How to Estimate the Probability of Tolerance Long-Term in Liver Transplant Recipients.

BACKGROUND: Operational tolerance as the ability to accept the liver transplant without pharmacological immunosuppression is a common phenomenon in the long-term course. However, it is currently underutilized due to a lack of simple diagnostic support and fear of rejection despite its recognized benefits. In the present work, we present a simple score based on clinical parameters to estimate the probability of tolerance. PATIENTS AND METHODS: In order to estimate the probability of tolerance, clinical parameters from 82 patients after LT who underwent weaning from the IS for various reasons at our transplant center were extracted from a prospectively organized database and analyzed retrospectively. Univariate testing as well as multivariable logistic regression analysis were performed to assess the association of clinical variables with tolerance in the real-world setting. RESULTS: The most important factors associated with tolerance after multivariable logistic regression were IS monotherapy, male sex, history of hepatocellular carcinoma pretransplant, time since LT, and lack of rejection. These five predictors were retained in an approximate model that could be presented as a simple scoring system to estimate the clinical probability of tolerance or IS dispensability with good predictive performance (AUC = 0.89). CONCLUSION: In parallel with the existence of a tremendous need for further research on tolerance mechanisms, the presented score, after validation in a larger collective preferably in a multicenter setting, could be easily and safely applied in the real world and already now address all three levels of prevention in LT patients over the long-term course.

Liver Transplantation for Metamizole induced Acute Liver Failure.

Metamizole, or dipyrone, is a frequently prescribed analgetic drug that can cause drug-induced liver injury (DILI). Still, there are only a few metamizole-associated DILI cases (n = 61, including our study) described in the literature. So far liver transplantation has been reported in 6 patients with metamizole-induced acute liver failure. In 2020, a German group described a bigger cohort (n = 23) of metamizole-related DILI. Shortly thereafter, this issue gained wider attention as the German Federal Institute for Drugs and Medical Devices published a Direct Healthcare Professional Communication, emphasizing DILI as a potential adverse event caused by metamizole. We herein report 2 patients that were admitted to our liver transplant center due to acute liver failure (ALF) in April and May 2021. Both patients reported intake of metamizole as pain medication over a few weeks. After ruling out alternative reasons for ALF and fulfilling the King's College criteria both patients received emergency liver transplantations in our center. Pathology assessment of both explants were consistent with metamizole-associated DILI. As illustrated by our 2 cases of metamizole-induced liver failure with subsequent liver transplantation, this rare but presumably often overlooked adverse drug effect of metamizole should be considered as differential diagnosis in cases of cryptogenic liver failure.

[Differentiated Strategies for the Therapy of Liver Metastases in Gastro-entero-pancreatic Neuroendocrine Neoplasia]. / Differenzierte Therapiestrategie bei Lebermetastasen gastro-entero-pankreatischer Neuroendokriner Neoplasien.

Neuroendocrine neoplasias comprise a heterogenous group of malignant tumours, mostly arising from the gastro-entero-pancreatic system (GEP). Most of these tumours develop from the small intestine and pancreas and the liver is the predominant site for distant metastases. Patients may be asymptomatic for a long time and liver metastases are frequently diagnosed by chance or during operations for bowel obstruction, for example, during emergency surgery. The only curative therapy consists in complete removal of primary and metastases. In case of metastatic disease, various treatment modalities need to be discussed in interdisciplinary tumour boards comprised of specialists from gastroenterology, (liver-)surgery, radiology, nuclear medicine, radiotherapy, pathology and endocrinology. By combining different therapies, even patients with progressive disease may reach long-term overall survival with good quality of life. The most important factors for decisions on therapy are individual factors like tumour grading, hormonal functionality, type of metastases and evolution of the disease. Adequate treatment of liver metastases comprises various surgical strategies as well as locally ablative radiological interventions and nuclear medical therapies, in complement to systemic treatments.

Reducing Immunosuppression in Patients with De Novo Lung Carcinoma after Liver Transplantation Could Significantly Prolong Survival.

(1) Background: Liver transplantation (LT) is an established treatment for selected patients with end-stage liver disease resulting in a subsequent need for long-term immunosuppressive therapy. With cumulative exposure to immunosuppression (IS), the risk for the development of de novo lung carcinoma increases. Due to limited therapy options and prognosis after diagnosis of lung cancer, the question of the mode and extent of IS in this particular situation is raised. (2) Methods: All patients diagnosed with de novo lung cancer in the follow-up after LT were identified from the institution's register of liver allograft recipients (Charité-Universitätsmedizin Berlin, Germany) transplanted between 1988 and 2021. Survival analysis was performed based on the IS therapy following diagnosis of lung cancer and the oncological treatment approach. (3) Results: Among 3207 adult LTs performed in 2644 patients at our institution, 62 patients (2.3%) developed de novo lung carcinoma following LT. Lung cancer was diagnosed at a median interval of 9.7 years after LT (range 0.7-27.0 years). Median survival after diagnosis of lung carcinoma was 13.2 months (range 0-196 months). Surgical approach with curative intent significantly prolonged survival rates compared to palliative treatment (median 67.4 months vs. 6.4 months). Reduction of IS facilitated a significant improvement in survival (median 38.6 months vs. 6.7 months). In six patients (9.7%) complete IS weaning was achieved with unimpaired liver allograft function. (4) Conclusion: Reduction of IS therapy after the diagnosis of de novo lung cancer in LT patients is associated with prolonged survival. The risk of acute rejection does not appear to be increased with restrictive IS management. Therefore, strict reduction of IS should be an early intervention following diagnosis. In addition, surgical resection should be attempted, if technically feasible and oncologically meaningful.

[Laparoscopic Posterolateral Sectionectomy in Hepatocellular Cacinoma - Increasing Oncological Precision by Combining the Glissonean Pedicle Approach and Fluorescence Guidance]. / 1 Laparoskopische posterolaterale Sektionektomie beim hepatozellulären Karzinom ­ Erhöhung der onkologischen Präzision durch Kombination des Glissonean Pedicle Approach und der Fluoreszenznavigation.

AIM: Minimally invasive procedures have been increasingly performed in liver surgery. Benefits include lower intraoperative blood loss, reduced postoperative morbidity and shorter lengths of hospital stay in comparison to open liver surgery. Exact resection margins seem advantageous in primary liver cancer but challenging to implement with minimally invasive techniques. In this case report, we aimed to increase surgical precision by combining the Glissonean pedicle approach and intraoperative fluorescence guidance. INDICATION: A 73-year-old female patient with CHILD A liver cirrhosis with chronic hepatitis C virus infection was transferred to our hospital with high levels of alpha-fetoprotein (792 ng/ml). Sectional imaging confirmed the suspected diagnosis of a single hepatocellular carcinoma (HCC) with a size of 2.2 cm in segments VI/VII. In line with the local tumour board recommendation, an anatomical posterolateral sectionectomy using the Glissonean pedicle approach was planned. METHODS: The patient was placed in the French position. After mobilisation of the right liver, the posterolateral pedicle was encircled and transected. 0.2 mg/kg of body mass indocyanine green (ICG) was then injected intravenously. The perfused parenchyma of segments I-V and VIII turned green, but the unperfused posterolateral segment VI and VII remained native. The transection line was marked under ICG-imaging to indicate the transition of the posterolateral to the anteromedial sector. Parenchymal transection was performed under intermittent ICG-guided imaging. Pathological workup confirmed R0 resection of a well differentiated HCC in a cirrhotic liver (grade 4). The patient was discharged from the hospital on the 6th postoperative day after an uncomplicated course and was confirmed to be tumour-free six months after surgery. CONCLUSION: As an additional intraoperative tool, ICG-imaging may provide visualisation of segment and sector boundaries and thus may enable precise anatomical resection. Prospective studies are needed to evaluate the added value of this technique, especially with regard to the rate of R0 resections.

Incidence, Diagnosis and Repair of a Diaphragmatic Hernia Following Hepatic Surgery: A Single Center Analysis of 3107 Consecutive Liver Resections.

Diaphragmatic hernia (DH) after a liver resection (LR) is an uncommon but potentially severe complication. In this retrospective study, we aim to share our experience with DH in our hepatic surgery center. We retrospectively analyzed 3107 patients who underwent a liver resection between January 2012 and September 2019. The diagnosis of DH was based on clinical examination and radiological imaging and confirmed by intraoperative findings during surgical repair. Five out of 3107 (0.16%) patients after LR developed DH. Especially, all five DH patients had a major right-sided LR before (n = 716, 0.7%). The mean time interval between initial LR and occurrence of DH was 30 months (range 15 to 44 months). DH exclusively occurred after a right or extended right hepatectomy. Two patients underwent emergency surgery, three were asymptomatic, and DH was diagnosed in follow-up imaging. Three of these five treated patients (60%) developed DH recurrence: two of three (67%) patients after suture repair alone and the only patient after suture repair in combination with an absorbable mesh. The patient who was treated with a composite mesh implant did not show any signs of DH recurrence after 52 months of follow-up. In patients who develop DH after liver surgery, a mesh augmentation with nonresorbable material is generally recommended. In order to diagnose these patients in an early state, we recommend that special attention be paid and a prompt and targeted diagnostic examination of patients with abdominal complaints after right-sided liver resections take place.

Minimization of Immunosuppressive Therapy Is Associated with Improved Survival of Liver Transplant Patients with Recurrent Hepatocellular Carcinoma.

INTRODUCTION: Recurrence of hepatocellular carcinoma (rHCC) after liver transplantation (LT) is associated with limited survival. Therefore, identification of factors that prolong survival in these patients is of great interest. Surgical resection, radiotherapy, and transarterial chemoembolization (TACE) are established interventions to improve outcomes in these patients; however, the impact of immunosuppression is unknown. METHODS: All patients diagnosed with rHCC in the follow-up after LT were identified from a database of liver recipients transplanted between 1988 and 2019 at our institution (Charité Universitätsmedizin Berlin, Germany). Based on the immunosuppressive regimen following diagnosis of rHCC and the oncological treatment approach, survival analysis was performed. RESULTS: Among 484 patients transplanted for HCC, 112 (23.1%) developed rHCC in the follow-up. Recurrent HCC was diagnosed at a median interval of 16.0 months (range 1.0-203.0), with the majority presenting early after transplantation (63.0%, <2 years). Median survival after rHCC diagnosis was 10.6 months (0.3-228.7). Reduction of immunosuppression was associated with improved survival, particularly in patients with palliative treatment (8.4 versus 3.0 months). In addition, greater reduction of immunosuppression seemed to be associated with greater prolongation of survival. Graft rejection after reduction was uncommon (n = 7, 6.8%) and did not result in any graft loss. Patients that underwent surgical resection showed improved survival rates (median 19.5 vs. 8.7 months). CONCLUSION: Reduction of immunosuppressive therapy after rHCC diagnosis is associated with prolonged survival in LT patients. Therefore, reduction of immunosuppression should be an early intervention following diagnosis. In addition, surgical resection should be attempted, if technically feasible and oncologically meaningful.

Self-limited HBV infection of the recipient does not reactivate after liver transplantation: Observations from a 30-year liver transplant program.

BACKGROUND: A self-limited hepatitis B infection can reactivate in patients under immunosuppression or chemotherapy (reappearance of hepatitis B surface antigen (HBsAg) or HBV-DNA). Exact circumstances of HBV reactivation in patients undergoing liver transplantation (LT) for end-stage liver diseases (ESLD) unrelated to HBV are unknown, and recommendations on HBV prophylaxis remain unclear. PATIENTS AND METHODS: Among 1273 liver transplants, 168 patients with a self-limited HBV hepatitis B infection prior to LT were identified from our prospective liver transplant database. Patients with underlying chronic HBV infection and recipients of an anti-HBc-positive liver were not included in the analysis. Demographic, laboratory, serological, and virological data were analyzed retrospectively. Appearance of HBsAg or HBV-DNA was defined as reactivation. RESULTS: The median follow-up after LT was 12.0 years (0.6-30.7 years). The rate of HBV reactivation was 0% independent of antiviral prophylaxis (n = 7; 4.2%), the etiology of ESLD, hepatitis C treatment, or the anti-HBs concentration. The overall patient survival with a history of a self-limited HBV infection before LT did not significantly differ from the rest of the cohort. CONCLUSION: Antiviral treatment with nucleos(t)ide analogues post-liver transplantation in order to prevent HBV reactivation in patients with a resolved self-limited hepatitis B infection prior to LT seems to be omittable since the main viral reservoir is removed by the hepatectomy. These findings may clarify the current uncertainty in the recommendations regarding the risk of HBV reactivation in patients with self-limited hepatitis B prior to LT.

Laparoscopic liver resection in Caroli disease: A single-centre case series.

BACKGROUND: Liver resection is the treatment of choice for patients with localised Caroli disease. While liver resection was traditionally performed as open procedure, this case series aims to evaluate the safety and efficacy of minimally invasive, laparoscopic liver surgery in these patients. METHODS: A systematic review of electronic case files of patients seen between April 2015 and December 2017 at the Department of Surgery, Charité University Hospital Berlin, was conducted. Patients with Caroli disease in whom laparoscopic liver resection had been performed were identified and analysed in this single-centre case series. RESULTS: Seven patients who underwent laparoscopic liver surgery for Caroli syndrome were identified and presented with a median age of 49 (range = 44-66) years, of which four (57%) were female. Preoperatively, six patients were classified as the American Society of Anaesthesiologists (ASA) 2 and one patient as ASA 3. Two operations were performed as single-incision laparoscopic surgery, whereas the others were done as multi-incision laparoscopic surgery. One patient required a conversion to an open procedure. The length of operation varied between patients, ranging from 128 to 758 min (median = 355). The length of stay in the intensive care unit ranged from 0 to 2 days. Two patients presented with post-operative complications (Clavien-Dindo Grade ≥3a), whereas no patient died. In histopathological analysis, all patients demonstrated characteristic findings of Caroli disease and no cholangiocarcinoma was found. CONCLUSION: These results indicate that minimally invasive, laparoscopic liver surgery is a safe and efficacious treatment option for patients with Caroli disease who require liver resection.

Successful implementation of preventive measures leads to low relevance of SARS-CoV-2 in liver transplant patients: Observations from a German outpatient department.

BACKGROUND: Immunosuppressed liver transplant (LT) patients are considered to be at high risk for any kind of infection. What the outbreak of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) means for the transplant cohort is a question that, as of now, cannot easily be answered. Data on prevalence, relevance of the novel virus, and clinical course of the infection in stable LT patients are limited. METHODS: Nasopharyngeal swabs were performed in our outpatient department during the shutdown between March and April 2020 in Germany. RESULTS: The prevalence of SARS-CoV-2 was 3%. Three out of a cohort of 101 LT patients were asymptomatic for respiratory diseases. Respiratory complaints were common and not associated with SARS-CoV-2 infection. The overall monthly mortality rate was 0.22% and did not show alterations during the shutdown in Germany. CONCLUSIONS: If preventive measures are applied, LT patients do not seem to be at a higher risk for SARS-CoV-2 infection. Telemedicine in the outpatient setting may help to maintain distance and to reduce direct patient contact. However, standard of care must be guaranteed for patients with relevant comorbidities in spite of pandemics, because complications may arise from preexisting conditions.

Accuracy of Pretransplant Imaging Diagnostic for Hepatocellular Carcinoma: A Retrospective German Multicenter Study.

Selection and prioritization of patients with HCC for LT are based on pretransplant imaging diagnostic, taking the risk of incorrect diagnosis. According to the German waitlist guidelines, imaging has to be reported to the allocation organization (Eurotransplant) and pathology reports have to be submitted thereafter. In order to assess current procedures we performed a retrospective multicenter analysis in all German transplant centers with focus on accuracy of imaging diagnostic and tumor classification. 1168 primary LT for HCC were conducted between 2007 and 2013 in Germany. Patients inside the Milan, UCSF, and up-to-seven criteria were misclassified with definitive histologic results in 18%, 15%, and 11%, respectively. Patients pretransplant outside the Milan, UCSF, and up-to-seven criteria were otherwise misclassified in 34%, 43%, and 41%. Recurrence-free survival correlated with classification by posttransplant histological report, but not pretransplant imaging diagnostic. Univariate analysis revealed tumor size, vascular invasion, and grading as significant parameters for outcome, while tumor grading was the only parameter persisting by multivariate testing. Conclusion. There was a relevant percentage (15-40%) of patients misclassified by imaging diagnosis at a time prior to LI-RADS and guidelines to improve imaging of HCC. Outcome analysis showed a good correlation to histological, in contrast poor correlation to imaging diagnosis, suggesting an adjustment of the LT selection and prioritization criteria.

Loco-regional hepatocellular carcinoma treatment services as a bridge to liver transplantation.

BACKGROUND: Liver transplantation remains the main curative treatment option for hepatocellular carcinoma (HCC) patients. In the Eurotransplant area Milan criteria are used to assign priority extra points (exceptional MELD, exMELD) for patients on the waiting list. To prevent patients from tumor progression, loco-regional (neoadjuvant) treatment (LRT) is used. For patients unlikely to timely receive an organ via primary allocation, "extended critera donor (ECD) organs" are used. The present study aimed to investigate the survival after LT with a strategy of minimizing waiting list dropouts by using LRT for bridging and transplanting ECD organs if possible and necessary. METHODS: Between October 2010 and May 2015, 50 liver transplants for HCC were included in this retrospective study. Of those, 42 (84%) met the Milan criteria according to the preoperative radiological examination. Forty-one patients (82%) received LRT. The waiting time was analyzed according to LRT. Kaplan-Meier curves with log-rank statistics were used for survival analyses. RESULTS: One- and five-year overall survival within Milan criteria was 94.3% and 83.7% compared with 91.7% and 67.9% beyond Milan criteria, though statistical significance was not reached (P = 0.487). LRT had no impact on overall survival (P = 0.629). Median waiting time was shorter if no LRT was performed (4.6 months vs. 1.5 months, P = 0.006) and there were no cases of waiting list dropouts. Using ECD organs had no impact on overall survival (P = 0.663). CONCLUSIONS: Patients with an expected waiting time to transplantation of >6 months could be successfully treated with LRT as a bridge to transplant. Overall and disease-free survival for patients within and beyond Milan criteria was comparable and the use of ECD organs in this cohort of HCC patients proved to be a safe option.

Differential Roles of Tumor Necrosis Factor Ligand Superfamily Members as Biomarkers in Pancreatic Cancer.

The tumor necrosis factor⁻related weak inducer of apoptosis (TWEAK) belongs to the tumor necrosis factor ligand superfamily, which was shown to play an important role in inflammatory and malignant gastrointestinal diseases, including colitis or colorectal cancer. However, in contrast to other members of the TNF ligand superfamily, its role as a biomarker in pancreatic cancer is currently unknown. We analyzed serum levels of A proliferation-inducing ligand (APRIL) and TWEAK in 134 patients with pancreatic cancer. Results were compared with 50 healthy controls and correlated with clinical data. Intratumoral expression of APRIL and TWEAK in pancreatic cancer was analysed using the datasets made available by the TCGA-LIHC project. APRIL serum levels were significantly elevated in patients with pancreatic cancer compared to healthy controls, which is in line with previous findings. Notably, the diagnostic accuracy of circulating APRIL levels was similar to CA19-9, an established tumor marker for pancreatic cancer. In contrast, serum concentrations of TWEAK were decreased in pancreatic cancer patients. Interestingly, no differences in TWEAK concentrations became apparent between different clinical subgroups of pancreatic cancer. Moreover, within our cohort of patients, TWEAK levels did not correlate with the patients' prognosis and the diagnostic as well as prognostic potential of TWEAK was lower than CA 19-9, when analyzed in this setting. Finally, using data from the TCGA-LIHC project, we demonstrate that expression levels of TWEAK and APRIL represent prognostic markers for patients' survival according to Kaplan-Meier curve analyses. TWEAK and APRIL serum concentrations are regulated differently in patients with pancreatic cancer, highlighting diverse roles of variant TNF ligands in this type of cancer.

Serum levels of soluble urokinase plasminogen activator receptor (suPAR) predict outcome after resection of colorectal liver metastases.

BACKGROUND: In colorectal cancer (CRC), the liver is the most common site of metastasis. Surgical resection represents the standard therapy for patients with colorectal liver metastases (CRLM). However, 5-year survival rates after resection do not exceed 50%, and despite existing preoperative stratification algorithms it is still debated which patients benefit most from surgical treatment. The soluble urokinase plasminogen activator receptor (suPAR) has recently evolved as a promising biomarker for distinct clinical conditions. Here, we examined a potential role of suPAR as a biomarker in patients undergoing resection of CRLM. RESULTS: Correlating with upregulated uPAR tissue expression in resected metastases, serum concentrations of suPAR were significantly elevated in CRLM patients compared to healthy controls. Importantly, patients with preoperative suPAR serum levels above the identified ideal cut-off value of 4.83 ng/ml showed a significantly reduced overall survival after resection of CRLM, both in right- and left-sided primary CRC. Moreover, multivariate Cox regression analysis revealed preoperative suPAR serum levels as a prognostic factor for mortality. Additionally, elevated preoperative suPAR but not creatinine levels were a predictor of acute kidney injury (AKI) after CRLM resection, correlating with a longer postoperative hospitalization. CONCLUSION: SuPAR represents a promising novel biomarker in CRLM patients that might help to guide preoperative treatment decisions regarding patients' outcome and to identify patients particularly susceptible to AKI. METHODS: Expression levels of uPAR were analyzed in CRLM tissue using RT-PCR and immunohistochemistry. SuPAR serum levels were measured by ELISA in 104 CRC patients undergoing hepatic resection for CRLM and 50 healthy controls.

CEA but not CA19-9 is an independent prognostic factor in patients undergoing resection of cholangiocarcinoma.

Cholangiocarcinoma (CCA) represents a rare form of primary liver cancer with increasing incidence but dismal prognosis. Surgical treatment has remained the only potentially curative treatment option, but it remains unclear which patients benefit most from liver surgery, highlighting the need for new preoperative stratification strategies. In clinical routine, CA19-9 represents the most widely used tumor marker in CCA patients. However, data on the prognostic value of CA19-9 in CCA patients are limited and often inconclusive, mostly due to small cohort sizes. Here, we investigated the prognostic value of CA19-9 in comparison with other standard laboratory markers in a large cohort of CCA patients that underwent tumor resection. Of note, while CA19-9 and CEA were able to discriminate between CCA and healthy controls, CEA showed a higher accuracy for the differentiation between CCA and patients with primary sclerosing cholangitis (PSC) compared to CA19-9. Furthermore, patients with elevated levels of C-reactive protein (CRP), CA19-9 or CEA showed a significantly impaired survival in Kaplan-Meier curve analysis, but surprisingly, only CEA but not CA19-9 represented an independent predictor of survival in multivariate Cox-regression analysis. Our data suggest that CEA might help to identify CCA patients with an unfavourable prognosis after tumor resection.

The 28-year incidence of de novo malignancies after liver transplantation: A single-center analysis of risk factors and mortality in 1616 patients.

De novo malignancies (DNMs) are one of the leading causes of late mortality after liver transplantation (LT). We analyzed 1616 consecutive patients who underwent LT between 1988 and 2006 at our institution. All patients were prospectively observed over a study period of 28 years by our own outpatient clinic. Complete follow-up data were available for 96% of patients, 3% were incomplete, and only 1% were lost to follow-up. The median follow-up of the patients was 14.1 years. Variables with possible prognostic impact on the development of DNMs were analyzed, as was the incidence of malignancies compared with the nontransplant population by using standardized incidence ratios. In total, 266 (16.5%) patients developed 322 DNMs of the following subgroups: hematological malignancies (n = 49), skin cancer (n = 83), and nonskin solid organ tumors (SOT; n = 190). The probability of developing any DNM within 10 and 25 years was 12.9% and 23.0%, respectively. The respective probability of developing SOT was 7.8% and 16.2%. Mean age at time of diagnosis of SOT was 57.4 years (range, 18.3-81.1 years). In the multivariate analysis, an increased recipient age (hazard ratio [HR], 1.03; P < 0.001) and a history of smoking (HR, 1.92; P < 0.001) were significantly associated with development of SOT. Moreover, the development of SOT was significantly increased in cyclosporine A-treated compared with tacrolimus-treated patients (HR, 1.53; P = 0.03). The present analysis shows a disproportionate increase of de novo SOT with an increasing follow-up period. Increased age and a history of smoking are confirmed as major risk factors. Moreover, the importance of immunosuppression is highlighted. Liver Transplantation 23 1404-1414 2017 AASLD.

Evaluating twenty-years of follow-up after orthotopic liver transplantation, best practice for donor-recipient matching: What can we learn from the past era?

AIM: To characterize major determinants of 20-year survival after liver transplantation (LT). METHODS: This longitudinal single-institution study includes 313 consecutive patients who received a LT between 1988 and 1992. Pretransplant clinical characteristics and laboratory values were assessed and compared between 20-year survivors and non-survivors. Particular attention was paid to the Model for End-Stage Liver Disease (labMELD)-score and the Eurotransplant Donor Risk Index (ET-DRI) to unravel their impact on 20-year survival after LT. RESULTS: Twenty-year survivors were significantly younger (44 vs 50 years, P = 0.001), more likely to be female (49% vs 36%, P = 0.03) and less likely to be obese at the time of LT (19% vs 32%, P = 0.011). Mean labMELD-score (P = 0.156), rate of high-urgency LT (P = 0.210), cold-ischemia time (P = 0.994), rate of retransplantation (P = 0.12) and average donor age (28 vs 33 years, P = 0.099) were not statistically different. The mean estimated glomerular filtration rate was higher among survivors (P = 0.007). ET-DRI > 1.4 (P = 0.020) and donor age ≥ 30 years (P < 0.022) had significant influence on 20-year survival. The overall survival was not significantly impacted by labMELD-score categories (P = 0.263). CONCLUSION: LT offers excellent long-term results in case of optimal donor and recipient conditions. However, mainly due to the current organ shortage, these ideal circumstances are rarely given; thus algorithms for donor-recipient matching need to be refined, in order to enable a maximum benefit for the recipients of high quality as well as marginal organs.

Cerebrovascular events in 20 years of follow-up after liver transplantation: an underestimated issue?

BACKGROUND: Cardio- and cerebrovascular diseases are the third leading cause of late death after liver transplantation (LT). A new score (PROCAM-Stroke) has been established to estimate the 10-year risk of cerebrovascular events (CBVE) in a German standard population. We evaluate the applicability of the PROCAM-Stroke for long-term follow-up after LT. PATIENTS AND METHODS: A retrospective study of 313 consecutive LTs was conducted. Six months after LT (T1) and 10 years after LT (T2), CBVE risk factors were recorded and PROCAM-Stroke was calculated. Ten (T2) and 20 years (T3) after LT, recipients were screened regarding CBVE. PROCAM-Stroke estimates of CBVE were compared with the incidence of observed CBVE. RESULTS: In both 10-year time frames, the incidence of observed CBVE was higher than expected based on the PROCAM-Stroke estimates: 6 months-10 years after LT (T1-T2): observed: 11, expected: 3.2; 10 years-20 years after LT (T2-T3): observed: 7, expected: 3.4. CONCLUSION: LT recipients seem to have a considerably increased risk of CBVE. Long-term surveillance should take this into account, and screening may be extended accordingly. The progressive impairment of renal function in the long-term LT survivors may be one reason for the underestimation of CBVE in this patient group.

Gender Matches in Liver Transplant Allocation: Matched and Mismatched Male-Female Donor-Recipient Combinations; Long-term Follow-up of More Than 2000 Patients at a Single Center.

OBJECTIVES: The influence of donor-recipient sex mismatches on long-term graft survival after liver transplant is controversial. In this study, our aim was to characterize the differences in long-term graft outcome after liver transplant in more than 2000 cases with special regard to sex match and mismatch. MATERIALS AND METHODS: In this retrospective, single center study of 2144 adult primary liver transplant recipients (median follow-up of 92 months), we analyzed specific long-term graft survival and the effect of different donor and recipient sex combinations (Kaplan-Meier, multivariate regression). RESULTS: In the 15-year follow-up, female recipients (58.6%) had significantly better graft survival than male recipients did (51.6%, P = .031). Matched and mismatched male-female combinations revealed significant differences (P = .003): a male donor-female recipient combination showed the best 15-year graft survival (61.1%), and a female donor-male recipient combination showed the worst graft survival (48.6%), whereas male-male (53.3%) and female-female combinations (55.6%) were not significantly different (P = .967). Donor age (P ≤ .0001), body mass index (P = .021), female sex (P = .015), Eurotransplant Donor Risk Index > 1.4 (P ≤ .001), recipients' age (P < .0001), indication for liver transplant (P < .0001), and kidney function (P = .003) significantly affected graft survival. In the multivariate analysis model, a Eurotransplant Donor Risk Index > 1.4 and impaired kidney function at liver transplant again emerged as significant negative predictors. Female donors and male recipients showed significantly more unfavorable characteristics concerning long-term graft survival. CONCLUSIONS: The impressive long-term graft survival benefit of male donor-female recipient versus female donor-male recipient and of male donor-female recipient versus matched groups (male-male, female-female) in liver transplant may be caused by significant differences in donor quality and recipient characteristics and may not be related to sex itself.