Liver Transplantation for Hepatocellular Carcinoma beyond the Milan Criteria: A Specific Role for Living Donor Liver Transplantation after Neoadjuvant Therapy.

PURPOSE: This study was designed to elucidate the various new classifications and the use of LDLT and bridging therapy for HCC in this context beyond the Milan criteria (MC). METHODS: The clinical data of patients with HCC outside the MC who underwent LT at Jena University between January 2007 and August 2023 were retrospectively analysed. Eligible patients were classified according to various classification systems. Clinicopathological features, overall and disease-free survival rates were compared between LT and LDLT within the context of bridging therapy. THE RESULTS: Among the 245 patients analysed, 120 patients did not meet the MC, and 125 patients met the MC. Moreover, there were comparable overall survival rates between patients outside the MC for LT versus LDLT (OS 44.3 months vs. 28.3 months; 5-year survival, 56.4% vs. 40%; p = 0.84). G3 tumour differentiation, the presence of angioinvasion and lack of bridging were statistically significant risk factors for tumour recurrence according to univariate and multivariate analyses (HR 6.34; p = 0.0002; HR 8.21; p < 0.0001; HR 7.50; p = 0.0001). Bridging therapy before transplantation provided a significant survival advantage regardless of the transplant procedure (OS: p = 0.008; DFS: p < 0.001). CONCLUSIONS: Patients with HCC outside the MC who underwent LT or LDLT had worse outcomes compared to those of patients who met the MC but still had a survival advantage compared to patients without transplantation. Nevertheless, such patients remain disadvantaged on the waiting list, which is why LDLT represents a safe alternative to LT and should be considered in bridged HCC patients because of differences in tumour differentiation, size and tumour marker dynamics.

Transarterial Radioembolization (TARE) in Patients with Hepatocellular Carcinoma: A Comparison of Palliative with Bridging-to-Transplant Concepts.

We investigated transarterial radioembolization (TARE) as a palliative measure and bridging-to-transplant therapy in hepatocellular carcinoma (HCC) patients. A total of 167 patients (50 bridging, 117 palliative) with 245 TARE procedures were assessed. Fourteen patients underwent subsequent liver transplantation (LT). Patients undergoing LT exhibited significantly prolonged progression-free survival (PFS) compared to those with bridging-without-transplant (p = 0.033). No significant differences were observed between patients with bridging-without-transplant and palliative cases (p = 0.116). Median overall survival (OS) post-TARE was 16.6 months, with estimated OS rates at 6/12 months of 82.0%/60.5%, respectively. Patients who underwent LT demonstrated statistically significantly longer OS compared to those with bridging-without-transplant (p = 0.001). No marked outcome distinctions were found between bridging-without-transplant and palliative groups. The findings underscored the superiority of LT over alternative treatments. TARE served as an important component in non-LT scenarios, allowing for subsequent therapeutic options. The study reflected the highly variable and complex situations of patients with HCC, emphasizing the need for further investigations to define an optimal multimodal approach.

Sarcopenic obesity may predict worse liver regeneration after right graft living donor liver transplantation.

Sarcopenic obesity impairs the outcome after liver transplantation. The effect of this on liver regeneration has not yet been studied. The aim of this study was to evaluate the potential effect of body composition changes on liver volume gain after living donor liver transplantation. We observed liver regeneration in 100 patients who underwent living donor liver transplantation using right lobe grafts (Segments V-VIII). Liver volumetry and body composition analysis were performed based on CT images with special software. The gain of liver volume was calculated between 2 points in time considering the absolute and percentage values: before surgery and early after surgery, with a median time of 10 days. Pearson's correlation and multivariate analysis using stepwise multiple regression were used to examine the potential correlation between body composition and liver volume gain. The liver volume increase was significantly negatively correlated with adipose tissue in the body stem ( r = -0.4, p < 0.001) and positively correlated with psoas mass ( r = 0.24, p = 0.02). These results correspond with those of the multiple regression analysis, which indicated adipose tissue (ß = -1.0, p < 0.001) and psoas mass (ß = 0.12, p < 0.001). The presence of malignancy as an indication for liver transplantation was another significant independent factor negatively affecting liver growth (ß = -13.1, p = 0.046). Sarcopenic obesity predicts an impaired liver volume increase after living donation. This could worsen the postoperative outcome. The role of alimentary interventions and exercises in improving body composition and thus postoperative outcome should be evaluated through prospective interventional studies.

[Individualized curative treatment for malignant diseases through liver transplantation]. / Individualisierte kurative Therapie bei malignen Erkrankungen durch Lebertransplantation.

BACKGROUND: For patients with primary and secondary liver tumors that are functionally or technically nonresectable, liver transplantation remains the sole curative treatment option. Over the years the benefits of transplantation have also been validated for conditions other than hepatocellular carcinoma. Currently, amidst a period of organ shortage the broadening of transplantation indications is a topic of ongoing debate. Although recent studies have confirmed the long-term success of transplantation within multimodal treatment regimens, this approach has yet to become the standard treatment for many conditions. OBJECTIVE: This article explores the potential of liver transplantation in individualized multimodal oncological treatment strategies. RESULTS AND CONCLUSION: Liver transplantation has become an integral component of the treatment regimen for hepatocellular carcinoma. In Germany there is a prioritized organ allocation facilitated by the granting of a standard exception for cases with a smaller tumor burden. Over the years numerous studies have demonstrated comparable long-term results using different listing criteria. Both intrahepatic cholangiocarcinoma and perihilar cholangiocarcinoma can be curatively treated with transplantation in Germany, although this is typically within the context of clinical studies. The neoadjuvant therapy and patient selection, based on tumor burden and the response to preliminary treatment, play a crucial role in influencing long-term survival and recurrence rates. The success of transplantation for liver metastases from neuroendocrine malignancies or colorectal carcinomas, which cannot be removed by partial resection, also significantly hinges on the patient selection. The role of living donor liver transplantation is becoming increasingly more pivotal in this context.

Liver Transplantation for Incidental Cholangiocarcinoma or Combined Hepatocellular Carcinoma/Cholangiocarcinoma-Own Experiences and Review of the Literature.

BACKGROUND: Data about liver transplantation for mixed tumors from hepatocellular carcinoma to cholangiocarcinoma are limited. Furthermore, the diagnosis of intrahepatic cholangiocarcinoma or combined tumors in a cirrhotic liver is considered a contraindication for transplantation. Our aim was to evaluate the long-term outcomes of patients with incidental cholangiocarcinoma or combined tumors after liver transplantation. METHODS: In our descriptive analysis, data were evaluated from all patients since 2010 who received a liver transplant due to an assumed hepatocellular carcinoma at Jena University Hospital. Survival rates were determined using the Kaplan-Meier method. RESULTS: Between January 2010 and December 2022, an incidental intrahepatic cholangiocarcinoma was found in eight patients post-transplant. Four combined hepatocellular and cholangiocarcinoma and four sole intrahepatic cholangiocarcinomas were found. A recurrence through distant metastases from combined hepatocellular- and cholangiocarcinoma was found in one patient at one year after transplantation. Another patient developed a pulmonary primary tumor independently one year post-transplant. The recurrence rate was at 14.3%. While two patients died, the 1- and 5-year overall survival rates post-transplant were 87.5% and 75%, respectively. CONCLUSION: Patients with intrahepatic cholangiocarcinoma or combined hepatocellular- and cholangiocarcinoma could profit from liver transplantation.

Clinical Results of Transarterial Radioembolization (TARE) with Holmium-166 Microspheres in the Multidisciplinary Oncologic Treatment of Patients with Primary and Secondary Liver Cancer.

Holmium-166 microspheres are used for the transarterial radioembolization (TARE) treatment of primary and secondary liver cancers. In this study, its efficacy regarding local tumor control and integration into the oncological treatment sequence of the first 20 patients treated in our institution were examined. A total of twenty-nine 166Ho-TARE procedures were performed to treat hepatocellular carcinoma (HCC, fourteen patients), metastatic colorectal cancer (mCRC, four patients), intrahepatic cholangiocarcinoma (ICC, one patient), and hemangioendothelioma of the liver (HE, one patient). In eight patients, 166Ho-TARE was the initial oncologic treatment. In patients with HCC, the median treated-liver progression-free survival (PFS), overall PFS, and overall survival after 166Ho-TARE were 10.3, 7.3, and 22.1 months; in patients with mCRC, these were 2.6, 2.9, and 20.6 months, respectively. Survival after 166Ho-TARE in the patients with ICC and HE were 5.2 and 0.8 months, respectively. Two patients with HCC were bridged to liver transplantation, and one patient with mCRC was downstaged to curative surgery. In patients with HCC, a median treatment-free interval of 7.3 months was achieved. In line with previous publications, 166Ho-TARE was a feasible treatment option in patients with liver tumors, with favorable clinical outcomes in the majority of cases. It was able to achieve treatment-free intervals, served as bridging-to-transplant, and did not prevent subsequent therapies.

Adipose tissue induces a better liver regeneration after living liver donation in normal weight donors.

Background: Extrahepatic body fat could be a relevant factor affecting liver regeneration after partial hepatectomy. The aim of this study was to evaluate the potential role of body fatty tissue in liver regeneration capacity after liver resection in a cohort of living donors. Methods: We observed liver regeneration in 120 patients: 70 living donors who underwent right hepatectomy and 50 recipients who got a right graft transplantation. Liver volumetry and body fat analysis were performed based on the computed tomography images with volumetry software. The gain of liver volume was calculated between three points in time considering the absolute and percentage values: before surgery and early (median 10 days, range 4-21 days) and late (median 27 weeks, range 18-40 weeks) after surgery. Pearson's correlation was used to examine the potential correlation between adipose tissue and liver regeneration. Results: Pearson's correlation showed a significant correlation between the subcutaneous fat mass index (sFMI) and early (r=0.173, P=0.030), as well late (r=0.395, P=0.0004) percental liver volume gain in the whole collective. Under stratification in donor's and recipient's collectives, the effect of extrahepatic adipose tissue appears in multiple regression only in the donor's collective: early (ß =0.219, T =2.137, P=0.036) and late (ß =0.390, T =2.552, P=0.015) percental volume gain. Conclusions: Subcutaneous adipose tissue is a positive predictive factor to estimate the goodness of liver regeneration after partial hepatectomy in normosthenic donors.

Postoperative Outcomes in 415 Patients Following Liver Transplantation Using Extended Donor Criteria: A Study from a Single Center in Germany.

BACKGROUND Because of the massive organ shortage worldwide, marginal organs are increasingly being considered. The aim of this study was to present a comprehensive analysis of donor-related factors clinically supposed to influence the outcome after liver transplantation. This study from a single center in Germany aimed to evaluate postoperative outcomes in 415 patients following liver transplantation using extended donor criteria. MATERIAL AND METHODS Extended donor criteria (EDC) were considered according to the official guidelines issued through the German Medical Association. Other factors and the Eurotransplant Donor Risk Index (ET-DRI) were also considered. Correlation studies, logistic regression, and Kaplan-Meier-estimator were used to evaluate the outcome. RESULTS The postoperative outcomes with or without EDC were comparable. Other factors had an impact on early allograft failure (EAD), including male donors (χ²=14.135, P=0.0001). Other donor-unrelated factors, like cold ischemia time, also had an impact on EAD (r=0.135, P=0.010), especially in patients with model for end-stage liver disease (MELD) <25 (ß=0.001, P=0.008). ET-DRI was a crucial factor in estimating overall and allograft survival after liver transplantation. CONCLUSIONS The findings from this study support the possibility of liver transplantation using organs obtained by EDC. Other factors, like donor sex and cold ischemic time, are not part of the EDC, although they have an impact on EAD. Organs obtained by EDC continue to be an option to address the organ shortage.

Value of palliative surgery in perihilar cholangiocarcinoma.

PURPOSE: The survival rate of patients with irresectable perihilar cholangiocarcinoma is remarkably poor. An essential part of palliation is treatment of obstructive cholestasis caused by the tumor. Currently, this is mainly performed endoscopically by stent or via PTBD, requiring frequent changes of the stents and limiting health-related quality of life due to the multiple hospital stays needed. The aim of this study was to evaluate surgical palliation via extrahepatic bile duct resection as an option for palliative treatment. METHODS: Between 2005 and 2016, we treated 120 pCCC patients with primary palliative care. Three treatment strategies were retrospectively considered: extrahepatic bile duct resection (EBR), exploratory laparotomy (EL), and primary palliative (PP) therapy. RESULTS: The EBR group required significantly less stenting postoperatively, and the overall morbidity was 29.4% (EBR). After the surgical procedure, fewer subsequent endoscopic treatments for stenting or PTBD were necessary in the EBR group over time. The 30-day mortality was 5.9% (EBR) and 3.4% (EL). The median overall survival averaged 570 (EBR), 392 (EL), and 247 (PP) days. CONCLUSIONS: In selected pCCC patients, palliative extrahepatic bile duct resection is a feasible option for treatment of obstructive cholestasis and should be reconsidered as a therapy option for these patients even in a palliative setting.

Critical Evaluation of Discarded Donor Livers in the Eurotransplant Region: Potential Implications for Machine Perfusion.

BACKGROUND There are still many offered donor livers that are declined during the allocation process. Machine perfusion offers the option to evaluate (especially marginal) donor organs and to better decide whether a graft has the potential of being transplanted or not. There is a lack of clear detailed data on why organs are declined and how many donor livers would have the potential of being evaluated in the machine. MATERIAL AND METHODS We retrospectively reviewed 1356 donor livers between 2016 and 2018, which were offered by Eurotransplant and were declined during the allocation process; 284 grafts were from donor after cardiac death (DCD) and 1072 donations were from after brain death (DBD). The analysis was performed independently and blinded by senior transplant surgeons. RESULTS There were 904 (66.6%) donor livers with potential to be evaluated as suitable grafts in machine perfusion, whereas 417 (30.8%) organs were definitely not-transplantable, mainly due to liver cirrhosis, (untreated) donor malignancy, cardiac diseases of the donor leading to a hepatic congestion, and/or systemic infections in the donor. Donors in blood group "AB" were disproportionally often rejected. Due to missing data, 35 (2.6%) organs could not be sufficiently evaluated. CONCLUSIONS Our data suggest that many declined donor livers have potential of being evaluated by machine perfusion. Comprehensive use of machine perfusion is necessary and useful to improve the current organ shortage.

Auxilliary Liver Transplantation According to the RAPID Procedure in Noncirrhotic Patients: Technical Aspects and Early Outcomes.

OBJECTIVE: To present technical details and short-term experiences of liver transplantation as a 2-stage procedure using small for size grafts in a multicenter cohort study. BACKGROUND: Two-stage liver transplantation using small for size grafts should be a feasible procedure with lower morbidity and mortality rates. Retrospective cohort study between 2015 and 2022 with multicenter experience. Twenty-three resection and partial liver transplantation with delayed total hepatectomy procedures for noncirrhotic indications were performed in 6 European centers (20 with grafts from living donors and 3 after deceased donation). Procedure's feasibility, graft volumetric changes, morbidity, and mortality of donor and recipient were explored. RESULTS: There was a low donor morbidity (4.3%) in our cohort. Hypertrophy of the graft was rapid (mean graft volume increases 107% between both stages) and offered the opportunity for remnant hepatectomy after a median of 14 days. In all cases, portomesenteric flow was routed to the graft by right remnant portal vein ligation. Portal vein inflow modulation to alleviate transient harmful portal hypertension was not needed in any case. Early postoperative mortality (4.3%) of the recipients were low. Ten patients suffered from complications ≥IIIb according to the Clavien-Dindo classification. CONCLUSIONS: Two-stage liver transplantation is a feasible option for noncirrhotic patients allowing the safe use of small for size grafts and could possibly be extended with caution to liver diseases with portal hypertension and cirrhosis. The resection and partial liver transplantation with delayed total hepatectomy technique might be a viable option for expanding the donor pool given the current organ shortage especially for low-model of end stage liver disease patients.

Liver regeneration after two-stage liver transplantation is more effective than after other preconditioning procedures in colorectal liver metastases.

INTRODUCTION: Induction of liver regeneration represents an option to expand the resectability in patients with expected small future liver remnant (FLR). The aim of this cohort-study is to compare the liver regeneration between different surgical procedures, including novel procedures such as two-stage living donor liver transplantation using small-for-size grafts. METHODS: Forty-three patients with colorectal liver metastases were included between 2004 and 2020. They underwent one of the following three procedures: portal vein embolization (PVE), associated liver partition with portal vein ligation for staged hepatectomy (ALPPS), and living donor two-stage liver transplantation (LT). The volume gain of the future liver remnant was analyzed in comparison between the three mentioned procedures. RESULTS: The type of surgery performed had a significant correlation with liver regeneration with a strong effect on the benefit of ALPPS and liver transplantation, respectively (r = .6, p = .00003). The type of surgery was the only independent co-factor in the multiple regression, which showed a significant influence on FLR-increase favoring two-stage transplantation compared to the other two related procedures (ß = .12, T = 3.9, p = .0004). The histological and immunohistochemical studies also showed a clear advantage of proliferation to the benefits of two-stage liver transplantation compared with ALPPS. CONCLUSION: Two-stage liver transplantation using small-for-size grafts induces better FLR-increase than portal vein embolization or ALPPS in patients with colorectal liver metastases.

Pathogen detection in patients with perihilar cholangiocarcinoma: Implications for targeted perioperative antibiotic therapy.

BACKGROUND: Cholestasis should be relieved by biliary drainage prior to major liver resection. This condition is often associated with bacterial colonization of the otherwise sterile biliary system. Cholangitis reduces the regenerative capacity of the remaining liver. Therefore, targeted antibiotic therapy is a key feature in perioperative treatment in patients with perihilar cholangiocarcinoma (pCCC). METHODS: Between December 1999 and December 2017, 251 pCCC patients were treated in our center. In total, 115 patients underwent a microbiological analysis. In addition to the characterization of the specific microorganisms and antibiotic resistance, we analyzed subgroups according to preoperative intervention. RESULTS: Enterococci (87/254, 34%) and Enterobacteria (65/254, 26%) were the most frequently detected genera. In 43% (50/115) of patients, Enterococcus faecalis was found in the bile duct sample. Enterococcus faecium (29/115) and Escherichia coli (29/115) were detected in 25% of patients. In patients with percutaneous transhepatic biliary drainage (3/8, 38%) or stents (24/79, 30%), Enterococcus faecium was diagnosed most frequently (P < 0.05). Enterococcus faecium and Klebsiella oxytoca were significantly more frequently noted in the time period after 2012 (P < 0.05). With regard to fungal colonization, the focus was on various Candida strains, but these strains generally lacked resistance. CONCLUSIONS: pCCC patients exhibit specific bacterial colonization features depending on the type of preoperative biliary intervention. Specifically, targeted antibiosis should be applied in this patient cohort to minimize the risk of biliary complications after major liver resection. In our cohort, the combination of meropenem and vancomycin represents an effective perioperative medical approach.

Associations of Betatrophin/ANGPTL8 with Septic Dyslipidemia in Human Peritonitis: An Explorative Analysis.

Sepsis is defined by life-threatening organ dysfunction mediated by the host's response to infection. This can result in septic dyslipidemia, which is involved in the neutralization of pathogen-related lipids. Knowledge of the regulatory mechanisms of septic dyslipidemia is incomplete. The cytokine betatrophin/Angiopoietin-like protein 8 (ANGPTL8) plays a role in the regulation of triacylglyceride metabolism, though its function in septic dyslipidemia remains unknown. Sixty-six patients were enrolled in a cross-sectional study. Circulating concentrations and adipose tissue (AT) mRNA expression of betatrophin/ANGPTL8 were studied in patients suffering from peritoneal sepsis. Insulin-resistant individuals and subjects without metabolic derangement/systemic inflammation were enrolled as controls. All underwent open abdominal surgery. Circulating betatrophin/ANGPTL8 was analyzed by an enzyme-linked immunosorbent assay and AT mRNA expression levels were assessed by real-time PCR. Standard laboratory analyses including lipid electrophoresis were evaluated. Sepsis patients showed pronounced septic dyslipidemia (p < 0.05 for all major lipid classes). Despite comparable betatrophin/ANGPTL8 mRNA expression in AT (p = 0.24), we found significantly increased circulating betatrophin/ANGPTL8 with septic dyslipidemia (p = 0.009). Expression levels of betatrophin/ANGPTL8 in AT correlated with circulating concentrations in both control groups (r = 0.61; p = 0.008 and r = 0.43; p = 0.034), while this association was undetectable in sepsis. After stratification, betatrophin/ANGPTL8 remained associated with hypertriacylglyceridemia (p < 0.05).

Liver growth prediction in ALPPS - A multicenter analysis from the international ALPPS registry.

BACKGROUND: While ALPPS triggers a fast liver hypertrophy, it is still unclear which factors matter most to achieve accelerated hypertrophy within a short period of time. The aim of the study was to identify patient-intrinsic factors related to the growth of the future liver remnant (FLR). METHODS: This cohort study is composed of data derived from the International ALPPS Registry from November 2011 and October 2018. We analyse the influence of demographic, tumour type and perioperative data on the growth of the FLR. The volume of the FLR was calculated in millilitre and percentage using computed-tomography (CT) scans before and after stage 1, both according to Vauthey formula. RESULTS: A total of 734 patients were included from 99 centres. The median sFLR at stage 1 and stage 2 was 0.23 (IQR, 0.18-0.28) and 0.39 (IQR: 0.31-0.46), respectively. The variables associated with a lower increase from sFLR1 to sFLR2 were age˃68 years (p = .02), height ˃1.76 m (p ˂ .01), weight ˃83 kg (p ˂ .01), BMI˃28 (p ˂ .01), male gender (p ˂ .01), antihypertensive therapy (p ˂ .01), operation time ˃370 minutes (p ˂ .01) and hospital stay˃14 days (p ˂ .01). The time required to reach sufficient volume for stage 2, male gender accounts 40.3% in group ˂7 days, compared with 50% of female, and female present 15.3% in group ˃14 days compared with 20.6% of male. CONCLUSIONS: Height, weight, FLR size and gender could be the variables that most constantly influence both daily growths, the interstage increase and the standardized FLR before the second stage.

Living Donor Liver Transplantation for Intrahepatic Cholangiocarcinoma.

Intrahepatic cholangiocarcinoma is in most transplant regions a contraindication for liver transplantation, even ruling out an active waiting list registration. However, recent studies showed that well-selected patients after a neo-adjuvant treatment benefit from liver transplantation with good long-term outcomes. The role of living donor liver transplantation is unclear for this indication. The current study focuses on LDLT for intrahepatic cholangiocarcinoma.

Endoplasmic reticulum stress and the unfolded protein response in skeletal muscle of subjects suffering from peritoneal sepsis.

We provide a descriptive characterization of the unfolded protein response (UPR) in skeletal muscle of human patients with peritoneal sepsis and a sepsis model of C57BL/6J mice. Patients undergoing open surgery were included in a cross-sectional study and blood and skeletal muscle samples were taken. Key markers of the UPR and cluster of differentiation 68 (CD68) as surrogate of inflammatory injury were evaluated by real-time PCR and histochemical staining. CD68 mRNA increased with sepsis in skeletal muscle of patients and animals (p < 0.05). Mainly the inositol-requiring enzyme 1α branch of the UPR was upregulated as shown by elevated X-box binding-protein 1 (XBP1u) and its spliced isoform (XBP1s) mRNA (p < 0.05, respectively). Increased expression of Gadd34 indicated activation of PRKR-Like Endoplasmic Reticulum Kinase (PERK) branch of the UPR, and was only observed in mice (p < 0.001) but not human study subjects. Selected cell death signals were upregulated in human and murine muscle, demonstrated by increased bcl-2 associated X protein mRNA and TUNEL staining (p < 0.05). In conclusion we provide a first characterization of the UPR in skeletal muscle in human sepsis.

Acceptance of SARS-CoV-2 vaccines by liver transplant recipients and candidates.

Guidelines recommend vaccination against SARS-CoV-2 in transplant recipients, candidates, and their household contacts. However, little is known about the acceptance of COVID-19 vaccines in these groups.In March 2021, we surveyed 826 liver transplant recipients, candidates, and their household contacts to determine acceptance rates and factors influencing the acceptance of the COVID-19 vaccine; 341 patients (40%) and 237 household contacts (28%) returned the questionnaire. Ninety percent of patients returning the survey reported they were willing to receive the vaccine within the next 6 months or had already started vaccination. Only 2% of patients and 4% of household contacts reported refusing the vaccine, and 8% of patients and 9% of household contacts wanted to postpone vaccination because of concerns about side effects. Having received the influenza vaccine in the last 2 seasons was the strongest indicator of acceptance to receive the SARS-CoV-2 vaccine within 6 months (odds ratio 5.11; 95% confidence interval 2.43-10.74; p < 0.001). Thirty-two percent of responding patients reported fear of side effects as a reason for having refused vaccination before.Although the acceptance of the SARS-CoV-2 vaccine was particularly high among German liver transplant recipients, candidates, and household contacts in this survey, transplant physicians are encouraged to discuss safety concerns with patients who have refused the seasonal influenza vaccine in the past.