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Zusammenfassung Hintergrund Der Mangel an Spenderorganen für die Lebertransplantation limitiert die Verfügbarkeit dieser lebensrettenden Therapieoption in Deutschland. Die Qualität der potenziell verfügbaren Spenderorgane wurde bislang nicht bundesweit untersucht. Methoden Analyse aller durch die Deutsche Stiftung Organtransplantation an Eurotransplant gemeldeten Spenderorgane für die Lebertransplantation im Zeitraum von 2010 bis 2018. Kategorisierung transplantierter und nicht transplantierter Organe anhand der histopathologischen Befunde und definierten erweiterten Spenderkriterien. Ergebnisse Insgesamt wurden 8594 Spenderorgane für die Lebertransplantation gemeldet, wovon 15,2 % nicht transplantiert wurden. Im Untersuchungszeitraum stieg der Anteil von Spenderlebern, die mindestens ein erweitertes Spenderkriterium aufwiesen, von 65 % auf 70 % (p = 0,005). Im Jahr 2018 wurden 21 % der gemeldeten Spenderlebern nicht transplantiert; dabei erfüllte über die Hälfte (56 %) mehrere erweiterte Spenderkriterien. Nicht transplantierte Organe stammten signifikant häufiger von Spendern älter als 65 Jahre (41 % vs. 28 %) mit einem BMI > 30 kg/m2 (29 vs. 14 %) und mit erhöhten Leberenzymen (alle p Schlussfolgerung Trotz des bestehenden Organmangels in Deutschland wird ein relevanter Anteil der angebotenen Spenderlebern aufgrund unterschiedlicher Qualitätseinschränkungen nicht transplantiert. Dies gibt Anreiz, Konzepte wie z. B. die normotherme Ex-vivo-Maschinenperfusion zur Evaluation, Sicherung und potenziell Verbesserung der Organqualität in den Vordergrund zu rücken.

Context: Alcoholic liver cirrhosis is a significant risk factor for the development of hepatocellular carcinoma (HCC). The importance of tumour-associated cirrhosis in the development or progression of HCC is not understood. MiRNAs are important regulators for HCC development, but their role in HCC due to alcoholic liver cirrhosis is unclear.Objective: The aim of this study is the detection of miRNA expression in alcoholic liver cirrhosis, tumour-associated cirrhosis, and HCC.Materials and methods: We analysed the differences in the miRNA profiles of HCC, tumour-associated cirrhosis, and cirrhosis without HCC samples from 30 patients who underwent liver transplantation because of alcoholic liver disease.Results: Microarray analyses revealed 40 significantly differentially expressed miRNAs between HCC tissue and tumour-associated cirrhosis tissue. Furthermore, the microarray analysis discovered 56 differentially expressed miRNAs in tumour-associated cirrhosis and cirrhosis without HCC.Discussion: The differences of miRNA profile in alcoholic liver cirrhosis with and without HCC could improve understanding of HCC development, as well as lead to a new diagnostic tool in HCC screening.Conclusion: We were able to show for the first time, the differences of miRNA profile as promising biomarker in HCC, tumour-associated cirrhosis, and cirrhosis without HCC in context of alcoholic liver disease.

Background Minimal-invasive hepatectomy (MIH) has been increasingly performed for benign and malignant liver lesions with most promising results. However, the role of MIH for the treatment of patients with hepatocellular carcinoma (HCC) needs further investigation. Methods Clinicopathological data of patients who underwent liver resection for HCC between 2005 and 2016 were assessed. Postoperative outcomes und long-term survivals of patients following MIH were compared with those of patients undergoing conventional open hepatectomy (OH) after 1:1 propensity score matching. Results During the study period, 407 patients underwent liver resection for HCC with curative intent. Fifty-six patients underwent MIH and were compared with a matched cohort of 56 patients who underwent OH. The rate of patients with fibrosis/cirrhosis (82% vs. 86%, p = 0.959), multiple lesions (32% vs. 32%, p = 1.00), tumor size >30 mm (61% vs. 55%, p = 0.566), and major resection (16% vs. 16%, p = 1.00) was comparable between the two groups (MIH vs. OH). MIH was associated with lower 90-day complication rate (32% vs. 54%, p = 0.022), lower postoperative major complication rate (14% vs. 30%, p = 0.041), lower liver failure rate (0% vs. 7%, p = 0.042), lower 90-day mortality rate (0 vs. 7%, p = 0.042), and shorter length of hospital stay (9 vs. 12 days, p = 0.009) compared to OH. After a median follow-up time of 51 months, MIH and OH showed comparable 5-year overall survival (54% vs. 41%, p = 0.151), and 5-year disease-free survival rates (50% vs. 38%, p = 0.956). Conclusions MIH for HCC is associated with lower postoperative morbidity and mortality and shorter length of hospital stay, resulting in oncologic outcomes similar to those achieved with the established OH. Our findings suggest that MIH should be considered as the preferred method for the treatment of curatively resectable HCC.

Both liver transplantation (LT) and liver resection (LR) represent curative treatment options for hepatocellular carcinoma (HCC) in patients with liver cirrhosis. In this study, we have compared outcomes between historical and more recent patient cohorts scheduled either for LT or LR, respectively. Clinicopathological data of all patients with HCC and cirrhosis who underwent LT or LR between 1989 and 2011 were evaluated. Overall survival of patients with HCC within the Milan criteria (MC) was analyzed focusing on changes between different time periods. In total, 364 and 141 patients underwent LT and LR for HCC in cirrhosis, respectively. Among patients with HCC within MC, 214 and 59 underwent LT and LR, respectively. Postoperative morbidity (37 vs. 11%, P

Context: Non-invasive markers for diagnosis of acute rejection (AR) following liver transplantation have not been developed, yet.Objective: We analyzed the correlation of plasma microparticle levels (MP) with AR.Materials and Methods: MP (CD4, CD8, CD25, CD31, MHC) of 11 AR patients and 11 controls were analyzed within the first week after transplantation.Results: CD4, CD8 and CD31 positive MP were higher in the AR, whereas overall MP count, CD25 and MHCI positive MP proportions did not differ between both groups.Discussion and Conclusion: MP dynamics within the first period of transplantation could help to clarify on-going mechanisms of immunomodulation.

Background The new directly acting antivirals (DAAs) enable all-oral interferon-free treatment of chronic hepatitis C virus (HCV) infection. We here investigated the effect of DAAs on the enzymatic liver function of liver transplant recipients with recurrent hepatitis C. Methods Twenty-one patients with elevated liver enzymes or advanced fibrosis/compensated cirrhosis caused by recurrent HCV were treated with sofosbuvir either in combination with simeprevir, or in combination with ribavirin or daclatasvir with or without ribavirin for 12 weeks. Biochemical parameters, tacrolimus trough levels, and the maximal liver function capacity (LiMAx) were measured monthly during the treatment and 12 weeks after the end of treatment. Results All patients achieved sustained virological response 12 weeks after the end of the treatment. The transaminases and cholestasis parameters normalized until week 8 of treatment. The mean LiMAx (normal ranges >315 μg/kg/h) increased from 344±142 μg/kg/h before treatment to 458±170 μg/kg/h (P

The presence of hepatocellular carcinoma (HCC) is a significant complication of cirrhosis because it changes the prognosis and the treatment of the patients. By now, contrast-enhanced CT and MR scans are the most reliable tools for the diagnosis of HCC; however, in some cases, a biopsy of the tumor is necessary for the final diagnosis. The aim of the study was to develop a diagnostic tool using the microRNA (miRNA) profiles of the tissue surrounding the HCC tumor combined with clinical parameters in statistical models. At a transplantation setting, 32 patients with HCC and cirrhosis (B) were compared to 22 patients suffering from cirrhosis only (A). The diagnosis and exclusion of HCC was confirmed following the histopathological examination of the explanted liver. The HCC patients were significantly older than the patients with cirrhosis only (B: 60.6 and A: 49.9, p

Das hepatozellulare Karzinom (HCC) stellt die weltweit funfthaufigste Tumorerkrankung bei Mannern und die neunthaufigste Tumorerkrankung bei Frauen dar. Prinzipiell stehen 2 chirurgische Therapieverfahren zur Verfugung: die Resektion und die Lebertransplantation. In Abhangigkeit von der Grose des Tumors kann auch eine Radiofrequenzablation, z. B. im Rahmen einer laparoskopischen Exploration, als kurativ gelten. Die Therapieentscheidung wird in Deutschland aktuell masgeblich durch die S3-Leitlinie sowie durch die novellierten Richtlinien der Bundesarztekammer zur Organtransplantation geregelt und sollte im Rahmen einer interdisziplinaren Tumorkonferenz festgelegt werden. Die Resektion kann in kurativer Intention fur HCC ohne oder mit chronischer Lebererkrankung mit noch ausreichender Leberfunktion empfohlen werden. Parenchymsparende Resektionen sind dabei anatomischen Resektionen nicht unterlegen und sollten daher favorisiert werden. Insbesondere Patienten mit Zirrhose scheinen dabei von einem laparoskopischen Vorgehen zu profitieren. Bei Erfullen der „Mailand-Kriterien“ steht prinzipiell eine Indikation zur Lebertransplantation. Um eine zeitnahe Transplantation zu gewahrleisten, kann Patienten mit einem HCC auf Antrag des Transplantationszentrums eine Priorisierung mittels „match model for end-stage liver disease“ (matchMELD) zugewiesen werden. In Anbetracht des Organmangels sollte eine Leberlebendspende als Therapieoption fur Patienten zunehmend empfohlen werden. Wenn mit einer langeren Wartezeit bis zur Lebertransplantation zu rechnen ist, sind Bridgingverfahren wie die transartierelle Chemoembolisation indiziert.

Background Liver transplantation (LTx) is a potentially curative treatment option for hepatocellular carcinoma (HCC) in cirrhosis. However, patients, where HCC is already a systemic disease, LTx may be individually harmful and has a negative impact on donor organ usage. Thus, there is a need for improved selection criteria beyond nodule morphology to select patients with a favorable outcome for LTx in multifocal HCC. Evolutionary distance measured from genome-wide single-nucleotide polymorphism data between tumor nodules and the cirrhotic liver may be a prognostic marker of survival after LTx for multifocal HCC. Methods In a retrospective multicenter study, clinical data and formalin-fixed paraffin-embedded specimens of the liver and 2 tumor nodules were obtained from explants of 30 patients in the discovery and 180 patients in the replication cohort. DNA was extracted from formalin-fixed paraffin-embedded specimens followed by genome wide single-nucleotide polymorphism genotyping. Results Genotype quality criteria allowed for analysis of 8 patients in the discovery and 17 patients in the replication set. DNA concentrations of a total of 25 patients fulfilled the quality criteria and were included in the analysis. Both, in the discovery (P = 0.04) and in the replication data sets (P = 0.01), evolutionary distance was associated with the risk of recurrence of HCC after transplantation (combined P = 0.0002). In a univariate analysis, evolutionary distance (P = 7.4 × 10−6) and microvascular invasion (P = 1.31 × 10−5) were significantly associated with survival in a Cox regression analysis. Conclusions Evolutionary distance allows for the determination of a high-risk group of recurrence if preoperative liver biopsy is considered., The authors of this multicenter retrospective study assess whether the evolutionary distance measured from genome-wide single nucleotide polymorphism (SNP) data between tumor nodules and the cirrhotic liver may be a prognostic marker of survival after liver transplantation for multifocal hepatocellular carcinoma. Supplemental digital content is available in the text.

The diagnosis of acute cellular rejection (ACR) after liver transplantation is based on histological analysis of biopsies because noninvasive biomarkers for allograft rejection are not yet established for clinical routines. CD31, CD44, and chemokine (C-X-C motif) ligand (CXCL) 9 have previously been described as biomarkers for cross-organ allograft rejection. Here, we assessed the predictive and diagnostic value of these proteins as serum biomarkers for clinically significant ACR in the first 6 months after liver transplantation in a prospective study. The protein levels were measured in 94 patients immediately before transplantation, at postoperative days (PODs) 1, 3, 7, and 14 and when biopsies were performed during episodes of biochemical graft dysfunction. The CD44 serum protein levels were significantly lower at POD 1 in patients who experienced histologically proven ACR in the follow-up compared with patients without ACR (P 0.001). CXCL9 was significantly higher before transplantation (P = 0.049) and at POD 1 (P 0.001) in these patients. Low CD44 values (cutoff,200.5 ng/mL) or high CXCL9 values (cutoff,2.7 ng/mL) at POD 1 differentiated between rejection and no rejection with a sensitivity of 88% or 60% and a specificity of 61% or 79%, respectively. The combination of both biomarker cutoffs at POD 1 had a positive predictive value of 91% and a negative predictive value of 67% for clinically significant ACR. Moreover, CD44 was significantly lower at the time of ACR (P 0.001) and differentiated the rejection group from patients with graft dysfunction due to other reasons. Our results suggest that CD44 and CXCL9 may serve as predictive biomarkers to identify liver allograft recipients at risk for clinically significant ACR.

Introduction Hepatitis C virus (HCV) recurrence after liver transplantation (LT) used to be a serious problem in the era of interferon-based treatment. Since the introduction of modern directly acting antivirals, treatment has become easier and shorter. According to published data, in the natural course of hepatitis C infection the duration of antiviral treatment with sofosbuvir (SOF) und ledipasvir (LDV) may be shortened to 12 instead of 24 weeks, using ribavirin (RBV) in addition. Furthermore, the question of whether or not RBV is really necessary, in a 12-week SOF/LDV treatment in the post-transplant setting, is still unanswered. Patients and methods At our institution, 100 liver transplant patients with HCV recurrence underwent interferon-free SOF-based treatment. A total of 51 patients received SOF/LDV with or without RBV. Twenty-nine HCV genotype 1 or 4 patients with histologically proven stage 0-2 fibrosis were treated with SOF/LDV for 12 weeks; another 22 patients with advanced fibrosis (stage 3-4) either received SOF/LDV plus weight-adjusted RBV or prolonged treatment for 24 weeks. Results End of treatment response and sustained virological response (SVR) were achieved in 100% of the 51 patients, irrespective of the treatment group. Patients with prolonged treatment duration or with RBV developed significantly more adverse events (AEs) compared to the SOF/LDV group: 19 (86.4%) vs 8 (27.6%), P

Context: Bile rather than blood depicts the local inflammation in the liver and may improve prediction and diagnosis of acute cellular rejection (ACR) after liver transplantation (OLT).Methods: Secretome and miRNAs were analyzed during the first two weeks and on clinical suspicion of ACR in the bile of 45 OLT recipients.Results: Levels of CD44, CXCL9, miR-122, miR-133a, miR-148a and miR-194 were significantly higher in bile of patients who developed ACR within the first 6 months after OLT and during ACR.Conclusion: Analysis of secretome and miRNA in bile could improve our understanding of the local inflammatory process during rejection.

to the editor: Several recent studies investigated the role of microRNAs (miRNAs) in liver regeneration. These studies are typically based on microarray analyses of whole liver tissue, followed by quantitative real-time PCR or Northern blot confirmation. So far, nine studies have been published in