Piotr Milkiewicz

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

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Publications (151)814.22 Total impact

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    ABSTRACT: Cholestasis induces adaptive mechanisms protecting the liver against bile acids (BA) toxicity including modulation of BA synthesis. Whether fibroblast growth factor 19 (FGF19) or farnesoid X receptor (FXR) dependent signaling are involved in the regulation of BA homeostasis in primary biliary cirrhosis (PBC) remains unknown. Here we analyzed hepatic expression of FGF19 and other genes relevant to the adaptive response to cholestasis in tissues from non-cirrhotic (n = 24) and cirrhotic (n = 21) patients along with control tissues (n = 21). Moreover we searched for relationships between serum FGF19 and laboratory/clinical findings in 51 patients. Hepatic FGF19 mRNA expression was increased in non-cirrhotic and cirrhotic tissues (9-fold,p = 0.01; 69-fold,p < 0.0001, respectively). Protein levels of FGF19, FGF receptor 4, FXR and short heterodimer partner were increased in cirrhotic livers (9-fold, p < 0.001; 3.5-fold,p = 0.007; 2.4-fold,p < 0.0001; 2.8-fold,p < 0.0001 vs controls, respectively) which was accompanied by down-regulation of CYP7A1 (50% reduction, p = 0.006). Serum and liver levels of FGF19 correlated with worse liver biochemistry, BAs, quality of life and Mayo Risk Score. Serum FGF19 was elevated in UDCA non-responders. We conclude that PBC induces characteristic changes in liver expression of BAs synthesis regulatory molecules. FGF19 correlates with severity of liver disease and can potentially serve as an indicator of chronic cholestatic liver injury.
    Scientific Reports 08/2015; 5:13462. DOI:10.1038/srep13462 · 5.58 Impact Factor
  • M Krawczyk · W Ewa · A Kremer · J Trottier · O Barbier · F Lammert · P Milkiewicz
    Zeitschrift für Gastroenterologie 08/2015; 53(08). DOI:10.1055/s-0035-1559103 · 1.05 Impact Factor
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    ABSTRACT: Background/Aim. Sulphotransferase 2A1 (SULT2A1) exerts hepatoprotective effects. Transcription of SULT2A1 gene is induced by pregnane-X-receptor (PXR) and can be repressed by miR-378a-5p. We studied the PXR/SULT2A1 axis in chronic cholestatic conditions: primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC). Materials/Methods. Western-blot/PCRs for SULT2A1/PXR were performed in PSC (í µí±› = 11), PBC (í µí±› = 19), and control liver tissues (í µí±› = 19). PXR and SULT2A1 mRNA was analyzed in intestinal tissues from 22 PSC patients. Genomic DNA was isolated from blood of PSC patients (í µí±› = 120) and an equal number of healthy volunteers. Liver miRNA expression was evaluated using Affymetrix-Gene-Chip miRNA4.0. Results. Increased PXR protein was observed in both PSC and PBC compared to controls and was accompanied by a significant increase of SULT2A1 in PBC but not in PSC. Decreased expression of SULT2A1 mRNA was also seen in ileum of patients with PSC. Unlike PBC, miRNA analysis in PSC has shown a substantial increase in liver miR-378a-5p. Conclusions. PSC is characterized by disease-specific impairment of SULT2A1 expression following PXR activation, a phenomenon which is not noted in PBC, and may account for the impaired hepatoprotection in PSC. miRNA analysis suggests that SULT2A1 expression in PSC may be regulated by miR-378a-5p, connoting its pathogenic role.
    Journal of Immunology Research 06/2015; 2015(2):571353. DOI:10.1155/2015/571353 · 2.93 Impact Factor
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    ABSTRACT: Physical activity has an effect on long-term recovery after major surgical operations including liver transplant. Seven-Day Physical Activity Recall Questionnaire is a semistructured survey that assesses an individual's time spent in physical activity, strength, and flexibility activities during the 7 days prior to the interview. In this study we applied the Seven-Day Physical Activity Recall Questionnaire in patients who underwent liver transplant in our center. We surveyed 107 consecutive patients (62 male and 45 female), who were ≥ 6 months after liver transplant. Patients were divided into 3 groups, depending on time after liver transplant: group A (n = 21), 6 to 12 months posttransplant; group B (n = 48), 13 to 36 months posttransplant; and group C (n = 38), > 37 months posttransplant. Relations were analyzed between physical activity and various factors including sex, age at procedure and survey, time after grafting, original diagnosis, and body mass index. Female patients were significantly less active in daily and weekly measurements (981 ± 212 kcal vs 1267 ± 229 kcal; P < .0001) (6864 ± 1484 kcal vs 8866 ± 1607 kcal; P < .0001). There was a negative correlation between physical activity and age at transplant (P = .02) and survey (P = .02). Neither the time after liver transplant nor the original diagnosis before grafting affected physical activity. Female patients, when assessed with Seven-Day Physical Activity Recall Questionnaire, were significantly less physically active than male subjects after liver transplant. Younger patients were more active, but primary diagnosis had no significant effect on physical activity after grafting.
    06/2015; 13(3):243-6. DOI:10.6002/ect.2014.0201
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    ABSTRACT: Liver transplantation is a well-established treatment of patients with end-stage liver disease and selected liver tumors. Remarkable progress has been made over the last years concerning nearly all of its aspects. The aim of this study was to evaluate the evolution of long-term outcomes after liver transplantations performed in the Department of General, Transplant and Liver Surgery (Medical University of Warsaw). Data of 1500 liver transplantations performed between 1989 and 2014 were retrospectively analyzed. Transplantations were divided into 3 groups: group 1 including first 500 operations, group 2 including subsequent 500, and group 3 comprising the most recent 500. Five year overall and graft survival were set as outcome measures. Increased number of transplantations performed at the site was associated with increased age of the recipients (p<0.001) and donors (p<0.001), increased rate of male recipients (p<0.001), and increased rate of piggyback operations (p<0.001), and decreased MELD (p<0.001), as well as decreased blood (p=0.006) and plasma (p<0.001) transfusions. Overall survival was 71.6% at 5 years in group 1, 74.5% at 5 years in group 2, and 85% at 2.9 years in group 3 (p=0.008). Improvement of overall survival was particularly observed for primary transplantations (p=0.004). Increased graft survival rates did not reach the level of significance (p=0.136). Long-term outcomes after liver transplantations performed in the Department of General, Transplant and Liver Surgery are comparable to those achieved in the largest transplant centers worldwide and are continuously improving despite increasing recipient age and wider utilization of organs procured from older donors.
    Polish Journal of Surgery 05/2015; 87(5):221-30. DOI:10.1515/pjs-2015-0046
  • Journal of Hepatology 04/2015; 62(08):S774. DOI:10.1016/S0168-8278(15)31326-X · 11.34 Impact Factor
  • Journal of Hepatology 04/2015; 62:S794-S795. DOI:10.1016/S0168-8278(15)31372-6 · 11.34 Impact Factor
  • Journal of Hepatology 04/2015; 62:S803. DOI:10.1016/S0168-8278(15)31391-X · 11.34 Impact Factor
  • Journal of Hepatology 04/2015; 62:S789-S790. DOI:10.1016/S0168-8278(15)31360-X · 11.34 Impact Factor
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    M Krawczyk · E Wunsch · D Lütjohann · F Lammert · P Milkiewicz
    Zeitschrift für Gastroenterologie 01/2015; 53(01). DOI:10.1055/s-0034-1397148 · 1.05 Impact Factor
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    ABSTRACT: Introduction: Leisure time physical activity is of proven significance in surveys of fitness levels in various patient groups. Low physical functioning may affect recovery after liver transplantation (LTx). Aim: To assess patients' leisure time activity and health-related habits after transplantation. Material and methods: One hundred and seven patients after LTx were included. They were divided into groups depending on aetiology of liver problem and the period after LTx. Minnesota Leisure Time Physical Activity Questionnaire (MILTPAQ) and Health Behaviour Inventory (HBI) were applied. Results: Neither the primary indication for the procedure nor the period after surgery had a significant relationship with physical activity assessed with MILTPAQ; however, activity was lower in females than males (1804.3 ±1848.9 vs. 2619.9 ±2067; p = 0.03). Age at survey/surgery was inversely associated with higher activity (p = 0.02 and p = 0.03, respectively). Health Behaviour Inventory analysis showed a correlation between all four of its domains and age at transplantation/survey (p < 0.001 for both). There was a negative correlation between positive mental attitude and body mass index (BMI). Conclusions: The primary indications for grafting and, surprisingly, the period after surgery did not seem to be related to the patients' physical activity in leisure time. Younger and leaner patients appeared to understand the standards of healthy behaviour better and implement them in their daily activities. As higher BMI are associated with a negative mental attitude in patients after LTx, a particular emphasis should be placed on proper counselling in this subgroup of patients.
    Przegląd Gastroenterologiczny 01/2015; 10(2). DOI:10.5114/pg.2015.49002 · 0.38 Impact Factor
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    ABSTRACT: Background and Aims The only recognized biomarker for primary sclerosing cholangitis (PSC) is atypical anti-neutrophil cytoplasmic antibodies (aANCA), which, in addition to having low sensitivity and specificity, is an indirect immunofluorescence (IIF) test lacking the advantages of high throughput and objectivity. Recent reports have shown that antibodies to proteinase-3 (PR3-ANCA) might add diagnostic value in inflammatory bowel disease (IBD), specifically in ulcerative colitis (UC). As PSC is associated with IBD, the objective of this study was to evaluate the frequency and clinical significance of PR3-ANCA in a large cohort of patients. Methods A total of 244 PSC and 254 control [autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), hepatitis C viral infection (HCV), hepatitis B viral infection (HBV), and healthy controls] sera and their clinical correlations were retrospectively analyzed for PR3-ANCA determined by ELISA and a new chemiluminescence immunoassay (CIA). Testing was also performed for aANCA by IIF. Results When measured by CIA, PR3-ANCA was detected in 38.5% (94/244) of PSC patients compared to 10.6% (27/254) controls (p<0.0001). By ELISA, PR3-ANCA was detected in 23.4% (57/244) of PSC patients compared to 2.7% (6/254) controls (p<0.0001). PR3-ANCA in PSC patients was not associated with the presence or type of underlying IBD, and, in fact, it was more frequent in Crohn's disease (CD) patients with PSC than previously reported in CD alone. PR3-ANCA in PSC measured by CIA correlated with higher liver enzymes. Conclusion PR3-ANCA is detected in a significant proportion of PSC patients compared to other liver diseases including PBC and AIH. PR3-ANCA is associated with higher liver enzyme levels in PSC, and is not solely related to underlying IBD.
    PLoS ONE 11/2014; 9(11):e112877. DOI:10.1371/journal.pone.0112877 · 3.23 Impact Factor
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    ABSTRACT: In this paper we described the first Polish patient with ferroportin disease. Hereditary haemochromatosis (HH) is a condition associated with universal iron overload, and it is divided into four types, according to the Online Mendelian Inheritance in Man (OMIM) database. Ferroportin disease represented a rare type of HH, with autosomal dominant trait of inheritance. In our patient we detected a novel mutation in the ferroportin gene, with non-classical phenotype.
    Przegląd Gastroenterologiczny 11/2014; 9(5):307-9. DOI:10.5114/pg.2014.46167 · 0.38 Impact Factor
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    ABSTRACT: Background & AimsPrimary biliary cirrhosis and Primary sclerosing cholangitis are autoimmune cholestatic liver diseases sharing a lot in common, including a significant impairment of patients’ health-related quality of life HRQoL HRQoL in PBC is assessed with disease-specific PBC-40 and PBC-27 questionnaires. A PSC-specific questionnaire has not been developed. Neither PBC-40 nor PBC-27s applicability for PSC has been evaluated. We applied these three questionnaires for HRQoL assessment in a large homogenous cohort of PSC patients.Patients and Methods This cross-sectional study enrolled 102 Caucasian PSCs and 53 matched healthy controls and measured HRQoL using generic SF-36, and disease-specific (PBC-40/PBC-27) questionnaires.Results(i) SF-36. Most SF-36 domains were significantly lower in PSCs than controls. Physical Functioning and Mental Component Summary scores were significantly lower in female patients and correlated negatively with age but not with concurrent inflammatory bowel disease. Cirrhosis was associated with lower Physical Functioning, Role Physical, General Health, Vitality and Physical Component Summary. (ii) PBC-40 and PBC-27. Both tools showed similar HRQoL impairment scoring. Fatigue and Cognitive were impaired in female patients. Several correlations existed between HRQoL and laboratory parameters, including cholestatic tests and Itch. Cirrhosis correlated with Other symptoms and Fatigue PBC-40. (iii) PBC-40 vs PBC-27. Strong correlations among most domains of both questionnaires were seen, as well as between (iv) SF-36 vs PBC-40 or SF-36 vs PBC-27.Conclusion This is the first study directly comparing PBC-40, PBC-27 and SF-36 in PSC. PSC patients, especially females, show HRQoL impairment. PBC-40 and PBC-27 questionnaires could be of potential use for HRQoL assessment in PSC.
    Liver international: official journal of the International Association for the Study of the Liver 11/2014; 35(6). DOI:10.1111/liv.12730 · 4.85 Impact Factor
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    ABSTRACT: Lysophosphatidic acid (LPA) mediates cholestatic pruritus. Recently the enzyme PNPLA3, expressed in liver and skin, was demonstrated to metabolise LPA. Here we assess the association of the PNPLA3 variant p.Ile148Met, known to be associated with (non-)alcoholic fatty liver disease (NAFLD) in genome-wide association studies, with cholestatic itch in 187 patients with primary biliary cirrhosis (PBC) and 250 PBC-free controls as well as 201 women with intrahepatic cholestasis of pregnancy (ICP) and 198 female controls without a history of ICP. Our hypothesis was that the intensity of cholestatic itch differs in carriers of distinct PNPLA3 p.Ile148Met genotypes. Patients with PBC carrying the allele p.148Met that confers an increased NAFLD risk reported less itching than carriers of the p.148Ile allele (ANOVA P = 0.048). The PNPLA3 p.148Ile allele increased the odds of requiring plasmapheresis for refractory pruritus (OR = 3.94, 95% CI = 0.91-17.00, P = 0.048). In line with these findings, the PNPLA3 p.148Met allele was underrepresented in the ICP cohort (OR = 0.66, 95% CI = 0.47-0.92, P = 0.013). Notwithstanding the need for further replication of these findings, we conclude that the PNPLA3 allele p.148Met might confer protection against cholestatic pruritus, possibly due to increased LPA-acyltransferase activity in liver and/or skin.
    Scientific Reports 10/2014; 4:6374. DOI:10.1038/srep06374 · 5.58 Impact Factor
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    ABSTRACT: Background: Severity of liver disease evaluated with Model for End-Stage Liver Disease (MELD)/Child-Pugh-Turcotte (CPT) score is of importance in liver transplantation (LTx) assessment. The Medical Outcomes Study Short Form (SF-36) is a widely used generic questionnaire of health-related quality of life (HRQoL). This study was a prospective analysis of the effect of pretransplantation liver status on HRQoL after the procedure. Materials and methods: One hundred and seven (62 male, 45 female, median age 52 years) consecutive patients were included. MELD/CPT score and diabetes status were evaluated during LTx assessment. Patients were divided into 3 groups depending on the period after LTx: 6 to 12 months (group I), 13 to 36 months (group II), and >37 months (group III). They also were divided into 2 groups depending on the age at LTx: group I (<50 years) and group II (>50 years). SF-36 was used in the assessment of HRQoL. Results: Correlation between pretransplantation MELD/CPT score and HRQoL was only seen in the general health domain of the SF-36 in patients from group I (r = 0.64; P = .004 and r = 0.61; P = .02, respectively). Diabetes exerted a significant effect on the physical component summary (P = .02), again in group I. No significant correlation was observed between MELD/CPT score and the presence of diabetes in groups II and III. Regarding age at LTx, no significant correlation between MELD/CPT score and HRQoL was seen. Conclusions: Liver status assessed with MELD and CPT scores before transplantation has a minor effect on HRQoL after LTx and exerts no significant effect in patients evaluated >12 months after LTx. Patients with diabetes seem to have worse quality of life early after surgery; however, diabetic and nondiabetic patients had comparable HRQoL scores later on after LTx.
    Transplantation Proceedings 10/2014; 46(8):2770-3. DOI:10.1016/j.transproceed.2014.09.005 · 0.98 Impact Factor
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    ABSTRACT: Unlabelled: Ursodeoxycholic acid (UDCA) is no longer recommended for management of adult patients with primary sclerosing cholangitis (PSC). We undertook a prospective evaluation of UDCA withdrawal in a group of consecutive patients with PSC. Twenty six patients, all treated with UDCA (dose range: 10-15 mg/kg/day) were included. Paired blood samples for liver biochemistry, bile acids, and fibroblast growth factor 19 (FGF19) were collected before UDCA withdrawal and 3 months later. Liquid chromatography/tandem mass spectrometry was used for quantification of 29 plasma bile acid metabolites. Pruritus and health-related quality of life (HRQoL) were assessed with a 10-point numeric rating scale, the Medical Outcomes Study Short Form-36 (SF-36), and PBC-40 questionnaires. UDCA withdrawal resulted in a significant deterioration in liver biochemistry (increase of alkaline phosphatase of 75.6%; P<0.0001; gamma-glutamyl transpeptidase of 117.9%, P<0.0001; bilirubin of 50.0%, P<0.001; alanine aminotransferase of 63.9%, P<0.005; and aspartate aminotransferase 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 acid 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 acid 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. 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 09/2014; 60(3). DOI:10.1002/hep.27074 · 11.06 Impact Factor
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    ABSTRACT: Background Using high-density human recombinant protein microarrays, we identified two potential biomarkers, kelch-like 12 (KLHL12) and hexokinase-1 (HK1), in primary biliary cirrhosis (PBC). The objective of this study was to determine the diagnostic value of anti-KLHL12/HK1 autoantibodies in PBC.AimsInitial discovery used sera from 22 patients with PBC and 62 non-PBC controls. KLHL12 and HK1 proteins were then analyzed for immunoglobulin reactivity by immunoblot and enzyme-linked immunosorbent assay (ELISA) in two independent cohorts of PBC and disease/healthy control patients.Methods Serum samples from 100 patients with PBC and 165 non-PBC disease controls were analyzed by immunoblot and samples from 366 patients with PBC, 174 disease controls, and 80 healthy donors were tested by ELISA.ResultsAnti-KLHL12 and anti-HK1 antibodies were each detected more frequently in PBC compared with non-PBC disease controls (p < 0.001). Not only are both markers highly specific for PBC (≥ 95%), but they also yielded higher sensitivity than anti-gp210 and anti-sp100 antibodies. Combining anti-HK1 and anti-KLHL12 with available markers (MIT3, gp210 and sp100) increased the diagnostic sensitivity for PBC. Most importantly, anti-KLHL12 and anti-HK1 antibodies were present in 10~35% of AMA-negative PBC patients and adding these two biomarkers to conventional PBC assays dramatically improved the serological sensitivity in AMA-negative PBC from 55% to 75% in immunoblot and 48.3% to 68.5% in ELISA.Conclusions The addition of tests for highly specific anti-KLHL12 and anti-HK1 antibodies to AMA and ANA serological assays significantly improves efficacy in the clinical detection and diagnosis of PBC, especially for AMA-negative subjects.This article is protected by copyright. All rights reserved.
    Liver international: official journal of the International Association for the Study of the Liver 09/2014; 35(2). DOI:10.1111/liv.12690 · 4.85 Impact Factor
  • Zeitschrift für Gastroenterologie 08/2014; 52(08). DOI:10.1055/s-0034-1386139 · 1.05 Impact Factor
  • M Krawczyk · E Stachowska · F Lammert · P Milkiewicz · M Milkiewicz
    Zeitschrift für Gastroenterologie 08/2014; 52(08). DOI:10.1055/s-0034-1386150 · 1.05 Impact Factor

Publication Stats

2k Citations
814.22 Total Impact Points


  • 2003–2015
    • Pomeranian Medical University in Szczecin
      • Department of Laboratory Diagnostics and Molecular Medicine
      Stettin, West Pomeranian Voivodeship, Poland
    • Rosario National University
      Rosario, Santa Fe, Argentina
  • 2013–2014
    • Medical University of Warsaw
      • Department of General, Transplant and Liver Surgery
      Warszawa, Masovian Voivodeship, Poland
  • 2004–2011
    • Toronto Western Hospital
      Toronto, Ontario, Canada
  • 2008
    • Akademia Pomorska w Slupsku
      Cammin, West Pomeranian Voivodeship, Poland
    • University of Toronto
      • Department of Medicine
      Toronto, Ontario, Canada
  • 1998–2003
    • The Queen Elizabeth Hospital
      Tarndarnya, South Australia, Australia
  • 1997–2003
    • Queen Elizabeth Hospital Birmingham
      Birmingham, England, United Kingdom
  • 1998–2002
    • University of Birmingham
      • School of Biosciences
      Birmingham, England, United Kingdom