Single-centre experience of the macrophage activation marker soluble (s)CD163 - associations with disease activity and treatment response in patients with autoimmune hepatitis.

BACKGROUND: Autoimmune hepatitis (AIH) is characterised by liver inflammation with reversibility upon anti-inflammatory treatment. Soluble (s)CD163, a specific macrophage activation marker, is associated with inflammation in other liver diseases, but never investigated in AIH. AIM: To investigate sCD163 in patients with acute AIH and in complete and incomplete responders to standard anti-inflammatory pharmacotherapy, and during follow-up in treatment naive patients. METHODS: In a cross-sectional design, we studied 121 AIH patients (female/male 89/32, median age 49 years); of these, we prospectively studied 10 treatment naïve AIH patients during prednisolone treatment and tapering. Twenty patients had variant syndromes of AIH and primary biliary cholangitis or primary sclerosing cholangitis. sCD163 was compared with markers of disease activity, severity and treatment response. RESULTS: In the patients with acute AIH (n = 21), sCD163 was sixfold increased compared with the normalised levels in patients (n = 32) with complete response to standard treatment [9.5 (3.3-28.8) vs. 1.6 (0.8-3.2) mg/L, P < 0.01)], while the patients (n = 27) with incomplete response had higher sCD163 [2.2 (1.3-7.9), P < 0.05] than the complete responders. sCD163 was positively associated with ALAT, IgG and bilirubin (rho: 0.45-0.59, P < 0.001, all), and negatively to external coagulation factors (rho:-0.34, P < 0.001). In the treatment naïve patients, sCD163 fell during high-dose prednisolone treatment and tapering. Immunohistochemical staining confirmed increased CD163 expression in liver biopsies from patients with acute AIH. CONCLUSIONS: sCD163 was markedly elevated in AIH in the acute phase, normalised by successful treatment in complete responders, but remained higher in the incompletely responding cases. Our results demonstrate macrophage activation in AIH paralleling disease activity, severity and treatment response, suggesting a role for macrophage activation in AIH.

Double blind placebo controlled trial of pulse treatment with methylprednisolone combined with disease modifying drugs in rheumatoid arthritis.

OBJECTIVE: To assess whether monthly treatment with intravenous methylprednisolone enhances or accelerates the effect of disease modifying drugs in patients with rheumatoid arthritis. DESIGN: A 12 month double blind, placebo controlled, multicentre trial in which patients with active rheumatoid arthritis were randomly allocated to receive pulses of either methylprednisolone or saline every four weeks for six months. At the start of the pulse treatment all patients were started on penicillamine or azathioprine. SETTING: Four rheumatology departments in Denmark. PATIENTS: 97 Patients (71 women, 26 men) aged 23-84 (mean 60) who had active rheumatoid arthritis of at least four weeks' duration despite treatment with non-steroidal anti-inflammatory drugs. MAIN OUTCOME MEASURES: Monthly clinical recording of morning stiffness, number of tender and swollen joints, blinded observers' evaluation of therapeutic effect, and patients' self assessed condition. Concomitant laboratory measurements of erythrocyte sedimentation rate and concentrations of C reactive protein and haemoglobin. Radiography to determine the number of erosions at the start of treatment and after 12 months. RESULTS: 57 Patients completed the trial, taking the same disease modifying drug throughout. Evaluation four weeks after each pulse treatment and at 12 month follow up showed no significant differences between the methylprednisolone and placebo groups in any of the clinical or laboratory variables. Radiography showed the same degree of progression of erosions in both groups. Evaluation of the total data on 97 patients and on the 57 who completed the trial showed the same lack of significance between the treatment groups. CONCLUSIONS: Intravenous pulse treatment with steroids can be recommended only for rapid temporary relief of flares of disease in patients with rheumatoid arthritis. The response is short lived. Repeated pulses of methylprednisolone at four week intervals do not improve the results of treatment with drugs that induce remission such as penicillamine and azathioprine.

The diagnostic value of alpha 1-antitrypsin globules in liver cells as a morphological marker of alpha 1-antitrypsin deficiency.

In order to determine the diagnostic value of alpha 1-antitrypsin (AAT) globules as a morphological marker of AAT-deficiency of the Pi-Z type, liver needle biopsies from a prospective series of 600 patients were stained with PAS after pretreatment with diastase and by indirect immunoperoxidase staining for AAT deposits. Serum AAT phenotypes of the patients were determined by means of isoelectric focusing. Thirty-two biopsies were from patients with the Pi-Z allele (31 MZ, 1 Z), and 568 biopsies from patients without the Pi-Z allele. AAT globules larger than 3 micron were found in 16 biopsies of which 15 were from patients with the Pi-Z allele (diagnostic specificity 0.94), whereas 20 of 26 biopsies with AAT globules larger than 1 micron were from Pi-Z patients (diagnostic specificity 0.77). Only 47% of the biopsies from patients with the Pi-Z allele contained AAT globules larger than 3 micron. Thus, although AAT globules larger than 3 micron are highly specific as a morphological marker of the Pi-Z allele, their rather infrequent occurrence in carriers of the Pi-Z allele indicates that all investigations concerning the correlation between AAT deficiency of the Pi-Z type and liver disease should be based on phenotyping of sera from all the patients.

Absence of true pancreatic glucagon but persistence of circulating pancreatic glucagon-like immunoreactivity after pancreatectomy in pigs.

The possible existence of circulating pancreatic type glucagon (immunoreactive glucagon as measured with a highly specific antibody) of extrapancreatic origin was investigated in 20-25 kg pigs after pancreatectomy. In intact conscious animals intravenous arginine infusions stimulated glucagon as well as insulin secretion, while blood glucose remained unaffected. Two weeks after pancreatectomy, and 48 hours after insulin withdrawal, basal glucagon and glucose concentrations were elevated (from 22 +/- 3.7 to 55 +/- 9.5 pmol/1 and 5.8 +/- 0.4 to 16.2 +/- 2.0 mmol/l, respectively), (mean +/- SEM), while insulin concentrations were either undetectable or very low. After pancreatectomy, however, glucagon concentrations no longer increased during arginine infusion. Gut type glucagon levels were not affected by pancreatectomy, and did not change during arginine infusion. When examined by gel filtration, plasma from unoperated pigs contained two components of pancreatic type glucagon, one coeluting with the glucagon marker, the other eluting earlier, probably reflecting larger molecular size. After pancreatectomy only this larger component was found in the plasma. The role of this component in the control of blood glucose is unknown.