Patients Undergoing Liver Transplantation Research Articles

Intestinal Dysbiosis and Risk of Posttransplant Clostridioides difficile Infection in a Longitudinal Cohort of Liver Transplant Recipients.

ABSTRACTClostridioides difficile infection (CDI) has a higher incidence in solid organ transplant recipients than other hospitalized patients and can lead to poor outcomes. Perturbations to the intestinal microbiome are common in patients undergoing liver transplant (LT); however, the impacts of microbial diversity and composition on risk of CDI in this patient population is incompletely understood. Here, we assessed patients in an established, longitudinal LT cohort for development of CDI within 1 year of transplant. Clinical data were compared for patients with and without CDI using univariable models. 16S rRNA sequencing of fecal samples was performed at multiple pre- and posttransplant time points to compare microbiome α- and β-diversity and enrichment of specific taxa in patients with and without CDI. Of 197 patients who underwent LT, 18 (9.1%) developed CDI within 1 year. Pre-LT Child-Pugh class C liver disease, postoperative biliary leak, and use of broad-spectrum antibiotics were significantly associated with CDI. Patients who developed CDI had significantly lower α-diversity than patients without CDI overall and in samples collected at months 1, 3, and 6. Microbial composition (β-diversity) differed between patients with and without CDI and across sampling time points, particularly later in their posttransplant course. We also identified 15 (8%) patients with toxigenic C. difficile colonization who did not develop CDI and may have had additional protective factors. In summary, clinical and microbiome factors are likely to converge to impart CDI risk. Along with enhanced preventive measures, there may be a role for microbiome modulation to restore microbial diversity in high-risk LT patients.IMPORTANCE Liver transplant (LT) recipients have high rates of Clostridioides difficile infection (CDI), which has been associated with poor outcomes, including graft-related complications and mortality, in prior studies. Susceptibility to CDI is known to increase following perturbations in intestinal commensal bacteria that enable germination of C. difficile spores and bacterial overgrowth. In LT patients, changes in the intestinal microbiome resulting from advanced liver disease, surgery, and other clinical factors is common and most pronounced during the early posttransplant period. However, the relationship between microbiome changes and CDI risk after LT remains unclear. In this study, we investigated clinical and microbiome factors associated with development of CDI within the first year after LT. The importance of this work is to identify patients with high-risk features that should receive enhanced preventive measures and may benefit from the study of novel strategies to reconstitute the intestinal microbiome after LT.

Intraoperative Hypotension and 30-D Mortality After Liver Transplantation.

Background.Intraoperative hypotension (IOH) is common and associated with mortality in major surgery. Although patients undergoing liver transplantation (LT) have low baseline blood pressure, the relation between blood pressure and mortality in LT is not well studied. We aimed to determine mean arterial pressure (MAP) that was associated with 30-d mortality in LT.Methods.We performed a retrospective cohort study. The data included patient demographics, pertinent preoperative and intraoperative variables, and MAP using various metrics and thresholds. The endpoint was 30-d mortality after LT.Results.One thousand one hundred seventy-eight patients from 2013 to 2020 were included. A majority of patients were exposed to IOH and many for a long period. Eighty-nine patients (7.6%) died within 30 d after LT. The unadjusted analysis showed that predicted mortality was associated with MAP <45 to 60 mm Hg but not MAP <65 mm Hg. The association between MAP and mortality was further tested using adjustment and various duration cutoffs. After adjustment, the shortest durations for MAPs <45, 50, and 55 mm Hg associated with 30-d mortality were 6, 10, and 25 min (odds ratio, 1.911, 1.812, and 1.772; 95% confidence interval, 1.100-3.320, 1.039-3.158, and 1.008-3.114; P = 0.002, 0.036, and 0.047), respectively. Exposure to MAP <60 mm Hg up to 120 min was not associated with increased mortality.Conclusion.In this large retrospective study, we found IOH was common during LT. Intraoperative MAP <55 mm Hg was associated with increased 30-d mortality after LT, and the duration associated with postoperative mortality was shorter with lower MAP than with higher MAP.

Cardiovascular Risk Factors in Patients Before and After Successful Liver Transplantation.

BACKGROUND Liver transplantation (LTx) is useful in the treatment of end-stage liver disease. Outcomes of transplantation are dependent upon graft survival and can also be affected by superimposed cardiovascular morbidities. The present retrospective study was performed to assess the prevalence of cardiovascular risk factors before and after LTx. MATERIAL AND METHODS A retrospective review of 130 patients undergoing liver transplantation between October 2005 and April 2014 was completed. The mean age of the patients was 49.3±11.9 years. The prevalence of cardiovascular risk factors was assessed before and 2 years after transplantation. The prevalence of cardiovascular risk factors was assessed using a comparison based upon the etiologies of liver disease resulting in transplantation including alcohol, viral, and autoimmune processes using a chi-square analysis. RESULTS The prevalence of diabetes mellitus before and 2 years after liver transplantation (LTx) were 18% and 48% (P<0.001). Hypertension was documented in 24% of patients at baseline and 70% after 2 years of follow-up (P<0.001). The prevalence rates of diabetes mellitus before and 2 years after LTx were 18% and 48% (P<0.001). The prevalence of hypertriglyceridemia before and after LTx was 15% and 38%, respectively (P<0.001). Hypercholesterolemia was noted in 16% and 46%, respectively (P<0.001). Thirteen percent of patients before LTx and 18% after were obese (body mass index higher than 30 kg/m²). The annual incidence of diabetes mellitus, hypertension, hypertriglyceridemia, hypercholesterolemia, and obesity during the first 2 years after LTx was 15%, 23.5%, 15%, 18.5%, and 6%, respectively. Twenty-four percent of patients before and 10% after LTx admitted to tobacco use (P<0.001). The prevalence of diabetes (38% vs 67%, P=0.02), hypertriglyceridemia (19% vs 63%, P<0.001), hypercholesterolemia (28% vs 67%, P=0.002), and obesity (9% vs 33%, P=0.02) was lower in patients with an autoimmune cause of liver cirrhosis in comparison to patients with alcoholic disease. CONCLUSIONS The prevalence of hypertension and glucose and lipid metabolism abnormalities may increase in patients after liver transplantation. The prevalence of cardiovascular risk factors in patients after LTx may be related to the cause of liver injury before LTx.

The benefit of liver transplant beyond Milan criteria: An analysis using the National Cancer Database

BackgroundPublished studies examining the efficacy of liver transplantation in patients presenting with hepatocellular cancer beyond the traditional Milan criteria for liver transplantation have primarily been single institution series with limited ability to compare outcomes to alternative methods of management. MethodsWe queried the National Cancer Database to identify patients presenting between 2004 and 2016 with histologically confirmed clinical stage III and IVA hepatocellular cancer. Multivariable regression was used to identify factors associated with liver transplantation. Patients undergoing liver transplantation were 1:1 propensity score-matched for age, demographics, comorbid disease, clinical stage, and histologic resection margin to those undergoing surgical resection. The Kaplan-Meier method was used to compare overall survival profiles for matched cohorts. ResultsSeven hundred and ninety-two patients met inclusion criteria—590 (74.5%) underwent surgical resection and 202 (25.5%) liver transplantation. On adjusted analysis, patients undergoing liver transplantation were less likely to have advanced age (>60 years; odds ratio 0.39, 95% confidence interval [0.21–0.71]) and to be of Black race (odds ratio 0.42, 95% confidence interval [0.23–0.73]) or Asian (odds ratio 0.25, 95% confidence interval [0.11–0.53]) ethnicity but were more likely to have advanced (Charlson score >2) comorbidity scores, (odds ratio 2.48, 95% confidence interval [1.58–3.90]) and more likely to have private health insurance (odds ratio 4.17, 95% confidence interval [1.31–18.66]) than those undergoing surgical resection. On Kaplan-Meier analysis of matched cohorts, patients undergoing liver transplantation demonstrated significantly better rates of 5-year overall survival (65.3% vs 26.3%, P < .0001) and longer median overall survival times than those undergoing resection (53.1 ± 2.78 vs 26.9 ± 1.20 months, P < .0001). ConclusionLiver transplantation offers the potential to be an effective treatment modality in select patients presenting with stage III and IVA hepatocellular cancer.

The Impact of Bariatric-Surgery-Induced Weight Loss on Patients Undergoing Liver Transplant: A Focus on Metabolism, Pathophysiological Changes, and Outcome in Obese Patients Suffering NAFLD-Related Cirrhosis.

Because of their condition, patients with morbid obesity develop several histopathological changes in the liver, such as non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), cirrhosis, and end-stage liver disease (ESLD). Hence, a liver transplant (LT) becomes an opportune solution for them. Due to many challenges during the perioperative and postoperative periods, these patients are recommended to lose weight before the surgery. There are many proposals to achieve this goal, such as intragastric balloons and many different bariatric surgery (BS) procedures in combination with a preparation diet (very-low-calorie diet, ketogenic diet, etc.). All the interventions focus on losing weight and keeping the continuity and functionality of the digestive tract to avoid postoperative complications. Thus, this review analyzes recent publications regarding the metabolic and pathophysiological impacts of BS in LT patients suffering from NAFLD-related cirrhosis, the effect of weight loss on postoperative complications, and exposes the cost-effectiveness of performing BS before, after, and at liver transplantation. Finally, the authors recommend BS before the LT since there are many positive effects and better outcomes for patients who lose weight before the procedure. Nevertheless, further multicentric studies are needed to determine the generalizability of these recommendations due to their impact on public health.

Pediatric acute liver failure: An experience of a pediatric intensive care unit from resource limited settings.

IntroductionPediatric acute liver failure is a rare and serious disease. Though liver transplantation is considered as the established treatment option for patients who are unlikely to recover with medical management, however, with the advancement of medical care there has been an increase in spontaneous regeneration of liver, obviating the need for liver transplantation. We identified the etiologies, outcome and prognostic factors of acute liver failure and the validity of the existing liver transplantation criteria to predict the outcome of pediatric acute liver failure.Materials and methodsThis was a retrospective study done from January 2014 to December 2019 in a tertiary pediatric critical care unit in South India. All children aged between 1 month to 18 years admitted with acute liver failure were enrolled.ResultsOf 125 children with acute liver failure, the main etiologies were infections (32%), indeterminate (23%), paracetamol toxicity (21%), metabolic (13%) and others (11%). Dengue was the most common infection (55%). The median pediatric logistic organ dysfunction score at admission was 12 (4–27). Of 125 patients, 63.2% (n = 79) had spontaneous regeneration which was higher in paracetamol induced (92.3%) compared to non-paracetamol induced acute liver failure (55.5%). Only two patients underwent liver transplantation and 35% died. Peak alanine transaminase and use of inotropes significantly predicted the outcome of disease. Of 38 children meeting King's College Hospital criteria for liver transplantation, 57.9% had spontaneous regeneration and 36.8% died. Of 74 children meeting INR > 4 criteria, 54% (n = 40) had spontaneous regeneration and 43.2% died. INR >4 criteria was more sensitive than King's College Hospital criteria for predicting the need for liver transplantation.ConclusionPediatric acute liver failure is caused by varied etiologies and infections were the commonest cause. Despite having a seriously ill cohort of patients, medical management resulted in spontaneous regeneration in the majority of children with acute liver failure. The use of inotropes, advanced hepatic encephalopathy, and peak alanine transaminase were predictors of poor outcome in children with acute liver failure and these patients could be considered for liver transplantation as available. Therefore, we may need to develop better predictors of pediatric acute liver failure in resource limited settings.

Duration of operation and diagnosis of hepatitis B (HBV) is an independent risk factor for surgical site infections after liver transplantation.

Surgical site infections (SSI) are the most common complications after liver transplantation (LT). Although there are some risk factors known in the literature after LT, the available data is insufficient for routine use. In the present study, it was aimed to define the parameters that may be used to clearly determine the risk of SSI after LT in our clinic. In the present study, we evaluated 329 patients who underwent liver transplantation with regard to risk factors for surgical site infections. The relation between demographic data and SSI was evaluated using SPSS, Graphpad, and Medcalc statistical programs. In a total of 329 patients, SSIs were determined in 37 (11.24%). Among the 37 patients, 24 were classified as organ space (64.9%) and 13 as deep SSI (35.1%). None of these patients developed superficial incisional infection. SSI showed statistically significant relation with operation time (p= 0.008), diabetes (p= 0.004), and cirrhosis due to hepatitis B (p <0.001). As a result, deep and organ space infections are much more observed in patients undergoing liver transplantation with hepatitis B, diabetes mellitus and prolonged surgery. This is thought to have developed because of chronic irritation and increased inflammation. Since data on hepatitis B and duration of surgery are limited in the literature, this study is considered to be a contribution to the literature.

312.4: Surgical Management of Portal Venous Thrombosis in Patients Undergoing Liver Transplantation Proposed of an Algorithm

Introduction: Portal vein thrombosis (PVT) is common in patients with liver cirrhosis, undergoing liver transplantation (LT); In our environment, this is the first publication with an emphasis on results and surgical strategies.Objectives: It was to review the casuistry of the Guillermo Almenara Irigoyen National Hospital, determine characteristics, types of PVT and surgical management. Materials and Methods: The medical records of cirrhotic patients undergoing LT who presented PVT between March 2000 and June 2021 were analyzed. During this period, 304 liver transplants were performed in 285 patients, 256 adults and 29 pediatric patients; the latter were excluded. Results: We found 46 patients with PVT (17.9%), diagnosed before and during LT, none of malignant aetiology; The most frequent etiologies of cirrhosis were non-alcoholic steatohepatitis (37.4%), alcoholic steatohepatitis (22%), autoimmune hepatitis (AIH) (11%), hepatitis B virus (HBV) (7.4%) and others (11.5%). According to the Yerdel Classification, we find: Grade I: 22 (48%), Grade II: 15 (32.5%), Grade III: 6 (13%) and Grade IV: 3 (6.5%). The surgical strategies used were: thrombectomy in 40 (87.1%); Cavoportal hemitransposition in 2 (4.3%), reno-portal anastomosis with vein graft interposition in 2 (4.3%) and thrombovenectomy plus vein graft interposition in 2 (4.3%). In 3 cases there were re-PVTs (6.5%). We observed that PVT decreased patient survival after LT: One year (81.2%), 3 years (78.4%) and 5 years (78.4%) compared to patients without PVT at 1 year (84.6%) 3 years (82.3%) and 5 years (82.3%). Conclusion: Cirrhotic patients with PVT were clinically more decompensated, survival decreased with a higher degree of PVT. Surgical conduct was similar to other transplant centers; early diagnosis was essential to take an early surgical approach and reduce morbidity and mortality after liver transplantation. A management algorithm for portal vein thrombosis before liver transplantation is proposed. Key words: Portal Vein Thrombosis, Liver Transplantation, Yerdel Classification, Surgical Strategy.

211.6: ERAS in Liver Transplantation: A Decade Running a Comprehensive Fast-track Liver Transplant Protocol

Introduction: Enhanced recovery after surgery (ERAS) has been shown to facilitate discharge, decrease length of stay (LOS), improve outcomes and reduce costs. We used this concept to design a comprehensive fast-track pathway (OR-to- discharge) before starting our liver transplant activity and then applied this protocol prospectively to every single patient undergoing liver transplantation at our institution, monitoring the results periodically. We report our results after a decade of activity. Method: Prospective cohort study of all the liver transplants performed since we started our program in 2012. Balanced general anesthesia, fluid restriction, thromboelastometry, inferior vena cava preservation and tempo- rary portocaval shunt were strategies common to all cases. Our standard pro- tocol for immunosuppression included steroids, tacrolimus (delayed in the setting of renal impairment, with basiliximab induction added) and mycophe- nolate mofetil. Tacrolimus dosing was adjusted using a Bayesian estimation methodology. Oral intake and ambulation were started very early. LOS data refers to patients who were discharged (either from ICU or from the hospital) after transplantation. Results: A total of 359 liver transplants have been performed in 341 patients (269M/72F) over 114 months, mean age 57.3±9.5 years, raw MELD score 15.2±7.8 (MELD-Na 17.1±8.1). Predominant etiologies were alcohol (n = 203) and HCV (n = 105), with hepatocellular carcinoma present in 187 (52.1%). Twenty-six transplants were URGENT (7%) and 15 of them were performed for Fulminant Hepatic Failure. Eighteen patients underwent combined liver and kidney transplants. The median operating time was 307 min (range 167–546) with median cold ischemia time of 267 min (130–628). We transfused PRBCs in the OR in 51 cases (14.2%) at an average of 2.4 ± 1.2 units per case. Median ICU LOS was 12.7 h, and median post-transplant hospital LOS was 4 days (2–82) with 52 patients (16.3%) going home by the 2nd posttransplant day, 133 (41.6%) by the 3rd, and 190 (59.4%) by the 4th, which defines the LOS of our fast-track group (2–4 days). Overall thirty-day-readmission rate was 34.7%, and it was significantly lower (27.9% vs. 44.6% P = 0.002) in the fast-track group. Patient survival was 88% at 1 year and 79% at 5 years for the entire series. Conclusion: Fast-Tracking of Liver Transplant patients is feasible and remains the standard of care for our entire liver transplant population.

Femoral Pulse Pressure Variation Is Not Interchangeable with Radial Pulse Pressure Variation during Living Donor Liver Transplantation.

The radial artery is commonly used as the site measuring pulse pressure variation (PPV) during surgery. Accurate measurement of circulating blood volume and timely interventions to maintain optimal circulating blood volume is important to deliver sufficient oxygen to tissues and organs. It has not rather than never studied in patients undergoing liver transplantation whether PPV measured at peripheral sites, such as the radial artery, do represent central PPV for evaluating blood volume. In this retrospective study, 51 liver transplant recipients were enrolled. The two PPVs had been automatically recorded every minute in electrical medical records. A total 1878 pairs of the two PPVs were collected. The interchangeability of PPV measured at the radial and the femoral artery was analyzed by using the Bland–Altman plot, four-quadrant plot, Cohen’s kappa (k), and receiver operating curve. The bias and limits of agreement of the two PPVs were −1.3% and −8.8% to 6.2%, respectively. The percentage error was 75%. The concordance rate was 65%. The Kappa of PPV-radial determining whether PPV-femoral was >13% or ≤13% was 0.64. We found that PPV-radial is not interchangeable with PPV-femoral during liver transplantation. Additionally, PPV-radial failed to reliably track changes of PPV-femoral. Lastly, the clinical decision regarding blood volume status (depletion or not) is significantly different between the two PPVs. Therefore, PPV-femoral may help maintain blood volume circulating to major organs including the newly transplanted liver graft for liver transplant recipients.

Tissue Heavy Metals in Liver Diseases

Our objective was to determine the levels of heavy metals, oxidants, and antioxidants in liver tissue of patients with chronic liver disease (CLD) compared with healthy living liver donors (LLDs). We obtained liver specimens from patients undergoing liver transplant for CLD. Samples were also obtained from LLDs. Biochemical analyses were performed on all samples, and the levels of liver tissue, heavy metal, and oxidant-antioxidants biomarker levels in patients with CLD were compared with those measured in LLDs. One hundred and eighteen individuals were included for analyses. Fifty-nine were patients with CLD, and 59 were LLDs. The median levels of liver tissue of superoxide dismutase (P=.009), glutathione peroxidase (P=.042), total oxidant status (P=.006), oxidative stress index (P < .001), and copper (P=.035) were prominently more elevated in CLD than LLDs. On the other hand, the median levels of liver tissue of cadmium (P < .001), selenium (P=.042), and zinc (P < .001) levels were more elevated in the LLDs than patients with CLD. The 2 groups were similar in terms of total antioxidant status, manganese, arsenic, and lead levels. Superoxide accumulation in the liver was higher in patients with CLD. Concerning heavy metals, only the median tissue copper was elevated in patients with CLD with higher Cu/Zn ratio. Cadmium, selenium, and zinc were significantly higher in the healthy LLDs.

Elevated Pre- and Postoperative ROTEM™ Clot Lysis Indices Indicate Reduced Clot Retraction and Increased Mortality in Patients Undergoing Liver Transplantation.

Background: The ROTEM™ clot lysis index, describing the decrease in firmness of a clot with time, predicts mortality in various settings. The variability of the clot lysis index in surgical procedures and the involved pathophysiological mechanisms are unknown. We therefore compared pre- and postoperative clot lysis indices in liver transplantation (LTX) procedures, determined the eventual association with mortality, and investigated the mechanisms underlying decreased clot lysis index using inhibitors of fibrinolysis and clot retraction, respectively. Methods: In this retrospective cohort study, data on pre- and post-transplant ROTEM™ findings as obtained with EXTEM (tissue factor activation), INTEM (intrinsic system activation), FIBTEM (extrinsic system activation and inhibition of clot retraction), APTEM (extrinsic system activation and fibrinolysis inhibition), conventional laboratory coagulation tests, blood loss, transfusion of blood products, and outcome were registered. Results: Pre-transplant clot lysis indices showed a broad distribution ranging from 75% to 99% independent of the activator used (EXTEM, INTEM). During the surgical procedure, median clot lysis index values markedly increased from 92% to 97% (EXTEM) and 93% to 98% (INTEM), respectively (p < 0.0001 each). Aprotinin had no effect on either pre- or postsurgical clot lysis indices. Inhibition of platelet clot retraction with cytochalasin D (FIBTEM) markedly increased the preoperative clot lysis index. High pre- and post-transplantation clot lysis indices were associated with increased mortality irrespective of the activator used (EXTEM, INTEM) and the inhibition of fibrinolysis (APTEM). Inhibition of clot retraction (FIBTEM) abolished the association of clot lysis index with mortality in both pre- and post-transplantation samples. Conclusion: Both pre- and postoperative ROTEM™ clot lysis indices predict mortality in patients following liver transplantation. Inhibitor experiments reveal that the clot lysis index is not an indicator of fibrinolysis, but indicates platelet clot retraction. The marked increase of clot lysis index during liver transplantation is caused by a decrease in clot retraction with eventual consequences for clot stability, retraction of wound margins, and reperfusion of vessels in case of thrombosis.

Long-Term Improvement in Liver Function Following Transjugular Intrahepatic Portosystemic Shunt in Patients With Budd–Chiari Syndrome

Transjugular intrahepatic portosystemic shunt (TIPS) relieves hepatic venous obstruction in Budd-Chiari syndrome (BCS), but the effect on liver function is unclear, particularly outside the immediate post-treatment period. This study aims to evaluate the long-term impact of TIPS on liver function and outcomes in BCS patients. Twenty patients with BCS who underwent TIPS from 1999 to 2018 were included. Demographic data and clinical data at the time of TIPS procedure, 6 months, 12 months, 2 years, 5 years, and 10 years post-TIPS were collected. There were 13 (13/20, 65%) women and 7 (7/20, 35%) men with a mean age at the time of TIPS of 42.6±12.8 years. The median time from BCS diagnosis to TIPS was 41 (IQR: 4-165) days. The number of patients with severe ascites decreased significantly from 10/17 (58.8%) at the time of TIPS, to 1/16 (7.7%), 1/13 (7.7%), 2/16 (12.5%), 1/14 (7.1%), and 0/8 (0%) at 6 months, 12 months, 2 years, 5 years and 10 years post-TIPS, respectively.4/20 (20%) patients developed new hepatic encephalopathy post-TIPS procedure. Child-Pugh score significantly decreased from a score of 9.4±1.8 pre-TIPS to 7.6±1.8at 6 months, 7.4±1.5at 12 months, 7.3±1.6at 2 years, 6.8±1.5at 5 years, and 6.4±0.7at 10 years post-TIPS. Fifteen (15/20, 75%) patients required TIPS revision including 4 (4/15, 26.7%) within 30 days, 2 (2/15, 13.3% within 1 month to 1 year, and 9 (9/15, 60%) at more than 1 year. Eight (8/20, 40%) patients underwent liver transplantation (LT) at median time of 7.3 (IQR 3.2-12.9) years after TIPS. TIPS placement for BCS results in sustained resolution of symptoms and improved liver function. Despite the frequent need for revisions, the long-term durability of TIPS can forgo the need for LT in the majority of patients.

Successful use of intra‐operative continuous renal replacement therapy in pediatric liver transplant recipients: Single center case series

Acute kidney injury (AKI) is common in pediatric patients undergoing liver transplantation (LT), with an incidence 17%-55%. Fluid, metabolic, and acid-base aberrancies are often pronounced pre-operatively and further worsened by events during LT, making intra-operative continuous renal replacement therapy (CRRT) an option for critically ill LT recipients. All pediatric LT performed at our institution who underwent intra-operative CRRT between January 2017 and August 2021 were included. Patient demographics and clinical data including graft outcomes, intra-operative findings, and timing and indications for CRRT were collected from the electronic medical record. CRRT was used in nine of the 76 (12%) pediatric LT performed at our center during the study period. Ages at LT ranged from 39 to 17.7 years. Recipients requiring CRRT were more likely to have acute liver failure, status 1A, and higher calculated MELD/PELD scores. CRRT was initiated pre-transplant in three recipients and continued post-transplant in six recipients. Median duration of CRRT was two (range 0-14) days. Indications included hyperammonemia (3/9), acidosis (3/9), fluid overload (6/9), and hyperkalemia (2/9). The CRRT group had a significantly longer post-transplant intensive care unit length of stay in comparison to those that did not require CRRT (median 6, range 3-40 days vs. median 3, range 0-121 days, p=.02], but there were no significant differences in reoperations, hospital length of stay, or recipient or graft survival. We demonstrate that CRRT can be safely performed in pediatric LT recipients, including young infants through adolescents.

Hydroxocobalamin for treatment of catecholamine-resistant vasoplegia during liver transplantation: A single-center series of 20 cases.

IntroductionCatecholamine-resistant vasoplegia is a potentially devastating complication during liver transplantation. Hydroxocobalamin has emerged as a treatment for vasoplegia associated with cardiac surgery, liver transplantation, and septic shock.Presentation of caseWe performed a retrospective review of patients who underwent liver transplantation between October 2015 and May 2020 to evaluate the efficiency of hydroxocobalamin in this setting.DiscussionA total of 137 patients underwent liver transplantation, of which 20 received hydroxocobalamin for vasoplegia. Administration of hydroxocobalamin increased mean arterial pressure and reduced vasoactive drug requirements.ConclusionThis case series adds to the previous individual reports describing the use of hydroxocobalamin during liver transplantation suggesting hydroxocobalamin can mitigate refractory hypotension from catecholamine resistant vasoplegia during liver transplantation.

Epstein-Barr virus infection-associated cholangiocarcinoma: a report of one case and the review of literature

The clinical data of a patient with Epstein-barr virus (EBV) associated with cholangiocarcinoma was reported in this paper: a case of a 36-year-old female presented with abdominal pain and systemic skin yellowing combined with skin itching. Laboratory studies showed increase in alanine aminotransferase 242 U/L, aspartate aminotransferase 404 U/L, r-glutamyltransferase 1516 U/L, total bilirubin 308.2 µmol/L and CA199 (101.0 U/ml). AFP (4.5 ng/ml) was normal. CT revealed multiple space-occupying lesions in the liver. PET-CT revealed liver malignant tumor and lymph node metastasis. Liver puncture pathology revealed infiltrative growth of significant heterocyst nests in the liver tissue, which was morphologically consistent with malignant tumors, considering poorly differentiated carcinoma. Pathology suggestion: combining liver puncture with morphology, immunohistochemistry, and EBV in situ hybridization results, it was consistent with EB virus-associated poorly differentiated carcinoma, therefore, consider EBV infection-associated poorly differentiated cholangiocarcinoma (CCA) (LELC morphology). The patient underwent liver transplantation in Hangzhou Shulan Hospital on June 8, 2021 successfully. After surgery, the patient orally took tacrolimus for anti-rejection, entecavir for antiviral therapy, gemcitabine 1.2 g + cis-platinum 30 mg for chemotherapy. After following up for more than 5 months post liver transplantation, the condition of the patient deteriorated. The patient subsequently died. Based on the case of our patient and the review of existing literature, when the patient's serum CA199 increased, AFP did not change significantly, and there was no previous history of hepatitis B. CT revealed a low-density mass in the liver, ring enhancement in the arterial phase, and heterogeneous enhancement of the tumor in the delayed phase. Ring enhancement of the liver lesion mass was observed on MRI. Consider the might possibility of hepatic CCA. When patients showed recurrent tonsillitis at an early age, EBV virus infection should be vigilant and oropharyngeal tissue should persist, diagnosis of EBV-associated liver cancer should be considered. In particular, EBV infection-related liver cancer is relatively rare, the clinician should improve the recognition of the disease to strive for early diagnosis and therapy.

A Novel Digital Algorithm for Identifying Liver Steatosis Using Smartphone-Captured Images.

Background.Access to lifesaving liver transplantation is limited by a severe organ shortage. One factor contributing to the shortage is the high rate of discard in livers with histologic steatosis. Livers with <30% macrosteatosis are generally considered safe for transplant. However, histologic assessment of steatosis by a pathologist remains subjective and is often limited by image quality. Here, we address this bottleneck by creating an automated digital algorithm for calculating histologic steatosis using only images of liver biopsy histology obtained with a smartphone.Methods.Multiple images of frozen section liver histology slides were captured using a smartphone camera via the optical lens of a simple light microscope. Biopsy samples from 80 patients undergoing liver transplantation were included. An automated digital algorithm was designed to capture and count steatotic droplets in liver tissue while discounting areas of vascular lumen, white space, and processing artifacts. Pathologists of varying experience provided steatosis scores, and results were compared with the algorithm’s assessment. Interobserver agreement between pathologists was also assessed.Results.Interobserver agreement between all pathologists was very low but increased with specialist training in liver pathology. A significant linear relationship was found between steatosis estimates of the algorithm compared with expert liver pathologists, though the latter had consistently higher estimates.Conclusions.This study demonstrates proof of the concept that smartphone-captured images can be used in conjunction with a digital algorithm to measure steatosis. Integration of this technology into the transplant workflow may significantly improve organ utilization rates.

Renal function after liver transplantation: Real-world experience with basiliximab induction and delayed reduced-dose tacrolimus.

Routine use of delayed reduced-dose calcineurin-inhibitor treatment with induction immunosuppression in liver transplantation to minimize post-operative kidney injury is still scarce. To evaluate real-world experience of basiliximab induction with delayed reduced-dose tacrolimus. In a retrospective cohort study, kidney function was evaluated pre- and postoperatively by measured glomerular filtration rate (mGFR). Adult patients undergoing liver transplantation between 2000 and 2017 were divided into a conventional treatment group (immediate-introduction of tacrolimus, target trough levels 10-15ng/mL, and corticosteroids, n=203) and a revised treatment group (basiliximab induction, reduced-dose tacrolimus, target through levels 5-8ng/mL, delayed until day three, and mycophenolate mofetil 2000mg/day, n=343). Mean mGFR was similar between groups at wait-listing (85.3vs 84.1ml/min/1.73m², p=0.60), but higher in the revised treatment group at 3 (56.8vs 63.4ml/min/1.73m², p=0.004) and 12 months post-transplant (60.9vs 69.7ml/min/1.73m², p<0.001); this difference remained after correcting for multiple confounders and was independent of pre-transplant mGFR. In the revised treatment group, biopsy proven acute rejection rate was lower (38% vs. 21%, p<0.001), and graft-survival better (p=0.01). Basiliximab induction with delayed reduced-dose tacrolimus is associated with less kidney injury when compared to standard-dose tacrolimus, without increased risk of rejection, graft loss or death.

Predictors for Successful Liver Transplantation and Risk Factors

Liver transplantation is the only curative treatment option for end stage liver disease. Moreover, oncological liver disease (hepatocellular carcinoma) is an important relevant indication for liver transplantation, together with acute liver failure.Since the first successful liver transplantation by Professor Thomas Starzl in 1967, liver transplantation has changed in many aspects. This concerns not only surgical, anaesthesiological and immunological improvements and further technical developments, but also altered patient characteristics. Patients undergoing liver transplantation are nowadays often more challenging, due to their age and relevant comorbidities.The number of liver transplantations is constantly rising. However, there are more patients in need of liver transplantation than donor grafts are available. Discrepancies between liver transplant candidates and organ supply can only partially be compensated by split liver transplantation and liver transplantation from living donors.To boost the pool of donor grafts, even marginal organs within the extended donor criteria (EDC) are being increasingly allocated. In some countries, even "donation after cardiac death (DCD) organs" are allocated as well.Marginal donor grafts are often associated with reduced graft and patient survival after liver transplantation. To improve the quality of poor liver grafts, innovations in organ conservation with development of new techniques as the machine perfusion techniques have been established in recent years.In summary, the constellation of risk factors of donor grafts as well as transplant recipients has become more challenging in recent decades. It is important to know the specific risk factors and predictors for liver transplantation, in order to obtain the best possible graft and patient survival after liver transplantation.This review gives an overview of predictors for liver transplantation, specific risk scores and indices for donor/recipient match as well as new technical devices in liver transplantation.

New-Onset Atrial Fibrillation in Patients Undergoing Liver Transplantation: Retrospective Analysis of Risk Factors and Outcomes

The authors aimed to identify predictors of new-onset postoperative atrial fibrillation (POAF) during the initial 90 days following liver transplantation, and to assess the association between POAF in-hospital and 1-year mortality. A retrospective cohort study. At a university hospital between 2005 and 2017. Adults without a history of preoperative atrial fibrillation who underwent orthotopicliver transplantation. The authors assessed the univariate association between new-onset of POAF in the postoperative period and each potential factor through a logistic regression model. Moreover, they explored predictors for POAF through stepwise selection. Finally, the authors assessed the relationship between POAF and in-hospital and 1-year mortality using logistic regression models, and whether the duration of atrial fibrillation was associated with in-hospital and 1-year mortality. Among 857 patients, 89 (10.4%) developed POAF. Using only preoperative variables, pulmonary hypertension, age, Model for End-Stage Liver Disease (MELD) score, and White race were identified as the most important predictors. Model discrimination was 0.75 (95% CI: 0.69-0.80), and incorporating intraoperative variables was 0.77 (95% CI: 0.72-0.82). In-hospital mortality was observed in 7.2% (6/83) of patients with new-onset of POAF, and in 2.8% (22/768) without, with confounder-adjusted odds ratio (OR) 1.00 (97.5% CI: 0.29,3.45; p=0.996). One-year mortality was 22.4% (20/89) in patients who developed POAF and 8.3% (64/768) in patients who did not, confounder-adjusted OR 2.64 (97.5% CI: 1.35-5.16; p=0.001). The duration of POAF did not affect long-term postoperative mortality. Preoperative, mostly unmodifiable comorbidities are important risk factors for new-onset POAF after liver transplantation. The POAF was not associated with in-hospital mortality, but with increased 1-year mortality. Once developed, the duration of POAF did not affect long-term mortality after a liver transplant.