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Background: Hepatorenal syndrome (HRS) is a serious complication of liver cirrhosis with poor survival in the absence of liver transplantation (LT). HRS represents a state of profound circulatory and cardiac dysfunction. Whether it increases risk of perioperative major adverse cardiovascular events (MACE) following LT remains unclear., Methods: We performed a retrospective cohort study of 560 consecutive patients undergoing cardiac workup for LT of whom 319 proceeded to LT. All patients underwent standardized assessment including dobutamine stress echocardiography. HRS was defined according to International Club of Ascites criteria., Results: Primary outcome of 30-day MACE occurred in 74 (23.2%) patients. A significantly higher proportion of patients with HRS experienced MACE (31 [41.9%] versus 54 [22.0%]; P = 0.001). After adjusting for age, model for end-stage liver disease score, cardiovascular risk index, history of coronary artery disease, and a positive stress test, HRS remained an independent predictor for MACE (odds ratio [OR], 2.44; 95% confidence interval [CI], 1.13-5.78). Other independent predictors included poor functional status (OR, 3.38; 95% CI, 1.41-8.13), pulmonary hypertension (OR, 3.26; 95% CI, 1.17-5.56), and beta-blocker use (OR, 2.56; 95% CI, 1.10-6.48). Occurrence of perioperative MACE was associated with a trend toward poor age-adjusted survival over 3.6-year follow-up (hazard ratio, 2.0; 95% CI, 0.98-4.10; P = 0.057)., Conclusions: HRS, beta-blocker use, pulmonary hypertension, and poor functional status were all associated with over a 2-fold higher risk of MACE following LT. Whether inclusion of these variables in routine preoperative assessment can facilitate cardiac risk stratification warrants further study., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Purpose: Postoperative atrial fibrillation (POAF) is the commonest cardiovascular complication following liver transplantation (LT). This study sought to assess a possible association of POAF with subsequent thromboembolic events in patients undergoing LT., Methods: A retrospective cohort study of consecutive adults undergoing LT between 2010 and 2018 was undertaken. Patients were classified as POAF if atrial fibrillation (AF) was documented within 30 days of LT without a prior history of AF. Cases of ischemic stroke or systemic embolism were adjudicated by a panel of 2 independent physicians., Results: Among the 461 patients included, POAF occurred in 47 (10.2%) a median of 3 days following transplantation. Independent predictors of POAF included advancing age, postoperative sepsis and left atrial enlargement. Over a median follow-up of 4.9 (interquartile range, 2.9-7.2) years, 21 cases of stroke and systemic embolism occurred. Rates of thromboembolic events were significantly higher in patients with POAF (17.0% versus 3.1%; P <0.001). After adjustment, POAF remained a strong independent predictor of thromboembolic events (hazard ratio, 8.36 [95% CI, 2.34-29.79]). Increasing CHA 2 DS 2 VASc score was also an independent predictor of thromboembolic events (hazard ratio, 1.58 [95% CI, 1.02-2.46]). A model using POAF and a CHA 2 DS 2 VASc score ≥2 alone yielded a C statistic of 0.77, with appropriate calibration for the prediction of thromboembolic events. However, POAF was not an independent predictor of long-term mortality., Conclusions: POAF following LT is associated with an 8-fold increased risk of thromboembolic events and the use of the CHA 2 DS 2 VASc score may facilitate risk stratification of these patients. Prospective studies are warranted to assess whether the use of oral anticoagulants can reduce the risk of thromboembolism following LT.

Background: Low pretransplant serum testosterone has recently been associated with increased mortality in men awaiting liver transplantation, but the potential impact on rejection has not yet been investigated., Methods: Pretransplantation serum testosterone, SHBG, and other variables were collected on 190 consecutive men who received a liver transplant between 2007 and 2013. Rates of subsequent acute cellular rejection were recorded. Multivariable analysis was performed to define variables associated with rejection and other clinically important end points., Results: Thirty (16%) of 190 men experienced acute cellular rejection. Lower pretransplant testosterone was associated with lower rejection rates, -7% (95% confidence interval [CI], -2% to -12%) per nmol/L decrease in total testosterone and -4% (95% CI, -0.5% to -7%) per 10 pmol/L decrease in free testosterone. Total testosterone (correlation 0.29, P=0.04) and free testosterone (correlation 0.37, P=0.01) correlated significantly with the histological severity of rejection. Older age at transplant (+5% [95% CI, 9%-2%]) per year, and nonautoimmune etiology of liver disease (OR, 1.0 for autoimmune, 0.22 [95% CI, 0.07-0.73] for hepatitis C virus, and 0.58 [95% CI, 0.21-1.71] for other etiologies) were also associated with decreased rejection risk. In a generalized linear model including the covariates testosterone, SHBG, age, etiology, and MELD, total testosterone remained a significant predictor of rejection (adjusted OR, 1.06; P=0.03), as did age at transplant (OR, 0.95; P=0.01)., Conclusion: Low preliver transplant serum testosterone independently predicts a decreased risk of acute allograft rejection. Whether testosterone is a marker of disease-associated immune dysfunction or has immune-modulatory effects requires further study.

Background: Abnormal liver function tests are common in pregnancy; however, liver failure is rare. Pregnancy is a catabolic state that can precipitate illness in patients with underlying metabolic disorders., Case: A 19-year-old woman presented at 14 weeks of gestation with an alanine transaminase of 2,252 international units/L (less than 30), an international normalized ratio of 6.9 (0.9-1.2), and an ammonia of 58 micromole/L (11-51 micromole/L). No cause was identified on routine investigations including liver biopsy. Biochemical and clinical deterioration prompted investigation for a metabolic disorder. Urinary orotic acid was elevated, consistent with the urea cycle disorder type 1 citrullinemia. Appropriate management (arginine supplementation and dietary protein restriction) led to rapid improvement and later delivery of a healthy neonate., Conclusion: This is an unusual presentation that reminds us of the importance of considering metabolic disorders during the catabolic stress of pregnancy.

Passive immunoprophylaxis with hepatitis B immunoglobulin is used to reduce the risk of infection of grafts after liver transplantation and also to protect newborn children of hepatitis B virus-infected mothers. The use of hepatitis B immunoglobulin is associated with the emergence of variant viruses or escape mutants that have specific amino acid substitutions in immunodominant epitopes. Under these circumstances, high serum titres of the virus may be observed in the context of apparently protective levels of antibody to hepatitis B surface antigen. The potential impact of hepatitis B surface antigen variation on vaccination strategies remains a contentious issue. As the burden of hepatitis B virus is dramatically reduced by major vaccination programmes, a greater proportion of carriers will demonstrate hepatitis B surface antigen variation from wild-type. The degree of protection afforded by current vaccines from subsequent infection by variants of the virus is unknown. Concern is raised over the potential impact of hepatitis B surface antigen variation on hepatitis B virus polymerase inhibitor susceptibility, and the reduced sensitivity of current antigen assays for detection of hepatitis B surface antigen variants.