Myosteatosis is closely associated with sarcopenia and significantly worse outcomes in patients with cirrhosis.

BACKGROUND & AIMS: Sarcopenia and myosteatosis are common in patients with cirrhosis. This study aimed to determine the prevalence of these muscle changes, their interrelations and their prognostic impact over a 12-month period. METHODS: We conducted a prospective multicentre study involving 433 patients. Sarcopenia and myosteatosis were evaluated using computed tomography scans. The 1-year cumulative incidence of relevant events was assessed by competing risk analysis. We used a Fine-Gray model adjusted for known prognostic factors to evaluate the impact of sarcopenia and myosteatosis on mortality, hospitalization, and liver decompensation. RESULTS: At enrolment, 166 patients presented with isolated myosteatosis, 36 with isolated sarcopenia, 135 with combined sarcopenia and myosteatosis and 96 patients showed no muscle changes. The 1-year cumulative incidence of death in patients with either sarcopenia and myosteatosis (13.8%) or isolated myosteatosis (13.4%) was over twice that of patients without muscle changes (5.2%) or with isolated sarcopenia (5.6%). The adjusted sub-hazard ratio for death in patients with muscle changes was 1.36 (95% CI 0.99-1.86, p = 0.058). The cumulative incidence of hospitalization was significantly higher in patients with combined sarcopenia and myosteatosis than in patients without muscle changes (adjusted sub-hazard ratio 1.18, 95% CI 1.04-1.35). The cumulative incidence of liver decompensation was greater in patients with combined sarcopenia and myosteatosis (p = 0.018) and those with isolated sarcopenia (p = 0.046) than in patients without muscle changes. Lastly, we found a strong correlation of function tests and frailty scores with the presence of muscle changes. CONCLUSIONS: Myosteatosis, whether alone or combined with sarcopenia, is highly prevalent in patients with cirrhosis and is associated with significantly worse outcomes. The prognostic role of sarcopenia should always be evaluated in relation to the presence of myosteatosis. IMPACT AND IMPLICATIONS: This study investigates the prognostic role of muscle changes in patients with cirrhosis. The novelty of this study is its multicentre, prospective nature and the fact that it distinguishes between the impact of individual muscle changes and their combination on prognosis in cirrhosis. This study highlights the prognostic role of myosteatosis, especially when combined with sarcopenia. On the other hand, the relevance of sarcopenia could be mitigated when considered together with myosteatosis. The implication from these findings is that sarcopenia should never be evaluated individually and that myosteatosis may play a dominant role in the prognosis of patients with cirrhosis.

Liver transplantation for Wilson disease: Current knowledge and future perspectives.

Liver transplantation currently represents a therapeutic option for patients with Wilson disease presenting with end-stage liver disease or acute liver failure. Indeed, it has been associated with excellent postoperative survival curves in view of young age at transplant and absence of recurrence. Attention has shifted over the past decades to a wise expansion of indications for liver transplantation. Evidence has emerged supporting the transplantation of carefully selected patients with primarily neuropsychiatric symptoms and compensated cirrhosis. The rationale behind this approach is the potential for surgery to improve copper homeostasis and consequently ameliorate neuropsychiatric symptoms. However, several questions remain unanswered, such as how to establish thresholds for assessing pretransplant neuropsychiatric impairment, how to standardize preoperative neurological assessments, and how to define postoperative outcomes for patients meeting these specific criteria. Furthermore, a disease-specific approach will be proposed both for the liver transplant evaluation of candidates with Wilson disease and for patient care during the transplant waiting period, highlighting the peculiarities of this systemic disease.

Evolution of Liver Transplantation Indications: Expanding Horizons.

Liver transplantation (LT) has significantly transformed the prognosis of patients with end-stage liver disease and hepatocellular carcinoma (HCC). The traditional epidemiology of liver diseases has undergone a remarkable shift in indications for LT, marked by a decline in viral hepatitis and an increase in metabolic dysfunction-associated steatotic liver disease (MASLD), along with expanded indications for HCC. Recent advancements in surgical techniques, organ preservation and post-transplant patients' management have opened new possibilities for LT. Conditions that were historically considered absolute contraindications have emerged as potential new indications, demonstrating promising results in terms of patient survival. While these expanding indications provide newfound hope, the ethical dilemma of organ scarcity persists. Addressing this requires careful consideration and international collaboration to ensure equitable access to LT. Multidisciplinary approaches and ongoing research efforts are crucial to navigate the evolving landscape of LT. This review aims to offer a current overview of the primary emerging indications for LT, focusing on acute-on-chronic liver failure (ACLF), acute alcoholic hepatitis (AH), intrahepatic and perihilar cholangiocarcinoma (i- and p-CCA), colorectal liver metastasis (CRLM), and neuroendocrine tumor (NET) liver metastases.

The non-invasive evaluation of liver involvement in patients with cystic fibrosis: A prospective study.

BACKGROUND AND AIMS: Porto-sinusoidal vascular disease (PSVD) has been described as the prominent pathology in liver explants of patients with cystic fibrosis (CF), but data outside the transplant setting are lacking. We aimed to investigate the prevalence of portal hypertension (PH) in CF-associated liver disease (CFLD) and develop an algorithm to classify liver involvement in CF patients. METHODS: This is a cross-sectional study of consecutive paediatric and adult patients in a tertiary centre between 2018 and 2019, who underwent ultrasound, liver (LSM) and spleen stiffness (SSM) measurement. CFLD was defined according to physical examination, liver tests and ultrasound findings. PSVD was likely if there were PH signs in the absence of advanced chronic liver disease (CF-ACLD, LSM <10 kPa). A historical cohort was used to validate the prognostic significance of the new definitions. RESULTS: Fifty (27.5%) patients met CFLD criteria. At least one sign of PH was found in 47 (26%) patients, but most (81%) had LSM <10 kPa and were likely to have PSVD; only 9 (5%) had CF-ACLD. PSVD and CFLD (LSM <10 kPa) co-existed in most (23/36) cases. In the historical cohort (n = 599 patients), likely PSVD and CFLD+PH were independently associated with a 2-fold and 3.5-fold increase in mortality compared to patients without PH, respectively. In 34 patients with SSM, values <21 and >50 kPa accurately diagnosed specific signs of PH. CONCLUSIONS: PSVD is the prevailing cause of PH in CF patients. We developed a new diagnostic algorithm based on clinical and elastosonography criteria to classify liver involvement in patients with CF.

Validation of the INCREMENT-SOT-CPE score in a large cohort of liver transplant recipients with carbapenem-resistant Enterobacterales infection.

BACKGROUND: Management of infections due to carbapenemase-resistant Enterobacterales (CRE) in solid organ transplant (SOT) recipients remains a difficult challenge. The INCREMENT-SOT-CPE score has been specifically developed from SOT recipients to stratify mortality risk, but an external validation is lacking. METHODS: Multicenter retrospective cohort study of liver transplant (LT) recipients colonized with CRE infection who developed infection after transplant over 7-year period. Primary endpoint was all-cause 30-day mortality from infection onset. A comparison between INCREMENT-SOT-CPE and other selected scores was performed. A two-level mixed effects logistic regression model with random effects for the center was fitted. Performance characteristics at optimal cut-point were calculated. Multivariable Cox regression analysis of risk factors for all-cause 30-day mortality was carried out. RESULTS: Overall, 250 CRE carriers developed infection after LT and were analyzed. The median age was 55 years (interquartile range [IQR]: 46-62) and 157 were males (62.8%). All-cause 30-day mortality was 35.6%. A sequential organ failure assessment (SOFA) score ≥ 11 showed a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 69.7%, 76.4%, 62.0%, 82.0%, and 74.0%, respectively. An INCREMENT-SOT-CPE ≥ 11 reported a sensitivity, specificity, PPV, NPV, and accuracy of 73.0%, 62.1%, 51.6%, 80.6% and 66.0%, respectively. At multivariable analysis acute renal failure, prolonged mechanical ventilation, INCREMENT-SOT-CPE score ≥ 11 and SOFA score ≥ 11 were independently associated with all-cause 30-day mortality, while a tigecycline-based targeted regimen was found to be protective. CONCLUSIONS: Both INCREMENT-SOT-CPE ≥ 11 and SOFA ≥ 11 were identified as strong predictors of all-cause 30-day mortality in a large cohort of CRE carriers developing infection after LT.

HBV-positive and HIV-positive organs in transplantation: A clinical guide for the hepatologist.

Organ transplantation is a life-saving treatment for patients with end-stage organ disease, a severe condition associated with a high risk of waitlist mortality. It is primarily limited by a shortage of available organs. Maximising available donors can increase access to transplantation. Transplantation from donors positive for HBV and HIV has increased in many countries. However, antiviral therapies need to be readily available for recipients after transplantation to prevent possible reactivation of the virus following the administration of immunosuppressive therapies. Furthermore, the intentional transmission of a virus has practical, ethical, and clinical implications. In this review, we summarise the current research, focusing on grafts from donors positive for the HBV surface antigen, antibodies against the HBV core antigen, and HIV, to help hepatologists and physicians interested in transplantation to select the best antiviral and/or prophylactic regimens for after transplantation.

A Combined Baveno VII and Spleen Stiffness Algorithm to Improve the Noninvasive Diagnosis of Clinically Significant Portal Hypertension in Patients With Compensated Advanced Chronic Liver Disease.

INTRODUCTION: A noninvasive diagnosis of clinically significant portal hypertension (CSPH) has important prognostic and therapeutic implications for patients with compensated advanced chronic liver disease. We aimed to validate and improve the available algorithms for the CSPH diagnosis by evaluating spleen stiffness measurement (SSM) in patients with compensated advanced chronic liver disease. METHODS: This is a retrospective study including patients with liver stiffness measurement (LSM) ≥10 kPa, no previous decompensation, and available measurements of hepatic venous pressure gradient, LSM, and SSM by transient elastography referring to our center in Bologna. The diagnostic algorithms were adequate if negative and positive predictive values were >90% when ruling out and ruling in CSPH, respectively; these models were validated in a cohort from Verona. The 5-year decompensation rate was reported. RESULTS: One hundred fourteen patients were included in the derivation cohort. The Baveno VII diagnostic algorithm (LSM ≤15 kPa + platelet count ≥150 × 10 9 /L to rule out CSPH and LSM >25 kPa to rule in CSPH) was validated; however, 40%-60% of the patients remained in the gray zone. The addition of SSM (40 kPa) to the model significantly reduced the gray zone to 7%-15%, maintaining adequate negative and positive predictive values. The diagnostic algorithms were validated in a cohort of 81 patients from Verona. All first decompensation events occurred in the "rule-in" zone of the model including SSM. DISCUSSION: The addition of SSM significantly improves the clinical applicability of the algorithm based on LSM and platelet count for CSPH diagnosis. Our models can be used to noninvasively identify candidates for nonselective beta-blocker treatment and patients at a high risk of decompensation.

A prospective longitudinal assessment of de novo metabolic syndrome after liver transplantation.

BACKGROUND: De novo metabolic syndrome (MS) is a frequent complication after liver transplantation (LT). The aim of this prospective study is to identify potential risk factors longitudinally associated to post-LT de novo MS. Patients without pre-LT MS who underwent LT between April 2013 and October 2017 were prospectively included. Metabolic variables were collected at LT and at 6, 12, and 24 months post-LT. RESULTS: Sixty-three patients fulfilled the inclusion criteria (76% male, mean age 53.6±9.5 years). The prevalence of de novo MS was 46%, 43%, and 49% at 6, 12, and 24 months after LT, respectively. Among other MS components, the prevalence of type 2 diabetes, hypertension and hypertriglyceridemia significantly increased after LT. Considering the baseline characteristics at the adjusted analysis, alcoholic liver disease (OR 4.17, 95%CI 1.20-14.51; p = .03) and hypertension pre-LT (OR 11.3, 95% CI 1.49-85.46; p = .02) were confirmed as independent risk factors of post-LT de novo MS. In the time-varying analysis, only eGFR (OR .97, 95% CI .97-.98; p < .0001) was found associated with post-LT de novo MS. CONCLUSIONS: De novo MS frequently occurs shortly after LT, affecting nearly half of patients at 24 months post-LT. Lifestyle modifications should be recommended starting early post-LT, particularly for patients with established risk factors.

Nash Up, Virus Down: How the Waiting List Is Changing for Liver Transplantation: A Single Center Experience from Italy.

Background and Objectives: Non-alcoholic steatohepatitis (NASH) has become the leading indication for liver transplantation in many countries, with a growing rate in the Western world. NASH patients are older and share a higher risk of comorbidities and cancer than patients with viral and/or alcoholic etiologies. The aims of this study were to evaluate waiting list (WL) registration and liver transplantation rates in patients with NASH-related cirrhosis at Padua University Hospital in the last fifteen years (1.2006-6.2020) and to compare clinical characteristics and indications for liver transplantation between patients with and without NASH, as well as the WL survival and post-transplant outcome. Materials and Methods: All adult patients with cirrhosis listed for liver transplantation at Padua University Hospital between 1.2006 and 6.2020 were retrospectively collected using a prospectively updated database; patients with NASH-related cirrhosis were divided by indication for liver transplantation (Dec-NASH vs. hepatocellular carcinoma (HCC)-NASH) and compared with patients with other etiologies of liver disease. The outcomes in terms of waiting list survival and post-transplant outcome were assessed. Results: One thousand four hundred and ninety-one adult cirrhotic patients were waitlisted during the study period. NASH patients accounted for 12% of all WL registrations, showing an increasing trend over time (from 2.5% in 2006 to 23% in 2020). In the last five years, NASH was the third, but most rapidly growing, indication for liver transplantation at our center. This trend was confirmed both for patients with decompensated cirrhosis (from 1.8% to 18%) and HCC as leading indication for transplantation (from 4% to 30%). NASH patients were older than non-NASH ones (mean ± SD age 59 ± 9 vs. 56 ± 9 years; p < 0.01), whereas no difference was found in gender or Child-Pugh of the model for end-stage liver disease score at WL registration. A majority (60.9%) of NASH patients underwent liver transplantation, showing 1-, 5- and 10-y post-transplant survivals of 86%, 73% and 60%, respectively. Conclusion: NASH cirrhosis has become a rapidly growing indication for liver transplantation at our center, both for HCC and decompensated disease, with good post-transplant survival.

Development of a Risk Prediction Model for Carbapenem-resistant Enterobacteriaceae Infection After Liver Transplantation: A Multinational Cohort Study.

BACKGROUND: Patients colonized with carbapenem-resistant Enterobacteriaceae (CRE) are at higher risk of developing CRE infection after liver transplantation (LT), with associated high morbidity and mortality. Prediction model for CRE infection after LT among carriers could be useful to target preventive strategies. METHODS: Multinational multicenter cohort study of consecutive adult patients underwent LT and colonized with CRE before or after LT, from January 2010 to December 2017. Risk factors for CRE infection were analyzed by univariate analysis and by Fine-Gray subdistribution hazard model, with death as competing event. A nomogram to predict 30- and 60-day CRE infection risk was created. RESULTS: A total of 840 LT recipients found to be colonized with CRE before (n = 203) or after (n = 637) LT were enrolled. CRE infection was diagnosed in 250 (29.7%) patients within 19 (interquartile range [IQR], 9-42) days after LT. Pre- and post-LT colonization, multisite post-LT colonization, prolonged mechanical ventilation, acute renal injury, and surgical reintervention were retained in the prediction model. Median 30- and 60-day predicted risk was 15% (IQR, 11-24) and 21% (IQR, 15-33), respectively. Discrimination and prediction accuracy for CRE infection was acceptable on derivation (area under the curve [AUC], 74.6; Brier index, 16.3) and bootstrapped validation dataset (AUC, 73.9; Brier index, 16.6). Decision-curve analysis suggested net benefit of model-directed intervention over default strategies (treat all, treat none) when CRE infection probability exceeded 10%. The risk prediction model is freely available as mobile application at https://idbologna.shinyapps.io/CREPostOLTPredictionModel/. CONCLUSIONS: Our clinical prediction tool could enable better targeting interventions for CRE infection after transplant.

Machine learning in liver transplantation: a tool for some unsolved questions?

Machine learning has recently been proposed as a useful tool in many fields of Medicine, with the aim of increasing diagnostic and prognostic accuracy. Models based on machine learning have been introduced in the setting of solid organ transplantation too, where prognosis depends on a complex, multidimensional and nonlinear relationship between variables pertaining to the donor, the recipient and the surgical procedure. In the setting of liver transplantation, machine learning models have been developed to predict pretransplant survival in patients with cirrhosis, to assess the best donor-to-recipient match during allocation processes, and to foresee postoperative complications and outcomes. This is a narrative review on the role of machine learning in the field of liver transplantation, highlighting strengths and pitfalls, and future perspectives.

Hepatocellular carcinoma and the risk of de novo malignancies after liver transplantation - a multicenter cohort study.

Patients with hepatocellular carcinoma (HCC) are at high risk of second primary malignancies. As HCC has become the leading indication of liver transplant (LT), the aim of this study was to investigate whether the presence of HCC before LT could influence the onset of de novo malignancies (DNM). A cohort study was conducted on 2653 LT recipients. Hazard ratios (HR) of DNM development for patients transplanted for HCC (HCC patients) were compared with those of patients without any previous malignancy (non-HCC patients). All models were adjusted for sex, age, calendar year at transplant, and liver disease etiology. Throughout 17 903 person-years, 6.6% of HCC patients and 7.4% of non-HCC patients developed DNM (202 cases). The median time from LT to first DNM diagnosis was shorter for solid tumors in HCC patients (2.7 vs 4.5 years for HCC and non-HCC patients, respectively, P < 0.01). HCC patients were at a higher risk of bladder cancer and skin melanoma. There were no differences in cumulative DNM-specific mortality by HCC status. This study suggests that primary HCC could be a risk factor for DNM in LT recipients, allowing for risk stratification and screening individualization.

Diagnostic and prognostic role of presepsin in patients with cirrhosis and bacterial infection.

OBJECTIVES: Serum biomarkers have suboptimal accuracy for the early diagnosis of bacterial infection (BI) in cirrhosis. The aim of the study was to evaluate the diagnostic and prognostic accuracy of presepsin (PSP) in a cohort of hospitalized patients with cirrhosis. METHODS: All adult cirrhotics admitted between 03.2016 and 06.2019 were consecutively evaluated. PSP was measured using chemiluminescent enzyme immunoassay, and its accuracy was compared with that of common biomarkers. RESULTS: A total of 278 cirrhotic patients for a total of 448 hospitalizations were prospectively collected. Prevalence of BI at admission was 28.3%. Median (range) Log10PSP in the whole cohort was 2.83 (2.48-3.19) ng/L, significantly higher in patients with BI than in patients without (p<0.001). For a cutoff value of 2.87 ng/L, Log10PSP showed sensitivity, specificity and AUC-ROC of 0.66 (95% CI 0.57-0.74), 0.63 (95% CI 0.57-0.68) and 0.69 (95% CI 0.63-0.73), lower than that of C-reactive protein (p=0.002), but similar to procalcitonin (p=0.18) Patients with BI at hospitalization had higher probability of 28-day mortality (sub-hazard ratio [sHR] 2.65;95% CI 1.49-4.70; p=0.001). At multivariate Cox's regression analysis, Log10PSP (sHR 2.4; 95% CI 1.22-4.82; p=0.01) together with age and severity of liver disease, was an independent predictor of short-term mortality. CONCLUSIONS: PSP shows low diagnostic accuracy for BI in cirrhosis, but it is an independent predictor of short-term mortality. PSP may be a biomarker of systemic inflammation, commonly seen in end-stage liver disease.

Breakthrough invasive fungal infection after liver transplantation in patients on targeted antifungal prophylaxis: A prospective multicentre study.

OBJECTIVE: To investigate the rate of and the risk factors for breakthrough-IFI (b-IFI) after orthotopic liver transplantation (OLT) according to the new definition proposed by Mycoses-Study-Group-Education-and-Research-Consortium (MSG-ERC) and the European-Confederation-of-Medical-Mycology (ECMM). METHODS: Multicenter prospective study of adult patients who underwent OLT at three Italian hospitals, from January 2015 to December 2018. Targeted antifungal prophylaxis (TAP) protocol was developed and shared among participating centers. Follow-up was 1-year after OLT. B-IFI was defined as infection occurring during exposure to antifungal prophylaxis. Risk factors for b-IFI were analyzed among patients exposed to prophylaxis by univariable analysis. RESULTS: We enrolled 485 OLT patients. Overall compliance to TAP protocol was 64.3%, 220 patients received antifungal prophylaxis, 172 according to TAP protocol. Twenty-nine patients were diagnosed of IFI within 1 year after OLT. Of them, 11 presented with b-IFI within 17 (IQR 11-33) and 16 (IQR 4-30) days from OLT and from antifungal onset, respectively. Then out of 11 patients with b-IFI were classified as having high risk of IFI and were receiving anti-mould prophylaxis, nine with echinocandins and one with polyenes. Comparison of patients with and without b-IFI showed significant differences for prior Candida colonization, need of renal replacement therapy after OLT, re-operation, and CMV infection (whole blood CMV-DNA >100 000 copies/mL). Although non-significant, a higher rate of b-IFI in patients on echinocandins was observed (8.2% vs 1.8%, P = .06). CONCLUSIONS: We observed 5% of b-IFI among OLT patients exposed to antifungal prophylaxis. The impact of echinocandins on b-IFI risk in this setting should be further explored.

Outcomes of Liver Transplant for Adults With Wilson's Disease.

Wilson's disease (WD) is a rare genetic disorder with protean manifestations. Even if liver transplantation (LT) could represent an effective therapeutic option for patients with end-stage liver disease, it has remained controversial in the presence of neuropsychiatric involvement. This study aimed to examine the frequency of adult LT for WD in Italy, focusing on the disease phenotype at the time of LT. A retrospective, observational, multicenter study was conducted across Italy exploring the frequency and characteristics of adults transplanted for WD between 2006 and 2016. A total of 29 adult WD patients underwent LT during the study period at 11 Italian LT centers (accounting for 0.4% of all LTs performed), and 27 of them were considered in this analysis (male/female, n = 9/18; age at LT, 29 years [19-60 years]; median Model for End-Stage Liver Disease score at LT, 27 [6-49]). Isolated hepatic phenotype was the indication for LT in 17 (63%) patients, whereas 2 (7%) patients underwent LT for neurological impairment on compensated liver disease. Overall 1- and 5-year patient survival was excellent (88% and 83%, respectively). Neuropsychiatric symptoms early after LT completely recovered in only a few patients. In conclusion, WD remains an uncommon, unusual indication for LT in Italy, displaying good post-LT graft and patient survival. Because isolated neuropsychiatric involvement represents a rare indication to LT, more data are needed to properly assess the value of LT for WD in this subset of patients.

Allocation of liver grafts worldwide - Is there a best system?

BACKGROUND & AIMS: An optimal allocation system for scarce resources should simultaneously ensure maximal utility, but also equity. The most frequent principles for allocation policies in liver transplantation are therefore criteria that rely on pre-transplant survival (sickest first policy), post-transplant survival (utility), or on their combination (benefit). However, large differences exist between centers and countries for ethical and legislative reasons. The aim of this study was to report the current worldwide practice of liver graft allocation and discuss respective advantages and disadvantages. METHODS: Countries around the world that perform 95 or more deceased donor liver transplantations per year were analyzed for donation and allocation policies, as well as recipient characteristics. RESULTS: Most countries use the model for end-stage liver disease (MELD) score, or variations of it, for organ allocation, while some countries opt for center-based allocation systems based on their specific requirements, and some countries combine both a MELD and center-based approach. Both the MELD and center-specific allocation systems have inherent limitations. For example, most countries or allocation systems address the limitations of the MELD system by adding extra points to recipient's laboratory scores based on clinical information. It is also clear from this study that cancer, as an indication for liver transplantation, requires special attention. CONCLUSION: The sickest first policy is the most reasonable basis for the allocation of liver grafts. While MELD is currently the standard for this model, many adjustments were implemented in most countries. A future globally applicable strategy should combine donor and recipient factors, predicting probability of death on the waiting list, post-transplant survival and morbidity, and perhaps costs. LAY SUMMARY: An optimal allocation system for scarce resources should simultaneously ensure maximal utility, but also equity. While the model for end-stage liver disease is currently the standard for this model, many adjustments were implemented in most countries. A future globally applicable strategy should combine donor and recipient factors predicting probability of death on the waiting list, post-transplant survival and morbidity, and perhaps costs.

Outcome of a First Episode of Bacterial Infection in Candidates for Liver Transplantation.

Bacterial infection (BI) is a major cause of worsening of liver function and death in patients with cirrhosis who are awaiting liver transplantation (LT). This study aimed to evaluate the outcome of LT candidates after a first episode of BI between January 2006 and December 2014 at Padua University Hospital. Among 876 LT candidates with cirrhosis, 114 (13%) experienced an episode of BI. Of the 114 patients, 79 were male and 35 were female, and the median (interquartile range) age and Model for End-Stage Liver Disease scores were 58 (12) years and 19 (8), respectively. When compared with matched LT candidates who experienced no BI, they had a higher probability of death (P = 0.004) and a lower probability of undergoing LT (P = 0.01). Considering only patients who recovered from BI within 30 days, their probabilities of death and of undergoing LT were similar to those of matched controls (P = 0.34 and P = 0.43, respectively). The 90-day post-LT mortality was equal between groups (P = 0.90). BI was a strong predictor of early death on the waiting list for LT. Conversely, patients who fully recovered from a BI episode within 30 days did not have a higher mortality risk than matched controls without infection.

Short-term outcomes of paediatric liver transplant recipients after transition to Adult Healthcare Service.

BACKGROUND & AIMS: Survival rates after liver transplantation (LT) in paediatric recipients have significantly improved over time. However, data regarding outcomes after transition from Paediatric to Adult Healthcare Service (AHS) are still lacking. Therefore, we aimed to prospectively evaluate the outcome of LT recipients after transition, to access patients' non-adherence and identify potential risk factors for non-adherence. METHODS: All consecutive adolescent LT recipients moving to the AHS at Padua University Hospital were evaluated between 2010 and 2015. Demographic data, liver function tests, incidence of acute or chronic rejection episodes and adherence to medical prescription, were prospectively evaluated. An educational pilot study was implemented since 2015 to foster adherence during transition. RESULTS: In all, 32 patients (M/F 16/16, median age: 23 years) were evaluated. Median interval time between LT and transition was 15 years (range: 1-26 years). The main indication for LT was biliary atresia (31%), whereas immunosuppression regimen was tacrolimus-based in 75%. After a median follow-up of 29 months (range: 12-83), no significant modifications of liver function tests were observed. Biopsy-proven chronic rejection was diagnosed in 6/32 (18%) of patients, who had higher standard deviation of tacrolimus trough level than patients without (1.5 vs 1, P = .03). Non-adherence was reported in 8/32 (25%) of patients and was significantly associated with alcohol consumption (P = .003). Patient and graft survival were 96% and 93%, respectively. CONCLUSIONS: Adolescent LT patients who undergo transition to the AHS have good long-term outcomes. However, a multidisciplinary approach aiming at fostering adherence should be used.

Mortality in liver transplant recipients with portal vein thrombosis - an updated meta-analysis.

Portal vein thrombosis (PVT) is the most common thrombotic event in liver transplant (LT) recipients, but its impact on mortality after LT has been analyzed in heterogeneous cohorts with mixed results. To conduct a meta-analysis on the impact of PVT on post-LT survival. A systematic search was conducted on studies (published from January 1986 to January 2018) that reported 30-day and 1-year mortality after LT of PVT patients. Four hundred twenty-seven articles were reviewed and 44 were included. Among 98 558 LT, 7257 (7.3%) involved patients with PVT. The mean quality was high (7.1 on the Newcastle-Ottawa scale). The 30-day pooled mortality rate was higher for patients with PVT (64/490; 13%) than for others (259/3357; 7%) (OR 2.29; 95% CI 1.43-3.68; P < 0.0001). One-year mortality was likewise higher in recipients with (853/6302; 13.5%) than in those without PVT (7476/75 355; 9.9%) (OR 1.38; 95% CI 1.14-1.66; P < 0.0001). Heterogeneity wasn't significant (I2 46% and 65%). Patients whose PVT was complete had a higher 30-day pooled mortality rate (OR 5.65; 95% CI 2-15.96; P < 0.0001), and a 1-year mortality rate (OR 2.48; 95% CI 0.99-6.17; P = 0.38) than patients with partial PVT. PVT is common in LT candidates and it is associated with higher short- and medium-term mortality after LT.

Dropout rate from the liver transplant waiting list because of hepatocellular carcinoma progression in hepatitis C virus-infected patients treated with direct-acting antivirals.

Concerns about an increased hepatocellular carcinoma (HCC) recurrence rate following direct-acting antiviral (DAA) therapy in patients with cirrhosis with a prior complete oncological response have been raised. Data regarding the impact of HCV treatment with DAAs on wait-list dropout rates in patients with active HCC and HCV-related cirrhosis awaiting liver transplantation (LT) are lacking. HCV-HCC patients listed for LT between January 2015 and May 2016 at Padua Liver Transplant Center were considered eligible for the study. After enrollment, patients were divided into 2 groups, depending on whether they underwent DAA treatment while awaiting LT or not. For each patient clinical, serological, and virological data were collected. HCC characteristics were radiologically evaluated at baseline and during follow-up (FU). For transplanted patients, pathological assessment of the explants was performed and recurrence rates were calculated. A total of 23 patients treated with DAAs and 23 controls were enrolled. HCC characteristics at time of LT listing were comparable between the 2 groups. Median FU was 10 and 7 months, respectively, during which 2/23 (8.7%) and 1/23 (4.3%) dropout events due to HCC progression were registered (P = 0.90). No significant differences in terms of radiological progression were highlighted (P = 0.16). A total of 9 out of 23 (39%) patients and 14 out of 23 (61%) controls underwent LT, and histopathological analysis showed no differences in terms of median number and total tumor volume of HCC nodules, tumor differentiation, or microvascular invasion. During post-LT FU, 1/8 (12.5%) DAA-treated patient and 1/12 (8.3%) control patient experienced HCC recurrence (P = 0.60). In conclusion, viral eradication does not seem to be associated with an increased risk of dropout due to neoplastic progression in HCV-HCC patients awaiting LT. Liver Transplantation 23 1103-1112 2017 AASLD.