Birgit Terjung

Bleeding Complications after Percutaneous Liver Biopsy

Background and Aims: To assess the risk of bleeding after percutaneous liver biopsy, we retrospectively analyzed 629 procedures with particular respect to patients with an increased a priori bleeding risk. Methods: Factors possibly related to the risk of bleeding were analyzed by univariate analysis. Those variables which were significant in the univariate analysis were then entered into a forward conditional logistic regression model. Results: Biopsy-related bleeding events defined as clinically overt complication (n = 10; 1.6%), an otherwise unexplained drop in serum hemogloblin concentration of greater than 2 g/dl (n = 45; 7.1%) or intra- or extrahepatic hematoma assessed by ultrasound (n = 17; 2.7%) were identified in 72 patients. 58% of the bleeding events occurred in patients with particular risk factors for bleeding. Biopsy-related mortality in the study cohort was 0.48%. Logistic regression analysis indicated mycobacterial infection [odds ratio (OR) 24.0], pre-biopsy prophylactic platelet substitution (OR 9.9), acute liver failure (OR 9.1), heparin administration on the day of biopsy (OR 8.7), advanced liver cirrhosis (OR 5.1), therapy with corticosteroids (OR 3.5) or metamizole (OR 2.8) and leukemia or lymphoma (OR 2.8) as significant (p ≤ 0.05) independent risk factors. Delayed bleeding (>24 h after biopsy) was identified in 70% of the bleeding events. Conclusions: In our study cohort which comprised a high proportion of patients with particular risk factors for bleeding, biopsy-related bleeding occurred more frequently and later than commonly observed and was associated with only a few prognostic factors. Considering these predictors before liver biopsy will aid to reduce the rate of bleeding complications.

p-ANCAs in autoimmune liver disorders recognise human b-tubulin isotype 5 and cross-react with microbial protein FtsZ

Objective Autoimmune hepatitis and primary sclerosing cholangitis are chronic inflammatory disorders of unknown aetiology, frequently associated with the presence of perinuclear antineutrophil cytoplasmic antibodies (p-ANCAs) directed against an unknown antigen of myeloid cells. Methods and Results Here, it is reported that p-ANCAs in autoimmune liver disorders react with β-tubulin isotype 5 (TBB-5) as autoantigen as well as with its evolutionary bacterial precursor protein FtsZ. Both proteins were confirmed as antigens of p-ANCAs in autoimmune liver disorders by demonstrating reactivity of ANCA-positive sera with recombinant TBB-5 (72–88%) and FtsZ (64–82%) on immunoblots and antigen-specific abrogation of ANCA immunofluorescence when sera had been preabsorbed with tubulin and FtsZ. Using sera from interleukin 10-deficient mice (Il10–/–), an animal model of inflammatory bowel disease, it was also demonstrated that antibodies against TBB-5 are generated in response to intestinal microorganisms. However, unlike autoimmune liver disorders, human antibodies to FtsZ in the absence of TBB-5 antibodies were also a frequent finding in non-autoimmune liver diseases (up to 95%). Reactivity to TBB-5 without the presence of FtsZ antibodies was found in very few cases (<1%) in autoimmune liver disorders. Conclusions Thus, p-ANCAs in autoimmune liver diseases are directed against human TBB-5 cross-reacting with the bacterial protein FtsZ, probably reflecting an abnormal immune response to intestinal microorganisms in susceptible, possibly genetically predisposed individuals.

Atypical p-ANCA in PSC and AIH: a hint toward a "leaky gut"?

Primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) are enigmatic chronic inflammatory diseases of the liver, which are frequently associated with chronic inflammatory bowel diseases. Both types of liver disease share various distinct autoantibodies such as atypical perinuclear antineutrophil cytoplasmic antibodies (p-ANCA), and thus are considered autoimmune disorders with atypical features. The discovery that atypical p-ANCA recognize both tubulin beta isoform 5 in human neutrophils and the bacterial cell division protein FtsZ has renewed the discussion on the potential role of microorganisms in the pathogenesis of both diseases. In this paper, we review the evidence for microbial infection in PSC and AIH and discuss new concepts how cross-recognition between microbial antigens in the gut and host components by the immune system along with stimulation of pattern recognition receptors might give rise to chronic hepatic inflammatory disorders with features of autoimmunity.

Role of auto-antibodies for the diagnosis of chronic cholestatic liver diseases

Auto-antibodies are an integral part of the diagnostic armentarium in chronic cholestatic liver disorders, such as primary sclerosing cholangitis (PSC), primary biliary cirrhosis (PBC), auto-immune cholangitis, or overlap syndromes among these disorders. However, care should be taken not to overestimate the diagnostic specificity. Auto-antibodies to mitochondrial antigens (AMAs) with reactivity to the E2 subunit of the pyruvate dehydrogenase complex represent the hallmark antibody for the diagnosis of PBC, whereas antinuclear antibodies (ANAs) with low disease specificity are found in up to 50% of these sera. Antibodies that recognize nuclear envelope proteins exert a similarly high diagnostic specificity as AMA in PBC but occur at a rather low prevalence. The role of auto-antibodies is less well-studied for patients with PSC, but there is growing evidence that only antineutrophil cytoplasmic antibodies (ANCAs) are of relevant diagnostic significance. In contrast, auto-antibodies—particularly AMAs—do not contribute to the diagnosis of auto-immune cholangitis, whereas ANCAs, ANAs, smooth muscle antibodies, and AMAs are of varying significance in PBC-auto-immune hepatitis (AIH) or PSC-AIH overlap syndromes. It has been widely accepted that the course of the auto-antibody serum end point titers are not suited for the clinical management of patients with chronic cholestatic liver disorders. Additionally, auto-antibodies in these disorders usually do not contribute to the immunopathogenesis of the disease.

White-Light or Narrow-Band Imaging Colonoscopy in Surveillance of Ulcerative Colitis: A Prospective Multicenter Study

BACKGROUND & AIMS Early detection of neoplastic lesions is essential in patients with long-standing ulcerative colitis but the best technique of colonoscopy still is controversial. METHODS We performed a prospective multicenter study in patients with long-standing ulcerative colitis. Two colonoscopies were performed in each patient within 3 weeks to 3 months. In white-light (WL) colonoscopy, stepwise random biopsy specimens (4 biopsy specimens every 10 cm), segmental random biopsies (2 biopsy specimens in 5 segments), and targeted biopsy specimens were taken. In NBI colonoscopy, segmental and targeted biopsy specimens were taken. The sequence of WL and NBI colonoscopy was randomized. RESULTS In 36 of 159 patients enrolled (22.6%), 54 lesions with intraepithelial neoplasia (IN) were found (51 low-grade, 3 high-grade). In WL colonoscopy we found 11 IN in stepwise biopsy specimens, 4 in segmental biopsy specimens, and 15 in targeted biopsy specimens. In NBI colonoscopy 7 IN were detected in segmental biopsy specimens and 24 IN were detected in targeted biopsy specimens. Almost all IN were found with one technique alone (κ value of WL vs NBI, -0.86; P < .001). Statistically equivalent numbers of IN were found in NBI colonoscopy with targeted and segmental biopsy specimens as in WL colonoscopy with targeted and stepwise biopsy specimens, but with fewer biopsy specimens (11.9 vs 38.6 biopsy specimens, respectively; P < .001), and less withdrawal time was necessary (23 vs 13 min, respectively; P < .001). CONCLUSIONS Stepwise biopsy specimens are indispensable in WL colonoscopy. The combination of targeted and segmental biopsy specimens in the NBI technique is as sensitive as targeted together with stepwise biopsy specimens in WL colonoscopy, but requires fewer biopsy specimens and less time. The highest sensitivity should be reached by combining the WL and NBI techniques by switching between the modes.

Hepatitis C-associated autoimmunity in patients coinfected with HIV

Abstract: Background: Hepatitis C virus (HCV) infection is associated with multiple extrahepatic manifestations. It is unclear to what extent extrahepatic manifestations occur in HIV/HCV coinfection.

Erkrankungen von Leber, Gallenwegen und Pankreas

Die wichtigsten therapierelevanten metabolischen und genetisch determinierten Lebererkrankungen sind die Hamochromatose und der Morbus Wilson. Beide Erkrankungen werden autosomal-rezessiv vererbt. Wahrend die Hamochromatose mit einer Haufigkeit von 1:200 bis 1:400 auftritt (Heterozygote 1:15), ist der Morbus Wilson deutlich seltener mit einer Frequenz von 1:30.000 (Heterozygote 1:90).