113 results on '"Pratt DS"'
Search Results
2. A novel histological lesion in glucocorticoid-responsive chronic hepatitis
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Pratt, DS, primary, Fawaz, KA, additional, Rabson, A, additional, Dellelis, R, additional, and Kaplan, MM, additional
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- 1997
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3. The successful treatment of autoimmune hepatitis with 6-mercaptopurine after failure with azathioprine
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Pratt, DS, primary, Flavin, DP, additional, and Kaplan, MM, additional
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- 1996
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4. Autoimmune hepatitis: current challenges in diagnosis and management in a chronic progressive liver disease.
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Schaefer EA and Pratt DS
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- 2012
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5. Editorial comment. Liver disorders.
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Pratt DS
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- 2008
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6. Cholangiocarcinoma: natural history, treatment, and strategies for surveillance in high-risk patients.
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Yachimski P, Pratt DS, Yachimski, Patrick, and Pratt, Daniel S
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- 2008
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7. Cholestasis and cholestatic syndrome.
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O'Leary JG and Pratt DS
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- 2007
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8. Primary care: evaluation of abnormal liver-enzyme results in asymptomatic patients.
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Pratt DS and Kaplan MM
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- 2000
9. Hepatitis B: significant advances and unmet challenges.
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Pratt DS and Pratt, Daniel S
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- 2009
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10. Case records of the Massachusetts General Hospital. Case 22-2012. A 34-year-old man with intractable vomiting after ingestion of an unknown substance.
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Macías Konstantopoulos W, Burns Ewald M, Pratt DS, Macías Konstantopoulos, Wendy, Burns Ewald, Michele, and Pratt, Daniel S
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- 2012
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11. Cultured Bacteria Isolated from Primary Sclerosing Cholangitis Patient Bile Induce Inflammation and Cell Death.
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Powell CE, McCurry MD, Quevedo SF, Ventura L, Krishnan K, Dave M, Mahmood SD, Specht K, Bordia R, Pratt DS, Korzenik JR, and Devlin AS
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Background: Primary sclerosing cholangitis (PSC) is a chronic liver disease characterized by inflammation and progressive fibrosis of the biliary tree. The pathogenesis of PSC remains poorly understood, and there are no effective therapeutic options. Previous studies have observed associations between changes in the colonic and biliary microbiome and PSC. We aimed to determine whether bacterial isolates cultured from PSC patient bile induced disease-associated phenotypes in cells., Methods: Bile was collected from PSC patients (n=10) by endoscopic retrograde cholangiography and from non-PSC controls (n=3) undergoing cholecystectomies. Biliary bacteria were cultured anaerobically, and 50 colonies per sample were identified by 16S rRNA sequencing. The effects of supernatants from seven PSC-associated bacterial strains on cellular phenotypes were characterized using human colonic (Caco-2), hepatic (HepG2), and biliary (EGI-1) cells., Results: No bacteria were isolated from non-PSC controls, while bacteria were cultured from most PSC patients. The PSC bile microbiomes exhibited reduced diversity compared to the gut or oral cavity, with one or two bacterial strains predominating. Overall, PSC-associated bacteria produced factors that were cytotoxic to hepatic and biliary cells. Enterococcus faecalis , and to a lesser extent Veillonella parvula , induced epithelial permeability, while Escherichia coli, Fusobacterium necrophorum , and Klebsiella pneumoniae induced inflammatory cytokines in biliary cells., Conclusions: Our data suggest that bacteria cultured from PSC bile induce cellular changes that may contribute to PSC disease pathogenesis. Enterococcus may promote intestinal permeability, facilitating bacterial migration to the biliary tree. Once there, Escherichia, Fusobacterium and Klebsiella , may cause inflammation and damage in biliary and liver cells.
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- 2024
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12. Prognostic scores for ursodeoxycholic acid-treated patients predict graft loss and mortality in recurrent primary biliary cholangitis after liver transplantation.
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Montano-Loza AJ, Lytvyak E, Hirschfield G, Hansen BE, Ebadi M, Berney T, Toso C, Magini G, Villamil A, Nevens F, Van den Ende N, Pares A, Ruiz P, Terrabuio D, Trivedi PJ, Abbas N, Donato MF, Yu L, Landis C, Dumortier J, Dyson JK, van der Meer AJ, de Veer R, Pedersen M, Mayo M, Manns MP, Taubert R, Kirchner T, Belli LS, Mazzarelli C, Stirnimann G, Floreani A, Cazzagon N, Russo FP, Burra P, Zigmound U, Houri I, Carbone M, Mulinacci G, Fagiuoli S, Pratt DS, Bonder A, Schiano TD, Haydel B, Lohse A, Schramm C, Rüther D, Casu S, Verhelst X, Beretta-Piccoli BT, Robles M, Mason AL, and Corpechot C
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- Humans, Female, Male, Middle Aged, Prognosis, Graft Survival drug effects, Alkaline Phosphatase blood, Cholangitis diagnosis, Cholangitis etiology, Cholangitis drug therapy, Retrospective Studies, Follow-Up Studies, Liver Transplantation adverse effects, Ursodeoxycholic Acid therapeutic use, Recurrence, Cholagogues and Choleretics therapeutic use, Liver Cirrhosis, Biliary surgery, Liver Cirrhosis, Biliary mortality, Liver Cirrhosis, Biliary diagnosis
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Background & Aims: Recurrent primary biliary cholangitis (rPBC) develops in approximately 30% of patients and negatively impacts graft and overall patient survival after liver transplantation (LT). There is a lack of data regarding the response rate to ursodeoxycholic acid (UDCA) in rPBC. We evaluated a large, international, multi-center cohort to assess the performance of PBC scores in predicting the risk of graft and overall survival after LT in patients with rPBC., Methods: A total of 332 patients with rPBC after LT were evaluated from 28 centers across Europe, North and South America. The median age at the time of rPBC was 58.0 years [IQR 53.2-62.6], and 298 patients (90%) were female. The biochemical response was measured with serum levels of alkaline phosphatase (ALP) and bilirubin, and Paris-2, GLOBE and UK-PBC scores at 1 year after UDCA initiation., Results: During a median follow-up of 8.7 years [IQR 4.3-12.9] after rPBC diagnosis, 52 patients (16%) had graft loss and 103 (31%) died. After 1 year of UDCA initiation the histological stage at rPBC (hazard ratio [HR] 3.97, 95% CI 1.36-11.55, p = 0.01), use of prednisone (HR 3.18, 95% CI 1.04-9.73, p = 0.04), ALP xULN (HR 1.59, 95% CI 1.26-2.01, p <0.001), Paris-2 criteria (HR 4.14, 95% CI 1.57-10.92, p = 0.004), GLOBE score (HR 2.82, 95% CI 1.71-4.66, p <0.001), and the UK-PBC score (HR 1.06, 95% CI 1.03-1.09, p <0.001) were associated with graft survival in the multivariate analysis. Similar results were observed for overall survival., Conclusion: Patients with rPBC and disease activity, as indicated by standard PBC risk scores, have impaired outcomes, supporting efforts to treat recurrent disease in similar ways to pre-transplant PBC., Impact and Implications: One in three people who undergo liver transplantation for primary biliary cholangitis develop recurrent disease in their new liver. Patients with recurrent primary biliary cholangitis and incomplete response to ursodeoxycholic acid, according to conventional prognostic scores, have worse clinical outcomes, with higher risk of graft loss and mortality in similar ways to the disease before liver transplantation. Our results supportsupport efforts to treat recurrent disease in similar ways to pre-transplant primary biliary cholangitis., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2024
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13. Intracardiac Echocardiography Guidance for Percutaneous Closure of Surgical Portocaval Shunt after Liver Transplant.
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Leon D, Tanaka M, Thabet A, Bozorgzadeh A, Pratt DS, Kalva SP, and Wu V
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- Humans, Echocardiography, Pericardium, Cardiac Catheterization, Treatment Outcome, Echocardiography, Transesophageal, Liver Transplantation
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- 2024
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14. Single-cell transcriptomics stratifies organoid models of metabolic dysfunction-associated steatotic liver disease.
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Hess A, Gentile SD, Ben Saad A, Rahman RU, Habboub T, Pratt DS, and Mullen AC
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- Humans, Transforming Growth Factor beta1 genetics, Transforming Growth Factor beta1 metabolism, Gene Expression Profiling, Disease Progression, Liver Cirrhosis genetics, Liver Cirrhosis metabolism, Fatty Liver genetics
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Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing cause of morbidity with limited treatment options. Thus, accurate in vitro systems to test new therapies are indispensable. While recently, human liver organoid models have emerged to assess steatotic liver disease, a systematic evaluation of their translational potential is still missing. Here, we evaluated human liver organoid models of MASLD, comparatively testing disease induction in three conditions: oleic acid, palmitic acid, and TGF-β1. Through single-cell analyses, we find that all three models induce inflammatory signatures, but only TGF-β1 promotes collagen production, fibrosis, and hepatic stellate cell expansion. In striking contrast, oleic acid ameliorates fibrotic signatures and reduces the hepatic stellate cell population. Linking data from each model to gene expression signatures associated with MASLD disease progression further demonstrates that palmitic acid and TGF-β1 more robustly model inflammation and fibrosis. Our findings highlight the importance of stratifying MASLD organoid models by signatures of clinical disease progression, provide a single-cell reference to benchmark future organoid injury models, and allow us to study evolving steatohepatitis, fibrosis, and HSC susceptibility to injury in a dynamic, multi-lineage human in vitro system., (© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)
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- 2023
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15. Beyond genome-wide association studies: Investigating the role of noncoding regulatory elements in primary sclerosing cholangitis.
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Pratt HE, Wu T, Elhajjajy S, Zhou J, Fitzgerald K, Fazzio T, Weng Z, and Pratt DS
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- Humans, Chromatin Immunoprecipitation Sequencing, Genotype, Genome-Wide Association Study, Cholangitis, Sclerosing genetics
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Background: Genome-wide association studies (GWAS) have identified 30 risk loci for primary sclerosing cholangitis (PSC). Variants within these loci are found predominantly in noncoding regions of DNA making their mechanisms of conferring risk hard to define. Epigenomic studies have shown noncoding variants broadly impact regulatory element activity. The possible association of noncoding PSC variants with regulatory element activity has not been studied. We aimed to (1) determine if the noncoding risk variants in PSC impact regulatory element function and (2) if so, assess the role these regulatory elements have in explaining the genetic risk for PSC., Methods: Available epigenomic datasets were integrated to build a comprehensive atlas of cell type-specific regulatory elements, emphasizing PSC-relevant cell types. RNA-seq and ATAC-seq were performed on peripheral CD4+ T cells from 10 PSC patients and 11 healthy controls. Computational techniques were used to (1) study the enrichment of PSC-risk variants within regulatory elements, (2) correlate risk genotype with differences in regulatory element activity, and (3) identify regulatory elements differentially active and genes differentially expressed between PSC patients and controls., Results: Noncoding PSC-risk variants are strongly enriched within immune-specific enhancers, particularly ones involved in T-cell response to antigenic stimulation. In total, 250 genes and >10,000 regulatory elements were identified that are differentially active between patients and controls., Conclusions: Mechanistic effects are proposed for variants at 6 PSC-risk loci where genotype was linked with differential T-cell regulatory element activity. Regulatory elements are shown to play a key role in PSC pathophysiology., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)
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- 2023
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16. Seladelpar efficacy and safety at 3 months in patients with primary biliary cholangitis: ENHANCE, a phase 3, randomized, placebo-controlled study.
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Hirschfield GM, Shiffman ML, Gulamhusein A, Kowdley KV, Vierling JM, Levy C, Kremer AE, Zigmond E, Andreone P, Gordon SC, Bowlus CL, Lawitz EJ, Aspinall RJ, Pratt DS, Raikhelson K, Gonzalez-Huezo MS, Heneghan MA, Jeong SH, Ladrón de Guevara AL, Mayo MJ, Dalekos GN, Drenth JPH, Janczewska E, Leggett BA, Nevens F, Vargas V, Zuckerman E, Corpechot C, Fassio E, Hinrichsen H, Invernizzi P, Trivedi PJ, Forman L, Jones DEJ, Ryder SD, Swain MG, Steinberg A, Boudes PF, Choi YJ, and McWherter CA
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- Humans, Ursodeoxycholic Acid adverse effects, Acetates, Alkaline Phosphatase, Pruritus etiology, Pruritus chemically induced, Cholagogues and Choleretics adverse effects, Liver Cirrhosis, Biliary drug therapy, Liver Cirrhosis, Biliary complications
- Abstract
Background and Aims: ENHANCE was a phase 3 study that evaluated efficacy and safety of seladelpar, a selective peroxisome proliferator-activated receptor-δ (PPAR) agonist, versus placebo in patients with primary biliary cholangitis with inadequate response or intolerance to ursodeoxycholic acid (UDCA)., Approach and Results: Patients were randomized 1:1:1 to oral seladelpar 5 mg (n=89), 10 mg (n=89), placebo (n=87) daily (with UDCA, as appropriate). Primary end point was a composite biochemical response [alkaline phosphatase (ALP) < 1.67×upper limit of normal (ULN), ≥15% ALP decrease from baseline, and total bilirubin ≤ ULN] at month 12. Key secondary end points were ALP normalization at month 12 and change in pruritus numerical rating scale (NRS) at month 6 in patients with baseline score ≥4. Aminotransferases were assessed. ENHANCE was terminated early following an erroneous safety signal in a concurrent, NASH trial. While blinded, primary and secondary efficacy end points were amended to month 3. Significantly more patients receiving seladelpar met the primary end point (seladelpar 5 mg: 57.1%, 10 mg: 78.2%) versus placebo (12.5%) ( p < 0.0001). ALP normalization occurred in 5.4% ( p =0.08) and 27.3% ( p < 0.0001) of patients receiving 5 and 10 mg seladelpar, respectively, versus 0% receiving placebo. Seladelpar 10 mg significantly reduced mean pruritus NRS versus placebo [10 mg: -3.14 ( p =0.02); placebo: -1.55]. Alanine aminotransferase decreased significantly with seladelpar versus placebo [5 mg: 23.4% ( p =0.0008); 10 mg: 16.7% ( p =0.03); placebo: 4%]. There were no serious treatment-related adverse events., Conclusions: Patients with primary biliary cholangitis (PBC) with inadequate response or intolerance to UDCA who were treated with seladelpar 10 mg had significant improvements in liver biochemistry and pruritus. Seladelpar appeared safe and well tolerated., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)
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- 2023
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17. In a tight spot.
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Przybyszewski EM and Pratt DS
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Competing Interests: The authors have no conflicts to report.
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- 2023
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18. Implications of extended terminal sedation.
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Sorum PC and Pratt DS
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- Humans, Palliative Care, Hypnotics and Sedatives, Conscious Sedation, Terminal Care, Euthanasia, Deep Sedation
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Competing Interests: Competing interests: None declared.
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- 2023
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19. Application of the Latest Advances in Evidence-Based Medicine in Primary Biliary Cholangitis.
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Kowdley KV, Bowlus CL, Levy C, Mayo MJ, Pratt DS, Vuppalanchi R, and Younossi ZM
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- Humans, Ursodeoxycholic Acid therapeutic use, Evidence-Based Medicine, Liver Cirrhosis, Biliary diagnosis, Liver Cirrhosis, Biliary drug therapy, Cholangitis diagnosis, Cholangitis drug therapy, Cholestasis complications
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Primary biliary cholangitis (PBC) is a chronic, cholestatic, autoimmune liver disease that can progress to end-stage liver disease and its complications. A previous expert review panel collaborated on a consensus document for gastroenterologists and other healthcare professionals regarding the care of patients with PBC. Subsequently, there have been several recent important developments in the diagnosis, treatment, and monitoring of patients with PBC. These include updates to prognostic models on risk stratification, new noninvasive tools for staging of disease, updates to the appropriate use of and long-term treatment results with obeticholic acid as a second-line treatment, the emerging therapeutic role of fibrates, and the advancement of investigational agents for managing PBC. In this updated expert consensus document, we provide updates on staging, the use of noninvasive prognostic tools, and a treatment algorithm to provide evidence-based and practical tools for clinicians who manage PBC, with the ultimate goal to improve the long-term outcomes for patients with this chronic liver disease., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)
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- 2023
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20. Next-generation sequencing in the evaluation of biliary strictures in patients with primary sclerosing cholangitis.
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Scheid JF, Rosenbaum MW, Przybyszewski EM, Krishnan K, Forcione DG, Iafrate AJ, Staller KD, Misdraji J, Lennerz JK, Pitman MB, and Pratt DS
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- Bile Ducts, Intrahepatic pathology, Constriction, Pathologic diagnosis, Constriction, Pathologic genetics, High-Throughput Nucleotide Sequencing, Humans, In Situ Hybridization, Fluorescence, Prospective Studies, Bile Duct Neoplasms complications, Bile Duct Neoplasms diagnosis, Bile Duct Neoplasms genetics, Cholangiocarcinoma complications, Cholangiocarcinoma diagnosis, Cholangiocarcinoma genetics, Cholangitis, Sclerosing complications, Cholangitis, Sclerosing diagnosis, Cholangitis, Sclerosing genetics
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Background: Primary sclerosing cholangitis (PSC) is a well-described risk factor for the development of cholangiocarcinoma (CCA). Early detection of CCA in these patients is of great importance because it expands options for therapeutic interventions, including liver transplantation. Current diagnostic tests for the evaluation of biliary strictures are limited to biliary brushing (BB) cytology and fluorescence in situ hybridization (FISH). Next-generation sequencing (NGS) has become an important diagnostic tool in oncology and may be a useful tool for diagnosing CCA on BBs. It is not clear how NGS performs when it is added to BB cytology and FISH in patients with PSC., Methods: This study reports the authors' experience with NGS performed as a prospective cotest with cytology and FISH on BBs obtained from 60 patients with PSC followed at Massachusetts General Hospital. A duct with malignancy was defined as a high-risk (HR) stricture with either high-grade dysplasia or CCA., Results: NGS was better than FISH and cytology in detecting HR strictures, which showed multiple genetic mutations in all cases. NGS provided specific mutational information, and NGS results were reproducible in longitudinal samples., Conclusions: Adding NGS to BB cytology and FISH in the evaluation of biliary strictures for patients with PSC may provide additional information that could help to inform clinical management., (© 2021 American Cancer Society.)
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- 2022
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21. Hepatic vascular remodelling in a patient with dyskeratosis congenita.
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Boyraz B, Agarwal S, Pratt DS, Simoneau T, Bhan I, Markmann JF, and Misdraji J
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- Female, Hepatopulmonary Syndrome pathology, Humans, Liver pathology, Liver Transplantation, Young Adult, Dyskeratosis Congenita pathology, Hepatopulmonary Syndrome surgery, Liver blood supply, Vascular Remodeling physiology
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- 2022
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22. Hepatology Consultants Often Disagree on Etiology of Abnormal Liver Biochemistries in COVID-19 but Agree on Management.
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Bloom PP, Pasricha TS, Andersson KL, Pratt DS, Hashemi N, Bhan I, and Viveiros K
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- Adult, Attitude of Health Personnel, Biomarkers blood, COVID-19 blood, COVID-19 complications, COVID-19 therapy, Consensus, Female, Health Knowledge, Attitudes, Practice, Humans, Liver Diseases blood, Liver Diseases etiology, Liver Diseases therapy, Male, Middle Aged, Observer Variation, Predictive Value of Tests, Prognosis, Risk Factors, COVID-19 diagnosis, Gastroenterologists, Liver metabolism, Liver Diseases diagnosis, Liver Function Tests, Referral and Consultation
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Background: Coronavirus disease 2019 (COVID-19) is associated with elevated liver biochemistries in approximately half of hospitalized patients, with many possible etiologies., Aim: To assess agreement on the etiology of abnormal liver biochemistries and diagnostic recommendations in COVID-19., Methods: Twenty hepatology consultations were reviewed by three senior hepatologists who provided a differential diagnosis and diagnostic recommendations. Kappa agreement on the primary etiology was calculated., Results: Kappa agreement between hepatologists on the primary etiology of elevated liver biochemistries was 0.10 (p = 0.03). Agreement was greater around drug-induced liver injury 0.51 (p < 0.0001) and SARS-CoV-2-related liver injury 0.17 (p = 0.03). Serial liver biochemistries were recommended in all consultations over other evaluations., Conclusion: In COVID-19, elevated liver biochemistries present a diagnostic challenge and can often be monitored conservatively.
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- 2021
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23. Clinical Best Practice Advice for Hepatology and Liver Transplant Providers During the COVID-19 Pandemic: AASLD Expert Panel Consensus Statement.
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Fix OK, Hameed B, Fontana RJ, Kwok RM, McGuire BM, Mulligan DC, Pratt DS, Russo MW, Schilsky ML, Verna EC, Loomba R, Cohen DE, Bezerra JA, Reddy KR, and Chung RT
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- COVID-19, Comorbidity, Coronavirus Infections drug therapy, Coronavirus Infections transmission, Drug Interactions, Gastroenterology education, Humans, Immunosuppression Therapy, Internship and Residency, Liver Diseases epidemiology, Occupational Health, Pandemics, Patient Safety, Pneumonia, Viral drug therapy, Pneumonia, Viral transmission, SARS-CoV-2, Tissue Donors, COVID-19 Drug Treatment, Betacoronavirus, Consensus, Coronavirus Infections epidemiology, Liver Diseases therapy, Liver Transplantation ethics, Liver Transplantation methods, Pneumonia, Viral epidemiology, Practice Guidelines as Topic
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Background and Aims: Coronavirus disease 2019 (COVID-19), the illness caused by the SARS-CoV-2 virus, is rapidly spreading throughout the world. Hospitals and healthcare providers are preparing for the anticipated surge in critically ill patients, but few are wholly equipped to manage this new disease. The goals of this document are to provide data on what is currently known about COVID-19, and how it may impact hepatologists and liver transplant providers and their patients. Our aim is to provide a template for the development of clinical recommendations and policies to mitigate the impact of the COVID-19 pandemic on liver patients and healthcare providers., Approach and Results: This article discusses what is known about COVID-19 with a focus on its impact on hepatologists, liver transplant providers, patients with liver disease, and liver transplant recipients. We provide clinicians with guidance for how to minimize the impact of the COVID-19 pandemic on their patients' care., Conclusions: The situation is evolving rapidly, and these recommendations will need to evolve as well. As we learn more about how the COVID-19 pandemic impacts the care of patients with liver disease, we will update the online document available at https://www.aasld.org/about-aasld/covid-19-and-liver., (© 2020 by the American Association for the Study of Liver Diseases.)
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- 2020
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24. Myelofibrosis and Portal Hypertension: The Case for Primary Variceal Screening.
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Sherman MS, Samore WR, and Pratt DS
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Myelofibrosis is a hematologic condition that predisposes to the formation of large and small portal venous clots. Portal injury is believed to underlie the mechanism of development of noncirrhotic portal hypertension in this population. We describe a patient with myelofibrosis, proven portal hypertension, and extramedullary hematopoiesis with no imaging or pathologic evidence of microvascular or macrovascular portal clot. We provide a concise review of the literature which highlights that patients with myelofibrosis and related conditions of polycythemia vera and essential thrombocytosis present not infrequently with portal hypertension and variceal bleeding. We propose this population may benefit from primary variceal screening., (© 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)
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- 2020
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25. Fecal Microbiota Transplantation in Patients With Primary Sclerosing Cholangitis: A Pilot Clinical Trial.
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Allegretti JR, Kassam Z, Carrellas M, Mullish BH, Marchesi JR, Pechlivanis A, Smith M, Gerardin Y, Timberlake S, Pratt DS, and Korzenik JR
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- Adult, Boston, Cholangitis, Sclerosing diagnosis, Cholangitis, Sclerosing immunology, Colonoscopy methods, Fecal Microbiota Transplantation adverse effects, Female, Humans, Male, Middle Aged, Multivariate Analysis, Pilot Projects, Prognosis, Regression Analysis, Risk Assessment, Severity of Illness Index, Treatment Outcome, Young Adult, Cholangitis, Sclerosing therapy, Fecal Microbiota Transplantation methods, Gastrointestinal Microbiome immunology, Patient Safety
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Background: Primary sclerosing cholangitis (PSC) is a cholestatic liver disease with no effective medical therapies. A perturbation of the gut microbiota has been described in association with PSC, and fecal microbiota transplantation (FMT) has been reported to restore the microbiome in other disease states. Accordingly, we aimed at evaluating the safety, change in liver enzymes, microbiota, and metabolomic profiles in patients with PSC after FMT., Methods: An open-label pilot study of patients with PSC with concurrent inflammatory bowel disease and alkaline phosphatase (ALP) > 1.5× the upper limit of normal was conducted. The patients underwent a single FMT by colonoscopy. Liver enzyme profiles and stool microbiome and metabolomic analysis were conducted at baseline and weeks 1, 4, 8, 12, and 24 post-FMT. The primary outcome was safety, and the secondary outcome was a decrease in ALP levels ≥50% from baseline by week 24 post-FMT; stool microbiota (by 16S rRNA gene profiling) and metabonomic dynamics were assessed., Results: Ten patients underwent FMT. Nine patients had ulcerative colitis, and 1 had Crohn's colitis. The mean baseline ALP level was 489 U/L. There were no related adverse events. Overall, 30% (3/10) experienced a ≥50% decrease in ALP levels. The diversity increased in all patients post-FMT, as early as week 1 (P < 0.01). Importantly, abundance of engrafter operational taxonomic units in patients post-FMT correlated with decreased ALP levels (P = 0.02)., Discussion: To our knowledge, this is the first study to demonstrate that FMT in PSC is safe. In addition, increases in bacterial diversity and engraftment may correlate with an improvement in ALP among patients with PSC.
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- 2019
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26. The Role of Bezafibrate, a Peroxisome Proliferator-Activated Receptor Alpha Agonist, in Patients With Primary Biliary Cholangitis.
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Pratt DS
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- Humans, PPAR alpha, Bezafibrate, Liver Cirrhosis, Biliary
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- 2019
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27. Evaluation of model performance to predict survival after transjugular intrahepatic portosystemic shunt placement.
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Allegretti AS, Frenk NE, Li DK, Seethapathy H, Vela Parada XF, Long J, Endres P, Pratt DS, Chung RT, Ganguli S, Irani Z, and Yamada K
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- Adult, Age Factors, Aged, Female, Hemoglobins analysis, Hemorrhage mortality, Humans, Male, Middle Aged, Models, Statistical, Patient Acuity, Prognosis, Sodium blood, Portasystemic Shunt, Transjugular Intrahepatic mortality
- Abstract
Background/aims: The MELD score was developed to predict survival after transjugular intrahepatic portosystemic shunt (TIPS) placement. Given changes in practice patterns and development of new prognostic tools in cirrhosis, we aimed to evaluate common models to predict mortality after TIPS placement., Methods: Analysis of consecutive patients who underwent TIPS placement for ascites or bleeding. Performance to predict 90-day mortality was assessed by C statistic for six models (MELD, MELD-Na, CLIF-C ACLF, Child-Pugh, Platelet-Albumin-Bilirubin, and Emory score). Added predictive value to MELD score was assessed for univariate predictors of 90-day mortality. Stratified analysis by TIPS indication, emergent placement status, and TIPS stent type was performed., Results: 413 patients were analyzed (248 with variceal bleeding, 165 with refractory ascites). 90-day mortality was 27% (113/413). Mean MELD score was 15 ± 7.9. MELD score best predicted mortality for all patients (c = 0.779), for variceal bleeding (c = 0.844), and for emergent TIPS (c = 0.817). CLIF-C ACLF score best predicted mortality for refractory ascites (c = 0.707). Addition of sodium to the MELD score did not improve predictive value across multiple strata. Addition of hemoglobin improved MELD score's predictive value in variceal bleeding. Addition of age improved MELD score's predictive value in refractory ascites., Conclusions: MELD score best predicted 90-day mortality. Addition of sodium to the MELD score did not improve its performance, though mortality prediction was improved using Age-MELD for ascites and Hemoglobin-MELD for bleeding. An individualized risk stratification approach may be best when considering candidates for TIPS placement., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2019
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28. Diagnostic Performance of Shear Wave Elastography in Patients With Autoimmune Liver Disease.
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Li C, Dhyani M, Bhan AK, Grajo JR, Pratt DS, Gee MS, and Samir AE
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- Autoimmune Diseases complications, Autoimmune Diseases pathology, Female, Humans, Liver diagnostic imaging, Liver pathology, Liver Cirrhosis diagnostic imaging, Liver Cirrhosis pathology, Liver Diseases complications, Liver Diseases pathology, Male, Middle Aged, Pilot Projects, Reproducibility of Results, Sensitivity and Specificity, Severity of Illness Index, Autoimmune Diseases diagnostic imaging, Elasticity Imaging Techniques methods, Liver Diseases diagnostic imaging
- Abstract
Objectives: To assess performance of shear wave elastography for evaluation of fibrosis and the histologic stage in patients with autoimmune liver disease (ALD) and to validate previously established advanced fibrosis cutoff values in this cohort., Methods: Shear wave elastography was performed on patients with ALD with an Aixplorer ultrasound system (SuperSonic Imagine, Aix-en-Provence, France) using an SC6-1 transducer. The median estimated tissue Young modulus was calculated from sets of 8 to 10 elastograms. A blinded, subspecialty-trained pathologist reviewed biopsy specimens. The METAVIR classification was used to stage liver fibrosis and necroinflammation. Steatosis was graded from 0 to 4+. The Kendall τ-b correlation test was performed to identify the correlation between the estimated tissue Young modulus and fibrosis, steatosis, and the necroinflammatory score. The Spearman correlation test was performed to identify the correlation between the estimated tissue Young modulus and clinical data. The diagnostic performance of shear wave elastography for differentiating METAVIR stage F2 or higher from F0 and F1 fibrosis was evaluated by a receiver operating characteristic (ROC) curve analysis., Results: Fifty-one patients with ALD were analyzed. The estimated tissue Young modulus was positively correlated with the fibrosis stage and necroinflammation score (r = 0.386; P < .001; r = 0.338; P = .002, respectively) but not steatosis (r = -0.091; P = .527). Serum aspartate aminotransferase, alanine aminotransferase, and total bilirubin values were positively correlated with the estimated tissue Young modulus (r = 0.501; P < .001; r = 0.44; P = .001; r = 0.291; P = .038). The serum albumin value was negatively correlated (r = -0.309; P = .033). The area under the ROC curve was 0.781 (95% confidence interval, 0.641-0.921) for distinguishing F2 or greater fibrosis from F0 and F1 fibrosis. Based on the ROC curve, an optimal cutoff value of 9.15 kPa was identified (sensitivity, 83.3%; specificity, 72.7%)., Conclusions: Shear wave elastography is a novel noninvasive adjunct to liver biopsy in evaluation and staging of patients with ALD, showing the potential for serial evaluations of disease progression and treatment responses., (© 2018 by the American Institute of Ultrasound in Medicine.)
- Published
- 2019
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29. Long-term clinical impact and cost-effectiveness of obeticholic acid for the treatment of primary biliary cholangitis.
- Author
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Samur S, Klebanoff M, Banken R, Pratt DS, Chapman R, Ollendorf DA, Loos AM, Corey K, Hur C, and Chhatwal J
- Subjects
- Adult, Biopsy, Needle, Chenodeoxycholic Acid adverse effects, Chenodeoxycholic Acid economics, Chenodeoxycholic Acid therapeutic use, Cholangitis pathology, Cohort Studies, Disease Progression, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Follow-Up Studies, Humans, Immunohistochemistry, Male, Middle Aged, Prospective Studies, Quality-Adjusted Life Years, Risk Assessment, Severity of Illness Index, Time, Treatment Outcome, Chenodeoxycholic Acid analogs & derivatives, Cholangitis drug therapy, Cholangitis economics, Cost-Benefit Analysis
- Abstract
Primary biliary cholangitis (PBC) is a chronic, progressive autoimmune liver disease that mainly affects middle-aged women. Obeticholic acid (OCA), which was recently approved by the Food and Drug Administration for PBC treatment, has demonstrated positive effects on biochemical markers of liver function. Our objective was to evaluate the long-term clinical impact and cost-effectiveness of OCA as a second-line treatment for PBC in combination with ursodeoxycholic acid (UDCA) in adults with an inadequate response to UDCA. We developed a mathematical model to simulate the lifetime course of PBC patients treated with OCA+UDCA versus UDCA alone. Efficacy data were derived from the phase 3 PBC OCA International Study of Efficacy trial, and the natural history of PBC was informed by published clinical studies. Model outcomes were validated using the PBC Global Study. We found that in comparison with UDCA, OCA+UDCA could decrease the 15-year cumulative incidences of decompensated cirrhosis from 12.2% to 4.5%, hepatocellular carcinoma from 9.1% to 4.0%, liver transplants from 4.5% to 1.2%, and liver-related deaths from 16.2% to 5.7% and increase 15-year transplant-free survival from 61.1% to 72.9%. The lifetime cost of PBC treatment would increase from $63,000 to $902,000 (1,330% increment). The discounted quality-adjusted life years with UDCA and OCA+UDCA were 10.74 and 11.78, respectively, and the corresponding costs were $142,300 and $633,900, resulting in an incremental cost-effectiveness ratio of $473,400/quality-adjusted life year gained. The results were most sensitive to the cost of OCA., Conclusion: OCA is a promising new therapy to substantially improve the long-term outcomes of PBC patients, but at its current annual price of $69,350, it is not cost-effective using a willingness-to-pay threshold of $100,000/quality-adjusted life year; pricing below $18,450/year is needed to make OCA cost-effective. (Hepatology 2017;65:920-928)., (© 2016 by the American Association for the Study of Liver Diseases.)
- Published
- 2017
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30. First-Year Analysis of a New, Home-Based Palliative Care Program Offered Jointly by a Community Hospital and Local Visiting Nurse Service.
- Author
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Pouliot K, Weisse CS, Pratt DS, and DiSorbo P
- Subjects
- Aged, Aged, 80 and over, Home Care Services organization & administration, Home Care Services standards, Humans, Interinstitutional Relations, Male, Middle Aged, Models, Organizational, New York, Palliative Care organization & administration, Palliative Care standards, Patient Satisfaction, Program Evaluation, Prospective Studies, Quality of Life, Hospitals, Community organization & administration, Nurses, Community Health organization & administration, Nurses, Community Health standards
- Abstract
Background: There is a growing need for home-based palliative care services, especially for seriously ill individuals who want to avoid hospitalizations and remain with their regular outside care providers., Aim: To evaluate the effectiveness of Care Choices, a new in-home palliative care program provided by the Visiting Nurse Services of Northeastern New York and Ellis Medicine's community hospital serving New York's Capital District., Methods: This prospective cohort study assessed patient outcomes over the course of 1 year for 123 patients (49 men and 74 women) with serious illnesses who were new enrollees in the program. Quality of life was assessed at baseline and after 1 month on service. Satisfaction with care was measured after 1 and 3 months on service. The number of emergency department visits and inpatient hospitalizations pre- and postenrollment was measured for all enrollees., Results: Patients were highly satisfied (72.7%-100%) with their initial care and reported greater satisfaction ( P < .05) and stable symptom management over time. Fewer emergency department ( P < .001) and inpatient hospital admissions ( P < .001) occurred among enrollees while on the palliative care service., Conclusion: An in-home palliative care program offered jointly through a visiting nurse service and community hospital may be a successful model for providing quality care that satisfies chronically ill patients' desire to remain at home and avoid hospital admissions.
- Published
- 2017
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31. Primary Biliary Cholangitis--A New Name and a New Treatment.
- Author
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Pratt DS
- Subjects
- Humans, Cholangitis
- Published
- 2016
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32. Ipilimumab-associated Hepatitis: Clinicopathologic Characterization in a Series of 11 Cases.
- Author
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Johncilla M, Misdraji J, Pratt DS, Agoston AT, Lauwers GY, Srivastava A, and Doyle LA
- Subjects
- Adult, Aged, Aged, 80 and over, Biomarkers blood, Biopsy, Chemical and Drug Induced Liver Injury blood, Chemical and Drug Induced Liver Injury drug therapy, Female, Humans, Immunohistochemistry, Immunosuppressive Agents therapeutic use, Ipilimumab, Liver enzymology, Liver Function Tests, Male, Middle Aged, Predictive Value of Tests, Remission Induction, Risk Factors, Time Factors, Treatment Outcome, Antibodies, Monoclonal adverse effects, Antineoplastic Agents adverse effects, Chemical and Drug Induced Liver Injury etiology, Chemical and Drug Induced Liver Injury pathology, Liver drug effects, Liver pathology
- Abstract
Ipilimumab is a monoclonal antibody that inhibits the CTLA4 receptor on cytotoxic T lymphocytes, resulting in immune-mediated tumor cell death. Ipilimumab is most often used in the treatment of metastatic melanoma, and rarely liver toxicity necessitating cessation of treatment occurs. The aim of this study was to characterize the histologic features and clinical course of ipilimumab-associated hepatitis. Eleven patients with clinical suspicion of ipilimumab-induced hepatitis, due to the development of abnormal liver function tests (LFTs) while receiving treatment, and who underwent liver biopsy, were identified over a 6-year period. Ten patients were male and 1 female (median age 58 y), and all received 1 to 4 doses of ipilimumab. None had known preexisting liver disease. Two patients were obese, and another had a history of alcohol abuse. Viral and autoimmune serologies were negative in all patients except 1 who had a mildly elevated ANA titer. Nine biopsies showed active hepatitis with 2 distinct histologic patterns: panlobular hepatitis in 6 cases and zone 3 hepatitis in 3. The inflammatory infiltrate was similar in composition in both patterns, composed predominantly of CD8+ T lymphocytes, admixed histiocytes, scattered plasma cells, and eosinophils. Prominent histiocytic sinusoidal infiltrates were present in 7 cases and frequently formed loose histiocytic aggregates. Central vein endothelialitis was present in 8 cases. Patients in this group tended to have markedly elevated ALT, AST, and total bilirubin. Two cases did not fit into the above 2 histologic groups: 1 showed portal inflammation with cholangitis, and the other showed morphologic features indistinguishable from nonalcoholic steatohepatitis. Discontinuation of ipilimumab and administration of immunosuppressives resulted in resolution or marked improvement of LFTs in all patients within 3 months of presentation. Ipilimumab may potentially unmask previously subclinical liver disease, for example, fatty liver disease, and the diagnosis of ipilimumab-induced liver injury may only be recognized with certainty after cessation of the drug leads to normalization of LFTs. Overall, ipilimumab-associated hepatitis most often presents with a panlobular active hepatitis that resembles autoimmune hepatitis. Prominent sinusoidal histiocytic infiltrates and central vein damage with endothelialitis may be helpful histologic clues to the diagnosis of ipilimumab-associated hepatitis.
- Published
- 2015
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33. Time to update radiological criteria for non-invasive diagnosis of hepatocellular carcinoma.
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Saini S and Pratt DS
- Subjects
- Female, Humans, Male, Carcinoma, Hepatocellular diagnosis, Liver Neoplasms diagnosis, Magnetic Resonance Imaging methods, Neoplasm Recurrence, Local diagnosis
- Published
- 2015
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34. Widespread morbilliform eruption associated with telaprevir: use of dermatologic consultation to increase tolerability.
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Strazzula L, Pratt DS, Zardas J, Chung RT, Thiim M, and Kroshinsky D
- Subjects
- Aged, Dermatology, Drug Eruptions classification, Drug Eruptions etiology, Female, Hepatitis C, Chronic drug therapy, Humans, Male, Middle Aged, Referral and Consultation, Antiviral Agents adverse effects, Drug Eruptions drug therapy, Oligopeptides adverse effects
- Abstract
Importance: Telaprevir, combined with pegylated interferon alfa and ribavirin, is an efficacious approach to treat hepatitis C virus infection. A morbilliform eruption associated with telaprevir is a common adverse effect experienced by patients. Current guidelines mandate telaprevir discontinuation in any patient with a severe, progressive, or unresponsive cutaneous eruption., Observations: Eight patients with a grade 3 (severe) widespread morbilliform eruption associated with telaprevir were referred to dermatology for evaluation and treatment. Each patient received a combination of antihistamines, topical corticosteroids, and thick emollient creams, rendering their eruption tolerable for the duration of treatment. No patients had evidence of a systemic or life-threatening drug reaction, developed a systemic drug eruption, or had to prematurely stop triple therapy secondary to a cutaneous eruption., Conclusions and Relevance: Patients with an uncomplicated grade 3 (severe) widespread morbilliform eruption associated with telaprevir may be able to continue triple therapy with close monitoring and dermatologic consultation. Given our findings, we propose an additional clinical classification of the telaprevir-associated eruption to better reflect the dermatologic classification of drug eruptions.
- Published
- 2014
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35. Seasonal influenza vaccination and technologies.
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Nafziger AN and Pratt DS
- Subjects
- Animals, Antigenic Variation, Antigens, Viral chemistry, Antigens, Viral genetics, Antigens, Viral metabolism, Health Priorities, Humans, Influenza A virus metabolism, Influenza Vaccines biosynthesis, Influenza, Human epidemiology, Influenza, Human immunology, Influenza, Human virology, Betainfluenzavirus metabolism, Pandemics prevention & control, Seasons, Vaccines, Synthetic chemistry, Vaccines, Synthetic metabolism, Vaccines, Synthetic therapeutic use, Influenza A virus immunology, Influenza Vaccines therapeutic use, Influenza, Human prevention & control, Betainfluenzavirus immunology, Mass Vaccination, Technology, Pharmaceutical trends
- Abstract
Seasonal influenza is a serious respiratory illness that causes annual worldwide epidemics resulting in significant morbidity and mortality. Influenza pandemics occur about every 40 yrs, and may carry a greater burden of illness and death than seasonal influenza. Both seasonal influenza and pandemic influenza have profound economic consequences. The combination of current vaccine efficacy and viral antigenic drifts and shifts necessitates annual vaccination. New manufacturing technologies in influenza vaccine development employ cell culture and recombinant techniques. Both allow more rapid vaccine creation and production. In the past 5 years, brisk, highly creative activity in influenza vaccine research and development has begun. New vaccine technologies and vaccination strategies are addressing the need for viable alternatives to egg production methods and improved efficacy. At present, stubborn problems of sub-optimal efficacy and the need for annual immunization persist. There is an obvious need for more efficacious vaccines and improved vaccination strategies to make immunization easier for providers and patients. Mitigating this serious annual health threat remains an important public health priority., (© 2014, The American College of Clinical Pharmacology.)
- Published
- 2014
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36. Immunoglobulin g4-associated cholangitis: the next great masquerader.
- Author
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Delemos AS and Pratt DS
- Published
- 2013
37. High prevalence of diabetes among Indo-Guyanese adults, Schenectady, New York.
- Author
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Hosler AS, Pratt DS, Sen KA, Buckenmeyer EM, Simao A Jr, Back EE, Savadatti S, Kahn JL, and Hunt GS
- Subjects
- Adult, Cross-Sectional Studies, Diabetes Complications ethnology, Diabetes Mellitus diagnosis, Diabetes Mellitus ethnology, Emigrants and Immigrants statistics & numerical data, Female, Guyana ethnology, Humans, India ethnology, Male, Middle Aged, Mortality ethnology, New York epidemiology, Prevalence, Diabetes Mellitus epidemiology, Health Status Indicators
- Abstract
Introduction: The Indo-Guyanese population is the largest immigrant minority population in Schenectady, New York. A clinic-based study in Schenectady and surveillance reports from Guyana found high diabetes prevalence and mortality among Guyanese of Indian descent. No community-based study has focused on diabetes among Indo-Guyanese immigrants in the United States. We sought information on the prevalence of diabetes and its complications in Indo-Guyanese adults in Schenectady and compared it with the prevalence among non-Hispanic white adults in Schenectady., Methods: We administered a cross-sectional health survey at community venues in Schenectady in 2011. We identified diagnosed diabetes and its complications through self-reports by using a reliability-tested questionnaire. The final data set included 313 Indo-Guyanese and 327 non-Hispanic white adults aged 18 years or older. We compared the prevalence of diagnosed diabetes and diabetes complications between Indo-Guyanese and non-Hispanic whites., Results: Most Indo-Guyanese participants were born in Guyana, whereas most non-Hispanic whites were born in the United States. The crude prevalence of diagnosed diabetes among Indo-Guyanese participants and non-Hispanic whites was 30.3% and 16.1%, respectively. The age-standardized prevalence was 28.7% among Indo-Guyanese participants, significantly higher than that among non-Hispanic whites (14.5%, P < .001). Indo-Guyanese participants who had diabetes had a lower body mass index and were more likely to report poor or fair general health and eye or vision complications than non-Hispanic whites who had diabetes., Conclusion: Our study confirms the higher prevalence of diabetes in Indo-Guyanese adults in Schenectady. The higher prevalence of complications suggests poor control of diabetes. Excess burden of diabetes in this population calls for further research and public health action.
- Published
- 2013
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38. Non-high-density lipoprotein cholesterol as a biomarker for nonalcoholic steatohepatitis.
- Author
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Corey KE, Lai M, Gelrud LG, Misdraji J, Barlow LL, Zheng H, Andersson KL, Thiim M, Pratt DS, and Chung RT
- Subjects
- Adult, Aged, Diagnosis, Differential, Female, Humans, Male, Middle Aged, Non-alcoholic Fatty Liver Disease, Prospective Studies, Biomarkers blood, Cholesterol, LDL blood, Clinical Laboratory Techniques methods, Fatty Liver diagnosis
- Abstract
Background & Aims: There are no clinically available biomarkers for nonalcoholic steatohepatitis (NASH); differentiating between steatosis and NASH requires histologic evaluation. Noninvasive methods are needed to replace liver biopsy and its associated risks. Production of very low density lipoprotein (VLDL) contributes to the development of NASH and might be used to distinguish steatosis from NASH. However, it is not possible to measure levels of VLDL directly in the clinic. Non-high-density lipoprotein-cholesterol (non-HDL-C) encompasses all apolipoprotein-B-containing lipoproteins, including VLDL, and can be calculated from standard lipid panels without additional cost., Methods: We evaluated the ability of non-HDL-C to differentiate steatosis from NASH in a prospective study of 218 patients with suspected NASH (steatosis, n = 100 and NASH, n = 118)., Results: Patients with NASH had a trend toward increased levels of non-HDL-C, compared with those with steatosis (P = .08). However, among subjects not on lipid-lowering medications, those with NASH had significantly higher levels of non-HDL-C (144.6 mg/dL) than those with steatosis (129.3 mg/dL; P = .025). This difference remained significant when adjusted for levels of cholesterol and triglycerides, indicating that the difference results from increased levels of apolipoprotein B including VLDL. These findings were validated in a cohort of 40 patients with steatosis or NASH who were not taking lipid-lowering agents. The NASH group had significantly higher levels of non-HDL-C than the steatosis group (162.8 vs 145.9 mg/dL; P = .04)., Conclusions: NASH is associated with significantly higher levels of non-HDL-C than steatosis in patients who do not take lipid-lowering agents. This low-cost biomarker could be used in noninvasive differentiation between steatosis and NASH., (Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.)
- Published
- 2012
- Full Text
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39. A histopathologic pattern of centrilobular hepatocyte injury suggests 6-mercaptopurine-induced hepatotoxicity in patients with inflammatory bowel disease.
- Author
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Masia R, Pratt DS, and Misdraji J
- Subjects
- Adult, Female, Humans, Immunosuppressive Agents therapeutic use, Liver pathology, Male, Mercaptopurine therapeutic use, Middle Aged, Retrospective Studies, Chemical and Drug Induced Liver Injury pathology, Immunosuppressive Agents adverse effects, Inflammatory Bowel Diseases drug therapy, Liver drug effects, Mercaptopurine adverse effects
- Abstract
Context: Hepatotoxicity is an important side effect of thiopurine analog treatment for inflammatory bowel disease. A variety of histopathologic findings have been observed in patients with inflammatory bowel disease with thiopurine-induced hepatotoxicity, including nodular regenerative hyperplasia, vascular injury, and cholestasis., Objective: To describe the histologic features shared by 3 cases of thiopurine-induced hepatotoxicity in patients with inflammatory bowel disease., Design: We identified 3 patients with inflammatory bowel disease who developed hepatotoxicity due to 6-mercaptopurine from the educational files of the Department of Pathology at Massachusetts General Hospital (Boston). Histology slides (stained with hematoxylin-eosin, trichrome, periodic-acid Schiff with diastase digestion, and iron stains) and patients' medical records were reviewed retrospectively., Results: All 3 patients were receiving 6-mercaptopurine monotherapy at therapeutic doses, had normal thiopurine metabolite levels, and presented with elevated aminotransferase levels. Biopsies from all 3 cases exhibited a pattern of centrilobular hepatocyte injury characterized by ceroid-laden macrophages, hepatocyte anisonucleosis, and increased lipofuscin pigment, as well as centrilobular steatosis. Aminotransferase levels trended downward and either normalized or remained at borderline elevated levels after 6-mercaptopurine dose was reduced (in 1 patient) or discontinued (in 2 patients)., Conclusions: Recognition of a pattern of centrilobular injury enables pathologists to suggest thiopurine-induced liver injury as the cause of elevated aminotransferases in patients with inflammatory bowel disease.
- Published
- 2012
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40. Enhanced innate immune responsiveness and intolerance to intestinal endotoxins in human biliary epithelial cells contributes to chronic cholangitis.
- Author
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Mueller T, Beutler C, Picó AH, Shibolet O, Pratt DS, Pascher A, Neuhaus P, Wiedenmann B, Berg T, and Podolsky DK
- Subjects
- Adult, Blotting, Northern, Blotting, Western, Endotoxins metabolism, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Humans, Immunohistochemistry, Immunoprecipitation, Interleukin-8 metabolism, Middle Aged, NF-kappa B metabolism, Real-Time Polymerase Chain Reaction, Receptors, Pattern Recognition immunology, Reverse Transcriptase Polymerase Chain Reaction, Tumor Necrosis Factor-alpha metabolism, Biliary Tract cytology, Cholangitis, Sclerosing etiology, Endotoxins immunology, Epithelial Cells immunology, Immunity, Innate immunology, Intestinal Mucosa metabolism, Signal Transduction immunology
- Abstract
Background: Pattern recognition receptors (PRRs) orchestrate the innate immune defence in human biliary epithelial cells (BECs). Tight control of PRR signalling provides tolerance to physiological amounts of intestinal endotoxins in human bile to avoid constant innate immune activation in BECs., Aims: We wanted to determine whether inappropriate innate immune responses to intestinal endotoxins contribute to the development and perpetuation of chronic biliary inflammation., Methods: We examined PRR-mediated innate immune responses and protective endotoxin tolerance in primary BECs isolated from patients with primary sclerosing cholangitis (PSC), alcoholic liver disease and patients without chronic liver disease. Expression studies comprised northern blots, RT-PCR, Western blots and immunocytochemistry. Functional studies comprised immuno-precipitation Western blots, FACS for endotoxin uptake, and NF-κB activation assays and ELISA for secreted IL-8 and tumour necrosis factor (TNF)-α., Results: Primary BECs from explanted PSC livers showed reversibly increased TLR and NOD protein expression and activation of the MyD88/IRAK signalling complex. Consecutively, PSC BECs exhibited inappropriate innate immune responses to endotoxins and did not develop immune tolerance after repeated endotoxin exposures. This endotoxin hyper-responsiveness was probably because of the stimulatory effect of abundantly expressed IFN-γ and TNF-α in PSC livers, which stimulated TLR4-mediated endotoxin signalling in BECs, leading to increased TLR4-mediated endotoxin incorporation and impaired inactivation of the TLR4 signalling cascade. As TNF-α inhibition partly restored protective innate immune tolerance, endogenous TNF-α secretion probably contributed to inappropriate endotoxin responses in BECs., Conclusion: Inappropriate innate immune responses to intestinal endotoxins and subsequent endotoxin intolerance because of enhanced PRR signalling in BECs probably contribute to chronic cholangitis., (© 2011 John Wiley & Sons A/S.)
- Published
- 2011
- Full Text
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41. IgG4-associated cholangitis: a comparative histological and immunophenotypic study with primary sclerosing cholangitis on liver biopsy material.
- Author
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Deshpande V, Sainani NI, Chung RT, Pratt DS, Mentha G, Rubbia-Brandt L, and Lauwers GY
- Subjects
- Adult, Aged, Aged, 80 and over, Autoimmune Diseases immunology, Autoimmune Diseases pathology, Biopsy, Needle, Cholangiopancreatography, Magnetic Resonance, Cholangitis pathology, Cholangitis therapy, Cholangitis, Sclerosing pathology, Cholangitis, Sclerosing therapy, Diagnosis, Differential, Female, Hepatectomy, Humans, Immunohistochemistry, Immunophenotyping, Liver pathology, Liver surgery, Male, Middle Aged, Pancreatitis immunology, Pancreatitis pathology, Plasma Cells immunology, Predictive Value of Tests, Steroids therapeutic use, Autoimmune Diseases complications, Cholangitis immunology, Cholangitis, Sclerosing immunology, Immunoglobulin G blood, Liver immunology, Pancreatitis complications
- Abstract
IgG4-associated cholangitis is a steroid-responsive hepatobiliary inflammatory condition associated with autoimmune pancreatitis that clinically and radiologically mimics primary sclerosing cholangitis. In this study, we conducted a morphological and immunohistochemical analysis of liver material obtained from individuals with IgG4-associated cholangitis, and compared these with well-characterized cases of primary sclerosing cholangitis. The study group consisted of 10 patients (9 biopsy and 1 hepatectomy case) with IgG4-associated cholangitis and 17 patients with primary sclerosing cholangitis (16 needle biopsy and 1 hepatectomy case). All patients with IgG4-associated cholangitis had pancreatic involvement as well, and six pancreatectomy samples revealed characteristic histopathological features of autoimmune pancreatitis. Primary sclerosing cholangitis cases were defined by the presence of a characteristic ERCP appearance. Clinical, pathological, radiological, and follow-up data were recorded for all cases. Portal and periportal inflammation was graded according to Ishak's guidelines. Immunohistochemical stains for IgG and IgG4 were performed. The cohort of patients with IgG4-associated cholangitis (mean age: 63 years) was older than individuals with primary sclerosing cholangitis (mean age: 44 years). Seven of these cases showed intrahepatic biliary strictures. IgG4-associated cholangitis liver samples showed higher portal (P=0.06) and lobular (P=0.009) inflammatory scores. Microscopic portal-based fibro-inflammatory nodules that were composed of fibroblasts, plasma cells, lymphocytes, and eosinophils were exclusively observed in five of the IgG4-associated cholangitis cases (50%). More than 10 IgG4-positive plasma cells per HPF (high power field) were observed in 6 of the IgG4-associated cholangitis cases (mean: 60, range: 0-140 per HPF), whereas all primary sclerosing cholangitis cases showed significantly lesser numbers (mean: 0.08, range: 0-1 per HPF). On a liver biopsy, the histological features of IgG4-associated cholangitis may be distinctive, and in conjunction with IgG4 immunohistochemical stain, may help distinguish this disease from primary sclerosing cholangitis.
- Published
- 2009
- Full Text
- View/download PDF
42. Painless jaundice with serial multi-organ dysfunction.
- Author
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Khosroshahi A, Stone JR, Pratt DS, Deshpande V, and Stone JH
- Subjects
- Aged, Humans, Male, Paraproteinemias therapy, Immunoglobulin G, Jaundice etiology, Multiple Organ Failure etiology, Paraproteinemias complications, Paraproteinemias diagnosis
- Published
- 2009
- Full Text
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43. Current status of therapy for hepatocellular carcinoma.
- Author
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Corey KE and Pratt DS
- Abstract
The incidence of hepatocellular carcinoma (HCC) is increasing worldwide. A multi-disciplinary approach is required for its management. Screening high-risk patients allows for earlier diagnosis and the use of potentially curative therapies. Current recommendations for HCC screening for patients with cirrhosis are an abdominal ultrasound and serum alpha fetoprotein level every 6 to 12 months. Treatment choice depends on tumor stage, liver function and the patient's overall functional status. Curative therapies include surgical resection, liver transplantation (LT), transarterial chemoembolization, and radiofrequency ablation (RFA). Surgical resection, either primary resection or LT, is the treatment most likely to result in cure of HCC. Which option to pursue is based on multiple factors. LT has the potential benefit of treating both HCC and the underlying cirrhosis; however, long wait times incur the risk of tumor progression. Firm recommendations regarding the role of living donor LT for HCC are not yet possible because of conflicting data. HCC recurrence after LT is 8-11% and several adjuvant therapies have been investigated to reduce this. Bridging therapy and tumor downsizing are techniques that also may be considered to deal with long waiting periods and qualification for LT, respectively. If neither LT nor primary resection is possible, loco-regional therapies such as RFA and TACE should be considered. Systemic chemotherapies have proved disappointing for the treatment of HCC; however, newer targeted therapies such as sorafenib and cetuximab have provided new hope for the future.
- Published
- 2009
- Full Text
- View/download PDF
44. Liver disorders.
- Author
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Pratt DS
- Subjects
- Humans, Liver Diseases complications, Liver Transplantation, Metabolism, Inborn Errors complications, Liver Diseases etiology, Liver Diseases therapy
- Published
- 2008
- Full Text
- View/download PDF
45. The 5-10-25 challenge: an observational study of a web-based wellness intervention for a global workforce.
- Author
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Pratt DS, Jandzio M, Tomlinson D, Kang X, and Smith E
- Subjects
- Adult, Body Mass Index, Diet, Exercise, Female, Humans, Longitudinal Studies, Male, Obesity prevention & control, Patient Compliance, Health Education, Health Promotion, Internet, Occupational Health
- Abstract
We conducted and evaluated a 4-year, web-based wellness program involving 2498 global employees. The program was designed to encourage improvement in diet, exercise level, and weight control. Each month, after enrollment, participants were prompted to log on and enter personal data. Four years' worth of nonparametric data were analyzed. Seventy-seven percent of participants were men, 53% were overweight or obese, and mean beginning body mass index (BMI) was 25.9. Only 35% of starting participants ate five or more servings of fruit and vegetables daily, and fewer than 38% engaged in 30 min of activity or 10,000 steps. At the end of the intervention, there was a statistically significant (p < 0.05) improvement in the diet, exercise habits, and weight of participants. Results suggests that our web-based wellness intervention was successful in improving key health indicators for a mobile, global workforce.
- Published
- 2006
- Full Text
- View/download PDF
46. Obscure gastrointestinal hemorrhage from mesenteric varices diagnosed by video capsule endoscopy.
- Author
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Fix OK, Simon JT, Farraye FA, Oviedo JA, Pratt DS, Chen WT, and Cave DR
- Subjects
- Adult, Esophageal and Gastric Varices complications, Esophageal and Gastric Varices diagnosis, Female, Humans, Liver Cirrhosis, Alcoholic complications, Liver Cirrhosis, Alcoholic diagnosis, Male, Middle Aged, Phlebography, Portal Vein pathology, Video-Assisted Surgery, Endoscopy, Gastrointestinal methods, Gastrointestinal Hemorrhage etiology, Intestine, Small blood supply, Mesenteric Veins pathology, Varicose Veins complications, Varicose Veins diagnosis
- Published
- 2006
- Full Text
- View/download PDF
47. Cholestasis and cholestatic syndromes.
- Author
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Rutherford AE and Pratt DS
- Subjects
- ATP Binding Cassette Transporter, Subfamily B, Member 11, ATP-Binding Cassette Transporters genetics, Animals, Bile Acids and Salts metabolism, Bile Duct Diseases etiology, Biological Transport physiology, Female, Humans, Mutation, Osteoporosis drug therapy, Osteoporosis etiology, Pregnancy, Pregnancy Complications therapy, Pruritus drug therapy, Pruritus etiology, Bile Duct Diseases physiopathology, Bile Duct Diseases therapy
- Abstract
Purpose of Review: This review highlights recent advances in understanding the regulation of bile acid transport in cholestasis and in the pathogenesis, outcomes, epidemiology, and treatment of a variety of cholestatic liver diseases and their associated complications., Recent Findings: Highlights include additional understanding of the role of the nuclear receptors farsenoid X receptor, pregnane X receptor, and constitutive androstane receptor in bile acid homeostasis, new understanding of the pathogenesis of primary biliary cirrhosis, familial intrahepatic cholestasis, biliary atresia, and primary sclerosing cholangitis, and clinical trials of therapies for intrahepatic cholestasis of pregnancy, primary biliary cirrhosis, and primary sclerosing cholangitis., Summary: Our understanding of the molecular mechanisms, epidemiology and pathogenesis of cholestasis continues to advance. These advances will hopefully lead to more effective therapies for specific cholestatic conditions.
- Published
- 2006
- Full Text
- View/download PDF
48. Heterozygous alpha1-antitrypsin deficiency and chronic hepatitis C.
- Author
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Pratt DS, Trainer TD, and Krawitt EL
- Subjects
- Heterozygote, Humans, Liver Transplantation, Male, Middle Aged, Hepatitis C, Chronic complications, alpha 1-Antitrypsin Deficiency genetics
- Published
- 2005
- Full Text
- View/download PDF
49. Cholestasis and cholestatic syndromes.
- Author
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Pratt DS
- Subjects
- Biliary Atresia etiology, Biliary Atresia physiopathology, Biliary Atresia therapy, Cholangitis, Sclerosing etiology, Cholangitis, Sclerosing physiopathology, Cholangitis, Sclerosing therapy, Cholestasis therapy, Female, Humans, Pregnancy, Pregnancy Complications etiology, Pregnancy Complications physiopathology, Pregnancy Complications therapy, Syndrome, Bile Acids and Salts physiology, Cholestasis etiology, Cholestasis physiopathology
- Abstract
Purpose of Review: This review highlights recent advances in understanding the regulation of bile acid transport in cholestasis and the pathogenesis and treatment of a variety of cholestatic conditions., Recent Findings: Highlights include new understanding of the role of Mrp4 in bile acid homeostasis in cholestasis, new insights into the pathogenesis of specific cholestatic syndromes including primary biliary cirrhosis, primary sclerosing cholangitis, biliary atresia, and progressive familial intrahepatic cholestasis, and clinical trials of therapies for primary biliary cirrhosis, primary sclerosing cholangitis and intrahepatic cholestasis., Summary: Our understanding of the molecular mechanisms of cholestasis is advancing. These advances will hopefully lead to more effective therapies for specific cholestatic conditions.
- Published
- 2005
- Full Text
- View/download PDF
50. Adiponectin--tipping the scales from NAFLD to NASH?
- Author
-
Kowdley KV and Pratt DS
- Subjects
- Adiponectin, Humans, Insulin Resistance, Liver Diseases physiopathology, Receptors, Tumor Necrosis Factor physiology, Steatitis physiopathology, Fatty Liver physiopathology, Intercellular Signaling Peptides and Proteins physiology
- Published
- 2005
- Full Text
- View/download PDF
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