Andrzej Habior

Lack of evidence for association of primary sclerosing cholangitis and primary biliary cirrhosis with risk alleles for Crohn's disease in Polish patients

BackgroundNumerous papers have addressed the association of mutations and polymorphisms of susceptibility genes with autoimmune inflammatory disorders. We investigated whether polymorphisms that confer susceptibility to Crohns disease could be classified also as predisposing factors for the development of primary sclerosing cholangitis and primary biliary cirrhosis in Polish patients.MethodsThe study included 60 patients with CD, 77 patients with PSC, of which 61 exhibited IBD (40 UC, 8 CD, and 13 indeterminate colitis), and 144 patients with PBC. All the patients were screened against Crohns disease associating genetic polymorphisms.The polymorphisms were chosen according to previously confirmed evidence for association with Crohns disease, including Pro268Ser, Arg702Trp, Gly908Arg and 1007fs in NOD2/CARD15, Leu503Phe/-207G>C in SLC22A4/OCTN1/SLC22A5/OCTN2, Arg30Gln in DLG5, Thr300Ala in ATG16L1, and Arg381Gln, His3Gln and exon-3UTR in IL23R. Genotyping was carried out using TaqMan SNP genotyping assays.ResultsWe confirmed a strong association between three NOD2/CARD15 gene variants (Pro268Ser, OR = 2.52, 95% CI = 1.34 – 4.75); (Arg702Trp, OR = 6.65, 95% CI = 1.99 – 22.17); (1007fs, OR = 9.59, 95% CI = 3.94 – 23.29), and a weak association between both the protective OCTN1/OCTN2 CC haplotype (OR = 0.28, 95% CI = 0.08 – 0.94), and a variant of ATG16L1 gene (Thr300Ala, OR = 0.468, 95% CI = 0.24 – 0.90) with Crohns disease. In contrast, none of the polymorphisms exhibited association with susceptibility to primary sclerosing cholangitis and primary biliary cirrhosis, including a group of primary sclerosing cholangitis patients with concurrent IBD.ConclusionAlthough the clinical data indicate non-random co-occurrence of inflammatory bowel disease and primary sclerosing cholangitis, consistently with the previously published studies, no genetic association was found between the genetic variants predisposing to Crohns disease and hepatobiliary autoimmune disorders. However, since estimation of genetic variant disproportion is limited by sample size, these negative results may also indicate that eventually shared genetic predispositions are too little to be captured by small patient groups.

Laboratory-based scoring system for prediction of hepatic inflammatory activity in patients with autoimmune hepatitis

In autoimmune hepatitis (AIH), inflammation is closely related to fibrosis. Although transaminase levels are commonly used to assess hepatic inflammation, they may not relate directly to the histology. We developed a noninvasive diagnostic score as an alternative to liver biopsy to help optimize treatment for AIH and monitor disease progress.

S1838 Usefulness of a Large Set of Tests for the Diagnosis of Hepatic Encephalopathy

In patients with liver cirrhosis, minimal hepatic encephalopathy (MHE) is associated with a poor quality of life and difficulty in driving. It has also been suggested that MHE can precede the development of overt hepatic encephalopathy (OHE). No gold standard exists to detect MHE. Therefore the prevalence of this entity varies depending on the diagnostic methods used. Aims & Methods: To assess: a) the prevalence of MHE using standard (1) and nonstandard diagnostic methods, b) the usefulness of these tests for predicting of OHE, 51 patients with liver cirrhosis and portal hypertension (29 with primary biliary cirrhosis, 22 with HCV infection) were studied. In all patients we performed seven diagnostic tests: four psychometric tests (NTC-A, NTC-B, DST, BDT), EEG, spectral EEG, P300 auditory event related potential, critical flicker frequency (CFF), proton magnetic resonance spectroscopy of the brain (1HMRS) and serum concentration of astroglial protein S100β.Patients were followed up for a period of 4 years. Results: Based on the psychometric tests, 9 out of 51 patients (17.6%, 95% CI 7-28) were diagnosed to have MHE. If the results of EEG, P300 and spectral EEG were added, the prevalence of MHE raised to 16 of 51 patients (31.3%, 95% CI 18-44). Addition one nonstandard test (CFF, 1HMRS or S100β) raised the percentage of patients suspected of MHE to above 40%. During follow up OHE developed in 14 patients but MHE in this group was earlier diagnosed using psychometric tests in only 10 patients. Twelve of 14 patients with OHE had at least one abnormal result out of the seven tests. Multiple proportional hazard regression model showed a higher risk of OHE in patients with abnormal EEG (HR 8.4, 95% CI 2.6 -27.3, p < 0.001). Other factors, including psychometric and standard and nonstandard tests, did not predict the OHE. Conclusions: 1. Diagnosis of minimal hepatic encephalopathy needs further standardization. 2. Among the seven different diagnostic methods, only EEG has a predicting value for overt hepatic encephalopathy in cirrhotic patients. Reference: 1.Ferenci P.et al: Hepatology.2002;35:716 Supported by grant MNiSzW 3PO5B03926