Vitamin D Receptor Polymorphisms Predispose to Primary Biliary Cirrhosis and Severity of the Disease in Polish Population

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver condition characterized by the immune-mediated damage of the intrahepatic bile ducts. Polymorphisms of vitamin D receptor (VDR) are considered to contribute to its pathogenesis however their incidence varies in different populations and their potential association with the course of the disease has not been studied. In this paper we investigated the incidence and correlation of three VDR polymorphisms (BsmI, ApaI or TaqI) with various clinical, biochemical, and serological factors in a homogenous group of 143 Caucasian patients with PBC. Control group comprises 306 DNA samples from umbilical cord blood of healthy newborn children. When compared to controls, we observed a significant dominance of the b allele in the BsmI (OR = 1.69 [1.27–2.24]; P = 0.0003) and t allele in the TaqI (OR = 0.62 [0.47–0.82], P = 0.0001) in patients with PBC. Moreover the BsmI and TaqI polymorphisms were associated with the presence of advanced fibrosis/liver cirrhosis at the diagnosis of PBC. Pairwise linkage disequilibrium (LD) calculations proved that the analyzed SNPs are within an LD block (100% of LDs were D'>0.9). Our study showed, for the first time, that the analyzed polymorphisms of VRD may exert an effect on a natural history of PBC

The search for the Holy Grail: autoantigenic targets in primary sclerosing cholangitis associated with disease phenotype and neoplasia

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TRAF1-C5

Background. Previous studies reported associations between specific alleles of non-HLA immunoregulatory genes and higher fatigue scores in patients with primary biliary cirrhosis (PBC). Aim. To study the relationship between variables of health-related quality of life (HRQoL) and single nucleotide polymorphisms of TRAF1-C5, a member of the tumor necrosis factor receptor family. Patients and Methods. TRAF1-C5 gene polymorphisms, rs2900180 and rs3761847, were analysed in 120 Caucasian PBCs. The HRQoL was assessed with SF-36, PBC-40, and PBC-27 questionnaires. Results. We found a negative association between TT genotype of rs2900180 and SF-36’s domains vitality (P<0.05), mental health (P<0.05), and mental component summary score (P<0.05). GG homozygotes of rs3761847 had lower vitality (P<0.05), mental health (P<0.05), mental component summary score (P<0.05) and impairment of social functioning (P<0.01). Allelic analysis has shown that T allele of rs2900180 and G allele of rs3761847 related to SF-36’s vitality (P<0.05 and P<0.01), social functioning (P<0.05 and P<0.05), mental health (P<0.01 and P<0.05), and mental component summary score (P<0.01 and P<0.05), respectively. Genotyping and allelic analysis did not reveal correlation with PBC-40 and PBC-27 domains. Conclusion. The association between rs2900180 and rs3761847 polymorphisms and HRQoL variables indicates that TRAF1 is involved in the induction of impaired QoL in PBC

The search for the Holy Grail: autoantigenic targets in primary sclerosing cholangitis associated with disease phenotype and neoplasia

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PR3-ANCAs Detected by Third-Generation ELISA Predicts Severe Disease and Poor Survival in Primary Sclerosing Cholangitis

A highly sensitive detection of anti-neutrophil cytoplasmic antibodies to serine proteinase-3 (PR3-ANCAs) aids in the serological diagnosis of autoimmune liver disorders and the prediction of severity in primary sclerosing cholangitis (PSC). Here, we evaluate a novel thirdgeneration ELISA for the detection of PR3-ANCAs. In total, 309 patients with PSC, 51 with primary biliary cholangitis (PBC), and 120 healthy blood donors (BD) were analyzed. For the survival analysis in PSC, the outcome was defined as liver-transplantation-free survival during the followup. Positive PR3-ANCA levels were found in 74/309 (24.0%) of patients with PSC. No BDs and one patient with PBC demonstrated PR3-ANCA positivity. PR3-ANCAs were revealed as independent predictors for a poor PSC outcome (study endpoint: liver transplantation/death, log-rank test, p = 0.02). PR3-ANCA positivity, lower albumin levels, and higher bilirubin concentrations were independent risks of a poor survival (Cox proportional-hazards regression analysis, p < 0.05). The Mayo risk score for PSC was associated with PR3-ANCA positivity (p = 0.01) and the disease severity assessed with a model of end-stage liver disease (MELD) and extended MELD-Na (p < 0.05). PR3-ANCAs detected by a third-generation ELISA are diagnostic and prognostic markers for PSC. Their wider use could help to identify patients who are at-risk of a more severe disease

The Prevalence of Anti-Hexokinase-1 and Anti-Kelch-Like 12 Peptide Antibodies in Patients With Primary Biliary Cholangitis Is Similar in Europe and North America: A Large International, Multi-Center Study

Primary biliary cholangitis (PBC), formerly known as primary biliary cirrhosis, is present worldwide. Autoantibodies, in particular anti-mitochondrial antibodies (AMA) detected by indirect immunofluorescence assays or newer solid phase immunoassays can detect most, but not all individuals with PBC. Detection of antibodies to the anti-nuclear antigens sp100 and gp210 can identify additional PBC patients, but some seronegative patients remain, often resulting in delayed diagnosis and treatment. Antibodies to kelch-like 12 (KLHL12) and hexokinase 1 (HK-1) were recently identified as new biomarkers for PBC and notably identify patients who are negative for conventional autoantibodies. To become globally adopted, it is important to validate these new biomarkers in different geographic areas. In the present study we evaluated the prevalence of anti-KLHL12 (measured by a KLHL12-derived peptide referred to as KL-p) and anti-HK-1 antibodies by ELISA at five sites within Europe and North America and demonstrated the presence of these antibodies in patients with PBC in all geographies

Rekomendacje Sekcji Hepatologicznej Polskiego Towarzystwa Gastroenterologii dotyczące cholestatycznych chorób wątroby &#8212; adaptacja wytycznych europejskich

Celem publikacji jest przybliżenie polskim lekarzom europejskich wytycznych dotyczących diagnostyki i leczenia chorób przebiegających z cholestazą. Wytyczne europejskie przedyskutowano na forum Sekcji Hepatologicznej Polskiego Towarzystwa Gastroenterologii pod kątem możliwości ich zastosowania w polskich realiach, a następnie poddano głosowaniu przez członków Sekcji. W opracowaniu przedstawiono ogólne zasady diagnostyki cholestazy oraz omówiono wytyczne rozpoznawania i leczenia najczęstszych chorób przebiegających z cholestazą &#8212; pierwotnej żółciowej marskości wątroby, pierwotnego stwardniającego zapalenia dróg żółciowych, zespołów nakładania, polekowych cholestatycznych uszkodzeń wątroby i zespołów cholestazy występujących u ciężarnych i dzieci. Omówiono również IgG4-zależne stwardniające zapalenie dróg żółciowych &#8212; niedawno poznaną i często sprawiającą trudności diagnostyczne jednostkę należącą do spektrum układowej choroby IgG4-zależnej. Po każdym rozdziale przedstawiono komentarz panelistów odnoszący się do rozbieżności w głosowaniu

Esophageal duplication cysts: Endosonographic findings in asymptomatic patients

Esophageal duplication cysts are rare inherited lesions usually diagnosed in early childhood. Most of them are found in the mediastinum and manifest themselves as separate masses along or in continuity with the native esophagus. Their prevalence remains unknown and they are treated either surgically or endoscopically. In this report we describe a series of four adult patients in whom esophageal duplication cysts were localised intramurally as masses pressing on the esophageal lumen and who were diagnosed with endoscopic ultrasonography. All patients were initially referred to other centres for upper gastroduodenoscopy due to non-specific dyspeptic symptoms. After finding suspicious lesions in the esophagus their endoscopists referred them for endoscopic ultrasound examination at our centre. In two of the cases lesions mimicked esophageal varices and the other two submucosal tumours. In all four patients endoscopic ultrasonography has shown esophageal duplication cysts. Patients had no symptoms suggesting disease of the esophagus and required no treatment. As the true prevalence of esophageal cysts is unknown, it is very likely that in many patients, like in these four described by us, they may cause no symptoms, remain undetected and require no intervention. Increasing availability of new diagnostic modalities such as endoscopic ultrasonography may change the current view regarding the prevalence of esophageal duplication cysts and prove that they may, in fact, not be such rare findings

ApaI polymorphism of vitamin D receptor affects health-related quality of life in patients with primary sclerosing cholangitis.

BACKGROUND:Polymorphisms of vitamin D receptor (VDR) contribute to the pathogenesis of multiple autoimmune conditions. METHODS:We investigated the incidence of VDR polymorphisms (rs1544410-BsmI; rs7975232-ApaI; rs731236-TaqI) in a group of patients with primary sclerosing cholangitis (PSC, n = 275) and in healthy controls (n = 376). Additionally, correlations of the VDR polymorphisms with clinical and biochemical factors of the disease were analysed. RESULTS:The genotype and allele distributions of these polymorphisms in PSC patients were similar to those observed in controls. However, the ApaI polymorphism was associated with an impaired health-related quality of life (HRQoL). The generic SF-36 questionnaire showed that the Role-Physical (p = 0.01), Role-Emotional (p = 0.01), Physical Component Summary (p = 0.01) and Mental Component Summary (p = 0.003) scores were significantly affected. Similarly, the disease-specific questionnaires, PBC-40 and PBC-27, demonstrated that carriers of the C allele suffered from more severe Itch (p = 0.03 assessed by PBC-40 and PBC-27), more Fatigue (p = 0.02 assessed by PBC-40 and PBC-27) and Impaired Cognitive Capacity (p = 0.04 and p = 0.03). Correspondingly, individuals who were AA homozygotes (non-carriers of the C allele of ApaI) had higher summary scores for the Physical (p = 0.01) and Mental Components (p = 0.006) measured with SF-36. Moreover, they experienced less itch (p = 0.03) and less Fatigue (p = 0.03) and had better Cognitive Abilities (p = 0.04) as assessed by the PBC-40 and PBC-27 questionnaires. No associations between other VDR polymorphisms and clinical or laboratory findings were made. CONCLUSION:In summary, this study is the first to show that the ApaI polymorphisms in VDR may exert an effect on disease-related symptoms and quality of life in patients with PSC