Piotr Milkiewicz

Pomeranian Medical University in Szczecin, Stettin, West Pomeranian Voivodeship, Poland

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Publications (125)517.19 Total impact

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    ABSTRACT: The common PNPLA3 (adiponutrin) variant p.I148M represents a major genetic driver of progression in non-alcoholic fatty liver disease (NAFLD). NAFLD is commonly associated with traits of the metabolic syndrome, therefore it is mostly suspected in obese individuals. Here, we investigate the association between the PNPLA3 variant and anthropometric traits in a cohort of healthy individuals. We recruited 1,000 (500 females; age 18 - 66 years) healthy blood donors. The PNPLA3 variant was genotyped using TaqMan assays. All individuals were phenotyped with respect to anthropometric characteristics. We also determined the percentage of total fat (F%) and active tissue (TA%) of body weight. Healthy carriers of the PNPLA3 [IM] and [MM] genotypes, although not differing in height from individuals with the genotype [II], displayed significantly lower body weight and lower BMI (both P = 0.005), higher TA% (P = 0.03) but lower F% (P = 0.03) and smaller waist, chest and shin circumferences (all P < 0.05). Separate analysis for males and females demonstrated an association between the [IM] and [MM] genotypes and higher TA% but lower F% (P = 0.04) in females. In males, BMI and total weight were significantly (P = 0.04) lower among carriers of the [M] allele. Healthy individuals carrying the prosteatotic PNPLA3 allele p.I48M may be leaner as compared to the carriers of the common allele. Hence in clinical practice they might be overlooked since they do not necessarily present with the anthropometric characteristics commonly associated with severe hepatic steatosis.
    Journal of gastrointestinal and liver diseases: JGLD 03/2014; 23(1):33-7. · 1.86 Impact Factor
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    ABSTRACT: Ursodeoxycholic acid (UDCA) is no longer recommended for the management of adult patients with primary sclerosing cholangitis (PSC). We undertook prospective evaluation of UDCA withdrawal in a group of consecutive patients with PSC. Twenty six patients, all treated with UDCA (dose range 10-15mg/kg/day) were included. Paired blood samples for liver biochemistry, bile acids, fibroblast growth factor 19 (FGF19) were collected before UDCA withdrawal and 3 months later. Liquid chromatography coupled/mass spectrometry was used for the quantification of 29 plasma bile acid metabolites. Pruritus and Health Related Quality of Life (HRQoL) were assessed with 10-point numeric rating scale (NRS), SF-36 and PBC-40 questionnaires. UDCA withdrawal resulted in a significant deterioration in liver biochemistry (increase of ALP of 75.6 %; p<0.0001; GGT of 117.9%, p<0.0001; bilirubin of 50.0%, p<0.001; ALT of 63.9%, p<0.005 and AST of 45.0%, p<0.005) and increase of Mayo Risk Score for PSC (change from baseline of + 0.5 point; p<0.003). Bile acids analysis revealed a significant decrease in lithocholic acid and its derivatives after UDCA withdrawal but no effect on concentrations of primary bile acids aside from an increased accumulation of their taurine conjugates. After UDCA removal cholestatic parameters, taurine species of cholic acid and chenodeoxycholic correlated with serum FGF19 levels. No significant effect on HRQoL after UDCA withdrawal was observed however 42% of patients reported a deterioration in their pruritus. In conclusion, at 3 months, discontinuation of UDCA in patients with PSC causes significant deterioration in liver biochemistry and influences concentrations of bile acid metabolites. A proportion of patients report increased pruritus, but other short term markers of quality of life are unaffected. (Hepatology 2014;).
    Hepatology 02/2014; · 12.00 Impact Factor
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    ABSTRACT: Background/Aim. With the improvement of the outcomes after liver transplantation (LTx), health-related quality of life (HRQoL) and physical activity are becoming significant outcome parameters. We prospectively assessed these parameters in patients with autoimmune and nonautoimmune liver disorders undergoing LTx. Materials and Methods. Patients (n = 107) were subdivided into 3 groups depending on the time after LTx: group-A (n = 21): 6-12 months; group-B (n = 48): 13-36 months; and group-C (n = 38): >37 months. SF-36 and IPAQ were applied in HRQoL and physical activity assessment. Results. Females had impaired HRQoL in most SF-36 domains. Younger patients showed higher scores at SF-36 physical functioning domain but IPAQ was not influenced by age. Group-B had higher general health and physical component summary than group-A (P = 0.037, P = 0.04, resp.) and total IPAQ than group-C (P = 0.047). The sitting time domain was longer in group-A than in group-B and group-C (P = 0.0157; P = 0.042, resp.). Employed patients had better HRQoL and higher physical activity than those not working. SF-36 and IPAQ were unrelated to the autoimmune etiology of liver disease. Conclusions. These findings show that female and unemployed patients have worse HRQoL, while gender and age at LTx time do not affect IPAQ's physical activity. The autoimmune etiology of liver disease does not influence HRQoL and physical activity after LTx.
    Journal of immunology research. 01/2014; 2014:738297.
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    ABSTRACT: Background. Enhanced expression of cell cycle inhibitor p27(kip1) suppresses cell proliferation. Ursodeoxycholic acid (UDCA) delays progression of primary biliary cirrhosis (PBC) but its effect on p27(kip1) expression is uncertain. Aims. To analyze the expression of p27(kip1) and its transcription modulator FoxO1 in patients with PBC, and to assess the impact of UDCA on this pathway. Materials and Methods. The examined human tissue included explanted livers from patients with cirrhotic PBC (n = 23), primary sclerosing cholangitis (PSC; n = 9), alcoholic liver disease (ALD; n = 9), and routine liver biopsies from patients with non-cirrhotic PBC (n = 26). Healthy liver samples served as controls (n = 19). Livers of FoxO-deficient mice were also studied. mRNA and protein expressions were analyzed by real-time PCR and Western blot. Results. p27(kip1) expression was increased in cirrhotic and non-cirrhotic PBC. FoxO1 mRNA levels were increased in PBC (8.5-fold increase versus controls). FoxO1 protein expression in PBC was comparable to controls, but it was decreased in patients with PSC and ALD (63% and 70% reduction, respectively; both P < 0.05 versus control). UDCA-treated non-cirrhotic patients with PBC showed decreased expression of p27(kip1) mRNA. Conclusion. PBC progression is characterized by a FoxO1-independent increase of p27(kip1) expression. In early PBC, UDCA may enhance liver regeneration via p27(kip1)-dependent mechanism.
    Journal of immunology research. 01/2014; 2014:921285.
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    ABSTRACT: Fat may affect progression of liver damage in patients with non-alcoholic fatty liver disease (NAFLD). In this study we characterize the state of lipid metabolism in 22 patients with NAFLD and different Apo-E variants. Total concentration of plasma total fatty acids was quantified by gas chromatography, while their derivatives by liquid chromatography/tandem mass spectrometry (LC ESI MS/MS). The ratio of plasma saturated fatty acid to monounsaturated fatty acid increased, whereas the ratio of polyunsaturated fatty acids to saturated fatty acids was reduced in Apo-E4 carriers. Simultaneously, the levels of individual plasma linoleic, arachidonic, and alpha linolenic acids significantly increased in subjects with the Apo-E4 allele. The 15-lipoxygenase metabolite, 13-hydroxyoctadecadienoic acid, was significantly higher in Apo-E3 carriers (p<0.006). 5-oxo-6,8,11,14-eicosatetraenoic acid was significantly elevated in Apo-E4 carriers (p<0.009). A significant difference in hyaluronic acid concentration (p<0.0016) as well as predicted advanced fibrosis (using the BARD scoring system) was found in Apo-E4 carriers (p<0.01). We suggest that a distinct mechanism of fibrosis between Apo E alleles. In Apo-E4 carriers, an elevation in 5-oxo-6,8,11,14-eicosatetraenoic acid synthesis and fatty acid dysfunction may induce fibrosis, while an inflammatory process may be the main cause of fibrosis in Apo-E3 carriers.
    Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 12/2013; 64(6):711-7. · 2.48 Impact Factor
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    ABSTRACT: Anatomic variations of the right biliary system are one of the most common risk factors for sectoral bile duct injury (BDI) during cholecystectomy. Isolated right posterior BDI may in particular be a challenge for both diagnosis and management. Herein we describe two cases of isolated right posterior sectoral BDI that took place during laparoscopic cholecystectomy. Despite effective external biliary drainage from the liver hilum in both cases, there was a persistent biliary leak observed which was not visible on endoscopic retrograde cholangiogram. Careful evaluation of images from both endoscopic and magnetic resonance cholangiograms revealed the diagnosis of an isolated right posterior sectoral BDI. These were treated with a delayed bisegmental (segments 6 and 7) liver resection and a Roux-en-Y hepaticojejunostomy respectively with good outcomes at 24 and 4 mo of follow-up. This paper discusses strategies for prevention of such injuries along with the diagnostic and therapeutic challenges it offers.
    World Journal of Gastroenterology 09/2013; 19(36):6118-6121. · 2.55 Impact Factor
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    ABSTRACT: Liver cirrhosis is associated with latent systemic inflammatory response syndrome as evidenced by elevated levels of proinflammatory cytokines. It has been proposed that inflammatory mediators play a role in the pathogenesis of minimal and overt hepatic encephalopathy (HE); hence, they may also have an effect on health-related quality of life (HRQL). The aim of this study was to investigate the relationship between serum levels of interleukin-1β (IL-1β), IL-6, and IL-18 and the occurrence of minimal HE and HRQL. Forty-two consecutive patients with liver cirrhosis were prospectively enrolled to the study. Minimal HE was detected by the Psychometric Hepatic Encephalopathy Score (PHES) and critical flicker frequency. HRQL was assessed with Chronic Liver Disease Questionnaire and 36-Item Short Form Health Survey (SF-36) questionnaires. The interleukins studied were determined using colorimetric sandwich enzyme-linked immunosorbent assay. Serum levels of interleukins correlated with liver dysfunction, but did not discriminate patients with minimal HE from those with overt or absent HE. IL-1β and IL-6 showed significant correlations with PHES, but showed no relationship with critical flicker frequency. Serum IL-6 and IL-18 correlated with both physical-related general health and mental component summary evaluated by the SF-36 questionnaire. This study shows that chronic inflammation plays a role in impaired HRQL in patients with cirrhosis irrespective of minimal HE.
    European journal of gastroenterology & hepatology 09/2013; · 1.66 Impact Factor
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    ABSTRACT: Mini-Mental State Examination (MMSE) is one of the most commonly used methods in the assessment of cognitive mental status. MMSE has been used in hepatology but its usefulness in the evaluation of hepatic encephalopathy (HE) has never been properly assessed. The aim of the study was to investigate the value of MMSE in detection of HE in patients with cirrhosis. One hundred and one consecutive patients with liver cirrhosis underwent neurological examination, MMSE and electroencephalography (EEG). Spectral analysis of EEG was done with calculation of mean dominant frequency (MDF) and relative power of delta, theta, alpha and beta rhythms. Minimal HE was diagnosed in patients with normal neurological status and alterations in spectral EEG. Statistical analysis included Fisher's exact and Anova analysis. Categorical data were compared using Levene's test for equality of variances. Correlation-coefficient analysis was performed by the Pearson's r or Z-test, as needed. Tests performance was assessed by the calculating the area under the ROC curve (AUC) and evaluating its difference from reference area (AUC=0.5). A p value <0.05 was considered statistically significant. Overt HE was identified in 49 (48.5%) and minimal HE in 22 (21.8%) patients. Although there were significant correlations between both severity of liver disease (Child-Pugh classification), overt HE (West-Haven criteria) and various MMSE items, MDF showed no correlation with any of MMSE items as well as MMSE summary score. MMSE (score and items) did not discriminate patients without HE and minimal HE. The only significant differences between patients without HE and with overt HE were seen in respect of MMSE score (p<0.02), orientation to place (p<0.003), repetition (p<0.01) and complex commands-understanding (p<0.02). Test performance analysis has shown that MMSE has no value as a prediction method in determining minimal HE and in respect of overt HE has a sensitivity of 63% and specificity of 52% by a cut-off level at 27.5 points to diagnose overt HE. In conclusion, although MMSE score and single items are altered in patients with overt HE, MMSE has no value in the assessment of minimal HE. Because MMSE could be impaired in several cognitive dysfunctions, more specific test should be used for measuring HE.
    BMC Gastroenterology 07/2013; 13(1):107. · 2.11 Impact Factor
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    Gastroenterology 05/2013; 144(5):S-944. · 12.82 Impact Factor
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    ABSTRACT: Primary sclerosing cholangitis (PSC) is a severe liver disease of unknown etiology leading to fibrotic destruction of the bile ducts and ultimately to the need for liver transplantation. We compared 3,789 PSC cases of European ancestry to 25,079 population controls across 130,422 SNPs genotyped using the Immunochip. We identified 12 genome-wide significant associations outside the human leukocyte antigen (HLA) complex, 9 of which were new, increasing the number of known PSC risk loci to 16. Despite comorbidity with inflammatory bowel disease (IBD) in 72% of the cases, 6 of the 12 loci showed significantly stronger association with PSC than with IBD, suggesting overlapping yet distinct genetic architectures for these two diseases. We incorporated association statistics from 7 diseases clinically occurring with PSC in the analysis and found suggestive evidence for 33 additional pleiotropic PSC risk loci. Together with network analyses, these findings add to the genetic risk map of PSC and expand on the relationship between PSC and other immune-mediated diseases.
    Nature Genetics 04/2013; · 35.21 Impact Factor
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    ABSTRACT: BACKGROUND: The psychometric hepatic encephalopathy score (PHES) is recommended as a gold standard in evaluation of minimal hepatic encephalopathy (HE). Normative databases have been collected in few countries, clearly showing differences among studied groups. Thus, the standardization of PHES for selected populations remains necessary. AIMS: To standardize PHES in a large cohort of Polish healthy subjects and to evaluate the normograms in patients with cirrhosis with quantified electroencephalography (EEG). METHODS: Three hundred and sixteen (142 males/174 females, aged 44.5 ± 12.1) normal individuals and 50 (31 males/19 females, aged 52.8 ± 12.4) patients with cirrhosis without overt HE were included. Key correction variables of psychometric tests were performed. The multivariate linear regression was used to calculate PHES normograms. RESULTS: Age and education levels were identified as predictors of all tests, therefore age- and education-adjusted normograms were developed. A weighted time-errors regression model for line tracing test (LTT) scoring was used. The PHES ranged between +5 and -15 points and the cut-off between normal and pathological PHES was set on ≤-5 points. By this cut-off level, PHES had a sensitivity of 57% and specificity of 97% to diagnose minimal HE (AUC = 0.866 ± 0.028). In patients with cirrhosis, PHES correlated with severity of liver disease (MELD, r = -0.475, P < 0.001 and Child-Pugh classification, r = -0.452, P < 0.002) and EEG (r = 0.547, P < 0.002). In patients with impaired EEG, PHES was lower than in individuals with unaltered EEG (P < 0.02); however, agreement between these two modalities was limited. CONCLUSIONS: Valid Polish PHES normograms, which incorporates w-LTT scoring system have been developed. Future multi-centre international studies are needed to validate widely applicable norms.
    Liver international: official journal of the International Association for the Study of the Liver 04/2013; · 3.87 Impact Factor
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    Journal of Hepatology 04/2013; 58(S1):S396. · 9.86 Impact Factor
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    ABSTRACT: To investigate the indications, resection rate, and safety of endoscopic submucosal dissection (ESD) for neoplastic lesions in the gastrointestinal tract at a European referral center. We carried out a retrospective analysis of the ESD procedures performed in our center for mucosal neoplastic and submucosal lesions of the gastrointestinal tract. The duration of the procedure, en bloc and complete (R0) resection rates, and complication rates were evaluated. Variables were reported as mean ± SD or simple proportions. Univariate analysis and comparisons of procedure times and resection rates were performed using Mann-Whitney U tests, or χ(2) tests for dichotomous variables. Between 2007 and 2011, ESD was performed in a total of 103 patients (46.7% male, mean age 64.0 ± 12.7 years). The indications for the procedure were epithelial tumor (n = 54), submucosal tumor (n = 42), or other (n = 7). The total en bloc resection rate was 90.3% (93/103) and R0 resection rate 80.6% (83/103). The median speed of the procedure was 15.0 min/cm(2). The complete resection rate was lower for submucosal tumors arising from the muscle layer (68%, 15/22, P < 0.05). Resection speed was quicker for submucosal tumors localized in the submucosal layer than for lesions arising from the muscularis propria layer (8.1 min/cm(2) vs 17.9 min/cm(2), P < 0.05). The R0 resection rate and speed were better in the last 24 mo (90.1%, 49/54 and 15.3 min/cm(2)) compared to the first 3 years of treatment (73.5%, 36/49, P < 0.05 and 22.0 min/cm(2), P < 0.05). Complications occurred in 14.6% (n = 15) of patients, including perforation in 5.8% (n = 6), pneumoperitoneum in 3.9% (n = 4), delayed bleeding in 1.9% (n = 2), and other in 2.9% (n = 3). Only one patient with delayed perforation required surgical treatment. During the mean follow-up of 26 ± 15.3 mo, among patients with R0 resection, recurrence occurred in one patient (1.2%). ESD is an effective and safe method for resection of neoplastic lesions with low recurrence. Speed and the R0 resection rate increased after 50 procedures.
    World Journal of Gastroenterology 03/2013; 19(12):1953-61. · 2.55 Impact Factor
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    ABSTRACT: Impaired regulation of apoptosis has been suggested to play a role in the pathogenesis of Primary Biliary Cirrhosis (PBC). In this study, we analysed a signalling pathway that comprises the transcription factor FoxO3a and its downstream target Bim, a Bcl-2 interacting mediator of apoptosis. The tissues examined included livers explanted from patients with cirrhotic PBC, primary sclerosing cholangitis (PSC), alcoholic liver disease (ALD) and liver biopsies from patients with non-cirrhotic PBC. Large margin resections of hepatocellular carcinoma were used as controls. Expression of FoxO3a and Bim mRNA was significantly enhanced in both non-cirrhotic and end-stage PBC (2.2-fold and 4.3-fold increases, respectively), but not in the other disorders. Similarly, FOXO3a protein level was increased in end-stage PBC (P < 0.05 vs. control). A significant increase in Bim mRNA in non-cirrhotic and cirrhotic PBC was observed (2.2-fold and 8.2-fold respectively). In addition, the most pro-apoptotic isoform of Bim dominated in livers of PBC patients (2.5- fold increase vs. control; P < 0.05). Enhanced FoxO3a and Bim expression was associated with a substantial activation of caspase-3 in PBC (2-fold increase vs. controls; P < 0.0001), whereas it was decreased in both ALD and PSC (46% and 67% reductions respectively). The relationship between FoxO3a and Bim was further investigated in the livers of FoxO-deficient mice. The somatic deletion of FoxO3a caused a significant decrease in Bim, but not caspase-3 protein expression confirming the crucial role of FoxO3a in induction of Bim gene transcription. Our results imply that the FoxO3/Bim signalling pathway can be of importance in the livers of patients with PBC.
    Liver international: official journal of the International Association for the Study of the Liver 02/2013; 33(2):231-8. · 3.87 Impact Factor
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    ABSTRACT: 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.
    Clinical and Developmental Immunology 01/2013; 2013:510547. · 3.06 Impact Factor
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    ABSTRACT: Biliary obstruction, a severe cholestatic condition, results in a huge accumulation of toxic bile acids (BA) in the liver. Glucuronidation, a conjugation reaction, is thought to protect the liver by both reducing hepatic BA toxicity and increasing their urinary elimination. The present study evaluates the contribution of each process in the overall BA detoxification by glucuronidation. Glucuronide (G), glycine, taurine conjugates, and unconjugated BAs were quantified in pre- and post-biliary stenting urine samples from 12 patients with biliary obstruction, using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The same LC-MS/MS procedure was used to quantify intra- and extracellular BA-G in Hepatoma HepG2 cells. Bile acid-induced toxicity in HepG2 cells was evaluated using MTS reduction, caspase-3 and flow cytometry assays. When compared to post-treatment samples, pre-stenting urines were enriched in glucuronide-, taurine- and glycine-conjugated BAs. Biliary stenting increased the relative BA-G abundance in the urinary BA pool, and reduced the proportion of taurine- and glycine-conjugates. Lithocholic, deoxycholic and chenodeoxycholic acids were the most cytotoxic and pro-apoptotic/necrotic BAs for HepG2 cells. Other species, such as the cholic, hyocholic and hyodeoxycholic acids were nontoxic. All BA-G assayed were less toxic and displayed lower pro-apoptotic/necrotic effects than their unconjugated precursors, even if they were able to penetrate into HepG2 cells. Under severe cholestatic conditions, urinary excretion favors the elimination of amidated BAs, while glucuronidation allows the conversion of cytotoxic BAs into nontoxic derivatives.
    PLoS ONE 01/2013; 8(11):e80994. · 3.73 Impact Factor
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    ABSTRACT: Alcoholic liver disease (ALD) begins with the accumulation of lipid droplets in the liver. Lipids which accumulate in the liver can stimulate inflammation, and the fatty acid derivatives, hydroxyeicosatetraenoic acids (HETEs) and hydroxyoctadecadienoic acids (HODEs), may play an important role in this process. We evaluated the concentrations of linoleic and arachidonic acid derivatives in the plasma of patients with ALD, non-alcoholic fatty liver disease (NAFLD) and healthy individuals. The groups consisted of 173 subjects: 63 patients with ALD, 90 with NAFLD and 20 healthy volunteers. Plasma 12-, 15-, and 5-HETE as well as 9- and 13-HODE were assessed using HPLC and isoprostane 8-epi-PGF 2α III was evaluated with an ELISA. In addition the mRNA expression of lipoxygenases (5-LOX, 15-LOX-1, 15-LOX-2) in the liver samples of patients with ALD cirrhosis was measured. A significant difference between the plasma concentrations of the analyzed derivatives was found when divided according to gender. The most significant differences were found between healthy individuals and ALD patients, as well as ALD and NAFLD individuals regardless of gender. The increased plasma HODEs and HETEs concentrations were in line with the increase in 5- and 15-LOX-1 and 15-LOX-2 mRNA in liver samples from ALD cirrhosis patients. LOXs expression and peroxidation of polyunsaturated fatty acids by free radical-propagated chemical oxidation may be contributing factors in liver necroinflammatory injury in ALD.
    Prostaglandins & other lipid mediators 11/2012; · 2.42 Impact Factor
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    ABSTRACT: To further characterize the genetic basis of primary biliary cirrhosis (PBC), we genotyped 2426 PBC patients and 5731 unaffected controls from three independent cohorts using a single nucleotide polymorphism (SNP) array (Immunochip) enriched for autoimmune disease risk loci. Meta-analysis of the genotype data sets identified a novel disease-associated locus near the TNFSF11 gene at 13q14, provided evidence for association at six additional immune-related loci not previously implicated in PBC and confirmed associations at 19 of 22 established risk loci. Results of conditional analyses also provided evidence for multiple independent association signals at four risk loci, with haplotype analyses suggesting independent SNP effects at the 2q32 and 16p13 loci, but complex haplotype driven effects at the 3q25 and 6p21 loci. By imputing classical HLA alleles from this data set, four class II alleles independently contributing to the association signal from this region were identified. Imputation of genotypes at the non-HLA loci also provided additional associations, but none with stronger effects than the genotyped variants. An epistatic interaction between the IL12RB2 risk locus at 1p31and the IRF5 risk locus at 7q32 was also identified and suggests a complementary effect of these loci in predisposing to disease. These data expand the repertoire of genes with potential roles in PBC pathogenesis that need to be explored by follow-up biological studies.
    Human Molecular Genetics 08/2012; · 7.69 Impact Factor
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    ABSTRACT: This report summarizes a single center's experience with liver transplantation (LT) performed for secondary biliary cirrhosis resulting from iatrogenic bile duct injury (BDI) sustained during cholecystectomy. Secondary biliary cirrhosis was the indication for LT in 5 (1.7%) out of 300 LTs performed in our center between Feb 2002 and April 2011. We analyzed the medical history of the patients, perioperative course and outcome following LT. The BDI was classified as Strasberg A in 1 case, B in two cases, and E in 2 cases. There was no hepatic arterial or portal vein injury in any patient. All of the surgical repairs prior to the development of cirrhosis were performed in general surgical units. The median time between BDI and listing the patient for LT was 11 years. The cadaveric whole-organ LT was done in all patients using the Piggy-Back technique. All patients are alive with a median follow-up of 53 months. Liver transplantation in patients with secondary biliary cirrhosis appears to result from a series of inadequate multiple surgical repairs following BDI. The immediate referral of such patients to centers with bile duct surgery experience is crucial.
    Annals of transplantation: quarterly of the Polish Transplantation Society 06/2012; 17(2):38-44. · 0.82 Impact Factor
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    ABSTRACT: Alcoholic liver disease (ALD) begins with the accumulation of lipid droplets in the liver. Lipids which accumulate in the liver can stimulate inflammation, and the fatty acid derivatives, hydroxyeicosatetraenoic acids (HETEs) and hydroxyoctadecadienoic acids (HODEs), may play an important role in this process. We evaluated the concentrations of linoleic and arachidonic acid derivatives in the plasma of patients with ALD, non-alcoholic fatty liver disease (NAFLD) and healthy individuals. The groups consisted of 173 subjects: 63 patients with ALD, 90 with NAFLD and 20 healthy volunteers. Plasma 12-, 15-, and 5-HETE as well as 9- and 13-HODE were assessed using HPLC and isoprostane 8-epi-PGF 2α III was evaluated with an ELISA. In addition the mRNA expression of lipoxygenases (5-LOX, 15-LOX-1, 15-LOX-2) in the liver samples of patients with ALD cirrhosis was measured. A significant difference between the plasma concentrations of the analyzed derivatives was found when divided according to gender. The most significant differences were found between healthy individuals and ALD patients, as well as ALD and NAFLD individuals regardless of gender. The increased plasma HODEs and HETEs concentrations were in line with the increase in 5- and 15-LOX-1 and 15-LOX-2 mRNA in liver samples from ALD cirrhosis patients. LOXs expression and peroxidation of polyunsaturated fatty acids by free radical-propagated chemical oxidation may be contributing factors in liver necroinflammatory injury in ALD.
    Prostaglandins & other lipid mediators 06/2012; 99(1-2):51-6. · 2.42 Impact Factor

Publication Stats

984 Citations
517.19 Total Impact Points

Institutions

  • 2006–2014
    • Pomeranian Medical University in Szczecin
      • Department of Laboratory Diagnostics and Molecular Medicine
      Stettin, West Pomeranian Voivodeship, Poland
  • 2013
    • Medical University of Warsaw
      Warszawa, Masovian Voivodeship, Poland
  • 2011–2013
    • Medical University of Silesia in Katowice
      • Department of Gastroenterology and Hepatology
      Catowice, Silesian Voivodeship, Poland
  • 2006–2013
    • Laval University
      • Faculty of Pharmacy
      Québec, Quebec, Canada
  • 2005–2011
    • Toronto Western Hospital
      Toronto, Ontario, Canada
  • 2009
    • INOVA Diagnostics
      San Diego, California, United States
  • 2004–2009
    • University of Toronto
      • Department of Medicine
      Toronto, Ontario, Canada
  • 2008
    • Akademia Pomorska w Slupsku
      Cammin, West Pomeranian Voivodeship, Poland
  • 2007
    • University of Zurich
      Zürich, Zurich, Switzerland
  • 2000–2003
    • The Queen Elizabeth Hospital
      Tarndarnya, South Australia, Australia
  • 1997–2003
    • Queen Elizabeth Hospital Birmingham
      Birmingham, England, United Kingdom
  • 2000–2002
    • University of Birmingham
      • School of Biosciences
      Birmingham, England, United Kingdom