The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Piotr Milkiewicz - One of the best experts on this subject based on the ideXlab platform.
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effect of s adenosyl l methionine on Liver Biochemistry and quality of life in patients with primary biliary cholangitis treated with ursodeoxycholic acid a prospective open label pilot study
Journal of Gastrointestinal and Liver Diseases, 2018Co-Authors: Ewa Wunsch, Joanna Raszejawyszomirska, Olivier Barbier, Malgorzata Milkiewicz, Marcin Krawczyk, Piotr MilkiewiczAbstract:Background & Aims: Chronic Liver disease induces an acquired deficiency of S-adenosyl-L-methionine (SAMe) leading to impairment of detoxifying processes in the Liver. Ursodeoxycholic acid (UDCA) represents the standard treatment in primary biliary cholangitis (PBC). As both compounds exert their hepatoprotective effects by different mechanisms, it is conceivable that when used together their effect might be additive. The aim of this study was to analyse the effect of SAMe supplementation on Liver Biochemistry and health-related quality of life (HRQoL) in patients with PBC, treated with UDCA. Methods. In this prospective pilot, proof of the principle, non-randomized and open label study we enrolled 24 patients with PBC treated with UDCA for at least 6 months. They had received both UDCA in a standard dose of 13-15 mg/kg b.w. and SAMe in the dose of 1200 mg daily over a period of 6 months. A group of 24 patients with PBC treated with UDCA served as control for Liver Biochemistry (Study registered on the platform ClinicalTrials.gov under ID: NCT02557360). Results. We observed a significant decrease of ALP, GGT and total cholesterol in non-cirrhotic patients treated with SAMe. There was also a significant improvement of fatigue and pruritus in PBC-40 questionnaire and amelioration of anxiety in STAI 2 questionnaire in the SAMe group. Treatment with SAMe neither increased sulfation capacity of the Liver nor had an effect on fibroblast growth factor-19 serum levels. Conclusions. Our pilot study demonstrates a positive effect of adding SAMe to UDCA in non-cirrhotic patients with PBC.
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serum autotaxin is a marker of the severity of Liver injury and overall survival in patients with cholestatic Liver diseases
Scientific Reports, 2016Co-Authors: Ewa Wunsch, Olivier Barbier, Malgorzata Milkiewicz, Marcin Krawczyk, Jocelyn Trottier, Markus F Neurath, Frank Lammert, Andreas E Kremer, Piotr MilkiewiczAbstract:Autotaxin (ATX) is involved in the synthesis of lysophosphatidic acid. Both have recently been linked to cholestatic pruritus and Liver injury. We aimed to investigate whether ATX is an indicator of cholestatic Liver injury, health-related quality of life (HRQoL) and prognosis based on a group of 233 patients, 118 with primary biliary cholangitis (PBC) and 115 with primary sclerosing cholangitis (PSC). Patients were followed for 1-60 months, cumulative survival rates were calculated. ATX activity was significantly higher in both groups than in the 103 controls, particularly in patients with cirrhosis and in patients with longer disease duration. Ursodeoxycholic acid (UDCA) non-responders with PBC exhibited increased ATX activity. ATX activity was correlated with Liver Biochemistry, MELD, Mayo Risk scores and was associated with worse disease-specific HRQoL aspects. In both groups, Cox model analysis indicated that ATX was a negative predictor of survival. Increased ATX levels were associated with a 4-fold higher risk of death/Liver transplantation in patients with PBC and a 2.6-fold higher risk in patients with PSC. We conclude that in patients with cholestatic conditions, ATX is not only associated with pruritus but also indicates impairment of other HRQoL aspects, Liver dysfunction, and can serve as a predictor of survival.
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expression of hepatic fibroblast growth factor 19 is enhanced in primary biliary cirrhosis and correlates with severity of the disease
Scientific Reports, 2015Co-Authors: Ewa Wunsch, Olivier Barbier, Malgorzata Milkiewicz, Piotr Milkiewicz, Jocelyn Trottier, E Elias, Urszula Wasik, Agnieszka KempinskapodhorodeckaAbstract: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.
Carsten Heilmann - One of the best experts on this subject based on the ideXlab platform.
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gastrointestinal toxicity systemic inflammation and Liver Biochemistry in allogeneic hematopoietic stem cell transplantation
Biology of Blood and Marrow Transplantation, 2017Co-Authors: Karina Jordan, Peter Erik Lotko Pontoppidan, Hilde Hylland Uhlving, Katrine Kielsen, Sarah Weischendorff, Marianne H Jorgensen, Douglas G Burrin, Ib Jarle Christensen, Carsten HeilmannAbstract:Liver toxicity is frequently seen in relation to allogeneic hematopoietic stem cell transplantation (HSCT), but pathogenesis and the risk factors are poorly understood. The purpose of this study was to investigate associations between Liver toxicity, gastrointestinal toxicity, and levels of immune-regulating cytokines during the early post-transplantation period. We prospectively included 81 children and adults undergoing HSCT after myeloablative conditioning. Alanine aminotransferase (ALT), total bilirubin levels, and international normalized ratio were measured longitudinally until 3 months after the transplantation and related to levels of inflammatory markers (C-reactive protein [CRP], IL-6, and IL-10) and to plasma citrulline as a marker of intestinal toxicity during the first 3 weeks after HSCT. The majority of patients experienced ALT levels above the normal range (45 U/L) with significant increases at 3 months after HSCT. Increased levels of total bilirubin were observed in 26% during the 3-month period. Citrulline levels decreased significantly to a nadir at day 7 (B = .23; 95% confidence interval [CI], .12 to .35; P < .0001), but citrulline levels at nadir were not associated with parameters of Liver toxicity. However, a faster reconstitution of mucosa with higher citrulline levels at day +21 correlated with lower bilirubin levels 3 months after HSCT (r = -.26, P = .034) and increased overall survival (hazard ratio, .88; 95% CI, .79 to .97; P = .008) . Increased levels of CRP and IL-6 at day 7 after HSCT correlated positively with ALT and bilirubin, and in the multivariate analysis, IL-6 at day 7 appeared to be the only predicting risk factor for increased mean bilirubin during the early post-transplantation phase (B = .01; 95% CI, .01 to .02; P = .001) as well as maximum levels of bilirubin (B = .3; 95% CI, .12 to .48; P= .001) and occurrence of sinusoidal obstruction syndrome during the first 3 months after HSCT (odds ratio, 1.003; 95% CI, 1.001 to 1.005; P = .002). The results of this study indicate that Liver toxicity after HSCT is associated with an increased inflammatory response mounted during the phase of maximal gastrointestinal toxicity in the early phase after transplantation.
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Gastrointestinal Toxicity, Systemic Inflammation, and Liver Biochemistry in Allogeneic Hematopoietic Stem Cell Transplantation.
Biology of Blood and Marrow Transplantation, 2017Co-Authors: Karina Jordan, Peter Erik Lotko Pontoppidan, Hilde Hylland Uhlving, Katrine Kielsen, Sarah Weischendorff, Marianne H Jorgensen, Douglas G Burrin, Ib Jarle Christensen, Carsten Heilmann, Henrik SengeløvAbstract:Liver toxicity is frequently seen in relation to allogeneic hematopoietic stem cell transplantation (HSCT), but pathogenesis and the risk factors are poorly understood. The purpose of this study was to investigate associations between Liver toxicity, gastrointestinal toxicity, and levels of immune-regulating cytokines during the early post-transplantation period. We prospectively included 81 children and adults undergoing HSCT after myeloablative conditioning. Alanine aminotransferase (ALT), total bilirubin levels, and international normalized ratio were measured longitudinally until 3 months after the transplantation and related to levels of inflammatory markers (C-reactive protein [CRP], IL-6, and IL-10) and to plasma citrulline as a marker of intestinal toxicity during the first 3 weeks after HSCT. The majority of patients experienced ALT levels above the normal range (45 U/L) with significant increases at 3 months after HSCT. Increased levels of total bilirubin were observed in 26% during the 3-month period. Citrulline levels decreased significantly to a nadir at day 7 (B = .23; 95% confidence interval [CI], .12 to .35; P
Ib Jarle Christensen - One of the best experts on this subject based on the ideXlab platform.
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gastrointestinal toxicity systemic inflammation and Liver Biochemistry in allogeneic hematopoietic stem cell transplantation
Biology of Blood and Marrow Transplantation, 2017Co-Authors: Karina Jordan, Peter Erik Lotko Pontoppidan, Hilde Hylland Uhlving, Katrine Kielsen, Sarah Weischendorff, Marianne H Jorgensen, Douglas G Burrin, Ib Jarle Christensen, Carsten HeilmannAbstract:Liver toxicity is frequently seen in relation to allogeneic hematopoietic stem cell transplantation (HSCT), but pathogenesis and the risk factors are poorly understood. The purpose of this study was to investigate associations between Liver toxicity, gastrointestinal toxicity, and levels of immune-regulating cytokines during the early post-transplantation period. We prospectively included 81 children and adults undergoing HSCT after myeloablative conditioning. Alanine aminotransferase (ALT), total bilirubin levels, and international normalized ratio were measured longitudinally until 3 months after the transplantation and related to levels of inflammatory markers (C-reactive protein [CRP], IL-6, and IL-10) and to plasma citrulline as a marker of intestinal toxicity during the first 3 weeks after HSCT. The majority of patients experienced ALT levels above the normal range (45 U/L) with significant increases at 3 months after HSCT. Increased levels of total bilirubin were observed in 26% during the 3-month period. Citrulline levels decreased significantly to a nadir at day 7 (B = .23; 95% confidence interval [CI], .12 to .35; P < .0001), but citrulline levels at nadir were not associated with parameters of Liver toxicity. However, a faster reconstitution of mucosa with higher citrulline levels at day +21 correlated with lower bilirubin levels 3 months after HSCT (r = -.26, P = .034) and increased overall survival (hazard ratio, .88; 95% CI, .79 to .97; P = .008) . Increased levels of CRP and IL-6 at day 7 after HSCT correlated positively with ALT and bilirubin, and in the multivariate analysis, IL-6 at day 7 appeared to be the only predicting risk factor for increased mean bilirubin during the early post-transplantation phase (B = .01; 95% CI, .01 to .02; P = .001) as well as maximum levels of bilirubin (B = .3; 95% CI, .12 to .48; P= .001) and occurrence of sinusoidal obstruction syndrome during the first 3 months after HSCT (odds ratio, 1.003; 95% CI, 1.001 to 1.005; P = .002). The results of this study indicate that Liver toxicity after HSCT is associated with an increased inflammatory response mounted during the phase of maximal gastrointestinal toxicity in the early phase after transplantation.
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Gastrointestinal Toxicity, Systemic Inflammation, and Liver Biochemistry in Allogeneic Hematopoietic Stem Cell Transplantation.
Biology of Blood and Marrow Transplantation, 2017Co-Authors: Karina Jordan, Peter Erik Lotko Pontoppidan, Hilde Hylland Uhlving, Katrine Kielsen, Sarah Weischendorff, Marianne H Jorgensen, Douglas G Burrin, Ib Jarle Christensen, Carsten Heilmann, Henrik SengeløvAbstract:Liver toxicity is frequently seen in relation to allogeneic hematopoietic stem cell transplantation (HSCT), but pathogenesis and the risk factors are poorly understood. The purpose of this study was to investigate associations between Liver toxicity, gastrointestinal toxicity, and levels of immune-regulating cytokines during the early post-transplantation period. We prospectively included 81 children and adults undergoing HSCT after myeloablative conditioning. Alanine aminotransferase (ALT), total bilirubin levels, and international normalized ratio were measured longitudinally until 3 months after the transplantation and related to levels of inflammatory markers (C-reactive protein [CRP], IL-6, and IL-10) and to plasma citrulline as a marker of intestinal toxicity during the first 3 weeks after HSCT. The majority of patients experienced ALT levels above the normal range (45 U/L) with significant increases at 3 months after HSCT. Increased levels of total bilirubin were observed in 26% during the 3-month period. Citrulline levels decreased significantly to a nadir at day 7 (B = .23; 95% confidence interval [CI], .12 to .35; P
Karina Jordan - One of the best experts on this subject based on the ideXlab platform.
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gastrointestinal toxicity systemic inflammation and Liver Biochemistry in allogeneic hematopoietic stem cell transplantation
Biology of Blood and Marrow Transplantation, 2017Co-Authors: Karina Jordan, Peter Erik Lotko Pontoppidan, Hilde Hylland Uhlving, Katrine Kielsen, Sarah Weischendorff, Marianne H Jorgensen, Douglas G Burrin, Ib Jarle Christensen, Carsten HeilmannAbstract:Liver toxicity is frequently seen in relation to allogeneic hematopoietic stem cell transplantation (HSCT), but pathogenesis and the risk factors are poorly understood. The purpose of this study was to investigate associations between Liver toxicity, gastrointestinal toxicity, and levels of immune-regulating cytokines during the early post-transplantation period. We prospectively included 81 children and adults undergoing HSCT after myeloablative conditioning. Alanine aminotransferase (ALT), total bilirubin levels, and international normalized ratio were measured longitudinally until 3 months after the transplantation and related to levels of inflammatory markers (C-reactive protein [CRP], IL-6, and IL-10) and to plasma citrulline as a marker of intestinal toxicity during the first 3 weeks after HSCT. The majority of patients experienced ALT levels above the normal range (45 U/L) with significant increases at 3 months after HSCT. Increased levels of total bilirubin were observed in 26% during the 3-month period. Citrulline levels decreased significantly to a nadir at day 7 (B = .23; 95% confidence interval [CI], .12 to .35; P < .0001), but citrulline levels at nadir were not associated with parameters of Liver toxicity. However, a faster reconstitution of mucosa with higher citrulline levels at day +21 correlated with lower bilirubin levels 3 months after HSCT (r = -.26, P = .034) and increased overall survival (hazard ratio, .88; 95% CI, .79 to .97; P = .008) . Increased levels of CRP and IL-6 at day 7 after HSCT correlated positively with ALT and bilirubin, and in the multivariate analysis, IL-6 at day 7 appeared to be the only predicting risk factor for increased mean bilirubin during the early post-transplantation phase (B = .01; 95% CI, .01 to .02; P = .001) as well as maximum levels of bilirubin (B = .3; 95% CI, .12 to .48; P= .001) and occurrence of sinusoidal obstruction syndrome during the first 3 months after HSCT (odds ratio, 1.003; 95% CI, 1.001 to 1.005; P = .002). The results of this study indicate that Liver toxicity after HSCT is associated with an increased inflammatory response mounted during the phase of maximal gastrointestinal toxicity in the early phase after transplantation.
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Gastrointestinal Toxicity, Systemic Inflammation, and Liver Biochemistry in Allogeneic Hematopoietic Stem Cell Transplantation.
Biology of Blood and Marrow Transplantation, 2017Co-Authors: Karina Jordan, Peter Erik Lotko Pontoppidan, Hilde Hylland Uhlving, Katrine Kielsen, Sarah Weischendorff, Marianne H Jorgensen, Douglas G Burrin, Ib Jarle Christensen, Carsten Heilmann, Henrik SengeløvAbstract:Liver toxicity is frequently seen in relation to allogeneic hematopoietic stem cell transplantation (HSCT), but pathogenesis and the risk factors are poorly understood. The purpose of this study was to investigate associations between Liver toxicity, gastrointestinal toxicity, and levels of immune-regulating cytokines during the early post-transplantation period. We prospectively included 81 children and adults undergoing HSCT after myeloablative conditioning. Alanine aminotransferase (ALT), total bilirubin levels, and international normalized ratio were measured longitudinally until 3 months after the transplantation and related to levels of inflammatory markers (C-reactive protein [CRP], IL-6, and IL-10) and to plasma citrulline as a marker of intestinal toxicity during the first 3 weeks after HSCT. The majority of patients experienced ALT levels above the normal range (45 U/L) with significant increases at 3 months after HSCT. Increased levels of total bilirubin were observed in 26% during the 3-month period. Citrulline levels decreased significantly to a nadir at day 7 (B = .23; 95% confidence interval [CI], .12 to .35; P
Britt Christensen - One of the best experts on this subject based on the ideXlab platform.
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vedolizumab in patients with concurrent primary sclerosing cholangitis and inflammatory bowel disease does not improve Liver Biochemistry but is safe and effective for the bowel disease
Alimentary Pharmacology & Therapeutics, 2018Co-Authors: Britt Christensen, Dejan Micic, Peter R Gibson, Emanuelle Bellaguarda, Paul M Corsello, John N Gaetano, Andres Yarur, Jami KinnucanAbstract:BACKGROUND Blocking of lymphocyte trafficking to bile ducts is a potential mechanism to alter the disease course of patients with primary sclerosing cholangitis (PSC). AIM To describe the effect of the α4 β7 integrin antibody, vedolizumab, on Liver Biochemistry and disease activity in patients with PSC and inflammatory bowel disease (IBD). METHODS This is a retrospective multi-centre study of adult patients with a diagnosis of both IBD and PSC. The primary outcome was change in serum alkaline phosphatase level at weeks 14 and 30. Secondary outcomes included changes in other Liver biochemistries and in clinical outcomes for the bowel disease. A safety analysis for adverse events was performed. RESULTS Thirty-four patients (16 Crohn's disease, 18 ulcerative colitis) were included. Nine (26%) had a history of Liver transplant. Median follow-up on vedolizumab was 9 months (IQR: 7-16). There was no overall change in serum alkaline phosphatase level with vedolizumab therapy (median 268 [IQR: 105-551] IU/L at baseline versus 249 [IQR: 183-634] IU/L, P = 0.99 at week 30). No significant changes in other Liver biochemistries or the Mayo PSC Risk Score were demonstrated at week 30. Clinical remission was achieved at week 30 in 55% of Crohn's disease and 29% of ulcerative colitis patients. Seven (21%) patients ceased vedolizumab; six patients stopped therapy due to persistent IBD activity and one for worsening of Liver biochemistries. CONCLUSION Vedolizumab treatment in patients with PSC and IBD did not improve Liver Biochemistry but was associated with improvement in bowel disease and a favourable safety profile.
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p410 vedolizumab is safe and effective for ibd but has no effect on Liver Biochemistry in patients with concurrent psc
Journal of Crohn's and Colitis, 2017Co-Authors: Britt Christensen, Dejan Micic, Peter R Gibson, S Singh, Emanuelle Bellaguarda, Paul M Corsello, John N Gaetano, Jami Kinnucan, Vijaya L Rao, S ReddyAbstract:Background: Blocking of lymphocyte trafficking is a potential mechanism to alter the disease course of primary sclerosing cholangitis (PSC). We studied the effect of the selective α4β7 integrin antibody, vedolizumab, on Liver Biochemistry and inflammatory bowel disease (IBD) activity in patients with IBD and PSC (IBD-PSC). Methods: We reviewed electronic medical records of adult patients who had an established diagnosis of IBD-PSC from five tertiary centers. We assessed baseline patient and disease characteristics and treatment exposures. The primary outcome was change in serum alkaline phosphatase at weeks 14 and 30. Secondary outcomes included changes in other Liver biochemistries, the Mayo Risk Score for PSC and IBD clinical and endoscopic remission. We also performed a safety analysis for the development of adverse events including Liver-related complications. Results: We identified 34 patients with IBD-PSC. Nine (26%) had a history of orthotopic Liver transplant, 7 were on stable doses of ursodeoxycholic acid (UDCA) and 2 patients commenced UDCA during the study period. Median follow-up was 9 (IQR: 7–16) months; 28 (92%) had at least 6 months of clinical follow-up. Serum alkaline phosphatase activities did not significantly decrease with vedolizumab therapy (median 268 (IQR: 105–551) IU/L at baseline versus 249 (IQR: 183–634) IU/L, p=0.9899 at week 30). Of the 18 patients with an abnormal alkaline phosphatase at baseline (>120IU/L), 11 (61%) had improvement with treatment. In these patients, alkaline phosphatase trended down from 475 IU/L (IQR: 241–757) at baseline to 283 IU/L (IQR: 207–658), p=0.267 at week 30 but none of these normalized (Figure 1). Median alkaline phosphatase changes remained similar when patients exposed to UDCA were excluded. Of the 8 patients (31%) with normal alkaline phosphatase at baseline, 4 (50%) had a subsequent increase to abnormal levels by week 30, from a baseline median of 98 IU/L (IQR: 77–102) to 146 IU/L (IQR: 90–203), p=0.036 at week 30 (Figure 2). No significant changes in other Liver biochemistries or the Mayo PSC Risk Score were demonstrated at week 30. 55% of Crohn's disease and 21% of ulcerative colitis patients achieved clinical remission at week 30. Seven patients (21%) ceased vedolizumab therapy; one for a deterioration in Liver Biochemistry thought to be a drug reaction and six for IBD primary non-response. Two patients developed ascending cholangitis but continued vedolizumab. Conclusions: Vedolizumab therapy in patients with IBD-PSC has little overall effect on Liver Biochemistry, but is safe and does improve IBD clinical activity. Treatment earlier in the disease course of PSC and assessment of longer-term exposure of lymphocyte trafficking blockade in IBD-PSC remains of interest.