Assessment of standard laboratory tests and rotational thromboelastometry for the prediction of postoperative bleeding in liver transplantation.

BACKGROUND: Perioperative bleeding remains a major challenge in liver transplantation. We aimed to compare standard laboratory tests with thromboelastometry (ROTEM ® ) with regard to their ability to predict postoperative non-surgical bleeding. METHODS: Data from 243 adult liver transplant recipients from January 2012 to May 2014 were evaluated retrospectively. Upon admission to the intensive care unit, coagulation status was assessed using standard laboratory tests [prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen concentration, and platelet count] and ROTEM ® whole blood coagulation assays. Bleeding was defined as transfusion of ≥ 3 units of red blood cells or reoperation for non-surgical bleeding within 48 h after transplantation. Coagulation test results were analysed using receiver operating characteristics (ROC) in order to identify variables predictive of postoperative bleeding. Coagulation management was based on ROTEM ® -guided factor concentrate treatment. RESULTS: The overall incidence of bleeding was 12.3% ( n =30). Twenty-three (9.5%) patients underwent reoperation and seven (2.9%) received ≥3 units of red blood cells and non-operative management. Standard laboratory tests predictive of postoperative bleeding were aPTT and PT [area under the ROC curve (AUC) 0.688 and 0.623, respectively]. Tests predictive of bleeding with ROTEM ® were CT EXTEM , CFT INTEM , A10 FIBTEM , and MCF FIBTEM , with AUCs of 0.682, 0.615, 0.615, and 0.611, respectively. Fibrinogen concentration, platelet count, and other ROTEM ® variables failed to demonstrate predictive value for postoperative bleeding (AUC <0.6). Dialysis-dependent kidney failure, 30 day mortality, and median model for endstage liver disease score were all significantly higher in bleeding patients. CONCLUSIONS: Although both postoperative standard laboratory tests and ROTEM ® assays could identify patients at risk for postoperative bleeding, ROTEM ® assays demonstrated a greater predictive value for impaired fibrinogen polymerization-related coagulopathy.

The significance of resection margins on R0 results in intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma is the second most common primary liver cancer after hepatocellular carcinoma with an increasing incidence worldwide. Surgical resection is still the only potential cure, and survival rates are dismal due to disease relapse after resection and/or metastatic disease. Positive resection margins are associated with recurrence, with conflicting studies regarding the benefits of wide resection margins to reduce recurrence rates. METHODS: 126 patients with an R0 resection treated with hepatic surgery for intrahepatic cholangiocarcinoma at the Surgical Department at the Medical University Centre Essen, Germany were identified in a database and retrospectively analysed. Patients were grouped into three groups according to margin width, <1 mm (very narrow margin width) 1-5 mm (narrow margin width) and >5 mm (wide margin width). Epidemiological as well as perioperative data was analysed, and a univariate analysis as well as Kaplan-Meier plots carried out to investigate recurrence-free and overall survival. RESULTS: Wider resection margins did not lead to better recurrence-free survival. A wider resection margin >5 mm was not significantly associated with improved overall survival. Positive lymph nodes (HR 2.50, 95% CI 1.11-5.61, p=0.027) and non-anatomic resections (HR 2.06, 95% CI 1.13-3.75, p=0.019) are significantly associated with poorer overall survival. Regarding recurrence-free survival, V2 vascular invasion was the only risk factor statistically significantly associated with poorer recurrence-free survival (HR 8.83, 95% CI 0.85-2.83, p=0.005). CONCLUSION: Resection margins did not have a significant impact on disease free survival or overall survival following hepatic resection for intrahepatic cholangiocarcinoma. Non-anatomical resections, lymph node and vascular invasion all significantly impacted oncological outcomes.

Idiosyncratic Drug-Induced Liver Injury in a Healthy Patient following PCSK9-Inhibitor Injection.

Background: Acute liver injury is a life-threatening condition with disparate aetiology. Swift and adequate interdisciplinary treatment is essential to assure the best possible outcomes in these patients. Investigations to identify the cause of the condition and the implementation of quick and appropriate treatment can be lifesaving. Case Presentation. In October 2022, an otherwise healthy 66-year-old male presented at the University Hospital Essen with acute liver injury following an inclisiran injection for hypercholesterinaemia. Four weeks following admission, the patient fully recovered after initially receiving short-term cortisol therapy and open albumin (OPAL) dialysis, and the indices of liver, kidney, and coagulation function were normal at discharge. Conclusion: This is to our knowledge the first reported acute liver injury due to an inclisiran injection. Cortisol in combination with OPAL dialysis is an effective method for the treatment of acute liver injury caused by inclisiran injury, and in this case, it led to a near-complete reversal of the acute liver injury at the time of discharge.

[Liver parameters in intensive care medicine]. / Leberparameter in der Intensivmedizin.

Elevated liver function tests in ICU-bound patients are associated with a greater risk of mor-tality. Chronic liver diseases as well as acute events and complications of therapy are among the causes. The disorder could further be investigated by assessment of liver cell integrity markers (AST, ALT and GLDH), cholestasis parameters -(bilirubin, GGT, ALP) and liver synthethic function (albumin, coagulation profile). Ultrasound and elastography are cheap and mobile options to evaluate chronic liver disease, cholestasis or perfusion of the liver. The interpretation of the results should include the medical history on the ICU. Liver injury could be due to septic or isch-aemic complications as well as toxic side effects or parenteral nutrition. The main therapeutic option is to identify the cause of the liver dysfuntion and to eliminate it as far as possible.

Prognostic factors of poor postoperative outcomes in gastrectomies.

Background: Gastric cancer is one of the most common cancers worldwide and is the third most common cause of cancer related death. Improving postoperative results by understanding risk factors which impact outcomes is important. The current study aimed to compare immediate perioperative outcomes following gastrectomy. Methods: 302 patients following gastric resections over a 10-year period (January 2009-January 2020) were identified in a database and retrospectively analysed. Epidemiological as well as perioperative data was analysed, and a univariate and multivariate analysis performed to identify risk factors for in-hospital mortality. Results: In general, gastrectomies were mainly performed electively (total vs. subtotal 95% vs. 85%, p = 0.004). Patients having subtotal gastrectomy needed significantly more PRBC transfusions compared to total gastrectomy (p = 0.039). Most emergency surgeries were performed for benign diseases, such as ulcer perforations or bleeding and gastric ischaemia. Only emergency surgery was significantly associated with poorer overall survival (HR 2.68, 95% CI 1.32-5.05, p = 0.003). Conclusion: In-hospital mortality was comparable between total and subtotal gastrectomies. Only emergency interventions increased postoperative fatality risk.

Acute management of refractory variceal bleeding in liver cirrhosis by self-expanding metal stents.

BACKGROUND AND AIMS: Current treatment strategies of variceal bleeding (VB) include banding and sclerotherapy. However, up to 10% of bleeding events remain refractory to standard therapy with high mortality. With this study, we aimed to evaluate the implantation of self-expanding metal stents (SEMS) for the management of therapy-refractory variceal bleeding. PATIENTS AND METHODS: Eight cirrhotic patients who presented to our unit with a total of 9 refractory bleeding events were treated by SEMS placement. RESULTS: Stenting resulted in immediate hemostasis in all cases without recurrent bleeding with SEMS in situ. After stabilization, 1 patient was treated by transjugular intrahepatic portosystemic shunt (TIPS) and after the second bleeding episode by TIPS dilation. One patient underwent orthotopic liver transplantation (OLT). The remaining patients were treated with standard drug regimens to reduce portal pressure. The SEMS were removed after a median of 11 days. No acute hemorrhage was noted on stent retrieval. While no early rebleeding occurred in the patients after TIPS implant, TIPS dilation or OLT, 3 out of 5 patients on conservative treatment experienced recurrence of VB within 9 days after SEMS removal. CONCLUSIONS: SEMS placement sufficiently stops hemorrhage in refractory VB. Due to the high rebleeding rate after conservative treatment alone following SEMS removal, this procedure may be utilized as a mere bridging method. Additional interventional and/or surgical methods to effectively reduce portal pressure (i.e. TIPS, OLT) should be considered. Further studies to evaluate the optimum treatment algorithm of refractory esophageal VB are warranted.

Efficacy and safety of linezolid in liver transplant patients.

Bacterial infections are the main cause of death within the first year after liver transplantation, and the increased incidence of multidrug-resistant gram-positive pathogens has created a major challenge in the treatment of these patients. Linezolid, the first US Food & Drug Administration-approved oxazolidinone, offers a valuable novel treatment option for serious gram-positive infections. Linezolid is relatively non-toxic but prolonged treatment with linezolid was associated with thrombocytopenia. Here we report on the experience of linezolid treatment in adult liver transplant patients, who are at an increased risk for thrombocytopenia because of hypersplenism. From November 2003 until December 2009, we evaluated the clinical course of 46 liver transplant patients (27 male/19 female) in our surgical intensive care unit. For proven or probable gram-positive infection, all patients received linezolid 600 mg intravenously every 12 h. On clinical improvement, treatment was changed to oral linezolid 600 mg twice daily. Treatment duration was 11 ± 7 days. Treatment indications were pneumonia (n = 8), blood stream infection (n = 30), and surgical site/abdominal infection (n = 3). Clinical cure was achieved in 43 out of 46 patients. During the course of treatment, no cases of severe thrombocytopenia occurred and a statistically significant platelet count increase was seen from day 1 (110 ± 73/nL) to day 7 (165 ± 116/nL) and day 14 (180 ± 140/nL). We did not observe any further adverse events, especially no severe neurological complications (e.g., serotonin syndrome) or signs of lactate acidosis. Two patients died from uncontrolled vancomycin-resistant Enterococcus faecium sepsis with septic shock and one due to uncontrolled methicillin-resistant Staphylococcus aureus pneumonia. These deaths were considered to be unrelated to linezolid treatment, and linezolid was regarded as the optimal treatment choice in these patients. A subgroup analysis of patients treated for >14 days revealed no statistically significant differences when compared with patients on shorter treatment. In particular, no cases of thrombocytopenia occurred during longer treatment. In conclusion, linezolid is a safe and effective treatment for adult liver transplant patients with gram-positive infections.

Glutathione-S-transferase subtypes α and π as a tool to predict and monitor graft failure or regeneration in a pilot study of living donor liver transplantation.

OBJECTIVE: Glutathione-S-transferase (GST) subtype α and π are differentially expressed in adult liver tissue. Objective of the study was if GST α and π may serve as predictive markers for liver surgery, especially transplantations. METHODS: 13 patients receiving living donor liver transplantation (LDLT) and their corresponding donors were analyzed for standard serum parameters (ALT, AST, γGT, bilirubin) as well as GST-α and -π before LDLT and daily for 10 days after LDLT. Patients (R) and donors (D) were grouped according to graft loss (R1/D1) or positive outcome (R2/D2) and above named serum parameters were compared between the groups. RESULTS: R1 showed significantly increased GST-α and significantly lower GST-π levels than R2 patients or the donors. There was a positive correlation between GST-α and ALT, AST as well as bilirubin and a negative correlation to γGT. However, γGT correlated positively with GST-π. Graft failure was associated with combined low GST-π levels in donors and their recipients before living donor liver transplantation. CONCLUSION: Our data suggest that high GST-α serum levels reflect ongoing liver damage while GST-π indicates the capacity and process of liver regeneration. Additionally, GST-π may be useful as marker for optimizing donor and recipient pairs in living donor liver transplantation.

Outbreak due to a Klebsiella pneumoniae strain harbouring KPC-2 and VIM-1 in a German university hospital, July 2010 to January 2011.

We describe the epidemiology and characteristics of the pathogen and patients (n=7) associated with an outbreak of a carbapenem-resistant Klebsiella pneumoniae (CRKP) strain in a German university hospital from July 2010 to January 2011. Species identification and detection of carbapenem resistance were carried out using standard microbiological procedures. Carbapenemases were detected by phenotypic methods and specific polymerase chain reactions (PCRs). DNA fingerprinting profiles were performed with repetitive sequence-based PCR. Medical records of colonised or infected patients were retrospectively reviewed. Antibiotic resistance profiles, PCR-specific amplification products and genotyping demonstrated that the outbreak occurred because of the spread of a single CRKP clone harbouring both KPC-2 and VIM-1. Five of the seven patients had invasive infections with the CRKP strain; the deaths of four of them were directly related to the infection. Early implementation of infection control interventions brought about efficient containment of further cross-transmission. Rapid dissemination of carbapenemase-producing Enterobacteriaceae is a serious concern in patient care and is a problem that has emerged in western Europe.

Infectious complications in the early postoperative period in liver transplant patients.

Liver transplantation (LTx) is a technically well established procedure in acute and in end-stage liver diseases. However, opportunistic infections remain one of the important complications in short and long-term outcome of LTx patients. Bloodstream and pulmonary infections are the major cause of death in the first year following liver transplantation. Due to extended use of chinolons and third generation cephalosporines there is a shift towards multidrug-resistant bacteria including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and extended b-lactamase-producing gram negative rods. Fungal infections are mainly due to Candida spp. Viral infections, such as with cytomegalovirus, human herpesvirus 6, herpes simplex virus, and Epstein-Barr virus infections are another major cause of morbidity in patients receiving solid organ transplants, including liver transplant patients. Studies of infection following LTx are necessary to improve management and to provide a better outcome after LTx. This review focuses on the most important bacterial, fungal and viral infections in LTx patients.

Territorial belonging of the middle hepatic vein in living liver donor candidates evaluated by three-dimensional computed tomographic reconstruction and virtual liver resection.

BACKGROUND: Postoperative venous congestion can lead to graft and remnant liver failure in living donor liver transplantation. This study was designed to delineate 'territorial belonging' of the middle hepatic vein (MHV) and to identify hepatic venous anatomy at high risk of outflow congestion. METHODS: MHV belonging patterns for right (RHL) and left (LHL) hemilivers were evaluated by three-dimensional computed tomographic reconstruction and virtual hepatectomy in 138 consecutive living liver donor candidates. RESULTS: The right hepatic vein (RHV) was dominant in 84.1 per cent and an accessory inferior hepatic vein (IHV) was present in 47.1 per cent of livers. Three MHV belonging types were identified for the RHL. Strong and complex MHV types A and C were associated with large RHL venous congestion. The MHV belonged to the LHL in 65.9 per cent, draining 37 per cent of this hemiliver. In virtual liver resections, left MHV type D was a risk category for small left liver remnants. CONCLUSION: MHV territorial belonging types A and C were identified as high risk for RHL venous congestion. Their presence should prompt consideration of either inclusion of the MHV with the right graft or reconstruction of its tributaries, and preservation of IHV territory.

Invasive aspergillosis in two liver transplant recipients: diagnosis by SeptiFast.

We report the clinical features, diagnosis, and monitoring findings of invasive aspergillosis (IA) in 2 liver transplant recipients. Blood/serum samples and bronchoalveolar lavage (BAL) fluids were analyzed by a novel commercial polymerase chain reaction (PCR) assay (SeptiFast) and an Aspergillus galactomannan (GM) enzyme-linked immunoassay (EIA). The diagnosis of IA could be performed in <6 h with the detection of Aspergillus fumigatus DNA in blood and BAL fluid. High GM values (mean: 9.1, range: 7.3-10.8) in serum and BAL fluid confirmed the SeptiFast result. Follow-up of the SeptiFast findings and GM index correlated with the clinical course. The molecular detection of A. fumigatus-specific DNA and GM test in blood/serum and BAL samples appears to be a useful tool for prompt diagnosis of IA. Further prospective clinical trials are necessary to evaluate the accuracy of SeptiFast and the GM test in diagnosing IA.

Successful salvage therapy with daptomycin after linezolid and vancomycin failure in a liver transplant recipient with methicillin-resistant Staphylococcus aureus endocarditis.

Infective endocarditis is a rare complication affecting solid organ transplant recipients. Staphylococcus aureus is a common cause of infective endocarditis accounting for about 30% of cases. We present a case of nosocomial methicillin-resistant S. aureus endocarditis with persistent bacteremia, in a patient following orthotopic liver transplantation. We were unable to eradicate this infection with primary linezolid therapy or with secondary treatment with combined vancomycin and rifampicin, but successfully treated it with daptomycin, in addition to tricuspid and aortic valve replacement.

Acute liver failure in a metropolitan area in Germany: a retrospective study (2002 - 2008).

OBJECTIVES: To determine current etiologies of acute liver failure (ALF) and clinical and laboratory parameters associated with the outcome upon ALF, so as to identify the frequency of present causes of ALF in Germany as well as potential new prognostic parameters. PATIENTS: 134 adult patients (63 % females / 37 % males) aged 41 +/- 16 years (median: 38 years) with established ALF criteria. DESIGN AND SETTING: A retrospective study (1 / 2002 - 4 / 2008) on ALF patients from the Ruhr Area, the largest urban region located in northwestern Germany. Clinical and laboratory data were collected for a period of four weeks after study admission. RESULTS: Etiologies of ALF were identified as drug toxicity (39.6 % of the cases); combined viral hepatitides (23.1 %); or miscellaneous (16.4 %). In 20.9 % of the cases, the etiology remained indeterminate. Overall patient survival at four weeks was 81.3 %. While 89 patients (66.4 %) recovered under best supportive therapy, 26 patients (19.4 %) had to undergo liver transplantation. Increased body mass indices were significantly (p < 0.003) associated with a poor outcome. Intriguingly, high levels of cholestatic enzymes significantly (p < 0.01) correlated with a positive outcome. CONCLUSIONS: In providing first data on current ALF etiologies Germany, this study reveals that drug toxicity - in particular due to acetaminophen - has replaced viral hepatitis as the most single frequent cause of ALF in a densely populated urban area; this correlates with similar findings in the USA, the UK and Scandinavia. Lower body mass indices and elevated cholestatic enzyme levels had statistically significant prognostic power.

Preoperative volume prediction in adult live donor liver transplantation: 3-D CT volumetry approach to prevent miscalculations.

BACKGROUND: The precise preoperative calculation of functional liver volumes for both donor and recipient is a crucial part of the evaluation process in adult living donor liver transplantation. The purpose of this study was to describe and validate our modus 3-D CT volumetry. PATIENTS AND METHODS: Native (unenhanced), arterial, and venous phase CT images from 62 consecutive live liver donors were subjected to 3-D CT liver volume calculations and virtual 3-D liver partitioning. Graft-volume estimates based on our modus 3-D volumetry, which subtracted intrahepatic vascular volume from the "smallest" (native) unenhanced CT phase, were subsequently compared to the intraoperative graft-weights obtained in all 62 cases. Calculated (preoperative) liver-volume-body-weight-ratios and measured (intraoperative) liver-weight-body-weight-ratios of liver grafts were analyzed. RESULTS: Preoperative calculations of graft-volume according to our modus 3-D CT volumetry did not yield statistically significant over- or under-estimations when compared to the intraoperative findings independent of their age or gender. CONCLUSION: Our modus 3-D volumetry, when based on the "smallest" (native) unenhanced CT phase, accurately accounted for intrahepatic vascular volumes and offered a precise virtual model of individualized operative conditions for each potential live liver donor.

Kidney failure following liver resection.

In the recent 20 years liver resection has become a routine operation with reasonably low risk. Experienced hepatobiliary centers have reported low mortality rates (0%-5%) even in series with high-risk resection (extended right or left resection). Acute kidney failure correlates well with mortality. In our series, more than 70% of patients with kidney failure, who require dialysis died. Acute renal failure develops if patients are kept hypovolemic or the patient suffers from postresectional liver failure. Herein we discuss how kidney failure following liver resection can be avoided.

Intensive care unit management of liver transplant patients: a formidable challenge for the intensivist.

Patients with end-stage liver disease, particular following liver transplantation, are a major challenge for the intensivist. The recipient is at risk for cardiac decompensation, respiratory failure following reperfusion, and kidney failure. This review will focus on these topics to provide useful information concerning pathophysiology and treatment. Intensivists, who are involved in the postoperative care of liver transplant patients, have to be aware of these problems.

Liver "compliance": a previously unrecognized preoperative predictor of small-for-size syndrome in adult living donor liver transplantation.

BACKGROUND: The purpose of this study was to investigate the effect of liver compliance on computed tomography (CT) volumetry and to determine its association with postoperative small-for-size syndrome (SFSS). PATIENTS AND METHODS: Unenhanced, arterial, and venous phase CT images of 83 consecutive living liver donors who underwent graft hepatectomy for adult-to-adult living donor liver transplantation (ALDLT) were prospectively subjected to three-dimensional (3-D) CT liver volume calculations and virtual 3-D liver partitioning. Graft volume estimates based on 3-D volumetry, which subtracted intrahepatic vascular volume from the "smallest" (native) unenhanced and the "largest" (venous) CT phases, were subsequently compared with the intraoperative graft weights. Calculated (preoperative) graft volume-to-body weight ratios (GVBWR) and intraoperative measured graft weight-to-body weight ratios (GWBWR) were analyzed for postoperative SFSS. RESULTS: Significant differences in minimum versus maximum total liver volumes, graft volumes, and GVBWR calculations were observed among the largest (venous) and the smallest (unenhanced) CT phases. SFSS occurred in 6% (5/83) of recipients, with a mortality rate of 80% (4/5). In four cases with postoperative SFSS (n = 3 lethal, n = 1 reversible), we had transplanted a small-for-size graft (real GWBWR < 0.8). The three SFS grafts with lethal SFSS showed a nonsignificant volume "compliance" with a maximum GVBWR < 0.83. This observation contrasts with the seven recipients with small-for-size grafts and reversible versus no SFSS who showed a "safe" maximum GVBWR of 0.92 to 1.16. CONCLUSION: The recognition and precise assessment of each individual's liver compliance displayed by the minimum and maximum GVBWR values is critical for the accurate prediction of functional liver mass and prevention of SFSS in ALDLT.

Hepatic hilar and sectorial vascular and biliary anatomy in right graft adult live liver donor transplantation.

INTRODUCTION: The aim of this study was to analyze vascular and biliary variants at the hilar and sectorial level in right graft adult living donor liver transplantation. METHODS: From January 2003 to June 2007, 139 consecutive live liver donors underwent three-dimensional computed tomography (3-D CT) reconstructions and virtual 3-D liver partitioning. We evaluated the portal (PV), arterial (HA), and biliary (BD) anatomy. RESULTS: The hilar and sectorial biliary/vascular anatomy was predominantly normal (70%-85% and 67%-78%, respectively). BD and HA showed an equal incidence (30%) of hilar anomalies. BD and PV had a nearly identical incidence of sectorial abnormalities (64.7% and 66.2%, respectively). The most frequent "single" anomaly was seen centrally in HA (21%) and distally in BD (18%). A "double" anomaly involved BD/HA (7.2%) in the hilum, and HA/PV and BD/PV (6.5% each) sectorially. A "triple" anomaly involving all systems was found at the hilum in 1.4% of cases, and at the sectorial level in 9.4% of instances. Simultanous central and distal abnormalities were rare. In this study, 13.7% of all donor candidates showed normal hilar and sectorial anatomy involving all 3 systems. A simultaneous central and distal "triple" abnormality was not encountered. A combination of "triple" hilar anomaly with "triple" sectorial normality was observed in 2 cases (1.4%). A central "triple" normality associated with a distal "triple" abnormality occurred in 7 livers (5%). CONCLUSIONS: Our data showed a variety of "horizontal" (hilar or sectorial) and "vertical" (hilar and sectorial) vascular and biliary branching patterns, providing comprehensive assistance for surgical decision-making prior to right graft hepatectomy.

Intrahepatic biliary anatomy derived from right graft adult live donor liver transplantation.

OBJECTIVE: The successful management of the bile duct in right graft adult live donor liver transplantation requires knowledge of both its central (hilar) and distal (sectorial) anatomy. The purpose of this study was to provide a systematic classification of its branching patterns to enhance clinical decision-making. PATIENTS AND METHODS: We analyzed three-dimensional computed tomography (3-D CT) imaging reconstructions of 139 potential live liver donors evaluated at our institution between January 2003 and June 2007. RESULTS: Fifty-four (n = 54 or 38.8%) donor candidates had a normal (classic) hilar and sectorial right bile duct anatomy (type I). Seventy-eight (n = 78 or 56.1%) cases had either hilar or sectorial branching abnormalities (types II or III). Seven (n = 7 or 5.1%) livers had a mixed type (IV) of a rare and complex central and distal anatomy. CONCLUSIONS: We believe that the classification proposed herein can aid in the better organization and categorization of the variants encountered within the right-sided intrahepatic biliary system.