Martha Behnke

Adult Living Donor Versus Deceased Donor Liver Transplantation: A 6‐Year Single Center Experience

No long‐term (>3 years) prospective comparison of adult‐to‐adult living donor liver transplantation (A2ALLTx) to adult deceased donor liver transplantation (ADDLTx) has been reported.

Hepatitis C virus infection and kidney transplantation : Predictors of patient and graft survival

Background. The effect of hepatitis C virus (HCV) infection on patients undergoing kidney transplantation (KTx) is uncertain. This study aimed to evaluate the outcomes of our HCV+/end-stage renal disease (ESRD) patient population based on the therapeutic option including KTx or continuation in dialysis. Methods. KTx performed at Virginia Commonwealth University Hospital between January 2000 and December 2004 were tracked prospectively. Forty-three out of a total of 394 KTx patients included in the analysis were HCV+. A group of 52 contemporaneous HCV+/ESRD patients listed, but never transplanted, was also analyzed. HCV-negative transplanted patients were used as the control group. Results. Patient survival posttransplantation was 81.4% and 68.5% at 1 and 3 years in the HCV+ group, and 97.1% and 92.9% at 1 and 3 years in the HCV- group, respectively (P=0.001). Graft survival was 81.2% and 64.1% at 1 and 3 years in the HCV+ group, and 93.2% and 84.1% at 1 and 3 years posttransplantation in the HCV- group (P=0.01). Univariate analysis identified Knodell score as a predictor of mortality in HCV+ patients (P=0.04). Cox proportional hazards multivariate analysis identified deceased donor (P=0.02), previous kidney transplant (P=0.007), pretransplant diabetes (P=0.05), and Knodell Score (P=0.012) as predictors of patient mortality. Patient survival was superior in HCV+ patients undergoing KTx versus remaining on dialysis. Conclusions. Patients with ESRD/HCV+ benefit from KTx without achieving the excellent survival of HCV-/ESRD patients. Liver biopsy is a useful tool to identify advanced liver disease at pretransplantation time.

Incidence of prolonged length of stay after orthotopic liver transplantation and its influence on outcomes

Orthotopic liver transplantation (OLT) is the only effective treatment for end‐stage liver disease. Although most patients do well and are discharged promptly, some require prolonged length of stay (PLOS). The prevalence of PLOS, associated factors, and their impact on survival are not well defined. We reviewed our adult OLT database for patients who survived > 30 days. PLOS was defined as hospitalization > 30 days following OLT. Of 521 OLT recipients, 68 (13%) had PLOS with a median duration of 50 days versus only 10 days for patients discharged within 30 days. Significant differences in pre‐OLT variables between patients with and without PLOS included the mean wait list time (P = 0.001), hospitalization at the time of OLT (P = 0.001), and prior OLT (P = 0.041). Factors independently associated with PLOS included intensive care unit status at the time of OLT [odds ratio (OR), 4; 95% confidence interval (CI), 1.6‐10.4], OLT prior to Model for End‐Stage Liver Disease implementation (OR, 2.27; 95% CI, 1.04‐5.26), in‐hospital post‐OLT bacterial infection (OR, 9.34; 95% CI, 4.65‐18.86), gastrointestinal bleeding (OR, 4.34; 95% CI, 1.4‐14.08), renal failure (OR, 10.86; 95% CI, 5.07‐23.25), and allograft rejection (OR, 3.7; 95% CI, 1.23‐11.11). One‐year graft survival and patient survival were significantly less in those with PLOS (for both, P < 0.0001). Among PLOS patients, factors independently associated with increased 1‐year mortality were donor age (OR, 1.07; 95% CI, 1.009‐1.13), primary diagnosis of hepatitis C virus (OR, 6.89; 95% CI, 1.40‐34.48), in‐hospital post‐OLT bacterial infection (OR, 13.3; 95% CI, 2.11‐83.33), and cardiac complications (OR, 20.4; 95% CI, 1.51‐250; c‐statistic for the model, 0.85). In conclusion, PLOS following OLT is associated with a significant decrease in survival despite a marked increase in cost and resource utilization. Efforts to modify those factors that contribute to PLOS may reduce this event, improve survival, and reduce OLT‐associated costs. Liver Transpl 15:273–279, 2009.

Donor Selection for Adult-to-adult Living Donor Liver Transplantation: Well Begun Is Half Done

Background Donor selection criteria for adult-to-adult living donor liver transplantation vary with the medical center of evaluation. Living donor evaluation uses considerable resources, and the nonmaturation of potential into actual donors may sometimes prove fatal for patients with end-stage liver disease. On the contrary, a thorough donor evaluation process is mandatory to ensure safe outcomes in otherwise healthy donors. We aimed to study the reasons for nonmaturation of potential right lobe liver donors at our transplant center. Methods A retrospective data analysis of all potential living liver donors evaluated at our center from 1998 to 2010 was done. Results Overall, 324 donors were evaluated for 219 potential recipients, and 171 (52.7%) donors were disqualified. Common reasons for donor nonmaturation included the following: (1) donor reluctance, 21%; (2) greater than 10% macro-vesicular steatosis, 16%; (3) assisted donor withdrawal, 14%; (4) inadequate remnant liver volume, 13%; and (5) psychosocial issues, 7%, and thrombophilia, 7%. Ten donors (6%) were turned down because of anatomic variations (8 biliary and 2 arterial anomalies). Donors older than 50 years and those with body mass index of more than 25 were less likely to be accepted for donation. Conclusions We conclude that donor reluctance, hepatic steatosis, and assisted donor withdrawal are major reasons for nonmaturation of potential into actual donors. Anatomic variations and underlying medical conditions were not a major cause of donor rejection. A system in practice to recognize these factors early in the course of donor evaluation to improve the efficiency of the selection process and ensure donor safety is proposed.

Multimodality therapy and liver transplantation for hepatocellular carcinoma: a 14-year prospective analysis of outcomes.

Background Hepatocellular carcinoma is a major cause of death among patients with cirrhosis. A standardized approach of multimodality therapy with intent-to-treat by transplantation for all patients with hepatocellular carcinoma was instituted at our transplant center in 1997. Data were prospectively collected to evaluate the impact of multimodality therapy on posttransplant patient survival, tumor recurrence, and patient survival without transplantation. Methods All patients with hepatocellular carcinoma were eligible for multimodality therapy. Multimodality therapy consisted of hepatic resection, radiofrequency ablation, transarterial chemoembolization, transarterial chemoinfusion, yttrium-90 microsphere radioembolization, and sorafenib. Results Approximately 715 patients underwent multimodality therapy; 231 patients were included in the intent-to-treat with transplantation arm, and 484 patients were treated with multimodality therapy or palliative therapy because of contraindications for transplantation. A 60.2% transplantation rate was achieved in the intent-to-treat with transplantation arm. Posttransplant survivals at 1 and 5 years were 97.1% and 72.5%, respectively. Tumor recurrence rates at 1, 3, and 5 years were 2.4%, 6.2%, and 11.6%, respectively. Patients with contraindications to transplant had increased 1- and 5-year survival from diagnosis with multimodality therapy compared with those not treated (73.1% and 46.5% versus 15.5% and 4.4%, P<0.0001). Conclusions Using multimodality therapy before liver transplantation for hepatocellular carcinoma achieved low recurrence rates and posttransplant survival equivalent to patients with primary liver disease without hepatocellular carcinoma. Multimodality therapy may help identify patients with less active tumor biology and result in improved disease-free survival and organ utilization.

Single pediatric kidney transplantation in adult recipients: comparable outcomes with standard-criteria deceased-donor kidney transplantation.

Background Single pediatric kidney transplantation (SKT) in adult recipients has traditionally been considered a high risk because of concerns of technical complications leading to poor graft outcomes. The primary goal of this single-center, retrospective analysis was to compare outcomes after SKT to standard-criteria deceased-donor kidney transplantation (SCDKT). Methods We compared outcomes in adult recipients after SKT (n=31; mean donor weight, 27 kg); SCDKT (n=283); pediatric en bloc (n=21), living-donor (n=275), and extended criteria–donor (n=100) kidney transplantations. Results The death-censored 5-year graft survival after SKT was significantly superior to SCDKT (81.4% vs. 74.5%, P=0.02). The serum creatinine level at 5 years after transplantation was significantly lower in SKT compared with that in SCDKT (1.2 vs. 1.6 mg/dL, P<0.0001). There was a significantly higher incidence of arterial anastomotic stenosis (6.8% vs. 0.4%, P=0.02) and hydronephrosis (12.9% vs. 5.3%, P=0.02) in the SKT cohort compared with SCDKT. Subgroup analysis of the SKT cohort by donor age less than 5 years vs. 6 to 10 years (mean weight, 16.4 vs. 32.7 kg) revealed no differences in patient or graft survival. Conclusions Despite a higher incidence of posttransplantation vascular and urological complications, long-term graft survival after SKT (in weight-matched pediatric donors and selected adult recipients) was comparable with that after SCDKT. SKT from very small donors (age, ⩽5 years) yielded excellent long-term patient and graft survivals. The use of pediatric donor kidneys should be encouraged to address the problem of organ shortage.

The Expression of Embryonic Liver Development Genes in Hepatitis C Induced Cirrhosis and Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) remains a difficult disease to study even after a decade of genomic analysis. Patient and disease heterogeneity, differences in statistical methods and multiple testing issues have resulted in a fragmented understanding of the molecular basis of tumor biology. Some researchers have suggested that HCC appears to share pathways with embryonic development. Therefore we generated targeted hypotheses regarding changes in developmental genes specific to the liver in HCV-cirrhosis and HCV-HCC. We obtained microarray studies from 30 patients with HCV-cirrhosis and 49 patients with HCV-HCC and compared to 12 normal livers. Genes specific to non-liver development have known associations with other cancer types but none were expressed in either adult liver or tumor tissue, while 98 of 179 (55%) genes specific to liver development had differential expression between normal and cirrhotic or HCC samples. We found genes from each developmental stage dysregulated in tumors compared to normal and cirrhotic samples. Although there was no single tumor marker, we identified a set of genes (Bone Morphogenetic Protein inhibitors GPC3, GREM1, FSTL3, and FST) in which at least one gene was over-expressed in 100% of the tumor samples. Only five genes were differentially expressed exclusively in late-stage tumors, indicating that while developmental genes appear to play a profound role in cirrhosis and malignant transformation, they play a limited role in late-stage HCC.

Outcomes of Kidney Transplants and Risk of Infection Transmission from Increased Infectious Risk Donors

Concern over transmission of viral infections has been reported to result in higher discard rates of high infectious risk kidneys (HIR) although data on actual viral transmission rates are lacking. At our center, we performed 89 HIR and 533 non‐HIR kidney transplants (KTs) between 2004 and 2011. Follow‐up screening labs in recipients of HIR kidneys tested for human immunodeficiency virus, hepatitis C virus, and hepatitis B virus did not reveal any cases of viral transmission over median follow‐up of 4.3 years. Patient and graft outcomes were similar at 5 years between HIR and non‐HIR KTs. An updated analysis of the Organ Procurement and Transplant Network (OPTN) registry of deceased‐donor kidney transplants between 2008 and 2012 included 57 526 transplants was performed. Retrospective calculation of KDRI (kidney donor risk index) differed (P<.001) between all groups with median KDRI of 0.99 for HIR kidneys, 1.07 for non‐HIR standard criteria donor kidneys, and 1.81 for non‐HIR expanded criteria donor (ECD) kidneys. This was reflected in the significantly improved 5‐year graft survival for HIR KTs when compared with non‐HIR ECD KTs (84% vs 78%; P<.001). Our data can guide counseling of KT candidates about the safety and benefits of HIR kidneys.

The mode of pretransplant dialysis does not affect postrenal transplant outcomes in african americans.

Background. In previous reports with a majority of Caucasian patients, peritoneal dialysis (PD) before kidney transplantation has been associated with poor outcomes and higher rates of graft thrombosis and infectious complications than hemodialysis (HD). We report our experience on the outcomes of prerenal transplant peritoneal dialysis in predominantly (73%) African American patient population. Methods. A retrospective data analysis of 401 kidney transplants performed at our center from 2000 to 2006 was performed. Adult recipients with at least three months of pretransplant HD or PD were included. Results. There were 339 patients on HD and 62 patients on PD. There was no difference in graft (P = 0.51) and patient survival (P = 0.52) at 1, 3, and 5-years. Patients on HD were more likely to experience delayed graft function than PD (38.8% versus 17.7%, P < 0.005). There was no difference in the incidence of vascular thrombosis or posttransplant infectious complications. When only the African American patients in the two groups were compared, there were no differences in graft or patient survival. Conclusions. Pretransplant peritoneal dialysis is associated with excellent patient and renal allograft outcomes in African Americans and does not predispose them to an increased risk of infectious or thrombotic complications.

Perioperative Desensitization Improves Outcomes Among Crossmatch Positive Recipients of Deceased Donor Renal Transplants

Context: Graft failure due to chronic rejection is greater among renal transplant patients with donor-specific antibody (DSA) than among DSA-free patients. For patients dependent on deceased donor transplantation, preoperative desensitization to eliminate DSAs may be impractical. We speculated that perioperative desensitization might eliminate preexisting DSAs and prevent de novo DSAs and improve graft outcomes. We report that brief perioperative desensitization using either intravenous immunoglobulin (IVIG) or plasmapheresis/IVIG (PP/IVIG) treatment improves clinical outcomes among patients with positive crossmatches. Design: Immediately following deceased donor transplantation, 235 renal recipients were assigned points for PRA and flow crossmatches (FCXM): delayed graft function (DGF) ≤ 1 point received standard therapy; 2 points received high-dose IVIG; and ≥3 points received PP/IVIG. The DSAs were serially monitored by single antigen bead luminex for 1 year. Five-year clinical outcomes were determined from the chart review. Results: All desensitized patients had preoperatively positive FCXM with DSA. Rejection was more common (P < .05) among desensitized than nonsensitized groups. However, overall graft survivals were similar between the groups (P = not significant) and superior to historic untreated patients (P < .05). Treatment with PP/IVIG more effectively eliminated preexisting DSAs (67% vs 33%, P < 0.05) than IVIG, but neither regimen prevented de novo formation of DSA (20%, P = not significant). Graft survival was >90% in all desensitizated patients with DSA elimination as well as PP/IVIG patients with residual DSA. In contrast, IVIG patients with persistent DSA had poorer graft survival (45%, P < .05). Conclusion: Preemptive perioperative desensitization improved overall graft survival of sensitized patients compared to historic untreated patients. Plasmapheresis/IVIG had greater impact on DSA eradication and graft survival than IVIG alone.