Joanna Musialik

Angiogenesis in chronic hepatitis C is associated with inflammatory activity grade and fibrosis stage.

Data regarding the assessment of angiogenesis in liver tissue in chronic hepatitis C (CHC) are rare. The study was performed to explain the association between the histopathological features and the number of new blood vessels in lobules and portal tracts in CHC. The second aim of the study was to define the localization of sprouting and pattern of formation of new vessels by estimating CD 34 antigen expression in the liver. The study involved 74 patients with CHC, infected with viral genotype 1b before antiviral therapy. The number of new-formatted blood vessels was positively associated with fibrosis stage and inflammatory activity grade in the liver biopsy from CHC patients. The relationship was evident in the portal tract, fibrous septa and periportal zones of lobules. The results suggest that inflammatory hepatocyte injury may promote neo-angiogenesis.

Taste and appetite disorders of chronic hepatitis C patients.

Objective Decreased appetite is one of the main factors that influences quality of life of patients with chronic liver diseases. The reason for appetite disorders remains unclear but taste perturbations are one of the postulated causes. The potential role of taste alterations and, connected to these, appetite disorders in chronic hepatitis C (CHC) patients are poorly investigated. The aim of this study was to evaluate potential taste alterations (dysgeusia) including all five tastes (sweet, salty, bitter, sour and umami) in CHC patients. Methods Forty CHC patients (16 men and 24 women) infected with genotype 1 hepatitis C virus participated in this study. All the patients had a compensated liver disease and were being treated with any agents. One hundred and ten healthy volunteers were matched to the patients by age and sex. The study included gustatory tests (taste recognition threshold, taste intensity with hedonic perception) and analysis of the pleasure derived from eating. Results In CHC patients, the recognition threshold of umami taste was increased (P<0.01) and the intensity of sweet taste perception was higher (P<0.05). The hedonic response did not differ between the groups. A significant increase in declared pleasure derived from eating (P<0.001 to P<0.05) was also observed. Some differences in case of the patients with more advanced disease were also found. Conclusion Alterations in taste, especially umami and sweet taste disorders, may alter real food perception and lead to a reduction in food intake in some CHC patients.

Effects of alendronate on bone mass in patients with primary biliary cirrhosis and osteoporosis: preliminary results after one year.

We report on an evaluation of the efficacy of alendronate in the treatment of osteoporosis coexisting with PBC. Twenty women with primary biliary cirrhosis (PBC) (AMA /) and no abnormalities of the upper gastrointestinal tract took part in the study. At the time of the study, all patients were receiving UDCA (15 mg/kg body-weight/day), calcium supplements (1000 mg/day) and vitamin D orally (0.25 mg/day). The patients were divided into two groups according to bone mineral density (BMD): group A consisted of 10 patients with osteoporosis treated with alendronate (10 mg/day) (Fosamax; MSD & Co., Whitehouse Station, N.J., USA) and group B consisted of 10 patients with osteopenia. BMD of the lumbar spine (L2-L4) was measured at entry and again after 12 months of therapy by dual X-ray absorptiometry (DXA). BMD values were expressed as grams hydroxyapatite per centimetre squared and T scores. Osteoporosis was defined according to WHO recommendations as a bone mineral density of the lumbar spine that was at least 2.5 SD below the mean value. Group A patients underwent a second endoscopy after the treatment was completed. Results are presented in the Table (mean, SD). It was found that alendronate had a positive effect on bone density after a 12-month period of therapy. A 5% increase in BMD from baseline was found in 9 out of 10 patients in Group A (no change in one), whereas in group B patients the mean value of BMD decreased (2.5% from baseline). These results obtained in Group A patients were similar to those found in postmenopausal women [1]. Guanabens et al. [2] reported that 2 years of therapy with etidronate in PBC patients resulted in only a 0.5% improvement in lumbar BMD. Some reports describe oesophagitis, oesophageal erosions and ulcerations in the upper gastrointestinal tract [3,4] during alendronate therapy. In our patients no symptoms or endoscopic signs were observed during treatment. Our study revealed that: 1) bisphosphonate therapy for patients with PBC without upper gastrointestinal symptoms is safe and 2) the potential of the beneficial effect on bone mass is large. However, careful selection of patients and close monitoring by the physician are needed.

Reduction of CD45RA isoform expression and decrease in CD4 and CD8 receptor density in lymphocytes of patients with primary biliary cirrhosis

Background: The immunological background of primary biliary cirrhosis (PBC) remains largely obscure. Methods: Using double colour flow cytometry, we estimated the distribution of functionally different lymphocyte subpopulations in the peripheral blood of 25 PBC patients and 18 controls. We examined: 1) the expression of CD3, CD4, CD8, CD 19 and CD56 surface receptors, 2) the distribution of lymphocyte subsets bearing ‘naive’ (CD45RA+) and ‘memory’ (CD45RO+) phenotypes in both CD4+ and CD8+ cell populations, 3) the expression of an early activation marker (CD69), 4) the distribution of C1.7 mAb binding cytotoxic effectors in CD3+, CD8+ and CD56+ cells. The surface marker expression was evaluated in terms of percentage of positive cells and receptor density. Results: We found: 1) a decrease in the percentage of total CD3+ and CD4+ cells, an unchanged proportion of CD8+ cells but elevated proportion of CD 19+ cells and NK lymphocytes; 2) a reduction in the percentage of ‘naive’ CD4+ but normal proportion of ‘naive’ CD8+ as well as CD4+ and CD8+ ‘memory’ cell subsets; 3) a decrease in the density of CD4 and CD8 receptors in the subsets of ‘naive’ and ‘memory’ T cells, 4) an increase in the percentage of CD69 receptor bearing T cells but unchanged proportion of C1.7 mAb. Conclusions: It is concluded that the reduction in number of suppressor-inducer-like ‘naive’ CD4+ T-cell subsets in association with the decrease in fluorescence intensity for CD4 and CD8 may significantly contribute to the mechanisms that could account for a development of PBC.

A novel approach to genome-wide association analysis identifies genetic associations with primary biliary cholangitis and primary sclerosing cholangitis in Polish patients

BackgroundPrimary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are forms of hepatic autoimmunity, and risk for both diseases has a strong genetic component. This study aimed to define the genetic architecture of PBC and PSC within the Polish population.MethodsSubjects were 443 women with PBC, 120 patients with PSC, and 934 healthy controls recruited from Gastroenterology Departments in various Polish hospitals. Allelotyping employed a pooled-DNA sample-based genome-wide association study (GWAS) approach, using Illumina Human Omni2.5-Exome BeadChips and the following novel selection criteria for risk loci: blocks of at least 10 single nucleotide polymorphisms (SNPs) in strong linkage disequilibrium, where the distance between each adjacent SNP pair in the block was less than 30 kb, and each SNP was associated with disease at a significance level of P < 0.005. A selected index SNP from each block was validated using TaqMan SNP genotyping assays.ResultsNineteen and twenty-one SNPs were verified as associated with PBC and PSC, respectively, by individual genotyping; 19 (10/9, PBC/PSC) SNPs reached a stringent (corrected) significance threshold and a further 21 (9/12, PBC/PSC) reached a nominal level of significance (P < 0.05 with odds ratio (OR) > 1.2 or < 0.83), providing suggestive evidence of association. The SNPs mapped to seven (1p31.3, 3q13, 6p21, 7q32.1, 11q23.3, 17q12, 19q13.33) and one (6p21) chromosome region previously associated with PBC and PSC, respectively. The SNP, rs35730843, mapping to the POLR2G gene promoter (P = 1.2 × 10-5, OR = 0.39) demonstrated the highest effect size, and was protective for PBC, whereas for PSC respective SNPs were: rs13191240 in the intron of ADGRB3 gene (P = 0.0095, OR = 0.2) and rs3822659 (P = 0.0051, OR = 0.236) along with rs9686714 (P = 0.00077, OR = 0.2), both located in the WWC1 gene.ConclusionsOur cost-effective GWAS approach followed by individual genotyping confirmed several previously identified associations and discovered new susceptibility loci associated with PBC and/or PSC in Polish patients. However, further functional studies are warranted to understand the roles of these newly identified variants in the development of the two disorders.

(13)CO2 breath tests in non-invasive hepatological diagnosis.

In liver diagnostics, a simple, non-invasive test with high sensitivity and specificity is permanently being sought in order to assess the degree of liver damage. In addition to liver biopsy, algorithms using blood parameters or elastometry are used in clinical practice. However, these methods do not provide information about the true liver reserve, so the liver breath test seem to be a promising diagnostic tool. The basis of this test depends on the ability of particular hepatocyte enzyme systems to metabolise a tested substance labelled with a stable carbon isotope. The kinetics of 13CO2 elimination with expiratory air then permits quantitative assessment of the functional liver reserve and the degree of organ damage. In this paper the most commonly used tests, grouped according to the main metabolic pathways, are described. The usefulness of liver breath tests in specific clinical situations, both as a diagnostic and prognostic tool, is presented.

Neural Network Ensemble Based on Feature Selection for Non-Invasive Recognition of Liver Fibrosis Stage

Contemporary medicine concentrates on providing high quality diagnostic services, yet it should not be forgotten that the comfort of the patient during the examination is also of high importance. Therefore non-invasive methods that allows to precisely predict the state of the disease are currently one of the key issues in the medical business. The paper presents a novel ensemble of neural networks applied to recognition of liver fibrosis stage from indirect examination method. Several neural network models are build on the basis of outputs of different feature selection algorithms. Then an ensemble pruning procedure with the usage of diversity measures is conducted in order to eliminate redundant predictors from the pool. Finally the weights of classifiers in the fusion process are assessed to establish their influence on the output of the whole ensemble. Proposed method is compared with several state-of-the-art ensemble methods. Extensive experimental investigations, carried out on a dataset collected by authors, show that the proposed method achieve a satisfactory level of the fibrosis level recognition, outperforming other machine learning algorithms and thus may be used as a real-time medical decision support system for this task.