The Addition of C-Reactive Protein and von Willebrand Factor to Model for End-Stage Liver Disease-Sodium Improves Prediction of Waitlist Mortality.

BACKGROUND AND AIMS: Patients with cirrhosis on the liver transplant (LT) waiting list may die or be removed because of complications of portal hypertension (PH) or infections. von Willebrand factor antigen (vWF-Ag) and C-reactive protein (CRP) are simple, broadly available markers of these processes. APPROACH AND RESULTS: We determined whether addition of vWF-Ag and CRP to the Model for End-Stage Liver Disease-Sodium (MELD-Na) score improves risk stratification of patients awaiting LT. CRP and vWF-Ag at LT listing were assessed in two independent cohorts (Medical University of Vienna [exploration cohort] and Mayo Clinic Rochester [validation cohort]). Clinical characteristics, MELD-Na, and mortality on the waiting list were recorded. Prediction of 3-month waiting list mortality was assessed by receiver operating characteristics curve (ROC-AUC). In order to explore potential mechanisms underlying the prognostic utility of vWF-Ag and CRP in this setting, we evaluated their association with PH, bacterial translocation, systemic inflammation, and circulatory dysfunction. In the exploration cohort (n = 269) vWF-Ag and CRP both improved the predictive value of MELD-Na for 3-month waitlist mortality and showed the highest predictive value when combined (AUC: MELD-Na, 0.764; MELD-Na + CRP, 0.790; MELD-Na + vWF, 0.803; MELD-Na + CRP + vWF-Ag, 0.824). Results were confirmed in an independent validation cohort (n = 129; AUC: MELD-Na, 0.677; MELD-Na + CRP + vWF-Ag, 0.882). vWF-Ag was independently associated with PH and inflammatory biomarkers, whereas CRP closely, and MELD independently, correlated with biomarkers of bacterial translocation/inflammation. CONCLUSIONS: The addition of vWF-Ag and CRP-reflecting central pathophysiological mechanisms of PH, bacterial translocation, and inflammation, that are all drivers of mortality on the waiting list for LT-to the MELD-Na score improves prediction of waitlist mortality. Using the vWFAg-CRP-MELD-Na model for prioritizing organ allocation may improve prediction of waitlist mortality and decrease waitlist mortality.

The 3-60 criteria challenge established predictors of postoperative mortality and enable timely therapeutic intervention after liver resection.

BACKGROUND: To date, definitions of liver dysfunction (LD) after hepatic resection rely on late postoperative time points. Further, the used parameters are markedly influenced by perioperative management. Thus, we aimed to establish a very early postoperative score to predict postoperative mortality. METHODS: Liver related parameters were evaluated after liver resection in a retrospective evaluation cohort of 228 colorectal cancer patients with liver metastasis (mCRC) and subsequent validation in a prospective set of 482 consecutive patients from 4 independent institutions undergoing hepatic resection was performed. RESULTS: C-reactive protein (CRP, AUC =0.739, P<0.001) and antithrombinIII-activity (ATIII, AUC =0.844, P<0.001) on the first postoperative day (POD) were found to be elevated in patients with LD. Cut-off values for CRP at 3 mg/dL and for ATIII at 60% significantly identified high-risk patients for postoperative LD and mortality (P<0.001) and thus defined the 3-60 criteria on POD1. The 3-60 criteria showed superior sensitivity and specificity compared to established criteria for LD [3-60 criteria: total positive patients: 26 patients (70% mortality detected), odds ratio (OR): 48.8; International Study Group for Liver Surgery: total positive patients: 43 (70% mortality detected), OR: 23.3; Peak7: total positive patients: 9 (30% mortality detected), OR: 27.8; 50-50: total positive patients: 9 (30% mortality detected), OR: 27.8]. These results could be validated in a multi-center analysis and ultimately the 3-60 criteria remained an independent predictor of postoperative mortality upon multivariable analysis. CONCLUSIONS: The 3-60 criteria on POD1 predict postoperative LD and mortality early after liver resection with a comparable or better accuracy than established criteria, allowing for immediate identification of high-risk patients.

Prevalence of genital dysplasia after kidney transplantation--a retrospective, non-interventional study from two centers.

OBJECTIVE: Renal transplant patients are at increased risk for human papillomavirus-related malignancies of the lower genital tract. Our aim was to describe the incidence of genital dysplasia, assess the most common cervical cancer screening intervals and identify independent risk factors for the development of genital dysplasia in renal transplant patients. DESIGN: Retrospective, non-interventional study from two centers. SETTING: Post-transplant nephrologic follow-up visit at the Medical University of Vienna and a Viennese teaching hospital. POPULATION: 262 consecutive female renal transplant patients with renal transplant performed between 1980 and 2012 at the Medical University of Vienna. METHODS: Sociodemographic patient characteristics, frequency of gynecological examinations, histo- and cytopathological test results were collected. MAIN OUTCOME MEASURES: Dysplasia rates in renal transplant patients. RESULTS: 16 patients (6.2%) with genital dysplasia after renal transplant were observed. The 1-year, 3-year and 10-year proportional incidence rates for genital dysplasia in general and cervical dysplasia in particular were 1.3 and 1.3%, 3.3 and 2.7%, and 13.6 and 12.0%, respectively. Patients attended cervical cancer screening on a regular basis once a year in 82.7% of cases. In multivariate analysis re-transplantation [odds ratio 12.1 (1.5-96.3)], and renal transplant at a young age [odds ratio 0.6 (0.4-0.9)] were identified as independent risk factors for the development of female genital dysplasia. CONCLUSIONS: Female renal transplant patients have an increased risk for the development of genital dysplasia in general and of cervical dysplasia in particular. Within this cohort, women at a young age at the time of transplantation and after re-transplantation are at highest risk for the development of genital dysplasia.