Publications by authors named "Marcela A Salomao"

15 Publications

  • Page 1 of 1

Pathology of Hepatic Iron Overload.

Clin Liver Dis (Hoboken) 2021 Apr 1;17(4):232-237. Epub 2021 May 1.

Department of Laboratory Medicine and Pathology Mayo Clinic Scottsdale AZ.

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http://dx.doi.org/10.1002/cld.1051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087935PMC
April 2021

Invasive carcinoma versus pseudoinvasion: interobserver variability in the assessment of left-sided colorectal polypectomies.

J Clin Pathol 2021 Apr 12. Epub 2021 Apr 12.

Department of Pathology and Cell Biology, Columbia University Medical Center, New York City, New York, USA.

Objectives: Misplaced epithelium in adenomas can occasionally be difficult to distinguish from invasive adenocarcinoma. We evaluated interobserver variability in the assessment of left-sided colon polypectomies for pseudoinvasion versus invasive adenocarcinoma and further investigated relevant histological findings.

Methods: 28 consecutive left-sided colon polyps with the keywords "pseudoinvasion", "epithelial misplacement", "herniation", "prolapse" or "invasive adenocarcinoma" were collected from 28 patients and reviewed by eight gastrointestinal pathologists. Participants assessed stromal hemosiderin, lamina propria/eosinophils surrounding glands, desmoplasia, high grade dysplasia/intramucosal adenocarcinoma and margin status and rendered a diagnosis of pseudoinvasion, invasive adenocarcinoma, or both.

Results: Agreement among pathologists was substantial for desmoplasia (κ=0.70), high grade dysplasia/intramucosal adenocarcinoma (κ=0.66), invasive adenocarcinoma (κ=0.63) and adenocarcinoma at the margin (κ=0.65). There was moderate agreement for hemosiderin in stroma (κ=0.53) and prolapse/pseudoinvasion (κ=0.50). Agreement was low for lamina propria/eosinophils around glands (κ=0.12). For invasive adenocarcinoma, seven or more pathologists agreed in 24 of 28 cases (86%), and there was perfect agreement in 19/28 cases (68%). For pseudoinvasion, seven or more pathologists agreed in 19 of 28 cases (68%), and there was perfect agreement in 16/28 cases (57%).

Conclusion: Moderate to substantial, though imperfect, agreement was achieved in the distinction of pseudoinvasion from invasive carcinoma.
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http://dx.doi.org/10.1136/jclinpath-2021-207406DOI Listing
April 2021

Cytomegalovirus haemorrhagic enterocolitis associated with severe infection with COVID-19.

BMJ Open Gastroenterol 2021 01;8(1)

Department of Critical Care Medicine, Mayo Clinic Hospital, Phoenix, Arizona, USA.

We present a case of haemorrhagic enterocolitis in a patient with SARS-CoV-2 who recovered from respiratory failure after support with venovenous extracorporeal membrane oxygenation. We describe clinicopathological features consistent with the systemic coinfection/reactivation of cytomegalovirus (CMV) concurrent with COVID-19 infection and the protracted clinical course of resolution of gastrointestinal inflammation after the treatment of CMV infection. Stool PCR, abdominal CT perfusion scan and histological examination of ileal and colonic tissues excluded enterocolitis secondary to other causes of infection (common viral, bacterial and protozoal gastrointestinal pathogens), macrovascularand microvascular ischaemia and classic inflammatory bowel disease, respectively. We propose possible synergistic pathophysiologic mechanisms for enterocolitis complicating severe COVID-19 infection: (1) T lymphocyte depletion and immune response dysregulation, (2) use of immunomodulators in the management of severe COVID-19 infection and (3) high concentration of ACE-2 receptors for COVID-19 virus in the gastrointestinal tract.
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http://dx.doi.org/10.1136/bmjgast-2020-000556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804824PMC
January 2021

Interobserver agreement and the impact of mentorship on the diagnosis of inflammatory bowel disease-associated dysplasia among subspecialist gastrointestinal pathologists.

Virchows Arch 2021 Jun 3;478(6):1061-1069. Epub 2021 Jan 3.

Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.

The diagnosis of inflammatory bowel disease (IBD)-associated dysplasia is challenging, and past studies have demonstrated considerable interobserver variability in such diagnoses. This study aimed to assess interobserver agreement in IBD dysplasia diagnoses among subspecialty GI pathologists and to explore the impact of mentorship on diagnostic variability. Twelve GI pathologist mentees and 7 GI pathologist mentors reviewed 163 digitized slides. Participants rendered a diagnosis of negative for dysplasia, indefinite for dysplasia, low-grade dysplasia, or high-grade dysplasia and provided a confidence level for each case. Interobserver agreement and reliability were assessed using Cohen's and Fleiss' kappa (κ) statistics and intraclass correlation coefficient (ICC) analysis. The overall κ coefficient was 0.42 (95% CI: 0.38-0.46). The overall ICC was 0.67 (95% CI: 0.62-0.72). Κ coefficients ranged from 0.31 to 0.49 for mentor/mentee pairs and from 0.34 to 0.55 for pairs of mentees of the same mentor. The combined κ coefficient was 0.44 (95% CI: 0.39-0.48) for all mentees and 0.39 (95% CI: 0.34-0.43) for all mentors. Common features in low agreement cases included mucosal atrophy, areas of stark contrast, serrations, decreased goblet cells, absent surface epithelium, and poor orientation. Participants were confident in most diagnoses, and increased confidence levels generally correlated with higher interobserver agreement. Interobserver agreement among subspecialist GI pathologists in this curated cohort of IBD dysplasia cases was fair to moderate. Mentorship during GI pathology fellowship does not appear to be a significant factor contributing to interobserver variability, but increased experience also does not seem to improve interobserver agreement.
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http://dx.doi.org/10.1007/s00428-020-02998-zDOI Listing
June 2021

Blood-Derived Biomaterial for Catheter-Directed Arterial Embolization.

Adv Mater 2020 Dec 11;32(52):e2005603. Epub 2020 Nov 11.

Division of Vascular & Interventional Radiology, Minimally Invasive Therapeutics Laboratory, Mayo Clinic, 13400 East Shea Blvd., Scottsdale, AZ, 85259, USA.

Vascular embolization is a life-saving minimally invasive catheter-based procedure performed to treat bleeding vessels. Through these catheters, numerous metallic coils are often pushed into the bleeding artery to stop the blood flow. While there are numerous drawbacks to coil embolization, physician expertise, availability of these coils, and their costs further limit their use. Here, a novel blood-derived embolic material (BEM) with regenerative properties, that can achieve instant and durable intra-arterial hemostasis regardless of coagulopathy, is developed. In a large animal model of vascular embolization, it is shown that the BEM can be prepared at the point-of-care within 26 min using fresh blood, it can be easily delivered using clinical catheters to embolize renal and iliac arteries, and it can achieve rapid hemostasis in acutely injured vessels. In swine arteries, the BEM increases cellular proliferation, angiogenesis, and connective tissue deposition, suggesting vessel healing and durable vessel occlusion. The BEM has significant advantages over embolic materials used today, making it a promising new tool for embolization.
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http://dx.doi.org/10.1002/adma.202005603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769968PMC
December 2020

Notch activity characterizes a common hepatocellular carcinoma subtype with unique molecular and clinicopathologic features.

J Hepatol 2021 Mar 8;74(3):613-626. Epub 2020 Oct 8.

Department of Medicine, Columbia University, New York, NY, USA. Electronic address:

Background & Aims: The hepatocyte Notch pathway is a pathogenic factor in non-alcoholic steatohepatitis (NASH)-associated fibrosis, but its role in hepatocellular carcinoma (HCC) is less well defined. Herein, we aimed to characterize the molecular and clinical features of Notch-active human HCC, and to investigate the mechanisms by which Notch affects NASH-driven HCC.

Methods: Using a 14-gene Notch score, we stratified human HCCs from multiple comprehensively profiled datasets. We performed gene set enrichment analyses to compare Notch-active HCCs with published HCC subtype signatures. Next, we sorted Notch-active hepatocytes from Notch reporter mice for RNA sequencing and characterized Notch-active tumors in an HCC model combining a carcinogen and a NASH-inducing diet. We used genetic mouse models to manipulate hepatocyte Notch to investigate the sufficiency and necessity of Notch in NASH-driven tumorigenesis.

Results: Notch-active signatures were found in ~30% of human HCCs that transcriptionally resemble cholangiocarcinoma-like HCC, exhibiting a lack of activating CTNNB1 (β-catenin) mutations and a generally poor prognosis. Endogenous Notch activation in hepatocytes is associated with repressed β-catenin signaling and hepatic metabolic functions, in lieu of increased interactions with the extracellular matrix in NASH. Constitutive hepatocyte Notch activation is sufficient to induce β-catenin-inactive HCC in mice with NASH. Notch and β-catenin show a pattern of mutual exclusivity in carcinogen-induced HCC; in this mouse model, chronic blockade of Notch led to β-catenin-dependent tumor development.

Conclusions: Notch activity characterizes a distinct HCC molecular subtype with unique histology and prognosis. Sustained Notch signaling in chronic liver diseases can drive tumor formation without acquiring specific genomic driver mutations.

Lay Summary: The Notch signaling pathway is known to be involved in the pathogenesis of liver fibrosis. However, its role in liver cancer has not been well defined. Herein, we show that Notch activity is increased in a subset of liver cancers and is associated with poor outcomes. We also used a mouse model to show that aberrant Notch activity can drive cancer progression in obese mice.
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http://dx.doi.org/10.1016/j.jhep.2020.09.032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897246PMC
March 2021

Bioactive-Tissue-Derived Nanocomposite Hydrogel for Permanent Arterial Embolization and Enhanced Vascular Healing.

Adv Mater 2020 Aug 23;32(33):e2002611. Epub 2020 Jun 23.

Division of Vascular & Interventional Radiology, Minimally Invasive Therapeutics Laboratory, Mayo Clinic, 13400 East Shea Blvd., Scottsdale, AZ, 85259, USA.

Transcatheter embolization is a minimally invasive procedure that uses embolic agents to intentionally block diseased or injured blood vessels for therapeutic purposes. Embolic agents in clinical practice are limited by recanalization, risk of non-target embolization, failure in coagulopathic patients, high cost, and toxicity. Here, a decellularized cardiac extracellular matrix (ECM)-based nanocomposite hydrogel is developed to provide superior mechanical stability, catheter injectability, retrievability, antibacterial properties, and biological activity to prevent recanalization. The embolic efficacy of the shear-thinning ECM-based hydrogel is shown in a porcine survival model of embolization in the iliac artery and the renal artery. The ECM-based hydrogel promotes arterial vessel wall remodeling and a fibroinflammatory response while undergoing significant biodegradation such that only 25% of the embolic material remains at 14 days. With its unprecedented proregenerative, antibacterial properties coupled with favorable mechanical properties, and its superior performance in anticoagulated blood, the ECM-based hydrogel has the potential to be a next-generation biofunctional embolic agent that can successfully treat a wide range of vascular diseases.
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http://dx.doi.org/10.1002/adma.202002611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7491606PMC
August 2020

Evaluation of NUC-1031: a first-in-class ProTide in biliary tract cancer.

Cancer Chemother Pharmacol 2020 06 21;85(6):1063-1078. Epub 2020 May 21.

Division of Hematology/Oncology, Department of Internal Medicine, Mayo Clinic, Scottsdale, AZ, USA.

Purpose: NUC1031 is a first-in-class ProTide, that is a gemcitabine pro-drug designed to overcome putative mechanisms of resistance, including decreased expression of hENT/hCNT transporters, absence of activating enzymes such as deoxycytidine kinase (dCK) and presence of degrading enzymes such as cytidine deaminase (CDA). We undertook comprehensive pre-clinical evaluation of NUC1031 in biliary tract cancer (BTC) models, given that gemcitabine/cisplatin is a standard first-line therapy in advanced BTC.

Methods: Here, we compared the in vitro activity of NUC1031 in comparison to gemcitabine, validate putative mechanism(s) of action, assessed potential biomarkers of sensitivity or resistance, and performed combination studies with cisplatin. We also evaluated the in vivo efficacy of NUC1031 and gemcitabine using a CDA-high cholangiocarcinoma patient-derived xenograft (PDX) model.

Results: In a panel of BTC cell lines (N = 10), NUC1031 had less potency than gemcitabine in multiple cellular assays. NUC1031 did not demonstrate evidence of greater synergy over gemcitabine in combination with cisplatin. Surprisingly, efficacy of both gemcitabine and NUC1031 was not found to be correlated with hENT/hCTN, dCK or CDA transcript levels. Gemcitabine and NUC1031 showed equivalent efficacy in a CDA-high PDX model in vivo contradicting the primary rationale of NUC1031 design.

Conclusion: NUC1031 did not exhibit evidence of superior activity over gemcitabine, as a single-agent, or in combination with cisplatin, in either our in vivo or in vitro BTC models. Given that the largest Phase 3 study (ClinicalTrials.gov: NCT0314666) to date in BTC is underway (N = 828) comparing NUC1031/cisplatin to gemcitabine/cisplatin, our results suggest that a more conservative clinical evaluation path would be more appropriate.
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http://dx.doi.org/10.1007/s00280-020-04079-zDOI Listing
June 2020

Multifocal Urinary Bladder Paragangliomas With Negative 68Ga-DOTATATE Uptake and Positive 123I-MIBG Uptake.

Clin Nucl Med 2020 Mar;45(3):e156-e157

From the Departments of Radiology.

We report a case of an adult male patient with multifocal urinary bladder paragangliomas, which were negative on Ga-DOTATATE PET/CT scan, but positive on I-MIBG SPECT/CT scan. While the Ga-DOTA analog PET/CT exhibits superior performance in diagnosis and staging of pheochromocytoma and paraganglioma, our case demonstrates negative somatostatin receptor expression in this rare entity and indicates that I-MIBG SPECT/CT still plays a vital role in characterization of bladder paraganglioma.
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http://dx.doi.org/10.1097/RLU.0000000000002853DOI Listing
March 2020

Severe Diarrhea in the Setting of Immune Checkpoint Inhibitors.

Case Rep Gastroenterol 2018 Sep-Dec;12(3):704-708. Epub 2018 Nov 28.

Division of Gastroenterology and Hepatology, Mayo Clinic Arizona, Scottsdale, Arizona, USA.

Immune checkpoint inhibitors (ICPIs) are novel therapeutic agents targeting a variety of cancers by enhanced T cell activation. Immune-related adverse events (irAEs) commonly occur with ICPI use and can affect multiple organ systems including the gastrointestinal tract. Due to irAEs, the use of ICPIs is limited in autoimmune diseases. We present a case of microscopic colitis diagnosed after the initiation of nivolumab and a case of ipilimumab colitis and in the setting of Crohn's colitis.
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http://dx.doi.org/10.1159/000493183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6323374PMC
November 2018

Pilot evaluation of PD-1 inhibition in metastatic cancer patients with a history of liver transplantation: the Mayo Clinic experience.

J Gastrointest Oncol 2018 Dec;9(6):1054-1062

Division of Hematology & Oncology, Department of Medicine, Mayo Clinic, Scottsdale, AZ, USA.

Background: Patients with solid organ transplants (SOTs) have been excluded from programmed death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitor clinical trials due to concern for allograft rejection. The use of immune checkpoint inhibitor therapy remains controversial in transplant patients.

Methods: A retrospective pilot evaluation was conducted to assess the safety and efficacy of PD-1 inhibitors in patients with liver transplantation (LT). The primary endpoint was the rate of allograft rejection. Secondary endpoints included overall response rate (ORR), progression free survival (PFS) and overall survival (OS). Translational objectives included evaluation of tumor PD-L1, tumor infiltrating lymphocytes (TILs) and allograft PD-L1 expression.

Results: Seven metastatic cancer patients with a history of LT who received PD-1 inhibitor therapy were included [hepatocellular carcinoma (HCC), n=5; melanoma, n=2]. Rejection was observed in 2 of 7 patients. When rejection occurs it appears to be an early event with a median time to rejection of 24 days in our cohort. One patient achieved a complete response (CR), 3 patients had progressive disease (PD) and 3 patients discontinued therapy prior to restaging assessments. Two of five patients with available tissue had PD-L1 expression in the allograft and both developed rejection. One of five evaluable patients had abundant TILs. Two of five evaluable patients had PD-L1 tumor staining. The single patient with both abundant TILs and PD-L1 staining obtained a response. The median OS and PFS were 1.1 (0.3-21.1) and 1.8 (0.7-21.1) months, respectively.

Conclusions: In this pilot evaluation both preliminary efficacy (1 of 4) and allograft rejection (2 of 7) were exhibited in evaluable patients. Larger, prospective trials are needed to elucidate optimal patient selection.
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http://dx.doi.org/10.21037/jgo.2018.07.05DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6286929PMC
December 2018

Novel immunotherapy strategies for hepatobiliary cancers.

Immunotherapy 2018 09;10(12):1077-1091

Department of Medicine, Division of Hematology & Oncology, Mayo Clinic, Scottsdale, AZ 85259, USA.

Despite recent advancements in therapeutic options for advanced hepatobiliary cancers, there remains an unmet need for innovative systemic treatments. Immunotherapy has shown an ability to provide prolonged clinical benefit, but this benefit remains limited to a small subset of patients. Numerous ongoing endeavors are investigating novel immunotherapy concepts. Immunotherapies that have demonstrated clinical efficacy in hepatobiliary cancers include PD-1 inhibitor therapy and CTLA-4 inhibitor therapy. Novel immunotherapy concepts include targeting emerging checkpoint proteins, bispecific T-cell engagers, combinatorial trials with checkpoint inhibitors, oncolytic virotherapy and chimeric antigen receptor T cells. The goal for these new treatment strategies is to achieve a meaningful expansion of patients deriving prolonged clinical benefit from immunotherapy.
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http://dx.doi.org/10.2217/imt-2018-0024DOI Listing
September 2018

Substantial Interobserver Agreement in the Diagnosis of Dysplasia in Barrett Esophagus Upon Review of a Patient's Entire Set of Biopsies.

Am J Surg Pathol 2018 03;42(3):376-381

Department of Pathology and Laboratory Medicine, Mayo Clinic Arizona, Scottsdale, AZ.

The pathologic diagnosis of dysplasia in Barrett esophagus (BE) suffers from interobserver disagreement. Many of the studies demonstrating disagreement in the diagnosis of dysplasia have pathologists review individual biopsy slides in isolation. To more closely mimic daily practice, 3 pathologists reviewed hematoxylin and eosin slides made from 549 individual biopsy jars obtained from 129 unique patients with a diagnosis of BE. Each pathologist reviewed the entirety of a given patient's biopsy material. The grade of dysplasia present in each biopsy jar was given as well as an overall highest grade of dysplasia from the patient's entire set of biopsies. The interobserver agreement in the diagnosis of dysplasia per biopsy jar and per patient's set of biopsies was measured by Fleiss κ statistic for multiple raters. The κ values for each diagnosis was higher in the per patient analysis compared with the per biopsy jar analysis indicating that pathologists are more likely to agree on the overall grade of dysplasia compared with the grade in an individual biopsy jar. In the per patient analysis, the interobserver agreement in the diagnosis of nondysplastic BE and high-grade dysplasia were substantial (κ=0.66; 95% confidence interval [CI], 0.56-0.76 and κ=0.76; 95% CI, 0.66-0.86, respectively). The interobserver agreement in the diagnosis of low-grade dysplasia (LGD) was fair (κ=0.31; 95% CI, 0.21-0.42). When LGD and high-grade dysplasia were collapsed into 1 category of positive for dysplasia, the interobserver agreement in the per patient analysis remained substantial (κ=0.70; 95% CI, 0.60-0.80), suggesting that much of the disagreement in LGD is not due to lack of recognition of dysplastic Barrett's mucosa, but rather the degree of dysplasia. These results indicate that pathologists can reliably distinguish between nondysplastic BE and dysplastic BE when a patient's entire set of biopsies is reviewed as a group. When second opinions are obtained, all available slides from that endoscopic procedure should be sent for review.
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http://dx.doi.org/10.1097/PAS.0000000000000988DOI Listing
March 2018

Current concepts in the immunohistochemical evaluation of liver tumors.

World J Hepatol 2015 Jun;7(10):1403-11

Anne K Koehne de Gonzalez, Marcela A Salomao, Stephen M Lagana, Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, United States.

Immunohistochemistry often plays an important role in the evaluation of liver tumors. Recent advances have established a classification system for hepatocellular adenomas (HCAs) based on morphology, molecular alterations, and immunohistochemistry. Specifically, loss of liver fatty acid binding protein is seen in HNF1α-inactivated HCA, staining with serum amyloid A is seen in inflammatory HCA, and diffuse staining with glutamine synthetase (GS) is seen in β-catenin activated HCA. A panel of immunohistochemical stains including glypican-3 (GPC-3), heat shock protein 70, and GS are useful in distinguishing HCC from non-malignant dysplastic nodules. Immunohistochemistry is also useful to determine whether a liver tumor is of primary hepatocellular or metastatic origin. Recently described markers useful for this purpose include arginase-1, GPC-3, and bile salt export pump. These newer markers may offer superior utility when compared to traditional markers of hepatocellular differentiation such as alpha-fetoprotein, hepatocyte paraffin-1, polyclonal carcinoembryonic antigen, and CD10. This paper will review recent advances in the immunohistochemical evaluation of liver tumors.
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http://dx.doi.org/10.4254/wjh.v7.i10.1403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4450203PMC
June 2015

Cholestatic hepatitis C following liver transplantation: an outcome-based histological definition, clinical predictors, and prognosis.

Liver Transpl 2013 Jan;19(1):78-88

Center for Liver Disease and Transplantation, Division of Digestive and Liver Diseases, Columbia University College of Physicians and Surgeons, New York, NY 10032-3784, USA.

Cholestatic hepatitis C virus (HCV) is a rare form of recurrent HCV following liver transplantation (LT) without specific diagnostic criteria. An outcome-based method to improve its diagnosis and a description of its prognosis are needed. All 1-year post-LT protocol liver biopsy samples and biopsy samples initially reported to show cholestatic HCV from patients transplanted with HCV between February 2002 and December 2009 were reviewed for the inflammation grade, the fibrosis stage, and 4 cholestatic HCV features: ductular proliferation, canalicular cholestasis with or without intracellular cholestasis, hepatocyte swelling with or without lobular disarray, and sinusoidal/pericellular fibrosis. We used patient and graft survival to define histological criteria for cholestatic HCV, and compared the clinical features of these patients to those of patients with minimal or significant post-LT fibrosis. One hundred seventy-nine patients were analyzed, the median age was 56 years, and 73% were male. Patients with 3 or more of the 4 cholestatic HCV criteria had significantly worse survival (log-rank P < 0.001) regardless of the fibrosis stage, and this was used as our novel definition of cholestatic HCV. Using this definition, we found that 27 patients (15%) had cholestatic HCV, 53 (30%) had significant fibrosis (stage ≥ 2/4), and 99 (55%) had minimal fibrosis (stage < 2/4). The final model for clinical predictors of cholestatic HCV included donor age [odds ratio (OR) = 1.37 per decade, P = 0.04] and previous rejection (Banff grade ≥ 5; OR = 4.19, P = 0.002). Total bilirubin was the strongest laboratory predictor of cholestatic HCV (area under the curve = 0.93), whereas the HCV viral load was not a significant predictor. The final model of post-LT survival included the pathology group {cholestatic HCV [hazard ratio (HR) = 6.07, P < 0.001] and significant fibrosis (HR = 2.53, P = 0.02)}, donor age (HR = 1.49 per decade, P < 0.001), and cold ischemia time (HR = 1.11 per hour, P = 0.02). In conclusion, we propose diagnostic criteria for cholestatic HCV that include specific criteria (the presence of at least 3 of the 4 histopathological features on biopsy) and other supportive and exclusionary criteria. Older donor age and rejection increase the risk of cholestatic HCV, and an elevation in the total bilirubin level may help to identify these patients. These criteria must be validated prospectively.
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http://dx.doi.org/10.1002/lt.23559DOI Listing
January 2013