Piotr Milkiewicz

Medical University of Warsaw, Warszawa, Masovian Voivodeship, Poland

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Publications (143)715.08 Total impact

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    Zeitschrift für Gastroenterologie 01/2015; 53(01). DOI:10.1055/s-0034-1397148 · 1.67 Impact Factor
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    Przegląd Gastroenterologiczny 01/2015; DOI:10.5114/pg.2015.49002 · 0.38 Impact Factor
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    ABSTRACT: 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.
    PLoS ONE 11/2014; 9(11):e112877. DOI:10.1371/journal.pone.0112877 · 3.53 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 · 4.41 Impact Factor
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    ABSTRACT: 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.
    Transplantation Proceedings 10/2014; 46(8):2770-3. DOI:10.1016/j.transproceed.2014.09.005 · 0.95 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 09/2014; 60(3). DOI:10.1002/hep.27074 · 11.19 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 · 4.41 Impact Factor
  • Zeitschrift für Gastroenterologie 08/2014; 52(08). DOI:10.1055/s-0034-1386139 · 1.67 Impact Factor
  • Zeitschrift für Gastroenterologie 08/2014; 52(08). DOI:10.1055/s-0034-1386150 · 1.67 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 03/2014; 2014:738297. DOI:10.1155/2014/738297 · 2.93 Impact Factor
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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. · 1.85 Impact Factor
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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 02/2014; 2014:921285. DOI:10.1155/2014/921285 · 2.93 Impact Factor
  • Zeitschrift für Gastroenterologie 01/2014; 52(01). DOI:10.1055/s-0033-1360902 · 1.67 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 01/2014; 9(5):307-9. DOI:10.5114/pg.2014.46167 · 0.38 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.
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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. · 2.72 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 11/2013; 8(11):e80994. DOI:10.1371/journal.pone.0080994 · 3.53 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. DOI:10.3748/wjg.v19.i36.6118 · 2.43 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; DOI:10.1097/MEG.0b013e328365a447 · 2.15 Impact Factor
  • Zeitschrift für Gastroenterologie 08/2013; 51(08). DOI:10.1055/s-0033-1352796 · 1.67 Impact Factor

Publication Stats

1k Citations
715.08 Total Impact Points


  • 2013–2014
    • Medical University of Warsaw
      • Department of General, Transplant and Liver Surgery
      Warszawa, Masovian Voivodeship, Poland
  • 2006–2014
    • Pomeranian Medical University in Szczecin
      • Department of Laboratory Diagnostics and Molecular Medicine
      Stettin, West Pomeranian Voivodeship, Poland
  • 2011–2013
    • Medical University of Silesia in Katowice
      • Department of Gastroenterology and Hepatology
      Catowice, Silesian 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
  • 2007
    • University of Zurich
      Zürich, Zurich, Switzerland
    • Jagiellonian University
      Cracovia, Lesser Poland Voivodeship, Poland
  • 2003
    • Rosario National University
      Rosario, Santa Fe, Argentina
  • 1998–2003
    • The Queen Elizabeth Hospital
      Tarndarnya, South Australia, Australia
  • 1996–2003
    • Queen Elizabeth Hospital Birmingham
      Birmingham, England, United Kingdom
  • 1998–2002
    • University of Birmingham
      • School of Biosciences
      Birmingham, England, United Kingdom