Long-term outcomes and health-related quality of life 20 years after pediatric liver transplantation.

Pediatric liver transplantation is a challenging surgical procedure requiring complex post-transplant patient management. Liver transplantation in children should ensure long-term survival and good health-related quality of life (HR-QOL), but data in the literature are conflicting. With the aim of investigating survival and psychosocial outcomes of patients transplanted during childhood, we identified 40 patients with ≥ 20-year follow-up after liver transplantation regularly followed up at our Institution. Clinical charts were reviewed to retrieve patients' data. Psychosocial aspects and HR-QOL were investigated by an in-person or telephonic interview and by administering the WHOQOL-BREF questionnaire through an online form. Ten- and 20-year patient survival was 97.5% (95% CI 92.8-100%), whereas 10- and 20-year graft survival was 77.5% (65.6-91.6%) and 74.8% (62.5-89.6%), respectively. At last follow-up visit, 31 patients (77.5%) were receiving a tacrolimus-based immunosuppression. Twelve (32.4%) patients obtained a university diploma or higher, whereas 19 (51.4%) successfully completed high school. 81.1% of patients were active workers or in education, 17.5% had children, and 35% regularly practiced sport. 25 patients answered to the WHOQOL-BREF questionnaire. More than 60% of respondents did not report any disability and the perceived physical status was invariably good or very good. Median scores for physical health, psychological health, social relationships, and environment were 16.6, 14.7, 16, and 15, respectively. Pediatric liver transplantation is associated with excellent long-term survival and good HR-QOL. Psychological health and environment represent areas in which support would be needed to further improve HR-QOL.

Outcome of liver transplantation with grafts from brain-dead donors treated with dual hypothermic oxygenated machine perfusion, with particular reference to elderly donors.

Prompted by the utilization of extended criteria donors, dual hypothermic oxygenated machine perfusion (D-HOPE) was introduced in liver transplantation to improve preservation. When donors after neurological determination of death (DBD) are used, D-HOPE effect on graft outcomes is unclear. To assess D-HOPE value in this setting and to identify ideal scenarios for its use, data on primary adult liver transplant recipients from January 2014 to April 2021 were analyzed using inverse probability of treatment weighting, comparing outcomes of D-HOPE-treated grafts (n = 121) with those preserved by static cold storage (n = 723). End-ischemic D-HOPE was systematically applied since November 2017 based on donor and recipient characteristics and transplant logistics. D-HOPE use was associated with a significant reduction of early allograft failure (OR: 0.24; 0.83; p = .024), grade ≥3 complications (OR: 0.57; p = .046), comprehensive complication index (-7.20 points; p = .003), and improved patient and graft survival. These results were confirmed in the subset of elderly donors (>75-year-old). Although D-HOPE did not reduce the incidence of biliary complications, its use was associated with a reduced severity of ischemic cholangiopathy. In conclusion, D-HOPE improves postoperative outcomes and reduces early allograft loss in extended criteria DBD grafts.

The Liver Retransplantation Risk Score: a prognostic model for survival after adult liver retransplantation.

High-risk combinations of recipient and graft characteristics are poorly defined for liver retransplantation (reLT) in the current era. We aimed to develop a risk model for survival after reLT using data from the European Liver Transplantation Registry, followed by internal and external validation. From 2006 to 2016, 85 067 liver transplants were recorded, including 5581 reLTs (6.6%). The final model included seven predictors of graft survival: recipient age, model for end-stage liver disease score, indication for reLT, recipient hospitalization, time between primary liver transplantation and reLT, donor age, and cold ischemia time. By assigning points to each variable in proportion to their hazard ratio, a simplified risk score was created ranging 0-10. Low-risk (0-3), medium-risk (4-5), and high-risk (6-10) groups were identified with significantly different 5-year survival rates ranging 56.9% (95% CI 52.8-60.7%), 46.3% (95% CI 41.1-51.4%), and 32.1% (95% CI 23.5-41.0%), respectively (P < 0.001). External validation showed that the expected survival rates were closely aligned with the observed mortality probabilities. The Retransplantation Risk Score identifies high-risk combinations of recipient- and graft-related factors prognostic for long-term graft survival after reLT. This tool may serve as a guidance for clinical decision-making on liver acceptance for reLT.

Combined liver kidney transplantation for primary hyperoxaluria type 1: Will there still be a future? Current transplantation strategies and monocentric experience.

Combined liver-kidney transplantation is a therapeutic option for children affected by type 1 primary hyperoxaluria. Persistently high plasma oxalate levels may lead to kidney graft failure. It is debated whether pre-emptive liver transplantation, followed by kidney transplantation, might be a better strategy to reduce kidney graft loss. Our experience of 6 pediatric combined liver-kidney transplants for primary hyperoxaluria type 1 in pediatric recipients was retrospectively analyzed. Plasma oxalate levels were monitored before and after transplantation. All the recipients were on hemodialysis at transplantation. Median [IQR] recipient's age at transplantation was 11 [1-14] years; in all cases, a compatible graft from a pediatric brain-dead donor aged 8 [2-16] years was used. In a median follow-up of 7 [2-19] years after combined liver-kidney transplantation, no child died and no liver graft failure was observed; three kidney grafts were lost, due to chronic rejection, primary non-function, and early renal oxalate accumulation. Liver and kidney graft survival remained stable at 1, 3, and 5 years, at 100% and 85%, respectively. Kidney graft loss was the major complication in our series. Risk is higher with very young, low-weight donors. The impact of treatment with glyoxalate pathway enzyme inhibitors treatment in children with advanced disease as well as of donor kidney preservation by ex vivo machine perfusion needs to be evaluated. At present, a case-by-case discussion is needed to establish an optimal treatment strategy.

Inflammatory bowel disease course in liver transplant versus non-liver transplant patients for primary sclerosing cholangitis: LIVIBD, an IG-IBD study.

BACKGROUND: Data regarding the effect of orthotopic liver transplantation (OLT) for primary sclerosing cholangitis (PSC) on inflammatory bowel disease (IBD) course are scarce and conflicting. AIMS: To compare the incidence of refractory IBD in two groups (OLT and non-OLT) of patients affected by IBD and PSC. METHODS: An observational, multicentre, cohort retrospective study was conducted by the Italian Group for the study of IBD in Italy. The primary outcome was the need for biologic therapy or bowel resection for medically refractory IBD or hospitalization due to IBD relapse during the follow-up. Secondary outcomes were rate of colonic dysplasia, colorectal cancer, other solid tumours, lymphoma. RESULTS: Eighty-four patients were included in the study. The primary outcome was not different between OLT and non-OLT groups (11/27, 40.7%, versus 20/57, 35.1%, respectively, p = 0.62). The lymphoma and other tumours (thyroid cancer, kidney cancer, ileal tumour, ovarian cancer, cervical cancer) rates were significantly higher in the OLT group (p = 0.04 and p = 0.005, respectively), at the limit of statistical significance for high-grade colonic dysplasia (p = 0.06). CONCLUSION: OLT in patients affected by IBD and PSC is not a risk factor for a more severe IBD course, but it is associated with a higher occurrence of cancer.

Genetic mutations in primary malignant melanoma of the esophagus: case report and literature review.

The most frequent genetic aberrations in mucosal melanoma are activating mutations of c-KIT. Primary malignant melanomas of esophagus (PMME) are uncommon entities, with aggressive biological behavior and poor prognosis. The better definition of their genotype could improve therapeutic options. We report a case of a 66 years old man with a PMME in the lower third of the esophagus. Analysis of c-kit, KRAS, NRAS and BRAF genes resulted negative for mutations. On the basis of a computerized (PuMed/Medline) bibliography search we retrieved a total of other 35 cases of PMME analyzed for genetic alterations in RAS, BRAF, and KIT. When we compared mutations frequency of PMME with those of other mucosal melanomas, it appeared that PMME are characterized by a relative higher percentage of NRAS mutations. PMME seem to show a specific pattern of genetic alterations suggesting that they could represent a distinct entity among mucosal melanomas.

Mortality after Transplantation for Hepatocellular Carcinoma: A Study from the European Liver Transplant Registry.

Background and Aims: Prognosis after liver transplantation differs between hepatocellular carcinoma (HCC) arising in cirrhotic and non-cirrhotic livers and aetiology is poorly understood. The aim was to investigate differences in mortality after liver transplantation between these patients. Methods: We included patients from the European Liver Transplant Registry transplanted due to HCC from 1990 to November 2016 and compared cirrhotic and non-cirrhotic patients using propensity score (PS) calibration of Cox regression estimates to adjust for unmeasured confounding. Results: We included 22,787 patients, of whom 96.5% had cirrhosis. In the unadjusted analysis, non-cirrhotic patients had an increased risk of overall mortality with a hazard ratio (HR) of 1.37 (95% confidence interval [CI] 1.23-1.52). However, the HR approached unity with increasing adjustment and was 1.11 (95% CI 0.99-1.25) when adjusted for unmeasured confounding. Unadjusted, non-cirrhotic patients had an increased risk of HCC-specific mortality (HR 2.62, 95% CI 2.21-3.12). After adjustment for unmeasured confounding, the risk remained significantly increased (HR 1.62, 95% CI 1.31-2.00). Conclusions: Using PS calibration, we showed that HCC in non-cirrhotic liver has similar overall mortality, but higher HCC-specific mortality. This may be a result of a more aggressive cancer form in the non-cirrhotic liver as higher mortality could not be explained by tumour characteristics or other prognostic variables.

Liver transplantation in hepatocellular carcinoma after tumour downstaging (XXL): a randomised, controlled, phase 2b/3 trial.

BACKGROUND: Indications for liver transplantation for hepatocellular carcinoma are evolving and so-called expanded criteria remain debated. Locoregional therapies are able to downstage hepatocellular carcinoma from beyond to within the Milan criteria. We aimed to investigate the efficacy of liver transplantation after successful hepatocellular carcinoma downstaging. METHODS: We did an open-label, multicentre, randomised, controlled trial designed in two phases, 2b and 3, at nine Italian tertiary care and transplantation centres. Patients aged 18-65 years with hepatocellular carcinoma beyond the Milan criteria, absence of macrovascular invasion or extrahepatic spread, 5-year estimated post-transplantation survival of at least 50%, and good liver function (Child-Pugh A-B7) were recruited and underwent tumour downstaging with locoregional, surgical, or systemic therapies according to multidisciplinary decision. After an observation period of 3 months, during which sorafenib was allowed, patients with partial or complete responses according to modified Response Evaluation Criteria in Solid Tumors were randomly assigned (1:1) by an interactive web-response system to liver transplantation or non-transplantation therapies (control group). A block randomisation (block size of 2), stratified by centre and compliance to sorafenib treatment, was applied. Liver transplantation was done with whole or split organs procured from brain-dead donors. The control group received sequences of locoregional and systemic treatment at the time of demonstrated tumour progression. The primary outcomes were 5-year tumour event-free survival for phase 2b and overall survival for phase 3. Analyses were by intention to treat. Organ allocation policy changed during the course of the study and restricted patient accrual to 4 years. This trial is registered with ClinicalTrials.gov, NCT01387503. FINDINGS: Between March 1, 2011, and March 31, 2015, 74 patients were enrolled. Median duration of downstaging was 6 months (IQR 4-11). 29 patients dropped out before randomisation and 45 were randomly assigned: 23 to the transplantation group versus 22 to the control group. At data cutoff on July 31, 2019, median follow-up was 71 months (IQR 60-85). 5-year tumour event-free survival was 76·8% (95% CI 60·8-96·9) in the transplantation group versus 18·3% (7·1-47·0) in the control group (hazard ratio [HR] 0·20, 95% CI 0·07-0·57; p=0·003). 5-year overall survival was 77·5% (95% CI 61·9-97·1) in the transplantation group versus 31·2% (16·6-58·5) in the control group (HR 0·32, 95% CI 0·11-0·92; p=0·035). The most common registered grade 3-4 serious adverse events were hepatitis C virus recurrence (three [13%] of 23 patients) and acute transplant rejection (two [9%]) in the transplantation group, and post-embolisation syndrome (two [9%] of 22 patients) in the control group. Treatment-related deaths occurred in four patients: two (8%) of 23 patients in the transplantation group (myocardial infarction and multi-organ failure) versus two (9%) of 22 patients in the control group (liver decompensation). INTERPRETATION: Although results must be interpreted with caution owing to the early closing of the trial, after effective and sustained downstaging of eligible hepatocellular carcinomas beyond the Milan criteria, liver transplantation improved tumour event-free survival and overall survival compared with non-transplantation therapies Post-downstaging tumour response could contribute to the expansion of hepatocellular carcinoma transplantation criteria. FUNDING: Italian Ministry of Health.

Semimechanical anastomosis during oesophagectomy reduces leaks and stenosis: a propensity score matched analysis.

OBJECTIVES: Several techniques for oesophageal anastomosis during oesophagectomy have been described, all of which are associated with variable leakage and stricture rates. Given the notable morbidity of oesophageal fistula, reducing its incidence is of paramount importance. We report our single-centre experience with the semimechanical (SM) technique as compared to a totally manual (TM) technique. METHODS: Three hundred and twelve partial and subtotal oesophagectomies performed between January 1998 and April 2018 were analysed. The series was split into a training period (January 1998-September 2015), when both TM and SM techniques were used, and a validation period (October 2015-April 2018), during which SM technique became standard practice. Propensity score matching was used to reduce confounding. RESULTS: The training period included 212 oesophagectomies (90 TM, 122 SM); SM technique was initially used in the neck and afterwards also in the thorax, mainly with gastric conduits (92%), whereas the TM group contained a prevalence of jejunal loops (48%). SM anastomosis was associated with a significant reduction in both leak (0.8% vs 12%; P < 0.001) and stricture rate (0% vs 7%; P = 0.005). After propensity score matching, the difference in leak (0% vs 14%; P = 0.013) and stricture rate (0% vs 10%; P = 0.022) was confirmed. During the validation period, which included 100 oesophagectomies performed with SM anastomosis, 1 leak (1%) and 1 stricture (1%) were observed. CONCLUSIONS: SM technique for oesophageal anastomosis outperforms TM technique and allows achieving very low complication rates.

Influence of donor and recipient gender on liver transplantation outcomes in Europe.

BACKGROUND & AIMS: The impact of gender and donor/recipient gender mismatch on LT outcomes is controversial. The aim of this study was to compare outcomes of LT in Europe, using the ELTR database, between male and female recipients, including donor/recipient gender mismatch. METHODS: Recipient, donor and transplant characteristics were compared between male and female patients. Patient survival was compared between groups, and the impact of donor/recipient gender matching as well as donor and recipient anthropometric characteristics were evaluated as potential risk factors for post-LT death/graft loss. RESULTS: A total of 46,334 LT patients were evaluated (70.5% men and 29.5% women). Ten-year survival rate was significantly higher in female than in male recipients (66% vs 59%, P < .0001). At multivariate analysis, adjusted for indication to LT and type of graft, donor/recipient gender mismatch (HR 1.12, 95% CI 1.04-1.2; P = .003), donor age > 60 years (HR 1.09, 95% CI 1.01-1.18; P = .027) and recipient age (HR 1.02, 95% CI 1.1-1.02; P < .0001) were significantly associated with post-LT lower survival rate in men. Conversely in female recipients, donor BMI > 30 (HR 1.32, 95% CI 1.09-1.6; P = .005), donor age > 60 years (HR 1.15, 95% CI 1.01-1.32; P = .027) and recipient age (HR 1.02, 95% CI 1.01-1.02; P < .0001) were significantly associated with lower post-LT survival rate. CONCLUSIONS: Donor/recipient gender mismatch in male recipients and the use of obese donor in female recipients are associated with reduced survival after LT. Therefore, the incorporation of donor and recipient anthropometric quantities in the allocation process should be a matter of further studies, as their matching can significantly influence long-term outcomes.

Intrahepatic Administration of Human Liver Stem Cells in Infants with Inherited Neonatal-Onset Hyperammonemia: A Phase I Study.

Previous studies have shown that human liver stem-like cells (HLSCs) may undergo differentiation in vitro into urea producing hepatocytes and in vivo may sustain liver function in models of experimentally induced acute liver injury. The aim of this study was to assess the safety of HLSCs intrahepatic administration in inherited neonatal-onset hyperammonemia. The study was approved by the Agenzia Italiana del Farmaco on favorable opinion of the Italian Institute of Health as an open-label, prospective, uncontrolled, monocentric Phase I study (HLSC 01-11, EudraCT-No. 2012-002120-33). Three patients affected by argininosuccinic aciduria (patient 1) and methylmalonic acidemia (patients 2 and 3) and included in the liver transplantation list were enrolled. In all patients, HLSCs were administered by percutaneous intrahepatic injections (once a week for two consecutive weeks) within the first months of life. The first patient received 125,000 HLSCs x gram of liver/dose while the other two patients received twice this dose. No immunosuppression was administered since HLSCs possess immunomodulatory activities. None of the patients experienced infections, hyperammonemia decompensation, or other adverse events during the whole observation period. No donor specific antibodies (DSA) against HLSCs were detected. Patients were metabolic stable despite an increase (~30%) in protein intake. Two patients underwent liver transplantation after 19 and 11 months respectively, and after explantation, the native livers showed no histological alterations. In conclusion, percutaneous intrahepatic administration of HLSCs was safe in newborn with inherited neonatal-onset hyperammonemia. These data pave the way for Phase II studies in selected inherited and acquired liver disorders.

Hypothermic Oxygenated Machine Perfusion of Liver Grafts from Brain-Dead Donors.

Hypothermic oxygenated machine perfusion (HOPE) was introduced in liver transplantation (LT) to mitigate ischemia-reperfusion injury. Available clinical data mainly concern LT with donors after circulatory-determined death, whereas data on brain-dead donors (DBD) are scarce. To assess the impact of end-ischemic HOPE in DBD LT, data on primary adult LTs performed between March 2016 and June 2018 were analyzed. HOPE was used in selected cases of donor age >80 years, apparent severe graft steatosis, or ischemia time ≥10 hours. Outcomes of HOPE-treated cases were compared with those after static cold storage. Propensity score matching (1:2) and Bayesian model averaging were used to overcome selection bias. During the study period, 25 (8.5%) out of 294 grafts were treated with HOPE. After matching, HOPE was associated with a lower severe post-reperfusion syndrome (PRS) rate (4% versus 20%, p = 0.13) and stage 2-3 acute kidney injury (AKI) (16% versus 42%, p = 0.046). Furthermore, Bayesian model averaging showed lower transaminases peak and a lower early allograft dysfunction (EAD) rate after HOPE. A steeper decline in arterial graft resistance throughout perfusion was associated with lower EAD rate. HOPE determines a significant reduction of ischemia reperfusion injury in DBD LT.

Vascular Remodeling of Visceral Arteries Following Interruption of the Splenic Artery During Liver Transplantation.

Splenic artery (SA) ligation can be performed during liver transplantation (LT) to avoid portal hyperperfusion, which is involved in the pathogenesis of both small-for-size and SA syndrome. The SA can also be used as an inflow for arterial reconstruction. Exceptionally, SA interruption or agenesis has been associated with positive remodeling of collateral arteries supplying the spleen via the left gastric artery (LGA), short gastric vessels, and the gastroepiploic arcade (GEA), with subsequent severe upper gastrointestinal (GI) bleeding. To determine incidence, magnitude, predictors, and clinical implications of vascular remodeling after SA interruption during LT, we identified 465 patients transplanted in the period 2007-2017 who had the SA ligated or interrupted at LT. Among them, 88 had a computed tomography angiography suitable for evaluation of vascular remodeling after LT. The presence of prominent gastric arterial collaterals and the increase in LGA and GEA diameter were evaluated on 2-dimensional axial images and multiplanar reconstructions. Of the 88 patients, 28 (31.8%), 32 (36.4%), and 22 (25.0%) developed gastric collateralization graded as mild, moderate, or severe. Of the patients for whom comparison with pre-LT imaging was possible (n = 54), 51 (94.4%) presented a median 37% and 55% increase in LGA and GEA diameter, respectively. Severe gastric collateralization was associated with lower body mass index (odds ratio, 0.84; 95% confidence interval [CI], 0.71-0.98; P = 0.03), whereas a GEA caliper measurement increase was positively correlated with Model for End-Stage Liver Disease score (r2 = 0.12; 95% CI, 0.65-4.15; P = 0.008). Out of 465 patients, 2 (0.43%) had severe episodes of arterial upper GI bleeding, possibly exacerbated by vascular remodeling. In conclusion, vascular remodeling after SA interruption during LT is frequent and can aggravate GI bleeding during follow-up.

A national mandatory-split liver policy: A report from the Italian experience.

To implement split liver transplantation (SLT) a mandatory-split policy has been adopted in Italy since August 2015: donors aged 18-50 years at standard risk are offered for SLT, resulting in a left-lateral segment (LLS) graft for children and an extended-right graft (ERG) for adults. We aim to analyze the impact of the new mandatory-split policy on liver transplantation (LT)-waiting list and SLT outcomes, compared to old allocation policy. Between August 2015 and December 2016 out of 413 potentially "splittable" donors, 252 (61%) were proposed for SLT, of whom 53 (21%) donors were accepted for SLT whereas 101 (40.1%) were excluded because of donor characteristics and 98 (38.9%) for absence of suitable pediatric recipients. The SLT rate augmented from 6% to 8.4%. Children undergoing SLT increased from 49.3% to 65.8% (P = .009) and the pediatric LT-waiting list time dropped (229 [10-2121] vs 80 [12-2503] days [P = .045]). The pediatric (4.5% vs 2.5% [P = .398]) and adult (9.7% to 5.2% [P < .001]) LT-waiting list mortality reduced; SLT outcomes remained stable. Retransplantation (HR = 2.641, P = .035) and recipient weight >20 kg (HR = 5.113, P = .048) in LLS, and ischemic time >8 hours (HR = 2.475, P = .048) in ERG were identified as predictors of graft failure. A national mandatory-split policy maximizes the SLT donor resources, whose selection criteria can be safely expanded, providing favorable impact on the pediatric LT-waiting list and priority for adult sick LT candidates.

Very Early Introduction of Everolimus in De Novo Liver Transplantation: Results of a Multicenter, Prospective, Randomized Trial.

Early everolimus (EVR) introduction and tacrolimus (TAC) minimization after liver transplantation may represent a novel immunosuppressant approach. This phase 2, multicenter, randomized, open-label trial evaluated the safety and efficacy of early EVR initiation. Patients treated with corticosteroids, TAC, and basiliximab were randomized (2:1) to receive EVR (1.5 mg twice daily) on day 8 and to gradually minimize or withdraw TAC when EVR was stable at >5 ng/mL or to continue TAC at 6-12 ng/mL. The primary endpoint was the proportion of treated biopsy-proven acute rejection (tBPAR)-free patients at 3 months after transplant. As secondary endpoints, composite tBPAR plus graft/patient loss rate, renal function, TAC discontinuation rate, and adverse events were assessed. A total of 93 patients were treated with EVR, and 47 were controls. After 3 months from transplantation, 87.1% of patients with EVR and 95.7% of controls were tBPAR-free (P = 0.09); composite endpoint-free patients with EVR were 85% (versus 94%; P = 0.15). Also at 3 months, 37.6% patients were in monotherapy with EVR, and the tBPAR rate was 11.4%. Estimated glomerular filtration rate was significantly higher with EVR, as early as 2 weeks after randomization. In the study group, higher rates of dyslipidemia (15% versus 6.4%), wound complication (18.32% versus 0%), and incisional hernia (25.8% versus 6.4%) were observed, whereas neurological disorders were more frequent in the control group (13.9% versus 31.9%; P < 0.05). In conclusion, an early EVR introduction and TAC minimization may represent a suitable approach when immediate preservation of renal function is crucial.

Endo-therapies for biliary duct-to-duct anastomotic stricture after liver transplantation: Outcomes of a nationwide survey.

BACKGROUND: The most appropriate endo-therapeutic approach to biliary anastomotic strictures is yet to be defined. AIM: To retrospectively report on the endo-therapy of duct-to-duct anastomotic strictures during 2013 in Italy. METHODS: Data were collected from 16 Endoscopy Units at the Italian Liver Transplantation Centers (BASALT study group). RESULTS: Complete endo-therapy and follow-up data are available for 181 patients: 101 treated with plastic multistenting, 26 with fully covered self-expandable metal stenting and 54 with single stenting. Radiological success was achieved for 145 patients (80%), that is, 88% of plastic multistenting, 88% of self-expandable metal stenting and 61% of single stenting (P < 0.001 vs plastic multistenting; P < 0.05 vs self-expandable metal stenting). After first-line endo-therapy failure, the patients underwent a second-line endo-therapy with plastic multistenting for 25%, fully covered self-expandable metal stenting for 53% and single stenting for 22% of cases, and radiological success was achieved for 84%, that is, 100%, 85% and 63% with plastic multistenting, self-expandable metal stenting and single stenting (P < 0.05 vs plastic multistenting or self-expandable metal stenting) respectively. Procedure-related complications occurred in 7.8% of endoscopic retrograde cholangiopancreatographies. Overall, clinical success was achieved in 87% of patients after a median follow-up of 25 months. CONCLUSION: Plastic multistenting is confirmed as the preferred first-line treatment, while fully covered self-expandable metal stenting as rescue option for biliary anastomotic strictures. Single stenting has sub-optimal results and should be abandoned.

Long-Term Outcome of Veno-Occlusive Disease After Liver Transplant: A Retrospective Single-Center Experience.

OBJECTIVES: Veno-occlusive disease after liver transplant has been sporadically reported, and significant uncertainty exists concerning the best treatment and the long-term outcomes. Here, we reviewed our experience to evaluate clinical presentation, treatment, and the long-term outcomes of these patients. MATERIALS AND METHODS: Between 2000 and 2015, 2165 patients underwent liver transplant at our center. The incidence of veno-occlusive disease was 0.3% (7/2165). RESULTS: Timing of veno-occlusive disease onset (median 4.7 mo; interquartile range, 2.5-11.1 mo) varied widely as did clinical presentation, which was characterized by a variable association of liver failure and portal hypertension and different disease pro-gression rates. In all cases, diagnosis of veno-occlusive disease was confirmed by liver biopsy. Six patients (85.7%) presented with veno-occlusive disease after a previous episode of acute cellular rejection. Three patients died due to veno-occlusive disease (n = 2) or due to hepatocellular carcinoma recurrence (n = 1). Two patients were treated by increasing immunosuppression and with interventional procedures (pleurodesis and transjugular intrahepatic portosystemic shunt, respectively), and 2 had successful retransplants. 5-year patient and graft survival rates were 57.1% and 28.6%, respectively. CONCLUSIONS: A tailored approach based on clinical features and including retransplant can achieve acceptable long-term survival in patients with veno-occlusive disease after liver transplant.

Effects of liver ischemia-reperfusion injury on respiratory mechanics and driving pressure during orthotopic liver transplantation.

BACKGROUND: During orthotopic liver transplantation (OLT), liver graft ischemia-reperfusion injury (IRI) triggers a cytokine-mediated systemic inflammatory response, which impairs graft function and disrupts distal organ homeostasis. The objective of this prospective, observational trial was to assess the effects of IRI on lung and chest wall mechanics in the intraoperative period of patients undergoing OLT. METHODS: In 26 patients undergoing OLT, we measured elastance of the respiratory system (ERS), partitioned into lung (EL) and chest wall (ECW), hemodynamics, and fluid and blood product intake before laparotomy (T1), after portal/caval surgical clamp (T2), and immediately (T3) and, at 90 and 180 minutes post-reperfusion (T4 and T5, respectively). Interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), IL-1ß and tumor necrosis factor-α plasma concentrations were assessed at T1, T4 and T5. RESULTS: EL significantly decreased from T1 to T2 (13.5±4.4 vs 9.7±4.8 cmH2O/L, P<0.05), remained stable at T3, while at T4 (12.3±4.4 cmH2O/L, P<0.05) was well above levels recorded at T2, reaching its highest value at T5 (15±3.9 cmH2O/L, P<0.05). Variations in ERS, EL, driving pressure (∆P) and trans-pulmonary pressure (∆PL) significantly correlated with changes in IL-6 and MCP-1 plasma concentrations, but not with changes in wedge pressure, fluid amounts, and red blood cells and platelets administered. No correlation was found between changes in cytokine concentrations and ECW. CONCLUSIONS: We found that EL, ECW, ∆P and ∆PL underwent significant variations during the OLT procedure. Further, we documented a significant association between the respiratory mechanics changes and the inflammatory response following liver graft reperfusion.

Recurrence of Hepatitis B Infection in Liver Transplant Patients Receiving Long-Term Hepatitis B Immunoglobulin Prophylaxis.

BACKGROUND Long-term real-world data are relatively sparse regarding recurrence of chronic hepatitis B virus (HBV) infection after liver transplantation using hepatitis B immunoglobulin (HBIg) and nucleos(t)ide analogue (NUC) prophylaxis. MATERIAL AND METHODS Data from 371 adults transplanted for HBV-related disease at 20 European centers and given HBIg for ³12 months ± NUC therapy were analyzed retrospectively. RESULTS HBIg comprised Hepatect® (iv HBIgB; n=299), subcutaneous Zutectra® (sc HBIg, n=236), and other HBIg preparations (n=130); 93.5% received NUC therapy. Mean follow-up was 6.8±3.5 years. The primary efficacy variable, freedom from HBV recurrence, occurred in 95.7% of patients (95% CI [93.1%, 97.5%]). The observed incidence of recurrence was 16/371 (4.3%) (annual rate 0.65%); 5/16 patients with recurrence had discontinued HBIg and 7/16 had anti-HBs <100 IU/l. Excluding these 7 patients, the HBV recurrence rate was 2.4%. The recurrence rate while on HBIg therapy was 1 per 2069 months. In patients who discontinued HBIg, risk of HBV recurrence versus sc HBIg users was increased by 5.2-fold (1 per 1 603 versus 1 per 8379 treatment months). The annual rate of HBV-related hepatocellular carcinoma (HCC) recurrence was 1.7%. CONCLUSIONS These results support the long-term use of HBIg with NUC therapy as an effective management strategy to minimize risk of HBV recurrence and virus-related complications after liver transplantation.

2018 Annual Report of the European Liver Transplant Registry (ELTR) - 50-year evolution of liver transplantation.

The purpose of this registry study was to provide an overview of trends and results of liver transplantation (LT) in Europe from 1968 to 2016. These data on LT were collected prospectively from 169 centers from 32 countries, in the European Liver Transplant Registry (ELTR) beginning in 1968. This overview provides epidemiological data, as well as information on evolution of techniques, and outcomes in LT in Europe over more than five decades; something that cannot be obtained from only a single center experience.