The Edge of Unknown: Postoperative Critical Care in Liver Transplantation.

Perioperative care of patients undergoing liver transplantation (LT) is very complex. Metabolic derangements, hypothermia, coagulopathy and thromboses, severe infections, and graft dysfunction can affect outcomes. In this manuscript, we discuss several perioperative problems that can be encountered in LT recipients. The authors present the most up-to-date information regarding predicting and treating hemodynamic instability, coagulation monitoring and management, postoperative ventilation strategies and early extubation, management of infections, and ESLD-related pulmonary complications. In addition, early post-transplant allograft dysfunction will be discussed.

Acquired Hemophilia A: A Permanent Challenge for All Physicians.

Acquired hemophilia A (AHA) is a rare disease with a prevalence in Europe of 1.5 per million. This diagnosis is significantly delayed in about one-third of all cases, leading to deferred treatment. The main signs of AHA are spontaneous bleeding seen in about two-thirds of all patients. AHA can be lethal in 20% of all symptomatic cases. This patient population's main standard laboratory finding is a prolonged aPTT (activated prothrombin Time) with otherwise normal coagulation results. In addition, antibodies against FVIII (in Bethesda Units) and a quantitative reduction of FVIII activity are necessary to confirm AHA. The therapy of acute bleeding related to AHA is based on the following main principles: Pharmacologic control of the bleeding is of absolute importance. It can be achieved by administering either recombinant activated FVIIa "bypass therapy"; activated prothrombin complex; or Emicizumab, a bispecific monoclonal antibody. Eradication of the FVIII antibodies should be initiated simultaneously. The combination of steroids with cyclophosphamide leads to the highest eradication rates. Causes of AHA may be related to neoplasms, autoimmune diseases, and pregnancy. We report on a patient who underwent four surgical procedures before the diagnosis of AHA was established.

[Surgery in patients with liver cirrhosis]. / Chirurgie bei Patienten mit Leberzirrhose.

BACKGROUND AND OBJECTIVE: Patients with liver cirrhosis who are in need of surgery show a high in-hospital mortality. This study examined the risk of postoperative morbidity and in-hospital mortality after operations on patients with liver cirrhosis. MATERIAL AND METHODS: In the time period from January 2010 to December 2017 a total of 321 patients with liver cirrhosis underwent general surgery in this department. Liver-specific scoring systems, such as the Child-Pugh score (CPS) and MELD score were retrospectively assessed and correlated with in-hospital mortality and perioperative morbidity using the Dindo-Clavien classification. RESULTS: Of the 321 patients (68% male) 21.2% underwent emergency surgery. These patients showed a mortality of 60%, which is significantly higher than in elective surgery (12%, p < 0.0001). Complex interventions showed a 41% mortality, minor interventions still 20.5% (p = 0.0001). The postoperative complication rate and mortality were significantly different sorted by CPS with 11.8%/6.3% in the CPS A category and 84%/73% in the CPS C category, respectively (p = 0.001). Statistically in-hospital mortality was increased by 20% for every point increase in the MELD score (odds ratio, OR 1.23, p = 0.0001). The presence of hepatic decompensation had the worst prognosis. CONCLUSION: Surgical interventions in patients with liver cirrhosis are associated with a high complication rate and in-hospital mortality. The CPS and MELD scores can be used for objective risk assessment, while clinical examination for signs of hepatic decompensation is also important. Laboratory values, such as sodium and creatinine can assist the assessment.

Efficacy of IgM-enriched Immunoglobulin for Vasopressor-resistant Vasoplegic Shock After Liver Transplantation.

BACKGROUND: Vasoplegia is a clinical condition typically manifested by cardiovascular instability unresponsive to the usual doses of inotropes or vasopressors. It can occur in a variety of clinical settings including liver transplantation (LT). Immunoglobulins have been used to treat sepsis-related vasoplegia. We performed a retrospective study to evaluate the efficacy of IgM-enriched immunoglobulin (IgMIg) on 30-day mortality and its ability to reverse vasoplegia in patients undergoing LT. METHODS: Between May 2013 and November 2017, 473 LT were performed at our institution. We identified 21 patients who received IgMIg for 3 days to treat vasoplegia. Patients included in the study met the criteria for having vasoplegia and required noradrenaline administration greater than 1 µg·kg·min for more than 24 hours to maintain a mean arterial pressure of 70 mm Hg or greater. Procalcitonin and interleukin-6 (IL-6) levels were used as surrogate markers for inflammation and were measured at the beginning and end of IgM treatment. RESULTS: After IgMIg administration, median noradrenaline infusion rates could be significantly reduced from 1.6 µg·kg·min (1.3-2 µg·kg·min) to 0.16 µg·kg·min (0.08-0.34 µg·kg·min) (P < 0.001). In addition, after treatment, procalcitonin levels decreased significantly from 44 ng/mL (24-158) to 26.1 ng/mL (10.9-48.7) (P < 0.001) and IL-6 levels decreased significantly from 63 pg/mL (29-102) to 20 pg/mL (11-20) (P < 0.001). Thirty-day morality was 14.3%. CONCLUSIONS: The administration of IgMIg in patients with vasoplegia after LT is associated with a return of hemodynamic stability. Despite a predicted mortality of over 90% by Sepsis-Related Organ Failure Assessment score, the mortality rate of patients receiving IgMIg in our study was less than 20%.

Transplantation of Renal Allografts From Organ Donors Reactive for HCV Antibodies to HCV-Negative Recipients: Safety and Clinical Outcome.

INTRODUCTION: Because of the shortage of available organs for renal transplantation, strategies enabling the safe use of organs from donors with potential chronic infections such as hepatitis C are necessary. The aim of this study was to analyze the outcome of renal transplant donation from hepatitis C virus (HCV)-positive donors. METHODS: Between September 2002 and May 2007, 51 kidneys (34 donors) reactive for HCV antibodies were further evaluated. Six kidneys (5 donors) were transplanted to 6 recipients with known chronic HCV infection. The remaining 29 donors underwent extended virological testing. Nine donors were HCV RNA positive and thus not suitable for HCV-negative patients. Twenty donors (21 kidneys) did not have detectable HCV RNA copies and were transplanted into 21 HCV-negative recipients. Clinical outcomes focusing on safety, allograft function, and de novo HCV infection in the recipient were collected. RESULTS: There were no de novo HCV infections detected in recipients who were HCV negative before transplantation. The extended virological donor screening did not have an impact on median cold ischemia time. Five-year graft survival was 75%. DISCUSSION: Organs from anti-HCV-reactive, nonviremic donors can be transplanted safely to HCV-negative recipients.

A non-interventional study of the genetic polymorphisms of NOD2 associated with increased mortality in non-alcoholic liver transplant patients.

BACKGROUND: Infections after liver transplantation are the main cause of death in the first year. Recent reports indicate that NOD2 gene mutations increase the risk for inflammatory bowl disease and the severity of graft-versus-host disease in bone marrow transplant patients. Data on polymorphisms in liver transplant patients are sparse. We analyzed 13 single-nucleotide polymorphisms (SNPs) of 13 different gene variants including the SNPs of NOD2 genes from liver recipients. The aim of the study was to evaluate the impact of the SNPs on dialysis-dependent kidney failure, the incidence of infections and patient survival. METHODS: During a period of 20-months, 231 patients were recruited in this non-interventional, prospective study. Thirteen different SNPs and their impact on the patients' survival, infection rate, and use of dialysis were assessed. RESULTS: NOD 2 wildtype genes were protective with respect to the survival of non-alcoholic, cirrhotic transplant patients (3 year survival: 66.8% wildtype vs. 42.6% gene mutation, p = 0.026). This effect was not observed in alcoholic transplant recipients.The incidence of dialysis-dependent kidney failure and infection in the liver transplant patients was not influenced by NOD 2 gene polymorphisms. No effect was noted in the remaining 12 SNPs.Patients with early allograft dysfunction experienced significantly more infections, required dialysis and had significantly worse survival.In contrast, the donor-risk-index had no impact on the infection rate, use of dialysis or survival. CONCLUSION: NOD2 gene variants seem to play a key role in non-alcoholic, liver transplant recipients. However these data should be validated in a larger cohort.

Liver transplantation using donor organs with markedly elevated liver enzymes: how far can we go?

BACKGROUND: The disparity between the demand for solid organs and the current supply is a growing problem for patients with end-stage liver disease. To overcome organ shortage, extended criteria donor organs are also accepted for liver transplantation. AIMS: We here unprecedentedly report the clinical course of patients receiving livers with markedly elevated liver enzymes. METHODS: Between November 2007 and December 2010, 15 donor livers with markedly elevated liver enzymes [median aspartate aminotransferase (AST) 1400 (500-7538) U/l, median alanine aminotransferase (ALT) 1026 (308-9179) U/l] were offered to our transplant centre. Based on elaborate judgment, seven of these donor livers were rejected and eight donor livers were transplanted. RESULTS: All eight transplanted patients showed a liver enzyme peak on the day of surgery (AST 2076 ± 1808 U/l, ALT 1087 ± 833 U/l) and a statistically significant decrease from day 0 to day 7 post-liver transplantation. INR decreased and platelet count increased statistically significantly within 1 week after liver transplantation. The patients were discharged from the hospital 28 ± 11 days after liver transplantation in good clinical condition. CONCLUSIONS: These data demonstrate that using donor livers with markedly elevated liver enzymes may be an acceptable option to expand the donor pool. Universal objective parameters for acceptance should be defined in future studies.