Peters, Brian E.

Abstract Background Antinuclear antibody (ANA)5 testing is routinely performed during evaluation of patients with a suspected connective tissue disease (CTD), yet the question of which method is most appropriate remains controversial. The purpose of this study was to evaluate the clinical utility of ANA testing by an enzyme immunoassay (EIA), an immunofluorescence assay (IFA), and a multiplex immunoassay (MIA) in a routine laboratory population. Methods Samples (n = 1000) were collected from specimens submitted for ANA testing by EIA (Bio-Rad). All samples were subsequently analyzed by IFA (Zeus) and MIA (Bio-Rad). The sample cohort was weighted to represent the routine testing population. Diagnostic information was obtained by chart review. Results For the diagnosis of a CTD, ROC curve analysis demonstrated no significant differences between IFA (area under the curve 0.81) and EIA (0.84) (P = 0.25), with overlay of a single point for the MIA. When normalized to a specificity of approximately 90%, the sensitivities of the MIA, EIA, and IFA were 67%, 67%, and 56%, respectively. By varying the clinical cutoff, the IFA could achieve the highest sensitivity of 94%; however, the corresponding specificity was only 43%. In contrast, a strongly positive EIA had a specificity of 97%, although, at this cutoff, the sensitivity was only 40%. Conclusions Although the overall diagnostic performance of the IFA, EIA, and MIA were not statistically different, the clinical sensitivity and specificity varied dramatically based on the positive/negative cutoff. Knowledge about the performance characteristics of each method will significantly aid in the interpretation of ANA testing.

Growing evidence suggests that pretransplant alpha‐fetoprotein (AFP) predicts outcomes of hepatocellular carcinoma (HCC) patients treated with liver transplantation. We aimed to determine whether pretransplant AFP, Lens culinaris agglutinin‐reactive alpha‐fetoprotein (AFP‐L3), and des‐gamma‐carboxyprothrombin (DCP) predicted HCC recurrence after transplantation. A retrospective cohort study of 313 HCC patients undergoing transplantation between 2000 and 2008 was conducted, and 48 (15.3%) developed recurrence during a median follow‐up of 90.8 months. The 127 patients with available serum drawn before transplantation were included; they included 86 without recurrence and 41 with recurrence. Serum was tested for AFP, AFP‐L3%, and DCP in a blinded fashion with the μTASWako i30 immunoanalyzer. All biomarkers were significantly associated with HCC recurrence. The hazard ratios (HRs) were 3.5 [95% confidence interval (CI), 1.9‐6.7; P < 0.0001] for DCP ≥ 7.5 ng/mL and 2.8 (95% CI, 1.4‐5.4; P = 0.002) for AFP ≥ 250 ng/mL. The HR increased to 5.2 (95% CI, 2.3‐12.0; P < 0.0001) when AFP ≥ 250 ng/mL and DCP ≥7.5 ng/mL were considered together. When they were combined with the Milan criteria, the HR increased from 2.6 (95% CI, 1.4‐4.7; P = 0.003) for outside the Milan criteria to 8.6 (95% CI, 3.0‐24.6; P < 0.0001) for outside the Milan criteria and AFP ≥ 250 ng/mL and to 7.2 (95% CI, 2.8‐18.1; P < 0.0001) for outside the Milan criteria and DCP ≥7.5 ng/mL. Our findings suggest that biomarkers are useful for predicting the risk of HCC recurrence after transplantation. Using both biomarkers and the Milan criteria may be better than using the Milan criteria alone in optimizing the decision of liver transplantation eligibility. Liver Transpl 21:599–606, 2015. © 2015 AASLD.