Low C-reactive Protein and Urea Distinguish Primary Nonfunction From Early Allograft Dysfunction Within 48 Hours of Liver Transplantation.

Primary nonfunction (PNF) is a life-threatening complication of liver transplantation (LT), but in the early postoperative period, it can be difficult to differentiate from early allograft dysfunction (EAD). The aim of this study was to determine if serum biomarkers can distinguish PNF from EAD in the initial 48 h following LT. Materials and Methods: A retrospective study of adult patients that underwent LT between January 2010 and April 2020 was performed. Clinical parameters, absolute values and trends of C-reactive protein (CRP), blood urea, creatinine, liver function tests, platelets, and international normalized ratio in the initial 48 h after LT were compared between the EAD and PNF groups. Results: There were 1937 eligible LTs, with PNF and EAD occurring in 38 (2%) and 503 (26%) patients, respectively. A low serum CRP and urea were associated with PNF. CRP was able to differentiate between the PNF and EAD on postoperative day (POD)1 (20 versus 43 mg/L; P < 0.001) and POD2 (24 versus 77; P < 0.001). The area under the receiver operating characteristic curve (AUROC) of POD2 CRP was 0.770 (95% confidence interval [CI] 0.645-0.895). The urea value on POD2 (5.05 versus 9.0 mmol/L; P = 0.002) and trend of POD2:1 ratio (0.71 versus 1.32 mmol/L; P < 0.001) were significantly different between the groups. The AUROC of the change in urea from POD1 to 2 was 0.765 (95% CI 0.645-0.885). Aspartate transaminase was significantly different between the groups, with an AUROC of 0.884 (95% CI 0.753-1.00) on POD2. Discussion: The biochemical profile immediately following LT can distinguish PNF from EAD; CRP, urea, and aspartate transaminase are more effective than ALT and bilirubin in distinguishing PNF from EAD in the initial postoperative 48 h. Clinicians should consider the values of these markers when making treatment decisions.

Acute-on-chronic liver failure: to admit to intensive care or not?

Acute-on-chronic liver failure is used to describe an acute decline in liver function in a patient with existing liver disease combined with other organ failure. Acute-on-chronic liver failure is associated with high short-term mortality, and the greater the number and severity of organ failures, the higher the mortality. The most commonly identified precipitants of acute-on-chronic liver failure include bacterial infection, gastrointestinal haemorrhage, viral hepatitis and recent excessive alcohol intake. Since some of these aetiologies are treatable, organ failure may return to pre-decompensation levels in up to 55% of patients. As a result, a trial of critical care treatment may be appropriate for many of these patients. Clinical scoring tools may help clinicians recognise futility, allowing timely withdrawal of organ support and shifting the focus of care toward palliation.

Variation in the human matrix metalloproteinase-9 gene is associated with arterial stiffness in healthy individuals.

BACKGROUND: Arterial stiffness is an important determinant of cardiovascular risk. Elastin is the main elastic component of the arterial wall and can be degraded by a number of enzymes including serine proteases and matrix metalloproteinases (MMPs). Serum MMP-9 levels correlate with arterial stiffness and predict cardiovascular risk. Polymorphisms in the MMP-9 gene are also associated with large artery function in subjects with coronary artery disease. Therefore, we investigated the influence of known MMP-9 (-1562C>T, R279Q) polymorphisms on arterial stiffness in a large cohort of healthy individuals (n=865). METHODS AND RESULTS: Aortic pulse wave velocity (PWV) and augmentation index were assessed. Supine blood pressure, biochemical markers, MMP-9 levels, and serum elastase activity (SEA) were also determined. Genomic DNA was extracted and genotyping performed. Aortic PWV, serum MMP-9, and SEA were higher in carriers of the rare alleles for the -1562C>T and R279Q polymorphisms. These polymorphisms were also associated with aortic PWV after correction for other confounding factors. Stepwise regression models with known or likely determinants of arterial stiffness revealed that approximately 60% of the variability in aortic PWV was attributable to age, mean arterial pressure, and genetic variants (P<0.001). CONCLUSIONS: We have demonstrated for the first time that aortic stiffness and elastase activity are influenced by MMP-9 gene polymorphisms. This suggests that the genetic variation in this protein may be involved in the process of large artery stiffening.