Donor-specific anti-HLA antibodies are not associated with non-anastomotic biliary strictures, but both are independent risk factors for graft loss after liver transplantation

Abstract Introduction Biliary leaks and anastomotic strictures are common early biliary complications (EBC) following liver transplantation. However, their impact on outcomes remains controversial and poorly described. Method The NHS registry on adult liver transplantation between 2006 and 2017 was retrospectively reviewed (n=8304). Multiple imputations were performed to account for missing data. Adjusted regression models were used to assess predictors of EBC, and their impact on outcomes. 35 potential variables were included, and backwards stepwise selection enabled unbiased selection of variables for inclusion in final models. Result EBC occurred in 9.6% of patients. Adjusted cox regression revealed that EBCs have a significant and independent impact on graft survival (Leak HR=1.325; P=0.021, Stricture HR=1.514; P=0.002, Leak plus stricture HR=1.533; P=0.034) and patient survival (Leak HR=1.218; P=0.131, Stricture HR=1.578; P<0.001, Leak plus stricture HR=1.507; P=0.044). Patients with EBC had longer median hospital stay (23 versus 15 days; P<0.001) and increased chance for readmission within the first year (56% versus 32%; P<0.001). On adjusted logistic regression the following were identified as independent risk factors for development of EBC: donation following circulatory death (OR=1.280; P=0.009), accessory hepatic artery (OR=1.324; P=0.005), vascular anastomosis time in minutes (OR=1.005; P=0.032) and ethnicity ‘other’ (OR=1.838; P=0.011). Conclusion EBCs prolong hospital stay, increase readmission rates and are independent risk factors for diminished graft survival and increased mortality in liver transplantation. We have identified factors that increase the likelihood of EBC occurrence; further research into interventions to prevent EBCs in these at-risk groups is vital to improve liver transplantation outcomes. Take-home message Using a large registry database we have shown that early anastomotic biliary complications are independent risk factors for decreased graft survival and increased mortality after liver transplantation. Research into interventions to prevent biliary complications in high risk groups are essential to improve liver transplant outcomes.

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Surgical Site Infection After Liver Transplantation: Risk Factors and Association With Graft Loss or Death

Transplantation Journal ◽

10.1097/tp.0b013e3181a25133 ◽

2009 ◽

Vol 87 (9) ◽

pp. 1387-1393 ◽

Cited By ~ 45

Author(s):

Walter C. Hellinger ◽

Julia E. Crook ◽

Michael G. Heckman ◽

Nancy N. Diehl ◽

Jefree A. Shalev ◽

...

Keyword(s):

Risk Factors ◽

Liver Transplantation ◽

Surgical Site Infection ◽

Graft Loss ◽

Site Infection

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P1646SURVIVAL OF KIDNEY TRANSPLANTS ACCORDING TO PRESENCE OF HLA ANTIBODIES WHEN DONORSPECIFIC ANTIBODIES ARE SCREENED DURING POSTTRANSPLANT FOLLOW-UP

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1646 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Inge Derad ◽

Johanna Busch ◽

Martin Nitschke ◽

Malte Ziemann

Keyword(s):

Risk Factors ◽

Confidence Interval ◽

Graft Survival ◽

Graft Loss ◽

Immunosuppressive Regimen ◽

Term Survival ◽

Hla Antibodies ◽

Transplant Survival ◽

The Mean

Abstract Background and Aims Posttransplant kidney survival depends on several risk factors. A careful immunogenetic matching and the absence of HLA donor specific antibodies (DSA) seem to determine the longevity of the transplant. Method Screening the presence of donor specific HLA antibodies in our posttransplant outpatients was implemented in 2010 (every 6 months in case of DSA free patients for two years, then yearly, and every 3 months in case of DSA + patients for two years, then twice a year). At the same time a treatment protocol was implemented, omitting reduction of immunosuppressive drugs in case of newly detected DSA, and most important with preventing steroid withdrawal in this case.The present single center study reports the long-term survival and kidney function from patients undergoing HLA-screening after transplantation between 2010 and 2016 with a follow-up until 2018. Using a Kaplan-Meier analysis patients without HLA antibodies (no HLA-ab), with HLA antibodies but without DSA (NDSA), and with donor-specific HLA antibodies (DSA) were compared by logrank-testing. Results A full dataset was obtained from 318 patients. The mean overall survival (patients and organ function) didn´t differ between the three groups, p=0.318: no HLA-ab 7.2 years (95%confidence interval 6.7;7.6), NDSA 6.6 (5.9;7.2), DSA 6.8 (6.1;7.5), overall 7.0 (6.6;7.3), events are given in Table1. Whereas the mean patient survival didn´t differ between the groups (p=0.715), the mean death-censored graft survival differed significantly, p=0.008, with a reduced transplant survival in the patients with HLA antibodies but without donorspecific antibodies: no HLA-ab 8.0 years (95%confidence interval 7.7;8.3), NDSA 7.0 (6.4;7.6), DSA 7.6 (7.1;8.2), overall 7.7 (7.4;8.0), numbers are given in Table1. Conclusion In conclusion, the presence of HLA antibodies was associated with a reduced transplant survival. Patients with HLA antibodies had a worse survival than patients with DSA undergoing HLA screening with a personalised immunosuppressive regimen. Immunosuppressive regimen of the groups, as well as other known risk factors of graft survival have to be further analysed. The results of these multivariate analyses have to be awaited to determine whether the risk for graft loss inferred by HLA antibodies is independent from other factors.

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A single-institution survey of de novo secondary malignancies in patients occurring after orthotropic liver transplantation.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.4_suppl.297 ◽

2012 ◽

Vol 30 (4_suppl) ◽

pp. 297-297

Author(s):

Quentin Gillebert ◽

Mohamed Bouattour ◽

Francois Durand ◽

Claire Francoz ◽

Valerie Paradis ◽

...

Keyword(s):

Risk Factors ◽

Liver Transplantation ◽

De Novo ◽

Secondary Malignancy ◽

Prior History ◽

Lung Cancers ◽

History Of ◽

Independent Risk Factors ◽

De Novo Cancer ◽

Tumor Types

297 Background: We aim to evaluate in our institution the incidence of de novo malignancies following orthotopic liver transplantation (OLT) and their impact the prognosis of patients (pts). Methods: Pts treated with OLT from August 1991 To March 2009 were considered in this analysis. All pts data had been prospectively recorded in the database of French “Bio-medecine Agence”. Pts were considered for this analysis only if they survived at least 3-months after. Occurrence of de novo malignancies we analyzed and additional data (including immunosuppressive profile, type of cancer, potential independent risk factors of cancers, prognosis and the influence of immunosuppression protocols or risk factors on occurrence of cancers) were collected in patients who developed secondary cancers. Results: A total of 833 patients who underwent OLT were considered for this analysis. With a median follow-up of 7.9 years, 72 pts developed 92 de novo malignancies. The overall incidence of cancers in our population was 10.4% occurring with a median time of 6.1 years following OLT. Sixteen pts developed 2 different types of cancer and 2 pts had more than 3 tumor types. Before 12/1998, immunosuppression was primarily based on cyclosporine, steroids and/or azathiopirine, and since 01/1999 was switched to tacrolimus. Incidence of cancers regarding these two periods is summarized in the table. Before 1998, only 3 pts (17.6%) with secondary cancer had prior history of alcoholism and/or smoking compared to 27 pts (50%) after 1999. Thirty one deaths were observed and the median overall survival (OS) after the time of diagnosis of secondary malignancy was 5.62 years. Conclusions: The risk of de novo cancer after OLT is similar to reported series. History of smoking and alcohol use, increase the incidence of de novo malignancies especially head and neck and lung cancers however, immunosuppression type may not interfere with this risk. [Table: see text]

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Risk factors and criteria predicting early graft loss after adult-to-adult living donor liver transplantation

Journal of Surgical Research ◽

10.1016/j.jss.2013.10.048 ◽

2014 ◽

Vol 187 (2) ◽

pp. 673-682 ◽

Cited By ~ 9

Author(s):

ZhengGui Du ◽

YongGang Wei ◽

KeFei Chen ◽

Xi Chen ◽

ZhiJun Zhang ◽

...

Keyword(s):

Risk Factors ◽

Liver Transplantation ◽

Living Donor ◽

Living Donor Liver Transplantation ◽

Graft Loss ◽

Donor Liver ◽

Donor Liver Transplantation ◽

Early Graft

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Chronic severe hepatitis and preoperative creatinine are independent risk factors for acute kidney injury after liver transplantation

Annals of Translational Medicine ◽

10.21037/atm-20-7680 ◽

2020 ◽

Vol 8 (24) ◽

pp. 1663-1663

Author(s):

Yingqi Chen ◽

Shanshan Mu ◽

Jing Wang ◽

Anshi Wu

Keyword(s):

Risk Factors ◽

Liver Transplantation ◽

Acute Kidney Injury ◽

Kidney Injury ◽

Severe Hepatitis ◽

Independent Risk Factors ◽

Preoperative Creatinine

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Homocysteine: A novel prognostic biomarker in liver transplantation for alpha-fetoprotein- negative hepatocellular carcinoma

Cancer Biomarkers ◽

10.3233/cbm-201545 ◽

2020 ◽

Vol 29 (2) ◽

pp. 197-206

Author(s):

Modan Yang ◽

Winyen Tan ◽

Xinyu Yang ◽

Jianyong Zhuo ◽

Zuyuan Lin ◽

...

Keyword(s):

Risk Factors ◽

Hepatocellular Carcinoma ◽

Liver Transplantation ◽

Tumor Recurrence ◽

Prognostic Biomarker ◽

Milan Criteria ◽

Recurrence Free Survival ◽

Free Survival ◽

Independent Risk Factors ◽

Hcc Recurrence

BACKGROUND: Precise recipient selection optimizes the prognosis of liver transplantation (LT) for hepatocellular carcinoma (HCC). Alpha-fetoprotein (AFP) is the most commonly used biomarker for diagnosis and prognosis of HCC in the clinical context. As a crucial molecule in methionine cycle, homocysteine (Hcy) level has been proved to be related to HCC progression and metastasis. OBJECTIVE: We aimed to explore the prognostic capacity of pre-transplant serum Hcy level in LT for HCC. METHODS: This study retrospectively enrolled 161 HCC patients who had underwent LT from donation after cardiac death (DCD) in the First Affiliated Hospital of Zhejiang University from 2015.01.01 to 2018.09.01. Pre-transplant serum Hcy level was incorporated into statistical analysis together with other clinical parameters and pathological features. RESULTS: From an overall perspective, significant difference was observed in Hcy level between recurrence (n= 61) and non-recurrence group (n= 100) though subsequent analysis showed unsatisfactory predicting performance. In the whole cohort, multivariate analysis showed that lnAFP (p= 0.010) and Milan criteria (MC, p< 0.001) were independent risk factors of HCC recurrence after LT. MA score based on MC and lnAFP performed well in predicting post-LT tumor recurrence with the AUROC at 0.836 (p< 0.001) and 3-year recurrence-free survival rate at 96.8% (p< 0.001) in the low risk group (n= 69). According to the clinical practice, serum concentration lower than 20 μg/L is considered as normal range of AFP. Elevated pre-transplant serum AFP (> 20 μg/L) predicts high HCC recurrence after LT. We further divided the 161 recipients into AFP- group (n= 77, AFP ⩽ 20 μg/L) and AFP+ group (n= 84, AFP > 20 μg/L). MA score was still well presented in the AFP+ group and the AUROC for tumor recurrence was 0.823 (p< 0.001), whereas the predicting accuracy was reduced in AFP- group (AUROC: 0.754, P< 0.001). After subsequent analysis, we found that elevated pre-transplant Hcy level (> 12.75 μmol/L) predicted increased tumor recurrence risk in AFP- group. The 3-year recurrence-free survival rates were 92.0% and 53.7% (p< 0.001) in low Hcy subgroup (n= 40) and high Hcy subgroup (n= 37) respectively. Multivariate analysis showed that Hcy (p= 0.040) and Milan criteria (p= 0.003) were independent risk factors for post-transplant tumor recurrence in AFP- group. Further combination of Hcy level and Milan criteria identified a subgroup of AFP- recipients with acceptable outcomes even though beyond Milan criteria (3-year recurrence-free survival rate: 77.7%, p< 0.001). CONCLUSION: As a classic predictor in HCC prognosis, AFP performed well in our study cohort when combined with Milan criteria. Homocysteine was an effective prognostic biomarker in LT for AFP- hepatocellular carcinoma. In recipients exceeding Milan criteria, acceptable post-transplant outcome could be seen in those with low Hcy and AFP level.

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