cyclic citrullinated peptide have been validated as specific diagnostic and prognostic markers of rheumatoid arthritis. Aim : To assess whether these antibodies are part of the autoantibody repertoire of type 1 autoimmune hepatitis and correlate with rheumatological manifestations. Methods : Antibodies against cyclic citrullinated peptide were tested by a commercially available enzyme-linked immunosorbent assay. Results : The antibodies were found in 12 of 133 (9%) type 1 autoimmune hepatitis, two of 49 (4%) with primary biliary cirrhosis, one of 80 (1%) with hepatitis C virus-related chronic liver disease and 53 of 89 (60%) with rheumatoid arthritis serum samples. High titres were found only in rheumatoid arthritis and type 1 autoimmune hepatitis. No clinical (in particular rheumatological manifestations), biochemical or immunoserological differences were detectable between antibodies against cyclic citrullinated peptide positive and negative type 1 autoimmune hepatitis sera, with the exception of rheumatoid factor, always negative in the positive ones. Conclusions : Antibodies against cyclic citrullinated peptide can be detected in a subgroup of patients with type 1 autoimmune hepatitis. They might be part of the wide range of autoantibody production characteristic of this condition and/or, less probably, be predictive of future rheumatoid arthritis development. [ABSTRACT FROM AUTHOR]

: The usual onset of type 1 autoimmune hepatitis occurs at puberty or around menopause, whereas disease presentation in the advanced age is less often reported.: To assess the clinical, immunological and histological features of Type 1 autoimmune hepatitis in elderly Italian patients.: We assessed, at diagnosis, the clinical and immunological features of 76 consecutive Italian patients with type 1 autoimmune hepatitis, focusing particularly on a subgroup of 20 patients presenting at≥65 years (females 95%, median age 72 years, range 65–82).: In comparison with the younger group, at the time of autoimmune hepatitis diagnosis, elderly Italian patients are more often asymptomatic (25% vs. 7%;P = 0.04), are more frequently positive for antinuclear autoantibodies (95% vs. 52%;P = 0.0004) andHLA-DR4 (45% vs. 18%;P = 0.03); among the extra-hepatic manifestations, autoimmune thyroid disorders are prevalent in the elderly group (25% vs. 5%;P = 0.02). However, no difference was observed in the histological/biochemical expression of the liver disease and response to immunosuppression.: In elderly Italian patients, autoimmune hepatitis has typical serological and genetic characteristics, is more frequently asymptomatic, although prognosis and response to therapy is similar to that of younger patients. As a concomitant autoimmune thyroid disorder is common, autoimmune hepatitis should be suspected and investigated in elderly patients with autoimmune thyroid disorder and abnormal liver function tests. [ABSTRACT FROM AUTHOR]

ABSTRACT- The ultrastructural morphology of mechanically and enzymatically isolated hepatocytes was compared. Plasma membrane integrity was evaluated by electron microscopy, both in the absence and in the presence of ruthenium red, which stains cell coat glycoproteins and makes it possible to identify even partially permeable cells, and by indirect immunofluorescence using experimental antibodies directed against epithelial submembranous components (prekeratin, actin). In order to evaluate the antigenic integrity of the hepatocellular plasma membrane after the isolation procedures, an immuno-electronmicroscopical technique (Staph. pA-colloidal gold) was applied using the IgG fraction from two liver-kidney microsomal antibody (LKM) positive sera, known to react with both plasma membranes and smooth endoplasmic reticulum (SER). Enzymatic procedure made it possible to isolate hepatocytes with a good preservation of both plasma membranes and subcellular organelles. Ruthenium red staining was confined to plasma membranes, thus indicating the preservation of both cell-coat glycoproteins and plasma membrane. Most cells were negative after exposure to experimental antibodies. After exposure to LKM positive sera colloidal gold was strictly confined to the plasma membrane. On the other hand, mechanically isolated hepatocytes showed wide interruptions of the plasma membrane and gross alterations of subcellular organelles. Most cells were stained by ruthenium red, thus confirming the plasma membrane permeability. In addition, a linear peripheral positivity was found in the vast majority of the cells tested with anti-prekeratin and anti-actin antibodies. LKM-colloidal gold complexes were found at the level of both residual plasma membrane and SER. Cytoplasmic structures of mechanically isolated hepatocytes can therefore be reached by a variety of antibodies, commonly found in liver patients' sera. Thus, mechanically isolated hepatocytes are not a reliable substrate for the immunopathological demonstration of antibodies to plasma membrane constituents. [ABSTRACT FROM AUTHOR]

Background & Aims: In recent years, primary biliary cirrhosis is mostly diagnosed in patients who are asymptomatic; however, a proportion of cases still present with typical complaints such as fatigue and/or pruritus. We compared biochemical, histological and immunological features of patients with or without fatigue and/or pruritus at onset to see whether the different clinical presentation may eventually impact on disease progression., Methods: We analysed the Bologna cohort of 216 patients with primary biliary cirrhosis referred to our Centre between 1997 and 2007, according to symptomatic (fatigue and/or pruritus) or asymptomatic presentation. Clinical, biochemical, histological and immunological feature at diagnosis, response to ursodeoxycholic acid and progression of the disorder were compared after a mean follow-up of 81 ± 75 months., Results: At diagnosis, symptomatic patients were significantly more often women (98.6% vs. 87.2%, P = 0.004), younger (mean age 49 ± 12 vs. 55 ± 12 years, P = 0.003) and with more pronounced biochemical activity, as indicated by higher alkaline phosphatase (mean 2.93 ± 2 vs. 2.12, P = 0.002) and aminotransferase (mean 1.92 ± 1 vs. 1.47 ± 1.27, P = 0.014) levels, whereas histological stage and autoantibody profile were similar. Symptomatic patients were less likely to respond to ursodeoxycholic acid therapy (63% vs. 81%, P = 0.006) and developed more often cirrhosis and its complications (31% vs. 13%, P = 0.004)., Conclusions: Fatigue and/or pruritus at onset identify a subset of patients with primary biliary cirrhosis who preferentially are women, younger, with a particularly active disease, less responsive to ursodeoxycholic acid treatment, and more inclined to evolve to cirrhosis and its complications., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)