Patients Undergoing Liver Transplantation Research Articles

Risk scores for allograft failure: Are they still useful in liver recipients from donation after circulatory death?

Liver grafts from donation after circulatory death (DCD) are associated with a higher risk of early graft dysfunction, determined by the warm ischemia and cold ischemia times. It is essential to have precise criteria to identify this complication in order to guide therapeutic strategies. To validate different graft and recipient survival scores in patients undergoing liver transplantation (LT) with DCD grafts. A retrospective and observational unicentric study was conducted on 65 LT patients with grafts obtained from controlled DCD donors from November 2013 to November 2022. The United Kingdom (UK) risk score, early allograft dysfunction (EAD) Olthoff score, and model for early allograft function (MEAF) score were used to evaluate the risk of graft and recipient survival post-transplant. For survival analysis purposes, we used the Kaplan-Meier method, and the differences between subgroups were compared using the log-rank (Mantel-Cox) test. Sixty-five patients were included in the study. The UK risk score did not demonstrate predictive capacity for recipient or graft survival. However, in donors aged over 70 years old (18.4%), it significantly predicted graft survival (P < 0.05). According to Kaplan-Meier survival curves, graft survival rates at 6 months, 2 years, and 5 years in the futility group dramatically decreased to 50% compared to the other groups (log-rank 8.806, P < 0.05). The EAD Olthoff and MEAF scores did not demonstrate predictive capacity for recipient or graft survival. Based on Kaplan-Meier survival curves, patients with a MEAF score ≥ 7 had a lower graft survival rate at 6 months, 2 years, and 5 years compared to patients with a lower MEAF score (log-rank 4.667, P < 0.05). In our series, both UK DCD risk score and MEAF score showed predictive capability for graft survival.

Subclinical cardiac dysfunction detected by speckle-tracking echocardiography in patients with liver cirrhosis undergoing liver transplantation

BackgroundCirrhosis is associated with chronic cardiovascular dysfunction termed cirrhotic cardiomyopathy (CCM), characterized by myocardial hypertrophy and diastolic dysfunction. Detecting early cardiac changes is crucial, especially in patients undergoing liver transplantation. Objective: This study aims to evaluate left ventricular systolic function in cirrhotic patients undergoing liver transplantation using speckle-tracking echocardiography.MethodsA prospective observational study was conducted involving 54 cirrhotic patients who underwent liver transplantation, along with 28 age- and sex-matched healthy controls. Echocardiography, including conventional and two-dimensional speckle tracking echocardiography (2D-STE), was performed at baseline and one-month post-transplantation.ResultsThe mean age in the cirrhotic group was 52.2 ± 12.7 years, with no significant difference compared to the control group. Viral hepatitis was the predominant etiology of cirrhosis (68.6%). Conventional echocardiography did not reveal significant differences between groups in LV ejection fraction [62% (56–69) vs. 59% (56–62); p = 0.830]. However, in cirrhotic patients, 2D-STE demonstrated significantly lower LV global longitudinal strain (LV-GLS) [17.5 (15.5–19.1) vs 19.0 (18.0–19.7), p = 0.006]. Post-transplantation, conventional echocardiography indices remained unchanged, while 2D-STE showed remarkable improvement in LV function, with increased LV-GLS compared to pre-transplantation value.Conclusions2D-STE is a valuable tool for detecting and monitoring left ventricular systolic dysfunction in liver cirrhosis patients, particularly following transplantation. While conventional echocardiography may not detect subtle changes, 2D-STE reveals improvements in LV function post-transplantation, emphasizing its role in assessing cirrhotic cardiomyopathy.

False-Positive Phosphatidylethanol Results Due to Blood Transfusion and Implications in the Process of Liver Transplantation Selection.

Phosphatidylethanol (PEth) testing is becoming increasingly common as a tool to assess for alcohol consumption in the practice of addiction medicine. Its potential to be an objective measure of ethanol exposure is appealing; however, the field has yet to develop a complete understanding of the factors that can influence a PEth level. Here we describe 3 patient cases in which blood transfusion within the preceding 28 days was the reason that PEth studies were positive in patients undergoing liver transplant evaluation. These patients all had in-depth evaluations by physicians on an addiction medicine consult service and were believed abstinent from alcohol. In the field of liver transplant, even a mildly elevated PEth level can result in listing delay or even liver transplant candidacy denial. Further study is needed to understand how PEth is impacted by medical procedures and events such as blood transfusion if we are to maintain a just and ethical practice in the setting of addiction and transplant medicine.

Perioperative administration of albumin in adult patients undergoing liver transplantation: A systematic review.

Hypoalbuminemia is a risk factor for mortality in patients with end-stage liver disease (ESLD) and in those undergoing orthotopic liver transplantation (OLT), since it represents a biomarker of post-operative delayed functional recovery of the graft. Despite albumin infusion during and after OLT is frequently adopted in recipients with hypoalbuminemia, it remains unclear whether this procedure could improve post OLT clinical outcomes. Observational studies indicated that treatment with albumin after OLT might be beneficial in reducing ascites and acute kidney injury (AKI) development. However, considering potential complications and the cost of albumin therapy, the decision to use albumin after OLT should be based on careful consideration of patient's individual needs and risks. In addition, the threshold plasma value of albumin below which it could be clinically useful to infuse albumin has not been clearly defined. This systematic review, prepared in accordance with the PRISMA 2020 guidelines, aimed to assess the efficacy of albumin infusion in patients undergoing OLT, in the prevention or treatment of ascites, AKI, and ischemia reperfusion syndrome, as well as its potential impact on patient survival. Furthermore, this review aimed to illustrate the pathophysiological bases justifying the use of albumin infusion in a subset of patients receiving OLT.

Myosteatosis Is Associated With Frailty and Poor Physical Function in Patients Undergoing Liver Transplant Evaluation: A Cohort Study.

Myosteatosis is fat infiltration within skeletal muscle. The impact of myosteatosis on physical function and clinical outcomes in patients referred for liver transplantation (LT) is unclear. We explored associations between myosteatosis and sarcopenia, frailty, physical function, and pre- and early post-LT outcomes. Myosteatosis was assessed by computed tomography (CT) in 237 patients referred for LT (March 2018 to September 2022). Chi-square/Fishers exact tests and multivariable regression compared myosteatosis and sarcopenia, frailty (liver frailty index), physical function (short physical performance battery, SPPB); and associations with pre-LT unplanned hospitalizations, post-LT surgical complications (Clavien-Dindo grade≥3), and LT admission length of stay (LOS). Kaplan-Meier and Cox-proportional hazards models explored myosteatosis and time to LT and unplanned admission. Fine-Gray model evaluated the competing risks of receiving an LT. Myosteatosis was present in 74 (31%) patients. Patients with myosteatosis were 2.5 times (95% confidence interval [CI] 1.1-5.7, p=0.03) more likely to be frail, and 3.0 times (95% CI 1.6-5.6, p<0.001) more likely to have a poor physical function (SPPB≤9/12) than those without myosteatosis. Patients with myosteatosis versus those without were more likely to have a pre-LT unplanned hospitalization (51% vs. 36%, p=0.03), but significance was lost after adjusting for age, sex, Model for End-stage Liver Disease (MELD), and the presence of hepatocellular carcinoma. Myosteatosis did not impact the likelihood of receiving an LT (p=0.39), post-LT complications (p=0.93), or LOS in intensive care unit (ICU) (p=0.66) or hospital (p=0.34). Myosteatosis is prevalent in patients referred for LT and is associated with impaired physical function. Using existing CTs to assess myosteatosis in practice may help identify physically compromised patients.

The impact of recipient hypernatremia on pediatric liver transplantation outcomes.

In pediatric liver transplants, dysnatremias have been found to have an impact on pre- and post-transplant outcomes. However, much of the current literature has focused on wait-list survival, secondary organ damage, and dysnatremia in donors rather than in recipients. To understand the effect of recipient immediate pre-transplant hypernatremia on post-transplant mortality, we conducted a multivariable retrospective review analyzing data from 8,011 pediatric patients undergoing liver transplantation provided by the United Network for Organ Sharing (UNOS). Multivariable analysis of hypernatremia showed an increased risk of mortality (odds ratio [OR]: 2.49, 95% confidence interval [CI]: 1.75, 3.54 for a serum sodium between 150-155mEq/L) while hyponatremia did not show a significant increase in relative risk for mortality (HR: 1.11, 95% CI: 0.75, 1.63 for a serum sodium between 125-130mEq/L). Kaplan-Meier (KM) curves stratified by sodium level showed statistically significant differences in outcomes with progressively increasing mortality associated with increasing serum sodium levels. In particular, there is a statistically significant increase in 90-day mortality with serum sodium levels above 150mEq/L. Hyponatremia had a moderate impact on mortality but was not statistically significant. Our analysis of immediate pre-transplantation resolution of hypernatremia also showed improved survival outcomes with a decreased mortality compared to transplant patients with unresolved hypernatremia. In conclusion, immediate pre-transplant recipient hypernatremia has a substantial impact on pediatric post-liver transplantation survival. Corrected hypernatremia resulted in decreased mortality compared to uncorrected hypernatremia. Recipient hypernatremia is an important indicator of disease processes and a predictor of poor post-transplantation mortality outcomes.

Hypermethioninemia due to methionine adenosyltransferase I/III deficiency and brain damage

Background and objectivesMethionine adenosyltransferase I/III deficiency used to be considered a relatively benign disease. This study aims to elucidate the clinical characteristics of methionine adenosyltransferase I/III deficiency patients with neurological manifestations.MethodsThe clinical data, blood amino acids, plasma total homocysteine, gene variants, brain imaging, treatments and outcomes of 15 patients with methionine adenosyltransferase I/III deficiency were retrospectively analyzed.ResultsOf these 15 patients, 10 demonstrated neurological abnormalities, with delayed language development, learning difficulties or abnormal brain imaging findings. Eleven patients were identified by newborn screening. Patients with demyelination showed significantly higher blood methionine concentrations at baseline (1102 vs. 396 µmol/L), and their blood methionine remained markedly elevated despite a low-methionine diet. Their plasma total homocysteine was normal to moderate elevated. One patient underwent liver transplantation aged 8 years, which reduced his serum methionine concentration to normal. Compound heterozygous and homozygous MAT1A variants were identified from the patients. Among the 21 variants observed, nine have been reported previously, while 12 were novel.ConclusionsMethionine adenosyltransferase I/III deficiency is not just a benign disease. Severe persistent hypermethioninemia can cause brain injuries, especially in the white matter. Liver transplantation may be a potential treatment option for refractory methionine adenosyltransferase I/III deficiency.

Preoperative nutritional scores to predict mortality after liver transplantation: a retrospective cohort study.

Malnutrition is a well-known risk factor for mortality and morbidity. We investigated whether preoperative malnutrition, diagnosed using an objective nutritional index, was associated with postoperative mortality in patients undergoing liver transplantation (LT). This retrospective cohort observational study assessed the preoperative nutritional status of 440 patients who underwent LT, using the Nutritional Risk Index (NRI), Prognostic Nutritional Index (PNI), and Controlling Nutritional Status (CONUT) score. We evaluated the association between preoperative malnutrition and 3-year postoperative mortality using the Kaplan-Meier curve and log-rank test. In addition, we identified prognostic factors for mortality using Cox proportional hazard analysis. Malnutrition was identified in 72.7% (n = 320), 66.1% (n = 291), and 97.3% (n = 428) of patients as assessed by the NRI, PNI, and CONUT score, respectively. The Kaplan- Meier survival curve demonstrated that mortality increased with the presence and severity of malnutrition risk, as assessed by the NRI and PNI, respectively; however, NRI was the only index identified as an independent risk factor for mortality, along with preoperative renal replacement therapy, platelet count, and C-reactive protein. After adjustment, lower NRI was associated with a higher risk of mortality (hazard ratio 0.97, 95% confidence interval 0.95- 0.99, P = 0.009). The malnutrition group (NRI ≤ 100) had a significantly greater incidence of postoperative acute kidney injury than that of the normal group. Preoperative NRI is an independent risk factor for mortality after LT, and therefore it would be a helpful tool for mortality risk stratification in patients undergoing LT.

Outcome of a Physical Rehabilitation Program on Functionality and Impact on Quality of Life in Postoperative Liver Transplant Patients: A Systematic Review

Objectives: To conduct a systematic review of the literature on the outcomes of a physical rehabilitation program on functionality and identify possible impacts on quality of life in patients after liver transplantation. Methods: Controlled clinical trials and observational studies were selected from the PubMed, SciELO, and BIREME databases that "t the PICO (P – population; I – intervention; C – comparison; O – outcomes) question “what are the bene"ts of a physical rehabilitation program on functionality and quality of life outcomes in patients undergoing liver transplantation?” Studies written in English, Portuguese, and Spanish, published in the last 10 years were selected. After selection, the Physiotherapy Evidence Database (PEDro) scale was used to perform the methodological evaluation of the studies. Results and Discussion: A total of "ve interventionist articles were selected, most of which had good methodological quality. Only one study did not associate resistance training with aerobic exercises, but all had signi"cant results regarding increased functional capacity and reduced perception of fatigue after liver transplantation. Conclusion: !e studies indicated that the association of a resistance training program associated with aerobic training is bene"cial in terms of muscle strength gain, exercise capacity, and perception of fatigue.

Risk Stratification for Chronic Kidney Disease After Liver Transplant for Metabolic Dysfunction-associated Steatohepatitis (MASH) Cirrhosis: Results From the NailMASH Consortium.

Chronic kidney disease (CKD) is a well-recognized complication in patients undergoing liver transplantation (LT), particularly those with metabolic dysfunction-associated steatohepatitis (MASH), a leading cause of cirrhosis in the modern era. This study sought to refine risk stratification for CKD events post-LT in cirrhosis patients with MASH by leveraging baseline renal function at transplant. A total of 717 MASH cirrhosis patients who had LT (1997-2017) at 7 US centers (NailMASH Consortium) were analyzed. Patients were categorized by estimated glomerular filtration rate (eGFR) at transplant: low (LGFR, eGFR ≤30 mL/min/1.73 m²), medium (MGFR, eGFR >30-≤60 mL/min/1.73 m²), and high (HGFR, eGFR >60 mL/min/1.73 m²). Time-related eGFR intercepts, slopes, and assessments of advanced-stage CKD (aCKD) events, defined as 2 eGFR levels <30 mL/min/1.73 m² separated by ≥90 d, were examined. Post-LT, LGFR group showed increased eGFR, whereas the HGFR group experienced a decline. The 3-mo mark was identified as a "reset point," signifying a new reference level, beyond which a different rate of decline was observed. After 3 mo, mean eGFRs of the LGFR group approached MGFRs, whereas the mean eGFR of the HGFR group continued to decrease but remained higher than other groups during a 60-mo follow-up. LGFR patients had significantly higher aCKD probability than MGFR and HGFR groups. Subanalysis at 3 mo post-LT revealed more aCKD events in the LGFR group compared with MGFR and HGFR groups (P < 0.0001). The study underscores renal impact of LT in MASH cirrhosis, indicating unique eGFR trajectories post-LT tied to baseline eGFR, with a reset point at 3 mo. Monitoring post-LT renal function, especially in those at aCKD risk, is crucial. Renal-sparing immunosuppression may help, regardless of baseline eGFR. Further studies are needed for interventions addressing renal dysfunction of patients with MASH post-LT.

A-355 Comparison of Arterial and Venous Whole Blood Samples Analyzed on the QuantraSystem With the QPlusand QStatCartridges

Abstract Background The Quantra Hemostasis System (HemoSonics, LLC) is a cartridge-based viscoelastic testing system used to monitor the coagulation status of whole blood samples. The clinical performance of the System with the QPlus and QStat Cartridges was demonstrated in patients undergoing surgical procedures using venous blood samples. However, depending on the nature of the surgical procedure, arterial or venous samples may be more accessible for testing. It is currently unknown if differences exist between the two samples for the Quantra System. This study compared QPlus and QStat parameters measurements in venous and arterial blood samples collected in parallel from patients undergoing cardiac or liver transplant surgery. Methods Two studies were conducted according to CLSI EP09. The cardiac study enrolled 50 adult patients undergoing cardiac surgery utilizing cardiopulmonary bypass to evaluate QPlus parameters. Matching arterial and venous samples were obtained at two time points: during bypass and post-protamine. The liver study enrolled 25 adult patients undergoing liver transplantation to evaluate QStat parameters. Matching arterial and venous samples from were obtained at three time points: baseline, anhepatic and reperfusion phases. All arterial samples were drawn from an existing arterial catheter whereas venous samples were drawn from the venous side of the bypass circuit or from the central venous catheter (proximal port to minimize infusion contamination). Linear regression analysis and means comparison (paired t-test) were used to assess whether the two sample types provided equivalent results, Results Table 1 provides the mean values for each parameter determined for venous and arterial samples. None of the parameters showed a significant difference between sample types (P &amp;gt; 0.05). Additionally, the linear regression analysis show strong correlation between the results for each parameter. Conclusions Both studies demonstrated that venous and arterial whole blood samples provide equivalent results on the Quantra System with the QPlus and QStat Cartridges.

Statin Therapy is Associated With Lower Risk of Mortality Among Liver Transplant Candidates With Metabolic Dysfunction-associated Steatohepatitis

BackgroundStatin therapy is historically underutilized in patients with chronic liver disease. There is increasing evidence to support the use of statins in patients with cirrhosis, though data in decompensated patients are limited. The primary aim of this study was to evaluate the association between statin use and mortality in patients with advanced liver disease, comparing MASH and non-MASH cirrhosis. MethodsThis single-center retrospective cohort study included patients undergoing liver transplant (LT) evaluation at a large quaternary care center. Patients were categorized by etiology as metabolic dysfunction-associated steatohepatitis (MASH) or non-MASH cirrhosis. Statin use was defined as having an active prescription at the time of LT evaluation. The association between statin use and mortality was evaluated using multivariable Cox proportional hazard regression. ResultsThe study included 623 patients; 24% had MASH cirrhosis and 20% were prescribed a statin. Statin users were older, had a higher BMI and were more likely to have coronary artery disease. At the end of the study, statin use was associated with lower mortality among MASH patients (16% vs. 35%, p=0.010) and higher mortality among non-MASH patients (31% vs. 19%, p=0.066). After controlling for age (HR 1.05, 95% CI 1.00 – 1.10, p=0.039), MELD-Na (HR 1.07, 95% CI 1.04 – 1.11, p<0.001), BMI (HR 1.09, 95% CI 1.05 – 1.14, p<0.001), and CAD (HR 1.20, 95% CI 0.54 – 2.69, p=0.653), statin use conferred a 53% lower risk of death compared to no statin use in patients with MASH cirrhosis (HR 0.47, 95% CI 0.22 – 0.98, p=0.043). ConclusionsStatin use was associated with reduced mortality in patients with decompensated MASH cirrhosis undergoing LT evaluation, but increased mortality in those with non-MASH cirrhosis, particularly those with high-MELD-Na. These findings underscore the importance of reviewing individual patient characteristics and disease etiology when considering the benefits of statin therapy in patients with cirrhosis.

Liver transplantation for unresectable Klatskin tumor: experience of two centers, first distant results

Aim. Evaluation of the first distant results of the combined experience of liver transplantation for unresectable portal cholangiocarcinoma from two large specialized clinical centers.Materials and methods. In total, 23 attempts at liver transplantation for unresectable Klatskin tumor were undertaken. Out of them, 10 were conducted at the A.M. Granov Russian Research Center for Radiology and Surgical Technologies (Granov Center), and 13 were conducted at the Minsk Scientific and Practical Center for Surgery, Transplantology, and Hematology (Minsk Center). The maximum tumor size was 5 and 3 cm in patients operated at the Granov and Minsk Centers, respectively. In the Granov Center, neoadjuvant therapy included a combination of endobiliary photodynamic therapy, regional and systemic chemotherapy. Patients were included in the waiting list only in cases of decreased tumor marker levels and in the absence of disease progression and acute cholangitis. In the Minsk Center, stereotactic radiotherapy was used for neoadjuvant treatment in the absence of active cholangitis; the first 3 patients underwent liver transplantation without prior neoadjuvant treatment.Results. Due to disease progression, six patients were excluded. In three patients at the Mink Center, the diagnosis was not morphologically confirmed after liver transplantation. A total of 14 liver transplantations were performed for unresectable hilar cholangiocarcinoma. After neoadjuvant treatment at the Granov Center, normalization of the CA19-9 marker was observed in four patients, its decrease by 3–4 times was observed in two patients. Liver transplantation was performed in six patients. The average time from the onset of treatment to transplantation was 9.1 months (6–14). Out of the six patients, one was alive for 34 months, with the median overall survival being 22.2 months. Progression was the cause of death in only one patient. Out of the three patients without neoadjuvant treatment at the Minsk Center, two were alive at 16 and 134 months without progression. One patient died after transplantation from disease progression at 24 months. Stereotactic radiotherapy achieved normalization of CA19-9 in four patients; its twofold reduction was observed in one patient. The average time from the onset of treatment to transplantation was six months (3–12). The average CA19-9 tumor marker level by the time of transplantation was 11.3 IU/mL. At 20–26 months, three patients were alive without evidence of disease progression; two patients died of progression after 9 and 59 months.Conclusion. Liver transplantation for unresectable portal cholangiocarcinoma after neoadjuvant treatment regardless of the methods used is highly promising in carefully selected recipients.

Clinical outcomes and predictors in patients with acute on chronic liver failure in Southern Taiwan

Background/aimsThe study is to analyze the clinical characteristics and identify prognostic factors as well as evaluate predictive models in patients with acute-on-chronic liver failure (ACLF) from Southern Taiwan. MethodsThe cohort study was conducted using the Chang Gung Research Database. We included patients with ACLF based on the definition provided by the Asian-Pacific Association for the Study of the Liver ACLF Research Consortium (AARC). ResultsA total of 231 patients diagnosed with ACLF were included in this study, out of which 26 patients underwent liver transplantation (LT). The primary cause of ACLF was acute exacerbation of hepatitis B virus (HBV) in 68.4% of cases and followed by severe alcoholic hepatitis (20.8%). Among LT-free patients, the 28-day mortality rate was observed to be 31%. Older age, higher INR and ammonia levels, and the presence of severe hepatic encephalopathy on 3–6 days of treatment were independent predictors of 28-day mortality. The CLIF-C ACLF and COSSH-ACLF scores, evaluated on 3–6 days, demonstrated the highest predictive performance for 28-day mortality. The optimal cut-off values for the CLIF-C ACLF and COSSH-ACLF scores were determined to be 47 and 6.3, respectively. Patients with CLIF-C ACLF score >63 or COSSH-ACLF score >8.1 experienced 100% mortality by day 28. ConclusionsThe CLIF-C ACLF and COSSH-ACLF scores, evaluated within one week after treatment, exhibit strong predictive capabilities for short-term mortality in ACLF patients. These models are valuable tools for guiding timely decision-making, including the consideration of liver transplantation or withdrawal from treatment.

P.006: Care management at hospital discharge: understanding the health needs of patients undergoing liver transplantation.

P.006: Care management at hospital discharge: understanding the health needs of patients undergoing liver transplantation.

The Effect of Enhanced Recovery After Surgery Nursing on the Recovery in Patients After Liver Transplantation

ObjectiveTo explore the effect of enhanced recovery after surgery nursing on the recovery in patients after liver transplantation. MethodsThis study was performed in 128 patients underwent liver transplantation in our hospital. According to the random number table, these patients were divided into the control group (n = 64) and the experimental group (n = 64). Patients in the control group received traditional nursing, while those in the experimental group received enhanced recovery after surgery nursing. Completion time of the operation, the amount of infused red blood cells during operation, intraoperative anhepatic period, intensive care unit (ICU) stay, the total length of hospitalization, the number of patients reintubated after surgery, the survival rate within 1 year after surgery, and the incidence of postoperative complications were compared between the two groups. ResultsIntraoperative anhepatic period and the amount of infused red blood cells during operation in the experimental group were lower than those in the control group (both P < .05). Postoperative ICU stay, the total length of hospitalization, and the number of patients reintubated after surgery in the experimental group were decreased when compared with the control group, while postoperative ventilator weaning time was increased (all P < .05). The survival rates at 3 months, 6 months, and 1 year after surgery in the experimental group were higher than those in the control group (all P < .05). Compared with the control group, the total incidence of complications in the experimental group was reduced (P < .05). ConclusionThe application of enhanced recovery after surgery nursing in liver transplantation patients contributes to the accelerated recovery of body function, shortened total length of hospitalization and ICU stay, declined complications, and increased survival rate within 1 year.

Machine-learning model to predict the tacrolimus concentration and suggest optimal dose in liver transplantation recipients: a multicenter retrospective cohort study

Titrating tacrolimus concentration in liver transplantation recipients remains a challenge in the early post-transplant period. This multicenter retrospective cohort study aimed to develop and validate a machine-learning algorithm to predict tacrolimus concentration. Data from 443 patients undergoing liver transplantation between 2017 and 2020 at an academic hospital in South Korea were collected to train machine-learning models. Long short-term memory (LSTM) and gradient-boosted regression tree (GBRT) models were developed using time-series doses and concentrations of tacrolimus with covariates of age, sex, weight, height, liver enzymes, total bilirubin, international normalized ratio, albumin, serum creatinine, and hematocrit. We conducted performance comparisons with linear regression and populational pharmacokinetic models, followed by external validation using the eICU Collaborative Research Database collected in the United States between 2014 and 2015. In the external validation, the LSTM outperformed the GBRT, linear regression, and populational pharmacokinetic models with median performance error (8.8%, 25.3%, 13.9%, and − 11.4%, respectively; P < 0.001) and median absolute performance error (22.3%, 33.1%, 26.8%, and 23.4%, respectively; P < 0.001). Dosing based on the LSTM model’s suggestions achieved therapeutic concentrations more frequently on the chi-square test (P < 0.001). Patients who received doses outside the suggested range were associated with longer ICU stays by an average of 2.5 days (P = 0.042). In conclusion, machine learning models showed excellent performance in predicting tacrolimus concentration in liver transplantation recipients and can be useful for concentration titration in these patients.

Myosteatosis and muscle loss impact liver transplant outcomes in male patients with hepatocellular carcinoma.

Sarcopenia is associated with unfavourable long-term survival in patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC). However, the impact of myosteatosis and muscle loss on patient prognosis has not been investigated. Seven hundred fifty-six HCC patients who received LT at 3 transplant centres were included. Computed tomography (CT) images of recipients were collected to measure skeletal muscle index (SMI) and skeletal muscle radiodensity (SMRA). The impact of myosteatosis on the prognosis of sarcopenic and non-sarcopenic patients was studied separately. Muscle status was evaluated based on the presence of sarcopenia and myosteatosis. The muscle loss of 342 males was calculated as the relative change of SMI between pre- and post-LT evaluations. Cox regression models were used to identify predictors of overall survival (OS) and recurrence-free survival (RFS). The study comprised 673 males and 83 females. The median follow-up time was 31months (interquartile range, 19-43months). Prior to LT, 267 (39.7%) and 187 (27.8%) males were defined as sarcopenic (low-SMI) and myosteatotic (low-SMRA), respectively. For sarcopenic recipients, the presence of myosteatosis was followed by a 23.6% decrease in 5year OS (P<0.001) and a 15.0% decrease in 5year RFS (P=0.014). Univariate and multivariate analyses revealed that muscle status was an independent predictor of OS [hazard ratio (HR), 1.569; 95% confidence interval (CI), 1.317-1.869; P<0.001] and RFS (HR, 1.369; 95% CI, 1.182-1.586; P<0.001). Postoperatively, a muscle loss >14.2% was an independent risk factor for poor OS (HR, 2.286; 95% CI, 1.358-3.849; P=0.002) and RFS (HR, 2.219; 95% CI, 1.418-3.471; P<0.001) in non-sarcopenic recipients (N=209). Pre-transplant myosteatosis aggravated the adverse impact of sarcopenia on liver transplant outcomes in male HCC patients. Post-transplant muscle loss might assist in prognostic stratification of recipients without pre-existing sarcopenia, intriguing new insights into individualized management.

MRI-serum-based score accurately identifies patients undergoing liver transplant without rejection avoiding the need for liver biopsy: A multisite European study.

Serum liver tests (serum tests) and histological assessment for T-cell-mediated rejection are essential for post-liver transplant monitoring. Liver biopsy carries a risk of complications that are preferably avoided in low-risk patients. Multiparametric magnetic resonance imaging (mpMRI) is a reliable noninvasive diagnostic method that quantifies liver disease activity and has prognostic utility. Our aim was to determine whether using mpMRI in combination with serum tests could noninvasively identify low-risk patients who underwent liver transplants who are eligible to avoid invasive liver biopsies. In a multicenter prospective study (RADIcAL2), including 131 adult and pediatric (children and adolescent) patients with previous liver transplants from the Netherlands, Portugal, and the United Kingdom, concomitant mpMRI and liver biopsies were performed. Biopsies were centrally read by 2 expert pathologists. T-cell-mediated rejection was assessed using the BANFF global assessment. Diagnostic accuracy to discriminate no rejection versus indeterminate or T-cell-mediated liver transplant rejection was performed using the area under the receiver operating characteristic curve. In this study, 52% of patients received a routine (protocol) biopsy, while 48% had a biopsy for suspicion of pathology. Thirty-eight percent of patients had no rejection, while 62% had either indeterminate (21%) or T-cell-mediated rejection (41%). However, there was a high interobserver variability (0 < Cohen's Kappa < 0.85) across all histology scores. The combined score of mpMRI and serum tests had area under the receiver operating characteristic curve 0.7 (negative predictive value 0.8) to identify those without either indeterminate or T-cell-mediated rejection. Combining both imaging and serum biomarkers into a composite biomarker (imaging and serum biomarkers) has the potential to monitor the liver graft to effectively risk stratify patients and identify those most likely to benefit from a noninvasive diagnostic approach, reducing the need for liver biopsy.

Open Abdominal Management for Damage Control in Liver Transplantation: A Single-center Experience.

Patients undergoing liver transplantation are in a state of coagulopathy before surgery because of liver failure. Intraoperative hemorrhage, massive transfusions, and post-reperfusion syndrome further contribute to coagulopathy, acidosis, and hypothermia. In such situations, temporary cessation of surgery with open abdominal management and resuscitation in the intensive care unit (ICU), which is commonly used as a damage control strategy in trauma care, may be effective. We assessed the outcomes of open abdominal management in liver transplantation and the corresponding complication rates. We retrospectively reviewed the outcomes of patients undergoing open abdominal management among 250 consecutive liver transplantation cases performed at our institution from 2009 to 2022. Open abdominal management was indicated in 16 patients. The open abdomen management group had higher Model for End-stage Liver Disease scores (24 versus 16, P < 0.01), a higher incidence of previous upper abdominal surgery (50% versus 18%, P < 0.01), more pretransplant ICU treatment (31% versus 10%, P = 0.03), and more renal replacement therapy (38% versus 12%, P = 0.01). At the time of the damage control decision, coagulopathy (81%), acidosis (38%), hypothermia (31%), and a high-dose noradrenaline requirement (75%) were observed. The abdominal wall was closed in the second operation in 75% of patients, in the third operation in 19%, and in the fourth operation in 6%. Postoperatively, the frequency of early allograft dysfunction was predominantly higher in the open abdominal management group (69%), whereas the frequency of vascular complications and intra-abdominal infection was the same as in other patients. Open abdominal management can be a crucial option in cases of complex liver transplant complicated by conditions such as hypothermia, acidosis, coagulopathy, and hemodynamic instability. Damage control management minimizes deterioration of the patient's condition during surgery, allowing completion of the planned procedure after stabilizing the patient's overall condition in the ICU.