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COVID-19 is a multi-system disorder with high variability in clinical outcomes among patients who are admitted to hospital. Although some cytokines such as interleukin (IL)-6 are believed to be associated with severity, there are no early biomarkers that can reliably predict patients who are more likely to have adverse outcomes. Thus, it is crucial to discover predictive markers of serious complications.In this retrospective cohort study, we analysed samples from 455 participants with COVID-19 who had had a positive SARS-CoV-2 RT-PCR result between April 14, 2020, and Dec 1, 2020 and who had visited one of three Mayo Clinic sites in the USA (Minnesota, Arizona, or Florida) in the same period. These participants were assigned to three subgroups depending on disease severity as defined by the WHO ordinal scale of clinical improvement (outpatient, severe, or critical). Our control cohort comprised of 182 anonymised age-matched and sex-matched plasma samples that were available from the Mayo Clinic Biorepository and banked before the COVID-19 pandemic. We did a deep profiling of circulatory cytokines and other proteins, lipids, and metabolites from both cohorts. Most patient samples were collected before, or around the time of, hospital admission, representing ideal samples for predictive biomarker discovery. We used proximity extension assays to quantify cytokines and circulatory proteins and tandem mass spectrometry to measure lipids and metabolites. Biomarker discovery was done by applying an AutoGluon-tabular classifier to a multiomics dataset, producing a stacked ensemble of cutting-edge machine learning algorithms. Global proteomics and glycoproteomics on a subset of patient samples with matched pre-COVID-19 plasma samples was also done.We quantified 1463 cytokines and circulatory proteins, along with 902 lipids and 1018 metabolites. By developing a machine-learning-based prediction model, a set of 102 biomarkers, which predicted severe and clinical COVID-19 outcomes better than the traditional set of cytokines, were discovered. These predictive biomarkers included several novel cytokines and other proteins, lipids, and metabolites. For example, altered amounts of C-type lectin domain family 6 member A (CLEC6A), ether phosphatidylethanolamine (P-18:1/18:1), and 2-hydroxydecanoate, as reported here, have not previously been associated with severity in COVID-19. Patient samples with matched pre-COVID-19 plasma samples showed similar trends in muti-omics signatures along with differences in glycoproteomics profile.A multiomic molecular signature in the plasma of patients with COVID-19 before being admitted to hospital can be exploited to predict a more severe course of disease. Machine learning approaches can be applied to highly complex and multidimensional profiling data to reveal novel signatures of clinical use. The absence of validation in an independent cohort remains a major limitation of the study.Eric and Wendy Schmidt.

Background: Measurement of parathyroid hormone related peptide (PTHrP) is helpful in the diagnosis and clinical management of patients suspected of humoral hypercalcemia of malignancy (HHM). In these patients uncontrolled release of PTHrP by tumor cells is responsible for the hypercalcemia and PTH concentrations are typically suppressed. Objective: Develop a sensitive and specific assay for quantitation of PTHrP in plasma. Method: Calibrators (PTHrP 1-86) and samples (50uL) were incubated with an anti-PTHrP goat polyclonal acridinium ester labeled antibody. Complexes were transferred and incubated in a microplate coated with an anti-PTHrP polyclonal rabbit antibody. After washing, the acridinium ester generated signal, which is directly proportional to the amount of PTHrP in sample, was quantified. Results: In this assay PTHrp was stable for 24 hours ambient, 3 days refrigerated, 34 days frozen and through 3 freeze/thaws. Intra and inter-assay imprecision in EDTA plasma (~0.16-35.0 pmol/L) ranged from 2.2-8.6% and 5-15%, respectively. The limit of detection was 0.04 pmol/L and the limit of quantitation was 0.16 pmol/L (15% CV). The analytical measuring range was 0.39-50.5 pmol/L (slope of 1.07 and r2 of 0.99). Average spike recovery was 98% (range 85-108%). The assay was not affected by hemoglobin of ≤500 mg/dL, triglycerides of ≤2000 mg/dL, or bilirubin of ≤50mg/dL. No hook effect was noted up to 500 pmol/L. PTH (1-84) did not cross-react in the assay. C-terminal PTHrP(107-139), and N-terminal PTHrP(1-36) had no significant cross-reactivity (≤1.1%). Mid-PTHrP(38-94) had 8.3% cross-reactivity. Comparison with an in-house PTHrP assay (n=267) showed an r2 of 0.96, and slope of 2.25 by Passing-Bablok regression fit. The 97.5% reference interval for PTHrP (n=114) was ≤0.7 pmol/L, however a higher concentration (≤4.2 pmol/L) was identified as a more specific clinical cut-off. A retrospective clinical validation study showed that using ≤4.2 pmol/L resulted in a 91% clinical sensitivity and a 98% clinical specificity. Conclusion: We have developed an analytically and clinically sensitive and specific PTHrP immunoassay. A cutoff of ≤4.2 pmol/L is clinically useful in the evaluation of patients suspected of hypercalcemia of malignancy.

Objective To report a case series of thyroid cancer patients in whom false positive results in immunometric assays for thyroglobulin (TgIMA) were caused by heterophilic antibody interference, describe the clinical scenario in which this interference should be suspected, and recommend methods to demonstrate the interference. Methods Three patients with unexpectedly elevated thyroglobulin results (range, 1.6-75 ng/mL) were studied. In the first patient, thyroglobulin was elevated despite the presence of Tg antibody. In the second patient, suppressed thyroglobulin was higher than a recent stimulated thyroglobulin. In the third patient, thyroglobulin became detectable years after treatment and did not change after thyroid-stimulating hormone stimulation. TgIMA concentration determination was compared to determination by a mass spectrometry method (TgMS). Thyroglobulin was also remeasured after preabsorption with heterophile antibody blocking reagents and after serial dilutions. Results In all cases, thyroglobulin was undetectable by TgMS. In 2 of 3 patients, dilutions provided nonlinear thyroglobulin results. After blocking agent preabsorption, thyroglobulin dropped by 35%, 45%, and 91% in the 3 samples. Conclusion False positive thyroglobulin concentrations from heterophilic antibody interference have significant impact on the management of thyroid cancer. Here we show that TgMS assays can be used to rule out heterophilic antibody interference. This interference should be suspected when a detectable thyroglobulin by TgIMA does not respond to thyroid-stimulating hormone or is discordant from the clinical assessment.

Adrenocorticotropic hormone (ACTH) has been reported to be labile in blood due to proteolytic degradation and stringent procedures are followed to prevent in vitro degradation after sample collection.The purpose of this study was to examine the effect of time and temperature before and after separation of plasma from cells in the quantitation of plasma ACTH.Our current protocol includes sample collection in a pre-chilled tube, transport on ice and immediate centrifugation at 4 °C. These reference conditions were compared against sample processing in tubes and centrifuge set at room-temperature; using delayed centrifugation at 4 °C. ACTH stability was evaluated at ambient and refrigerated temperatures after collection and plasma separation using the reference protocol. Plasma samples were analyzed using the Roche Elecsys ACTH immunoassay.Quantification of ACTH was not impacted by the use of non-chilled tubes and centrifuge and up to a 4 h delay in separation of plasma from cells. Average percent differences in plasma ACTH concentration from time 0 was10% up to 12 h at ambient temperature. Refrigeration of plasma did not preserve ACTH stability at 12 h and longer storage resulted in significant ACTH degradation at both ambient and refrigerated temperatures.As supported by these data, previously recommended strict specimen collection and processing requirements are not necessary for measuring ACTH with the Roche Elecsys immunoassay.

Parathyroid hormone (PTH) measurement in serum or plasma is a necessary tool for the exploration of calcium/phosphate disorders, and is widely used as a surrogate marker to assess skeletal and mineral disorders associated with chronic kidney disease (CKD), referred to as CKD-bone mineral disorders (CKD-MBD). CKD currently affects >10% of the adult population in the United States and represents a major health issue worldwide. Disturbances in mineral metabolism and fractures in CKD patients are associated with increased morbidity and mortality. Appropriate identification and management of CKD-MBD is therefore critical to improving clinical outcome. Recent increases in understanding of the complex pathophysiology of CKD, which involves calcium, phosphate and magnesium balance, and is also influenced by vitamin D status and fibroblast growth factor (FGF)-23 production, should facilitate such improvement. Development of evidence-based recommendations about how best to use PTH is limited by considerable method-related variation in results, of up to 5-fold, as well as by lack of clarity about which PTH metabolites these methods recognise. This makes it difficult to compare PTH results from different studies and to develop common reference intervals and/or decision levels for treatment. The implications of these method-related differences for current clinical practice are reviewed here. Work being undertaken by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) to improve the comparability of PTH measurements worldwide is also described.

Background and objective Leptomeningeal metastasis (LM) can occur as a late manifestation of breast cancer and has traditionally been diagnosed by CSF cytology; however, cytology suffers from low sensitivity and it is believed that many cases of LM go undiagnosed. Some studies have suggested the use of CA 15–3 in CSF (CA 15–3 CSF) to aid in the detection of LM. The purpose of this study was to compare the performance of CA 15–3 CSF to cytology for the detection and treatment monitoring of breast cancer LM. Methods CA 15–3 CSF requests between 2014 and 2016 were retrospectively reviewed. Fifty-two measurements from nine patients were from our health system and had corresponding CSF cytology measurements. Concordance between CA 15–3 CSF and CSF cytology was calculated. For patients with quantifiable CA 15–3 CSF, sequential determinations of CA 15–3 and cytology were compared over time to assess correlation of CA 15–3 CSF concentration and cytology with disease status. Results At the time of initial testing, seven of the nine patients (78%) had positive cytology. Two samples (22%) had quantifiable CA 15–3, both of which were also positive by cytology. The positive concordance between all cytology and CA 15–3 measurements was 9% (2/22), while negative concordance was 100% (30/30). Sequential CA 15–3 and cytology measurements showed a decrease in CA 15–3 that paralleled changes observed with cytology. Conclusions In this cohort of patients, CA 15–3 CSF performance was neither superior nor complementary to cytology for the detection of LM, nor did the combination of CA 15–3 CSF and cytology improve performance over cytology alone.

Background Parathyroid hormone (PTH) quantitation in fine needle aspirate biopsy (FNAB) saline washings complements current modalities for parathyroid tissue localization. Objectives To establish the performance characteristics of the Roche Elecsys intact PTH immunoassay in FNAB needle washings and its diagnostic performance for the identification of parathyroid tissue. Design and methods Accuracy, precision, reportable range, and analytical specificity and sensitivity for the intact PTH immunoassay in FNAB needle washings were established. For clinical validation, 93 specimens from 79 patients were evaluated. Diagnostic cut-offs were established via receiver operator characteristic (ROC) curve analysis. Performance of PTH in FNAB needle washings was compared to cytology. Results Measurement of the PTH in FNAB needle washings demonstrated a matrix interference that was overcome by supplementation of the samples with a protein based matrix prior to analysis. ROC area under the curve (AUC) was 0.96 for PTH in FNAB needle washings. A PTH concentration ≥ 100 pg/mL showed 100% specificity and 82% sensitivity for identifying parathyroid tissue. On histology-confirmed parathyroid specimens, 21/38 (55%) were correctly identified by cytology; whereas 31/38 (82%) were identified by PTH. Conclusions Measurement of PTH in FNAB washings complements cytology for identification of parathyroid tissue. Analytical validation to exclude interference in the PTH immunoassay and proper localization of the parathyroid tissue by ultrasound is necessary to ensure the robustness of the method.

Objective Thyroglobulin (Tg) quantitation by immunometric assays is compromised by anti-thyroglobulin antibodies (TgAbs), potentially resulting in falsely low Tg concentrations. TgAb screening is recommended when measuring Tg, but current TgAb immunoassays do not detect all possible TgAbs in circulation. We assessed the impact of a change in TgAb assay on apparent disease status of patients with differentiated thyroid carcinoma (DTC). Methods Patients seen at the Mayo Clinic, Rochester, Minnesota, for follow-up of DTC, who had been tested using 2 different TgAb assays (Beckman Access and Roche Elecsys) were identified. Electronic medical records were reviewed to evaluate any impact the change in TgAb assay had on clinical disease status assessment and follow-up. Results A total of 1,457 patients were tested using both assays. A change in TgAb status was found in 124 (8.5%) patients; a total of 117 patients who were TgAbnegative on the Beckman assay became TgAb-positive with the Roche assay. Additional testing was performed in 5 of these patients. Seven patients previously considered TgAb-positive were now TgAb-negative. In all 7 cases, physicians documented that they considered these patients now to be truly TgAb-negative and free of disease. Conclusion Discrepancies in TgAb status are seen when using different TgAb assays. Relying on Tg and TgAb measurements to determine disease status may lead to underestimation of residual cancer. A multimodal (clinical, biochemical, and radiologic) approach to follow up on patients with DTC should be continued, pending the development of Tg quantitation methods that are highly sensitive and not affected by TgAb interference. (Endocr Pract. 2014;20:1032-1036)

The purpose of this study was to define an appropriate nadir growth hormone (nGH) cutoff for patients with acromegaly in remission using the Access Ultrasensitive human growth hormone (hGH) assay (Beckman Coulter, Brea, CA).This cross-sectional study included 55 acromegalic subjects and 41 healthy adult volunteers. All subjects underwent oral glucose tolerance testing (OGTT) for growth hormones (GHs). An optimal cutoff for nGH for patients with active disease versus those in remission was determined using receiver-operating curve analysis.The nGH of 0.53 ng/mL revealed a sensitivity of 97% (95% confidence interval [CI], 83-100%) and a specificity of 100% (95% CI, 82-100%). All 22 patients with acromegaly in remission suppressed GH to1 ng/mL, 20/22 (91%) suppressed to0.4 ng/mL, and 19/22 (86%) of subjects suppressed to0.3 ng/mL (the maximum nGH measured in our healthy volunteer group).When using the Access Ultrasensitive hGH assay for OGTT, a cutoff of 0.53 ng/mL was found to most accurately differentiate patients with acromegaly in remission from those with active disease.

Objectives Tumor marker analysis in ascites has been proposed as a measure to aid in the diagnosis of malignancy. The objectives of this study were to establish tumor marker cut-offs and determine the diagnostic performance of measuring CEA, CA 19-9 and AFP in ascites for differentiating between non-malignant and malignant etiologies. Design and methods Ascites from 137 patients (83 non-malignant, 54 malignant) was assayed for CEA, CA 19-9 and AFP concentrations by immunoassay. Diagnostic cut-offs were established via ROC curve analysis. Performance was compared to cytology findings and patient history following medical chart review. Analysis based on cytological findings in combination with tumor marker testing, as well as subset analysis by tumor marker secretion was also performed. Results Concentrations of CEA, CA 19-9 and AFP were significantly higher in patients with malignant ascites versus non-malignant etiologies. The diagnostic cut-off, sensitivity and specificity for CEA were 3.5 ng/mL, 31% and 95%, respectively; for CA 19-9 were 72 U/mL, 30% and 95%; and for AFP were 5 ng/mL, 17% and 95%. Using cytological findings in conjunction with tumor marker results improved the sensitivity of CEA, CA 19-9 and AFP to 57.4%, 64.8%, and 59.3%, respectively. Improvement in sensitivity was seen when subset analysis by causative malignancy was performed. Conclusions Tumor marker analysis in ascites, especially in subset analysis by type of malignancy, demonstrated utility for differentiating non-malignant from malignant etiologies. This analysis should not replace cytology, but offers potential for differentiation in situations where cytology is inconclusive, or in patients with suspected malignancies known to secrete these markers.

To describe the experience with parathyroid fine-needle aspiration (FNA) and parathyroid hormone (PTH) washout at Mayo Clinic Rochester, Rochester, Minnesota.We retrospectively reviewed all parathyroid FNA procedures performed at Mayo Clinic Rochester between January 2000 and December 2007. Clinical, biochemical, and imaging information, parathyroid FNA procedure, and cytology, surgical, and pathology reports were reviewed, and descriptive statistics, sensitivity, specificity, and positive predictive values are presented.During the study period, 75 parathyroid FNAs were performed on 74 patients. Cytology results were available for 74 of 75 procedures, with only 31% interpreted as parathyroid cells. PTH washout was performed in 67 patients (91%). Parathyroid FNA with PTH washout had a sensitivity of 84%, specificity of 100%, positive predictive value of 100%, and accuracy of 84%. At the time of surgical treatment, 2 patients were noted to have an inflammatory response from the parathyroid FNA biopsy, 1 had a parathyroid abscess, and 2 had a hematoma. In 3 of these 5 patients, the necessary conversion of a minimally invasive surgical procedure to the standard surgical approach prolonged the surgical time.Parathyroid FNA with PTH washout had a superior performance in comparison with parathyroid scanning or ultrasonography alone. The main limitations of parathyroid FNA with PTH washout are (1) the need for initial identification of a potential parathyroid adenoma by ultrasonography and (2) the number of false-negative results. Parathyroid FNA resulted in complications affecting the surgical procedure in 3 patients.

Virus-host interactions are characterized by the selection of adaptive mechanisms by which to evade pathogenic and defense mechanisms, respectively. In primary T cells infected with HIV, HIV infection up-regulates TNF-related apoptosis inducing ligand (TRAIL) and death-inducing TRAIL receptors, but blockade of TRAIL:TRAIL receptor interaction does not alter HIV-induced cell death. Instead, HIV infection results in a novel splice variant that we call TRAIL-short (TRAIL-s), which antagonizes TRAIL-R2. In HIV patients, plasma TRAIL-s concentration increases with increasing viral load and renders cells resistant to TRAIL-induced death. Knockdown of TRAIL-s abrogates this resistance. We propose that TRAIL-s is a novel adaptive mechanism of apoptosis resistance acquired by HIV-infected cells to avoid their elimination by TRAIL-dependent effector mechanism.

Objectives Tumor markers analysis has been proposed as a less invasive alternative for categorizing malignant and non-malignant pleural effusions. This study establishes diagnostic cutoffs for CEA and CA19-9 in pleural fluid to differentiate etiologies of effusions. Design and methods Pleural effusions obtained from 198 patients (100 malignant, 98 non-malignant) were analyzed for CEA and CA19-9. ROC curve analysis was performed to determine analyte cutoffs, and cutoff performance was examined in various subsets of malignancies. Results CEA and CA19-9 concentrations were significantly higher in malignant effusions compared to non-malignant effusions, particularly in effusions caused by lung cancer and other cancers associated with elevated CEA and/or CA19-9 serum concentrations. Concentrations were not elevated in effusions caused by cancers not associated with serum tumor marker elevations. Conclusions Measurement of CEA and CA19-9 in pleural fluid complements cytology and other classifying tests. Performance is specifically enhanced in effusions caused by malignancies known to secrete CEA or CA19-9, and their use should be tailored to patients suspected of having those malignancies. Routine analysis of these markers is therefore not recommended in all pleural effusions. Moreover, negative results should be correlated with serum levels to assist in the clinical interpretation.

Genetic variability in drug-metabolizing enzymes and signaling pathways affects chemotherapy-related toxicity and treatment outcome in cancer. In breast and colorectal cancer, polymorphisms in metabolic enzymes involved in tamoxifen and irinotecan therapies has led the U.S. Food and Drug Administration to address genetic factors relevant to patient consideration of treatment with these compounds. Tamoxifen therapeutic failure in breast cancer has been associated with reduced CYP2D6 activity due to inefficient activation of tamoxifen. Irinotecan toxicity in colorectal cancer is more common in patients with reduced-activity UGT1A alleles, resulting in excessive exposure to the potent SN-38 metabolite. In colorectal and lung cancers, somatic mutations in the epidermal growth factor receptor and downstream signaling molecules have been associated with the therapeutic outcome of epidermal growth factor receptor-directed therapies. This review discusses the current knowledge regarding the utility of single gene—UGT1A1, CYP2D6, EGFR, and KRAS—or multigene analysis, for optimizing breast, colorectal, and lung cancer therapy. Current advances in these areas highlight how pharmacogenetics help personalized decision-making for patient management.

Genetic variability in drugmetabolizing enzymes affects the toxicity and efficacy of many compounds, including the chemotherapeutic agents irinotecan and tamoxifen. The correlation of clinical response to polymorphisms in enzymes associated with metabolism of these two drugs has led to the recommendation that patients who receive them undergo genotyping analysis. Irinotecan toxicity in patients who have colorectal cancer has been linked to reduced activity of uridine diphosphate-glucuronyltransferase 1A1 (UGT1A1). Reduced cytochrome P450 (CYP) 2D6 activity leads to therapeutic failure of tamoxifen in the prevention and treatment of breast cancer, as a result of absence of conversion of the prodrug to its active forms. This article discusses current knowledge of the usefulness of UGT1A1 and CYP2D6 genotyping in the context of cancer chemotherapy and highlights the need for additional studies to clarify the many issues remaining.

Caspases are well known for their role in the execution of the apoptotic program by cleaving specific target proteins, leading to the dismantling of the cell, as well as for mediating cytokine maturation. Recent work has highlighted novel non-apoptotic activities of apoptotic caspases. These reports indicate that caspases are much more versatile enzymes than we originally expected. In addition to regulating cell survival and cytokine maturation, caspases may be involved in regulating cell differentiation, cell proliferation, spreading and receptor internalization.

The nuclear factor of kappaB (NF-kappaB) is a ubiquitous transcription factor that is key in the regulation of the immune response and inflammation. T cell receptor (TCR) cross-linking is in part required for activation of NF-kappaB, which is dependent on the phosphorylation and degradation of IkappaBalpha. By using Jurkat and primary human T lymphocytes, we demonstrate that the simultaneous activation of two second messengers of the TCR-initiated signal transduction, protein kinase C (PKC) and calcineurin, results in the synergistic activation of the IkappaBalpha kinase (IKK) complex but not of another putative IkappaBalpha kinase, p90(rsk). We also demonstrate that the IKK complex, but not p90(rsk), is responsible for the in vivo phosphorylation of IkappaBalpha mediated by the co-activation of PKC and calcineurin. Each second messenger is necessary, as inhibition of either one reverses the activation of the IKK complex and IkappaBalpha phosphorylation in vivo. Overexpression of dominant negative forms of IKKalpha and -beta demonstrates that only IKKbeta is the target for PKC and calcineurin. These results indicate that within the TCR/CD3 signal transduction pathway both PKC and calcineurin are required for the effective activation of the IKK complex and NF-kappaB in T lymphocytes.

Background: There is limited data on the utility of the percentage of lens culinaris agglutininreactive α-fetoprotein (AFP-L3%) measured on the new μTASWako i30 Immunoanalyzer for the diagnosis of early stage HCC in the U.S. population. The utility of AFP, AFP-L3% or des-γ-carboxy prothrombin (DCP) for predictingHCC recurrence after liver transplantation is also unknown. Aims: To 1) determine the sensitivity and specificity of AFP, AFP-L3%, and DCP for the diagnosis of early stage HCC; and 2) evaluate the utility of AFP, AFP-L3% and DCP in predicting HCC recurrence after orthotopic liver transplantation (OLT). Methods: Three hundred and thirteen HCC patients and 307 non-HCC controls with end-stage liver disease who were transplanted at Mayo Clinic, Rochester, MN and Jacksonville, FL between 2000 2008 and had serum samples available for biomarker testing were included in the study. Demographic and clinical information were abstracted from the medical record. AFP, AFP-L3% and des-γ-carboxy prothrombin (DCP) assays were performed on the μTASWako i30 Immunoanalyzer. Receiver operating characteristic (ROC) curves were generated to determine the sensitivity and specificity of the biomarkers for diagnosis of HCC. Predictors of HCC development and HCC recurrence were analyzed using the Logistic regression model. Results: AFP had the best area under the ROC curve (0.75, 95%CI 0.72-0.78) for diagnosis of early stage HCC, followed by AFP-L3% (0.63, 95% CI 0.60-0.66) and DCP (0.46, 95%CI 0.43-0.49). The optimum cut-off value of AFP was 9.4 ng/ml with the sensitivity of 62.6% and specificity of 80% and of AFP-L3% was 15.8% with a sensitivity of 30.1% and specificity of 85.1%. AFP and AFP-L3% were independently associated with early stage HCC. Every 10 ng/mL increase in AFP value and every 10% increase in AFP-L3% value were associated with a 36.6% and 43.0% increased risk for HCC diagnosis (OR=1.37, 95%CI 1.20-1.56 for AFP, p,0.0001,and OR 1.43, 95% CI 1.18-1.58 for AFP-L3%, p,0.0001). Of the 313 HCC patients, 301 (96.2%) patients were treated with transarterial chemoembolization (TACE) prior to transplantation. Forty-seven (15%) patients had HCC recurrence after transplant (median time for recurrence was 18.4 months). The post-TACE pre-OLT AFP-L3% was significantly associated with HCC recurrence after OLT. Every 10% increase in post-TACE AFP-L3 was associated with a 48.2% increased risk of HCC recurrence after OLT (OR=1.48, 95% CI 1.11 to 1.97, p=0.007). AFP, AFP-L3% and DCP at the time of HCC diagnosis were not associated with HCC recurrence after OLT. Conclusions: AFP-L3% is potentially useful in predicting HCC recurrence after liver transplantation in US patients. Validation of these results in additional cohorts is needed.