Liver transplantation (LT) is closely associated with decreased immune function, a contributor to herpes zoster (HZ). However, risk factors for HZ in living donor LT (LDLT) remain unknown. Neutrophil-lymphocyte ratio (NLR) and immune system function are reportedly correlated. This study investigated the association between NLR and HZ in 1688 patients who underwent LDLT between January 2010 and July 2020 and evaluated risk factors for HZ and postherpetic neuralgia (PHN). The predictive power of NLR was assessed through the concordance index and an integrated discrimination improvement (IDI) analysis. Of the total cohort, 138 (8.2%) had HZ. The incidence of HZ after LT was 11.2 per 1000 person-years and 0.1%, 1.3%, 2.9%, and 13.5% at 1, 3, 5, and 10 years, respectively. In the Cox regression analysis, preoperative NLR was significantly associated with HZ (adjusted hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.02–1.09; p = 0.005) and PHN (HR, 1.08; 95% CI, 1.03–1.13; p = 0.001). Age, sex, mycophenolate mofetil use, and hepatitis B virus infection were risk factors for HZ versus age and sex for PHN. In the IDI analysis, NLR was discriminative for HZ and PHN (p = 0.020 and p = 0.047, respectively). Preoperative NLR might predict HZ and PHN in LDLT recipients.

Background: Given the severe shortage of donor liver grafts, coupled with growing proportion of cardiovascular death after liver transplantation (LT), precise cardiovascular risk assessment is pivotal for selecting recipients who gain the greatest survival benefit from LT surgery. We aimed to determine the prognostic value of pre-LT combined measurement of B-type natriuretic peptide (BNP) and high-sensitivity troponin I (hsTnI) in predicting early post-LT mortality. Methods: We retrospectively evaluated 2,490 consecutive adult LT patients between 2010 and 2018. Cut-off values of BNP and hsTnI for predicting post-LT 90-day mortality were calculated. According to the derived cut-off values of two cardiac biomarkers, alone and in combination, adjusted hazard ratios (aHR) of post-LT 90-day mortality were determined using multivariate Cox regression analysis.Results: Mortality rate after 90 days was 2.9% (72/2,490). Rounded cut-off values for post-LT 90-day mortality were 400 pg/ml for BNP (aHR 2.02 [1.15, 3.52], P = 0.014) and 60 ng/L for hsTnI (aHR 2.65 [1.48, 4.74], P = 0.001), respectively. Among 273 patients with BNP ≥ 400 pg/ml, 50.9% of patients were further stratified into having hsTnI ≥ 60 ng/L. Combined use of pre-LT cardiac biomarkers predicted post-LT 90-day mortality rate; both non-elevated: 1.0% (21/2,084), either one is elevated: 9.0% (24/267), and both elevated: 19.4% (27/139, log-rank P < 0.001; aHR vs non-elevated 4.23 [1.98, 9.03], P < 0.001).Conclusions: Concomitant elevation of both cardiac biomarkers posed significantly higher risk of 90-day mortality after LT. Pre-LT assessment cardiac strain and myocardial injury, represented by BNP and hsTnI values, would contribute to prioritization of LT candidates and help administer target therapies that could modify early mortality.

Background: Generally, lactate levels > 2 mmol/L represent hyperlactatemia, whereas lactic acidosis is often defined as lactate > 4 mmol/L. Although hyperlactatemia is common finding in liver transplant (LT) candidates, association between lactate and organ failures with Acute-on-chronic Liver Failure (ACLF) is poorly studied. We searched the important variables for pre-LT hyperlactatemia and examined the impact of preoperative hyperlactatemia on early mortality after LT. Methods: A total of 2,002 patients from LT registry between January 2008 and February 2019 were analyzed. Six organ failures (liver, kidney, brain, coagulation, circulation, and lung) were defined by criteria of EASL-CLIF ACLF Consortium. Variable importance of preoperative hyperlactatemia was examined by machine learning using random survival forest (RSF). Kaplan-Meier Survival curve analysis was performed to assess 90-day mortality.Results: Median lactate level was 1.9 mmol/L (interquartile range: 1.4, 2.4 mmol/L) and 107 (5.3%) patients showed > 4.0 mmol/L. RSF analysis revealed that the four most important variables for hyperlactatemia were MELD score, circulatory failure, hemoglobin, and respiratory failure. The 30-day and 90-day mortality rates were 2.7% and 5.1%, whereas patients with lactate > 4.0 mmol/L showed increased rate of 15.0% and 19.6%, respectively. Conclusion: About 50% and 5% of LT candidates showed pre-LT hyperlactatemia of > 2.0 mmol/L and > 4.0 mmol/L, respectively. Pre-LT lactate > 4.0 mmol/L was associated with increased early post-LT mortality. Our results suggest that future study of correcting modifiable risk factors may play a role in preventing hyperlactatemia and lowering early mortality after LT.

Background: We aimed to explore the distribution of intraoperative lactic acid (LA) level during liver transplantation (LT) and determine the optimal cutoff values to predict post-LT 30-day and 90-day mortality.Methods: Intraoperative LA data from 3,338 patients were collected between 2008 to 2019 and all-cause mortalities within 30 and 90 days were retrospectively reviewed. Of the three LA levels measured during preanhepatic, anhepatic, and neohepatic phase of LT, the peak LA level was selected to explore the distribution and predict early post-LT mortality. To determine the best cutoff values of LA, we used a classification and regression tree algorithm and maximally selected rank statistics with the smallest P value.Results: The median intraoperative LA level was 4.4 mmol/L (range: 0.5–34.7, interquartile range: 3.0–6.2 mmol/L). Of the 3,338 patients, 1,884 (56.4%) had LA levels > 4.0 mmol/L and 188 (5.6%) had LA levels > 10 mmol/L. Patients with LA levels > 16.7 mmol/L and 13.5–16.7 mmol/L showed significantly higher 30-day mortality rates of 58.3% and 21.2%, respectively. For the prediction of the 90-day mortality, 8.4 mmol/L of intraoperative LA was the best cutoff value.Conclusions: Approximately 6% of the LT recipients showed intraoperative hyperlactatemia of > 10 mmol/L during LT, and those with LA > 8.4 mmol/L were associated with significantly higher early post-LT mortality.

Background: Considering the importance of the inflammatory status of recipients on outcomes following liver transplantation (LT), we investigated the association between C-reactive protein-to-albumin ratio (CAR) and one-year mortality following LT and compared it with other parameters reflecting patients’ underlying inflammatory status.Methods: A total of 3,614 consecutive adult LT recipients were retrospectively evaluated. Prognostic parameters were analyzed using area under the receiver operating characteristic curve (AUROC) analysis, and subsequent cutoffs were derived. For survival analysis, Cox proportional hazards and Kaplan-Meier analyses were performed.Results: The AUROC for CAR to predict one-year mortality after LT was 0.68 (0.65–0.72), which was the highest compared with other inflammatory parameters, with the best cutoff of 0.34. A CAR ≥ 0.34 was associated with a significantly higher one-year mortality rate (13.3% vs. 5.8 %, log-rank P < 0.001) and overall mortality rate (24.5% vs. 12.9%, log-rank P = 0.039). A CAR ≥ 0.34 was an independent predictor of one-year mortality (hazard ratio, 1.40 [1.03–1.90], P = 0.031) and overall mortality (hazard ratio 1.39 [1.13–1.71], P = 0.002) after multivariable adjustment.Conclusions: Preoperative CAR (≥ 0.34) was independently associated with a higher risk of one-year and overall mortality after LT. This may suggest that CAR, a simple and readily available biomarker, maybe a practical index that may assist in the risk stratification of liver transplantation outcomes.