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Abraham Shaked

Publications and source records attributed to Abraham Shaked.

At least 19 recordsLinked to original sources
PubMed2025

Germline Variants Influence Chronic Liver Disease Progression through Distinct Pathways.

Cirrhosis and hepatocellular carcinoma (HCC) are long-term complications of chronic liver disease (CLD). In this large multi-ancestry genome-wide association study of all-cause cirrhosis (35,481 cases, 2.36M controls) and HCC (6,680 cases, 1.76M controls), we identified 27 loci associated with cirrhosis (10 novel) and 11 with HCC (three novel). Three novel cirrhosis loci were replicated in independent cohorts (e.g. FGF21, RPTOR, and IFNL3/4). Fifteen cirrhosis loci exhibited differential effects on cirrhosis risk via underlying etiologies, and six HCC loci influenced HCC risk indirectly via cirrhosis. In a gene-burden analysis of rare variants from whole-genome sequencing data in the VA Million Veteran Program (n=102,677), we identified GSTA5 as a novel cirrhosis-associated gene, while APOB and ATP9B were associated with and replicated for HCC. A high genetic risk score for cirrhosis was associated with a nearly doubled risk of CLD progressing to cirrhosis (HR=1.94, P=2×10-68) and of cirrhosis progressing to HCC (HR=1.65, P=7×10-08). Finally, among individuals with chronic hepatitis C who underwent antiviral therapy, cirrhosis risk was modified by variants in PNPLA3, IFNL3/4, and CD81 following pegylated interferon-α therapy, and by APOE lead variant following direct-acting antiviral therapy. These findings provide new insights into the complex genetic architecture of CLD progression with potential clinical and therapeutic implications.

Journal Article↗
PubMed2025

Expanded Chromatin Accessibility Mapping Explains Genetic Variation Associated with Complex Traits in Liver.

Genome-wide association studies (GWAS) have identified thousands of loci associated with a variety of common, complex human traits. Recent efforts have focused on characterizing chromatin accessibility to discover regulatory elements that modify the expression of nearby genes, suggesting that trait associations are mediated through changes in gene regulation. Genetic variants associated with differences in chromatin accessibility, known as chromatin accessibility quantitative trait loci (caQTLs), are established contributors to gene expression differences, providing mechanistic hypotheses for signals identified by GWAS. Using the assay for transposase-accessible chromatin with sequencing (ATAC-seq), we assessed chromatin accessibility in 189 diverse human liver samples, identifying over two million accessible chromatin regions enriched for gene regulatory features and, in 175 of these samples, over 14,000 caQTLs. Focusing subsequently on liver-relevant complex traits, we obtained publicly available blood lipids GWAS data and identified 157 loci where caQTLs, expression quantitative trait loci (eQTLs), and GWAS signals colocalized. This generated specific molecular hypotheses about regulatory elements, affected genes, and, in some cases, implicated transcription factors. Finally, we enumerated the set of blood lipid trait signals that lack an obvious proposed mechanism beyond catalogs of liver caQTLs and eQTLs. After integrating 10 multi-omic QTL regulatory mechanism datasets whilst considering limitations in statistical power, we found that approximately 20% of blood lipid GWAS signals lacked a statistical link to a proposed mechanism. Our results demonstrate the value of integrating multiple genomic datasets to improve understanding of GWAS signals, while emphasizing the need for additional experimental approaches to fully characterize complex trait associations.

Journal Article↗
PubMed2006

Lack of benefit of pre-transplant locoregional hepatic therapy for hepatocellular cancer in the current MELD era.

The potential for disease progression in patients awaiting liver transplantation for hepatocellular carcinoma (HCC) has encouraged many centers to employ pre-transplant radiofrequency ablation or chemoembolization in an attempt to control tumor burden while patients are on the wait list. Despite general acceptance by the transplant community, few objective data demonstrate pre-transplant treatment efficacy or improved post-transplant outcomes in HCC patients listed with Model for End-Stage Liver Disease (MELD) exception points. To evaluate the utility of pre-transplant therapy in the current MELD era, we retrospectively compared 31 treated patients (T) with 33 untreated (U) controls. Study endpoints included patient and disease-free survival, tumor recurrence, explant tumor viability, and the ability of MRI to detect viable tumor after therapy. Both cohorts had similar demographic, radiographic, and pathologic characteristics, although untreated patients waited longer for transplantation [119 (U) vs. 54 (T) days after MELD assignment, (P = .05); range: 1 day to 21 months]. Only 20% of treated tumors demonstrated complete ablation (necrosis) as defined by histologic examination of the entire lesion. Only 55% of lesions with histologic viable tumor were detected by MRI after pre-transplant therapy. After 36 months of follow-up, there was no difference between the treated and untreated groups in overall survival (84 vs. 91%), disease free survival (74% vs. 85%), cancer recurrence (23% vs. 12%), or mortality from cancer recurrence (57% vs. 25%) (P > 0.1). In conclusion, viable tumor frequently persists after pre-transplant locoregional therapy, and neoadjuvant treatment does not appear to improve post-transplant outcomes in the current MELD era.

Adult↗
PubMed2006

Inadequate hepatitis B vaccination and post-exposure evaluation among transplant surgeons: prevalence, correlates, and implications.

OBJECTIVES: To identify the proportion of U.S. transplant surgeons who are adequately vaccinated against hepatitis B virus (HBV), identify characteristics associated with inadequate vaccination, and assess the proportion who had been evaluated for immunization following potential HBV exposures. SUMMARY BACKGROUND DATA: It is unknown what proportion of transplant surgeons are appropriately vaccinated against HBV or evaluated for immunization following operative exposures. METHODS: We mailed questionnaires and to all active U.S. transplant surgeons. We compared demographic characteristics of responders and nonresponders to evaluate the potential for nonresponse bias. RESULTS: Of 619 eligible respondents, 347 (56.1%) returned completed questionnaires. Of the 311 surgeons for whom HBV vaccination was indicated (all surgeons with neither a prior history of HBV infection nor a prior adverse reaction to the vaccine itself), 70 (22.5%; 95% confidence interval [CI], 18.0-27.6%) received fewer than the recommended 3 injections. Surgeon characteristics associated with inadequate vaccination included length of clinical practice (odds ratio [OR], 1.5 per 10-year increment in duration of practice; 95% CI, 1.1-2.2), increased fear of infection (OR, 1.2 for each unit increase in fear out of 10; 95% CI, 1.1-1.4), and lack of recent testing for HBV infection (OR, 2.0; 95% CI, 1.1-3.8). Of the 94 surgeons (27.3%) reporting at least one needle-stick exposure while operating on an HBV-infected patient, 14 (14.9%) were inadequately vaccinated; of these 14, only 5 (35.7%) sought appropriate serologic testing and counseling for active immunization. Surgeons underestimated both the risks of percutaneous exposure while operating, and of becoming infected with HBV if exposed. CONCLUSIONS: Many transplant surgeons are inadequately vaccinated against HBV and fail to seek evaluation following possible exposures. Underestimation of the risks of HBV exposure and transmission may relate to these failures. Requiring documentation of HBV vaccination and immunity to maintain operating room privileges may protect surgeons, their patients, and operating room staff.

Attitude of Health Personnel↗
PubMed2005

Liver transplantation for metastatic neuroendocrine tumor: a case report and review of the literature.

Neuroendocrine tumors are divided into gastrointestinal carcinoids and pancreatic neuroendocrine tumors. The WHO has updated the classification of these lesions and has abandoned the term "carcinoid". Both types of tumors are divided into functional and non-functional tumors. They are characterized by slow growth and frequent metastasis to the liver and may be limited to the liver for long periods. The therapeutic approach to hepatic metastases should consider the number and distribution of the liver metastases as well as the severity of symptoms related to hormone production and tumor bulk. Surgery is generally considered as the first line therapy. In patients with unresectable liver metastases, alternative treatments are dependent on the type and the growth rate. Initial treatments consist of long acting somatostatin analogs and/or interferon. Streptozocin-based chemotherapy is usually reserved for symptomatic patients with rapidly advancing disease, but generally the therapy is poorly tolerated and its effects are short-lived. Locoregional therapy directed such as hepatic-artery embolization and chemoembolization, radiofrequency thermal ablation and cryosurgery, is often used instead of systemic therapy, if the disease is limited to the liver. However, liver transplantation should be considered in patients with neuroendocrine metastases to the liver that are not accessible to curative or cytoreductive surgery and if medical or locoregional treatment has failed and if there are life threatening hormonal symptoms. We report a case of liver transplantation for metastatic neuroendocrine tumor of unknown primary source and provide a detailed review of the world literature on this controversial topic.

Humans↗
PubMed2005

Renal function after orthotopic liver transplantation is predicted by duration of pretransplantation creatinine elevation.

In patients with recent onset renal insufficiency, the decision to perform combined kidney/liver transplantation (CKLT) vs. orthotopic liver transplantation alone (OLTa) can be difficult. We hypothesized that duration of renal dysfunction may correlate with creatinine elevation after liver transplantation. We retrospectively identified 69 liver transplantation patients with pretransplantation creatinine > or =1.5 mg/dL (53 OLTa, 13 CKLT). Variables analyzed were presence of hepatorenal syndrome, creatinine, Model for End-Stage Liver Disease score, albumin, age, race, gender, cause of liver disease, diabetes mellitus, hypertension, and history of ascites, spontaneous bacterial peritonitis, variceal bleeding, hepatic encephalopathy, renal replacement therapy (RRT), and transjugular intrahepatic portosystemic shunting. Duration of pretransplantation renal dysfunction was predictive of 6- and 12-month creatinine post-OLTa. Area under the receiver operating characteristic (ROC) curve for prediction of 12-month renal insufficiency by renal dysfunction duration was 0.71; optimal duration cutoff was 3.6 weeks. We applied a multivariable model, derived from OLTa patients, to CKLT subjects with definite or possible hepatorenal syndrome. Predicted 12-month creatinine without renal transplantation was >2.0 mg/dL for each patient. CKLT patients as opposed to OLTa patients had longer duration of renal dysfunction (median, 18.1 vs. 2.7 weeks, P < 0.001), higher creatinine (median 4.0 versus 1.7 mg/dL, P < 0.001), and higher rate of pretransplantation RRT (62% vs. 7%, P < 0.001). Adjusting for baseline characteristics, CKLT patients had lower creatinine than OLTa patients at 6 months (P =0.15) and 12 months (P =0.01) after transplantation. In conclusion, duration, but not cause, of renal dysfunction predicts renal outcome in OLTa recipients. Prospective studies may use duration of renal dysfunction to help identify CKLT candidates.

Cohort Studies↗
PubMed2005

Appendicitis among liver transplant recipients.

Appendicitis among liver transplant recipients has not been described in the current literature. We report 8 recipients who experienced appendicitis three weeks to 181 months after liver transplantation (LT). Initial presenting findings differed from the nonimmunosuppressed population in that a majority of the patients did not have leukocytosis (>10,000 cells/mm3). Four patients experienced perforation, three of whom presented three days after the development of abdominal pain. All patients recovered after surgery without untoward sequela.

Abdominal Pain↗
PubMed2005

Determinants of transplant surgeons' willingness to provide organs to patients infected with HBV, HCV or HIV.

The common provision of organs to patients infected with hepatitis B virus (HBV) and hepatitis C virus (HCV), but not to those infected with human immunodeficiency virus (HIV), has been attributed to perceived or real differences in transplantation efficacy among these populations. However, other explanations remain possible. We surveyed all active U.S. transplant surgeons to identify determinants of their views of the propriety of transplantation among HBV-, HCV-, and HIV-infected patients. The 347 surgeons (56.1%) returning completed questionnaires believed that HCV- and HIV-infected patients have similar post-transplant survival (p = 0.9), but that both groups fare worse than HBV-infected patients (p < 0.00001 for both comparisons). Most transplant surgeons considered HBV- and HCV-infected patients to be appropriate transplantation candidates (p = 1.0 for this comparison), whereas one-third considered HIV-infected patients to be appropriate candidates (p < 0.00001 when compared with HBV- or HCV-infected patients). That surgeons are generally willing to transplant HCV-infected patients but not HIV-infected patients, and yet believe these groups will have similar post-transplant survival, suggests that survival estimates alone do not explain surgeons' choices. HIV-infected patients should have equal access to organs unless or until evidence emerges that they fare substantially worse than other potential recipients.

Attitude of Health Personnel↗
PubMed2004

Early kidney dysfunction post liver transplantation predicts late chronic kidney disease.

BACKGROUND: Acute and chronic renal dysfunction (ARD, CRD) are common complications after liver transplantation and are associated with poor outcome. METHODS: We reviewed the results of 181 liver transplants performed in our institution between January 1, 1998 and December 31, 2000 in which the recipients were alive with good liver function at the end of the follow-up period (mean 2.7 years). Renal dysfunction was defined as a serum creatinine (Cr) greater than or equal to 2 mg/dL in both acute and chronic settings. RESULTS: The incidence of ARD during the first posttransplant week was 39.2% (n=71), whereas late CRD occurred in 6.0% (n=11) of the patients by the end of the follow-up period. Among the variables we examined for association with CRD, five factors were found to be statistically significant in univariate analysis: pretransplant diabetes (PRTDM) (0.000), Cr greater than or equal to 2 during the first postoperative week (0.003), posttransplant diabetes (POTDM) (0.014), age greater than 50 (0.025), and tacrolimus level greater than 15 ng/mL at postoperative day 15 (0.058). In binary logistic regression analysis, PRTDM (odds ratio [OR]=5.7, 95% confidence interval [CI]) and early postoperative ARD (OR=10.2 95% CI) remained consistently significant. Nine of 11 patients with CRD also had a history of ARD during the first postoperative week. These patients progressed to CRD despite the fact that seven of nine had normalized their renal function by day 90 posttransplant. CONCLUSION: We suggest that a combination of events during the first postoperative week after liver transplant serve as a physiologic "stress test" for the kidneys. Patients who fail the test (peak Cr >/=2 mg/dL during the first postoperative week) as well as the patients with diabetes mellitus are at increased risk of CRD. In such cases, conversion to a less nephrotoxic regimen may be beneficial.

Acute Disease↗
PubMed2004

Ascites after liver transplantation--a mystery.

Ascites after liver transplantation, although uncommon, presents a serious clinical dilemma. The hemodynamic changes that support the development of ascites before liver transplantation are resolved after transplant; therefore, persistent ascites (PA) after liver transplantation is unexpected and poorly characterized. The aim of this study was to define the clinical factors associated with PA after liver transplantation. This was a retrospective case-control analysis of patients who underwent liver transplantation at the University of Pennsylvania. PA occurring for more than 3 months after liver transplantation was confirmed by imaging studies. PA was correlated with multiple recipient and donor variables, including etiology of liver disease, preoperative ascites, prior portosystemic shunt (PS), donor age, and cold ischemic (CI) time. There were 2 groups: group 1, cases with PA transplanted from November 1990 to July 2001, and group 2, consecutive, control subjects who underwent liver transplantation between September 1999 and December 2001. Both groups were followed to censoring, May 2002, or death. Twenty-five from group 1 had ascites after liver transplantation after a median follow-up of 2.6 years. In group 1 vs group 2 (n = 106), there was a male predominance 80% vs 61% (P =.10) with similar age 52 years; chronic hepatitis C virus (HCV) was diagnosed in 88% vs 44% (P <.0001); preoperative ascites and ascites refractory to treatment were more prevalent in group 1 (P =.0004 and P =.02, respectively), and CI was higher in group 1, (8.5 hours vs 6.3 hours, P =.002). Eight of the 25 (group 1) had portal hypertension with median portosystemic gradient 16.5 mm Hg (range, 16-24). PS was performed in 7 of 25 cases, which resulted in partial resolution of ascites. The development of PA after liver transplantation is multifactorial; HCV, refractory ascites before liver transplantation, and prolonged CI contribute to PA after liver transplantation.

Ascites↗
PubMed2004

Liver transplantation for hepatocellular carcinoma validation of present selection criteria in predicting outcome.

Appropriate patient selection is crucial in ensuring acceptable outcomes from orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC). The United Network for Organ Sharing (UNOS) has elected to prioritize HCC patients for OLT based on criteria of tumor burden. However, it is unclear whether these criteria correlate with outcome, or with the pathobiological features associated with tumor recurrence. Therefore, we analyzed 109 consecutive patients undergoing OLT for HCC at our center, to determine the utility of present selection criteria in predicting outcome. Pathologic tumor staging of the explanted liver was based on the American Tumor Study Group modified tumor node metastases (pTNM) classification system. Multifocality was defined as >4 tumor nodules on explant. Survival analysis was performed using Kaplan-Meier and Cox proportional hazards regression methods. At a median follow-up of 18.9 months, the overall mortality was 19% with 15 patients (14%) dying of recurrent HCC. Kaplan-Meier 1, 3 and 5-year survival rates were 89.5%, 68%, and 65%, respectively. Recurrence-free rates of 1, 3, and 5 years were 89%, 75%, and 65%, respectively. On univariate analysis, the factors found to be significantly associated with recurrence of HCC were explant features of macrovascular invasion, tumor size (per centimeter increase), pTNM stage (per 1-stage increase), and pre-transplant serum alphafetoprotein (AFP) >300 ng/mL. In defining a threshold level, we found that explant tumor diameter > or =3 cm, and those tumors classified as at least pT3 on pathological examination, were significantly associated with recurrence (P =.01 and.03, respectively). Tumor size on explant was found to be strongly correlated with multifocality (P =.017) and vascular invasion (P =.02). Patients exceeding pathological UNOS criteria were 3.1 times more likely to have recurrence of HCC (P =.03). In conclusion, we found that tumor size appears to be a surrogate marker for negative pathobiological predictors of outcome, i.e., vascular invasion and multifocality. Present UNOS selection criteria for HCC based on tumor burden appear to provide adequate discriminatory power in predicting outcome of OLT.

Adult↗
PubMed2004

Summary report of a national conference: Evolving concepts in liver allocation in the MELD and PELD era. December 8, 2003, Washington, DC, USA.

A national conference was held to review and assess data gathered since implementation of MELD and PELD and determine future directions. The objectives of the conference were to review the current system of liver allocation with a critical analysis of its strengths and weaknesses. Conference participants used an evidence-based approach to consider whether predicted outcome after transplantation should influence allocation, to discuss the concept of minimal listing score, to revisit current and potential expansion of exception criteria, and to determine whether specific scores should be used for automatic removal of patients on the waiting list. After review of data from the first 18 months since implementation, association and society leaders, and surgeons and hepatologists with wide regional representation were invited to participate in small group discussions focusing on each of the main objectives. At the completion of the meeting, there was agreement that MELD has had a successful initial implementation, meeting the goal of providing a system of allocation that emphasizes the urgency of the candidate while diminishing the reliance on waiting time, and that it has proven to be a powerful tool for auditing the liver allocation system. It was also agreed that the data regarding the accuracy of PELD as a predictor of pretransplant mortality were less conclusive and that PELD should be considered in isolation. Recommendations for the transplant community, based on the analysis of the MELD data, were discussed and are presented in the summary document.

Adult↗
PubMed2004

Survival among pediatric liver transplant recipients: impact of segmental grafts.

Segmental liver transplantation with living donor (LD), reduced cadaveric (Reduced), and split cadaveric (Split) allografts has expanded the availability of size-appropriate organs for pediatric recipients. The relevance of recipient age to the selection of graft type has not been fully explored, but could offer the potential to maximize recipient outcome and donor utilization. We conducted a retrospective cohort study among children 12 years of age or less utilizing the United Network of Organ Sharing (UNOS) database. Cox proportional-hazards analysis was used to explore the association of recipient age and graft type to graft and patient survival. Among children <1 year of age and those 1 to 2 years of age, 3-year LD graft survival was superior to whole cadaveric (CAD) organs, Split grafts, and Reduced grafts (for children <1 year of age: 79.4 vs. 61.5, 66.0, and 61.1%, respectively, P = .0003; and for children 1-2 years of age: 79.2 vs 66.9, 57.1, and 63.9%, respectively, P = .02). However, in children 3 to 12 years of age, after controlling for multiple donor and recipient factors, LD grafts failed to offer a survival advantage (hazard ratio = .61; 95% confidence interval = .37-1.02) compared to CAD organs. In an adjusted analysis examining patient survival, there appeared to be minimal association between recipient age and graft type. Much of the difference in graft survival could be attributed to events in the perioperative period. In conclusion, LD liver transplantation provides improved graft survival in children 2 years of age or less.

Cadaver↗
PubMed2004

Patterns of transgene expression and viral clearance from the transplanted liver following ex vivo adenovirus-mediated gene transfer.

BACKGROUND/AIMS: In the rat liver transplant model, the liver graft can be transduced ex vivo by adenovirus encoding CTLA-4Ig (AdCTLA-4Ig) to achieve high level of immunosuppression in the liver after transplantation. To characterize the pattern of transgene expression following ex vivo gene transfer to the liver and examine whether immunosuppression would promote adenovirus persistence, we followed the life span of vector DNA and transgene expression in the transplanted liver. METHODS: Rat liver grafts were perfused ex vivo with adenovirus carrying the reporter gene beta-galactosidase (AdlacZ). The period of transgene expression was assessed at predetermined intervals after transplantation into syngeneic, allogeneic or nude (athymic) recipients. Clearance of vector DNA was assessed by PCR analysis of liver DNA after transplantation. RESULTS: Graft transduction with AdCTLA-4Ig or systemic cyclosporine treatment effectively abrogated the alloimmune response but did not result in sustained lacZ expression. The course of viral DNA clearance from the liver was also unaffected by immunosuppression as was the implied nucleolytic cleavage of viral DNA. CONCLUSIONS: In the transplant setting, local expression of CTLA-4Ig or systemic immunosuppression does not solve the problem of viral clearance from the liver. Non-adaptive immune mechanisms may have a significant role in the host response to adenovirus after liver transplantation.

Abatacept↗
PubMed2004

Redistribution of thorotrast into a liver allograft several years following transplantation: a case report.

Thorotrast was used as a radiographic contrast agent in the United States from about 1930 to the mid-1950 s. Its use was discontinued when it was recognized that its radioactivity caused long-term deleterious effects. Such long-term sequelae of intravascular Thorotrast injection include, most notably, hepatic and hematologic malignancies and hepatic fibrosis. Some patients who had received Thorotrast subsequently received liver transplants. However, it was not known whether or not Thorotrast could become redistributed within the new allograft. A single report in 1994 demonstrated that radioactivity was detected by gamma-ray spectroscopy in liver allografts shortly after transplantation. No report has identified Thorotrast in the allografts of long-term transplant survivors, and the redistribution of Thorotrast into allografts has not been documented histologically or by electron microscopy. We report a case of recurrent Thorotrast into a liver allograft 10 years post-transplant. We evaluated the native liver and allograft specimens for the presence of thorium utilizing light microscopy, electron microscopy and electron X-ray microanalysis. This case report demonstrates for the first time the redistribution of Thorotrast into a long-surviving liver allograft using histologic, electron microscopic and X-ray microanalysis techniques.

Cholangitis, Sclerosing↗
PubMed2004

Endoscopic management of biliary complications after adult living donor liver transplantation.

OBJECTIVES: Biliary complications and their treatment in adult cadaveric liver transplantation (CLT) are well described. However, biliary complications and their management in living donor liver transplantation (LDLT) are not well characterized. We assessed the role of endoscopic retrograde cholangiopancreatography (ERCP) in the diagnosis and management of biliary complications following LDLT. METHODS: We performed a retrospective cohort analysis of all LDLT recipients with duct-to-duct anastomoses (n = 15). Specific data included referral for ERCP, diagnosis, and therapy. Comparisons were made to a 260 CLT recipient cohort. RESULTS: Greater percentage of LDLT recipients underwent ERCP (73%) compared to CLT recipients (25%; p= 0.001). Biliary complications diagnosed by ERCP in LDLT recipients consisted of bile leaks and strictures, and were more frequent than in CLT recipients (leaks: 53%vs 12%; p= 0.001; strictures: 27%vs 5%; p= 0.01). Most leaks occurred at T-tube sites (LDLT: 87%; CLT: 65%). Diagnosis and therapy of leaks required a median of 2 ERCP procedures in both groups. Bile leaks were successfully treated endoscopically in 100% and 84% of LDLT and CLT recipients, respectively (p= 0.56). Most biliary strictures were anastomotic (LDLT: 100%; CLT: 64%). Strictures were diagnosed and treated with a median of 1.5 and 2 ERCP procedures in the LDLT and CLT groups, respectively. The duration of endoscopic therapy was a median of 10 and 14 wk, and success rates were 75% and 62% (p= 1.0) in LDLT and CLT groups, respectively. CONCLUSIONS: LDLT is associated with increased biliary complications as compared to CLT. ERCP is useful for diagnosis, can successfully treat most LDLT-related biliary complications, and should be attempted prior to more invasive interventions.

Adolescent↗
PubMed2004

Allograft survival following adult-to-adult living donor liver transplantation.

Adult-to-adult living donor liver transplantation (AALDLT) is emerging as a method to treat patients with end-stage liver disease. The aims of this study were to identify donor and recipient characteristics of AALDLT, to determine variables that affect allograft survival, and to examine outcomes compared with those achieved following cadaveric transplantation. Cox proportional hazards models were fit to examine characteristics associated with the survival of AALDLT. Survival of AALDLT was then compared with cadaveric allografts in multivariable Cox models. Older donor age (>44 years), female-to-male donor to recipient relationship, recipient race, and the recipient medical condition before transplant were factors related to allograft failure among 731 AALDLT. Despite favorable donor and recipient characteristics, the rate of allograft failure, specifically the need for retransplantation, was increased among AALDLT (hazard ratio 1.66, 95% C.I. = 1.30-2.11) compared with cadaveric recipients. In conclusion, among AALDLT recipients, selecting younger donors, placing the allografts in recipients who have not had a prior transplant and are not in the ICU, may enhance allograft survival. Analysis of this early experience with AALDLT suggests that allograft failure may be higher than among recipients of a cadaveric liver.

Adult↗