Biomedical subjects

Douglas G Farmer

Publications and source records attributed to Douglas G Farmer.

At least 19 recordsLinked to original sources

PubMed2007

Postresection hepatic failure: successful treatment with liver transplantation.

Postoperative liver failure (PLF) is a rare but often fatal complication of major hepatic resection. Use of orthotopic liver transplantation (OLT) for PLF remains undefined. We conducted a retrospective review of 435 patients who underwent hepatic resection between 1990 and 2004; 9 of them (2.0%) developed PLF. Indications for resection included primary hepatic malignancies (8), colonic metastases (2), and echinococcic cyst (1); all resections were multisegmental, 6 were extended, and 2 were lobectomies. A total of 7 patients underwent OLT at a mean of 25 days after resection. Patients developing PLF had significantly lower preoperative platelet counts and significant elevations of total bilirubin, direct bilirubin, prothrombin time, and international normalized ratio (INR) by postoperative day 2. Pathological cirrhosis and extended right lobectomy were associated with significantly increased risk of PLF. Following OLT, there were no in-hospital deaths, but 1 patient required retransplantation for primary nonfunction. Mean survival with and without OLT was 42.2 and 1.4 months, respectively (P = 0.03). Following OLT, 1- and 5-yr patient survivals were 88% and 40%, respectively; 1- and 5-yr graft survivals were 75% and 34%, respectively. In conclusion, patients with low platelets, biopsy-proven cirrhosis, or those undergoing extended resection are at increased risk for PLF. OLT for PLF has significant morbidity but allows salvage of an otherwise fatal condition.

Adult↗

PubMed2006

Incisional hernia after liver transplantation.

BACKGROUND: Incisional hernia is a potential complication of orthotopic liver transplantation (OLT), with various options for repair. STUDY DESIGN: We conducted a retrospective review of a series of adult patients with incisional hernias after OLT to identify risk factors and to compare methods of repair. RESULTS: Incisional hernia repair was performed in 44 of 959 patients (4.6%) who underwent OLT from 1999 to 2005. Mean age at time of OLT was 53 years, and 73% were men. One or more complications of OLT occurred in 33 patients (75%) and included reoperation for bile leak or hemoperitoneum (34%), pulmonary problems (27%), early acute rejection (7%), and severe ascites and retransplantation (5% each). Incisional hernia was diagnosed at 419 days (range 62 to 1,524 days) and repaired at 471 days (range 109 to 1,581 days) after OLT. Presentation included pain or discomfort (78%) and incarceration or strangulation (5%); 17% were asymptomatic. Herniorrhaphy techniques included fascial repair with onlay polypropylene mesh reinforcement (n=25, 57%); fascial repair only (n=15, 34%); or inlay mesh sewn to fascial edges (n=4, 9%). Complications of repair included recurrence in seven patients (16%) and wound infection and seroma in one patient each. Recurrence occurred in five patients with primary repair and two with mesh techniques (33% versus 6%, p=0.04). CONCLUSIONS: Incisional hernia is a late complication of OLT for which male gender and early post-OLT complications are risk factors. Repair is safe when undertaken after acute problems have resolved and is best accomplished using mesh reinforcement of autologous tissue.

Adult↗

PubMed2006

Mutant neurogenin-3 in congenital malabsorptive diarrhea.

BACKGROUND: Neurogenin-3 (NEUROG3) is expressed in endocrine progenitor cells and is required for endocrine-cell development in the pancreas and intestine. The NEUROG3 gene (NEUROG3) is therefore a candidate for the cause of a newly discovered autosomal recessive disorder characterized by generalized malabsorption and a paucity of enteroendocrine cells. METHODS: We screened genomic DNA from three unrelated patients with sparse enteroendocrine cells for mutations of NEUROG3. We then tested the ability of the observed mutations to alter NEUROG3 function, using in vitro and in vivo assays. RESULTS: The patients had few intestinal enteroendocrine cells positive for chromogranin A, but they had normal numbers of Paneth's, goblet, and absorptive cells. We identified two homozygous mutations in NEUROG3, both of which rendered the NEUROG3 protein unable to activate NEUROD1, a downstream target of NEUROG3, and compromised the ability of NEUROG3 to bind to an E-box element in the NEUROD1 promoter. The injection of wild-type but not mutant NEUROG3 messenger RNA into xenopus embryos induced NEUROD1 expression. CONCLUSIONS: A newly discovered disorder characterized by malabsorptive diarrhea and a lack of intestinal enteroendocrine cells is caused by loss-of-function mutations in NEUROG3.

Amino Acid Sequence↗

PubMed2006

Long-term analysis of combined liver and kidney transplantation at a single center.

OBJECTIVE: To analyze use of combined liver and kidney transplantation (CLKT) for patients with chronic primary diseases of both organs and for patients with hepatorenal syndrome. DESIGN: Retrospective case series. SETTING: Multiorgan transplantation service in a large university medical center. PATIENTS: A total of 98 patients underwent 99 CLKTs during a 16-year period; 76 had primary renal diseases, and 22 had hepatorenal syndrome. Patients receiving isolated liver and kidney transplants were analyzed for comparison. MAIN OUTCOME MEASURES: Patient and graft survival, rejection rates, and need for hemodialysis before and after transplantation. RESULTS: Overall patient survival was 76%, 72%, and 70% at 1, 3, and 5 years, respectively; liver graft survival was 70%, 65%, and 65%; and kidney graft survival was 76%, 72%, and 70%. No risk factors analyzed for recipients or donors were associated significantly with early posttransplantation mortality or graft loss. In 28 patients who received monoclonal antibody induction therapy with interleukin 2 blockers, there were significantly fewer episodes of acute liver rejection. For patients with hepatorenal syndrome, CLKT did not confer a survival advantage over liver-only transplantation (1-year patient survival was 72% vs 66%; P = .88). The 1-year acute kidney rejection rate in the adult CLKT group was 14% vs 23% in a 5-year cadaveric renal transplantation cohort (P<.01). CONCLUSIONS: First, CLKT is indicated in patients with dual organ disease and achieves excellent results. Second, CLKT for hepatorenal syndrome is indicated in patients receiving hemodialysis for longer than 8 weeks and confers advantages in patient survival and use of hospital resources. Third, the liver is immunoprotective for the kidney.

Adolescent↗

PubMed2006

Preoperative characteristics and intraoperative transfusion and vasopressor requirements in patients with low vs. high MELD scores.

Recent changes in organ allocation based on the model for end-stage liver disease (MELD) prioritize the most ill patients on the waiting list for liver transplantation. While patients undergoing liver transplantation in the MELD era are more acutely ill, the impact of the policy changes on perioperative management has not been completely assessed. We retrospectively reviewed the records of 124 primary adult liver transplant patients. Patients were divided into low (< or = 30) and high MELD (>30) score groups. Preoperative characteristics and intraoperative management were compared between the 2 groups. Patients with high MELD scores had lower baseline hematocrit and fibrinogen levels and were more likely to require ventilatory and vasopressor support before transplantation. Intraoperative transfusion requirements and use of vasopressors were also significantly increased in patients with high MELD scores compared to patients with low MELD scores. In conclusion, these data suggest that pretransplant MELD scores provide important information for perioperative management of patients undergoing liver transplantation.

Adult↗

PubMed2006

Portocaval hemitransposition in pediatric liver transplant recipients: a single-center experience.

Few studies have reported a series of patients who have undergone portocaval hemitransposition at the time of orthotopic liver transplantation (OLT). Furthermore, no series report the outcome of pediatric patients who required the procedure. This work analyzes the experience with portocaval hemitransposition in the pediatric liver transplant population at a single center since the initial description of the procedure. We carried out a retrospective analysis of all pediatric liver transplants performed in our institution during the 8-year period from January 1, 1997, to December 31, 2004. Of 320 pediatric patients who received OLT during the study period, 7 underwent portocaval hemitransposition (2.2%). Five of the patients had biliary atresia. Four grafts were whole cadaveric livers, while the remaining 4 were left lateral segments from either in situ cadaveric split (n = 3) or living donation (n = 1). One patient received a whole cadaveric allograft and was retransplanted with a segment 2/3 graft; in both cases portocaval hemitransposition was utilized. Average warm ischemia time was 54 +/- 16 minutes. Three patients had primary nonfunction of the allograft; 2 were retransplanted with successful outcome, and the remaining patient died before retransplantation. Another patient died from recurrent disease. Four of 7 are long-term survivors and demonstrate good liver function as long as 8 years posttransplant. In conclusions, long-term survival is possible following OLT with portocaval hemitransposition in pediatric patients. However, rates of primary graft nonfunction can be high. Appropriate selection of recipient and type of donor graft are essential for good outcomes. Portocaval hemitransposition should be used cautiously and as a last resort to establish portovenous inflow.

Adult↗

PubMed2006

Optimal utilization of donor grafts with extended criteria: a single-center experience in over 1000 liver transplants.

OBJECTIVE: Severely limited organ resources mandate maximum utilization of donor allografts for orthotopic liver transplantation (OLT). This work aimed to identify factors that impact survival outcomes for extended criteria donors (ECD) and developed an ECD scoring system to facilitate graft-recipient matching and optimize utilization of ECDs. METHODS: Retrospective analysis of over 1000 primary adult OLTs at UCLA. Extended criteria (EC) considered included donor age (>55 years), donor hospital stay (>5 days), cold ischemia time (>10 hours), and warm ischemia time (>40 minutes). One point was assigned for each extended criterion. Cox proportional hazard regression model was used for multivariate analysis. RESULTS: Of 1153 allografts considered in the study, 568 organs exhibited no extended criteria (0 score), while 429, 135 and 21 donor allografts exhibited an EC score of 1, 2 and 3, respectively. Overall 1-year patient survival rates were 88%, 82%, 77% and 48% for recipients with EC scores of 0, 1, 2 and 3 respectively (P < 0.001). Adjusting for recipient age and urgency at the time of transplantation, multivariate analysis identified an ascending mortality risk ratio of 1.4 and 1.8 compared to a score of 0 for an EC score of 1, and 2 (P < 0.01) respectively. In contrast, an EC score of 3 was associated with a mortality risk ratio of 4.5 (P < 0.001). Further, advanced recipient age linearly increased the death hazard ratio, while an urgent recipient status increased the risk ratio of death by 50%. CONCLUSIONS: Extended criteria donors can be scored using readily available parameters. Optimizing perioperative variables and matching ECD allografts to appropriately selected recipients are crucial to maintain acceptable outcomes and represent a preferable alternative to both high waiting list mortality and to a potentially futile transplant that utilizes an ECD for a critically ill recipient.

Adult↗

PubMed2006

Effect of nonviral factors on hepatitis C recurrence after liver transplantation.

OBJECTIVE: Hepatitis C (HCV) is now the most common indication for orthotopic liver transplantation (OLT). While graft reinfection remains universal, progression to graft cirrhosis is highly variable. This study examined donor, recipient, and operative variables to identify factors that affect recurrence of HCV post-OLT to facilitate graft-recipient matching. METHODS: Retrospective review of 307 patients who underwent OLT for HCV over a 10-year period at our center. Recurrence of HCV was identified by the presence of biochemical graft dysfunction and concurrent liver biopsy showing diagnostic pathologic features. Time to recurrence was the endpoint for statistical analysis. Five donor, 6 recipient, and 2 operative variables that may affect recurrence were analyzed by univariate comparison and Cox proportional hazard regression models. RESULTS: Recurrence-free survival in the 307 study patients was 69% and 34% at 1 and 5 years, respectively. Four predictive variables related to either donor or recipient characteristics were identified. Advanced donor age, prolonged donor hospitalization, increasing recipient age, and elevated recipient MELD scores were found to increase the relative risk of HCV recurrence. Examination of HLA disparity between donors and recipients demonstrated no correlation between class I or class II mismatches and recurrence-free survival. CONCLUSIONS: We have identified donor and recipient characteristics that significantly predict hepatitis C recurrence following liver transplantation. These factors are identifiable before transplant and, if considered when matching donors to HCV recipients, may decrease the incidence of HCV recurrence after OLT. A change in the current national liver allocation system would be needed to realize the full value of this benefit.

Adult↗

PubMed2006

The MELD score in advanced liver disease: association with clinical portal hypertension and mortality.

BACKGROUND: The Model for End-Stage Liver Disease (MELD) score is a measure of chronic liver disease severity. Patients awaiting transplantation are assessed using this score. However, it has recently been suggested that changes in MELD score may be as important as the absolute MELD score in predicting short-term survival. However, clinical factors that affect the MELD score are unknown. We sought to identify predictors of mortality for potential transplant patients and examine factors that might predict changes in MELD score. MATERIALS AND METHODS: Between January 1, 2002, and July 30, 2004, we retrospectively examined risk factors of 429 adult patients awaiting liver transplantation at the University of California at Los Angeles (UCLA). Analysis of the data was performed using demographics, manifestations of portal hypertension, time between last MELD recorded and event, and laboratory values. Significant factors in univariate analysis were further studied using Cox proportional hazards regression multivariate analysis. RESULTS: At mean follow-up of 2.15 years (+/-1.49 years), 71 patients (16.5%) had MELD scores that increased 5-10 points, 22 had changes of 10-15 points, and 14 had changes of 15-20 points. Manifestations of portal hypertension, laboratory values, and etiology of liver disease did not predict changes in MELD score. However, development of hepatic encephalopathy (HR, 3.95; P=.002; 95% CI, 1.70 to 9.42) and MELD score (HR, 1.04; P=.001; 95% CI, 1.004 to 1.08) were associated with variceal bleeding. Also, MELD score (HR, 1.07; P<.001; 95% CI, 1.05 to 1.09), refractory ascites (HR, 2.15; P=.002; 95% CI, 1.31 to 3.53), and alcoholic cirrhosis (HR, 0.40; P=.04; 95% CI, 0.18 to 0.94) were independent predictors of mortality. CONCLUSIONS: Encephalopathy and MELD score were associated with variceal bleeding. Patients with an elevated MELD score, refractory ascites, and alcoholic cirrhosis had increased mortality while on the liver transplant list. No factors predicting changes in the MELD score were identified.

Adult↗

PubMed2005

Fulminant hepatic failure from primary hepatic lymphoma: successful treatment with orthotopic liver transplantation and chemotherapy.

Systemic lymphomas may involve the liver but rarely cause fulminant hepatic failure (FHF). Acute liver failure from primary hepatic lymphoma (PHL) is even less common with most patients succumbing to the sequelae of FHF before the correct diagnosis is made. We report a patient who underwent successful orthotopic liver transplant (OLT) and chemotherapy for FHF secondary to PHL. This previously-well male developed profound coagulopathy and encephalopathy 6 weeks after the onset of jaundice and fatigue. Workup failed to reveal the underlying cause of his liver failure and the patient soon required urgent OLT. Pathologic evaluation of his explanted liver revealed a malignant T-cell rich, large B-cell non-Hodgkin's lymphoma with widespread hepatocellular necrosis. The patient made an excellent clinical recovery and is undergoing CHOP-Rituxan chemotherapy. This scenario demonstrates that lymphoma should be considered in the differential diagnosis of FHF without clear etiology because of the potential for intervention with transplant and chemotherapy.

Combined Modality Therapy↗

PubMed2005

Disruption of P-selectin signaling modulates cell trafficking and results in improved outcomes after mouse warm intestinal ischemia and reperfusion injury.

BACKGROUND: This study analyzes the role of T lymphocytes and neutrophils (PMN) in intestinal ischemia and reperfusion injury (IRI) using either P-selectin blockade or elimination. METHODS: Using a model of severe mouse warm intestinal IRI, the following groups were performed: group 1: wild type C57BL6 no treatment; group 2: wild type treated with r-PSGL1-Ig; group 3: C57BL6 genetically deficient in P-selectin. Survival was assessed at day 7; intestine was assayed for histopathology, apoptosis, myeloperoxidase (MPO), inflammatory cytokines, hemoxygenase-1 (HO-1), and CD3 lymphocytes. Standard statistical comparison was undertaken. RESULTS: The survival was significantly (P < 0.01) improved in the treatment groups: group 1, 50%; group 2, 90%; group 3, 100%. Graded histopathology and crypt apoptosis were improved in groups 2 and 3. MPO and CD3 positive cells were significantly reduced in groups 2 and 3. A significant reduction in inflammatory/Th1-type cytokines was seen in groups 2 and 3 as compared to group 1. Conversely, a significant increase in Th2-type cytokines and HO-1 production was seen selectively in groups 2 and 3. CONCLUSIONS: This study demonstrates the importance of P-selectin signaling in warm, murine intestinal IRI in that either the blockade of or the genetic deficiency in P-selectin confers a survival advantage and reduction in tissue injury/inflammation. The mechanism involves a reduction of PMN and CD3 T cell infiltration and an alteration in the cytokine microenvironment in favor of a Th2 profile. These data implicate T lymphocyte as an important regulatory cell in this inflammatory process.

Animals↗

PubMed2005

The CD154-CD40 T-cell co-stimulation pathway in liver ischemia and reperfusion inflammatory responses.

BACKGROUND: Ischemia-reperfusion (I/R) injury is a prime antigen-independent inflammatory factor in the dysfunction of liver transplants. The precise contribution of T cells in the mechanism of I/R injury remains to be elucidated. As the CD154-CD40 co-stimulation pathway provides essential second signal in the initiation and maintenance of T-cell-dependent immune responses, this study was designed to assess the role of CD154 signaling in the pathophysiology of liver I/R injury. METHODS: A mouse model of partial 90-min warm hepatic ischemia followed by 6 hr of reperfusion was used. Three animal groups were studied: (1) wild-type (WT) mice treated with Ad-(-gal versus Ad-CD40 immunoglobulin; (2) untreated WT versus CD154 (MR1) monoclonal antibody-treated WT mice; and (3) untreated WT versus CD154 knockout mice. RESULTS: The disruption of CD154 signaling in all three animal groups ameliorated otherwise fulminant liver injury, as evidenced by depressed serum glutamic oxaloacetic transaminase levels, compared with controls. These beneficial effects were accompanied by depressed hepatic T-cell sequestration, local decrease of vascular endothelial growth factor expression, inhibition of tumor necrosis factor-(and T-helper type 1 cytokine production, and induction of antiapoptotic (Bcl-2/Bcl-xl) but depression of proapoptotic (caspase-3) proteins. CONCLUSIONS: By using in parallel a gene therapy approach, pharmacologic blockade, and genetically targeted mice, these findings document the benefits of disrupting CD154 to selectively modulate inflammatory responses in liver I/R injury. This study reinforces the key role of CD154-CD40 T-cell co-stimulation in the pathophysiology of liver I/R injury.

Animals↗

PubMed2005

Infectious enteritis after intestinal transplantation: incidence, timing, and outcome.

BACKGROUND: The study reviews the incidence, timing, and outcome of infectious enteritis (IE) after intestinal transplantation (ITx). METHODS: A retrospective review of all patients who underwent ITx at a single institution between 1991 and 2003 was undertaken using database and medical records. Standard statistical analyses were performed. RESULTS: Of 33 ITx recipients, 13 (39%) developed 20 culture- or biopsy-proven episodes of IE. Recipient demographics included the following: 10 males, median age 34 (10-585) months, 11 liver + intestine grafts, and two isolated intestine grafts. Infections were diagnosed a median of 76 days (32-1,800 days) after ITx. There were 14 viral (one cytomegalovirus, eight rotavirus, four adenovirus, one Epstein-Barr virus), three bacterial (Clostridium difficile), and three protozoal (one Giardia lamblia, two Cryptosporidium) infections. The bacterial infections tended to present earlier than the viral infections, and the most frequent presenting symptom was diarrhea. Complete resolution was achieved in 17 (94%) incidences with the appropriate antimicrobial or conservative therapy. It was interesting that there were seven rejection episodes documented by biopsy at the approximate time of diagnosis of IE. There were two graft losses: one because of adenoviral enteritis and one because of rejection after rotavirus enteritis. Three-year patient survival is 74% with no deaths directly attributable to IE. CONCLUSIONS: IE can occur in 39% of recipients after ITx. Viral agents are the cause in two thirds of the cases. With supportive care and appropriate treatment, resolution is possible in the majority of cases. Differentiating rejection and infection on histopathology can be difficult and relies on cultures and immunostaining.

Adult↗

PubMed2005

CD62 blockade with P-Selectin glycoprotein ligand-immunoglobulin fusion protein reduces ischemia-reperfusion injury after rat intestinal transplantation.

BACKGROUND: Intestinal transplantation (ITx) is severely limited by ischemia-reperfusion (I/R) injury. This study investigates I/R injury and ameliorates its consequences by using a recombinant protein targeted against selectins (recombinant P-selectin glycoprotein ligand-immunoglobulin [rPSGL-Ig]). METHODS: An isogeneic model of ITx was undertaken with control animals (no therapy) and treatment animals (rPSGL-Ig). Survival was assessed. Separate groups underwent an analysis examining tissue at multiple time points after I/R injury including histopathology; myeloperoxidase staining; immunostaining for CD3 and ED2; polymerase chain reaction analysis of interleukin (IL)-8/cytokine-inducible neutrophil chemoattractant, IL1beta, IL-6, interferon-gamma, IL-2, IL-4, and IL10; and western blots for hemoxygenase-1, BCL-2, and BCL-xl. Standard statistical analysis was undertaken. RESULTS: Treatment with rPSGL-Ig resulted in significantly improved survival after ITx. Analysis demonstrated diminished injury on histopathology and reduced tissue infiltration of neutrophils and lymphocytes. Significant differences in the cytokine profile after ITx were seen between the two groups including the production of inflammatory cytokines at 24 hr and the Th1 and Th2 cytokines at 2 and 4 hr. Last, treatment resulted in increased production of hemoxygenase, BCL-2, and BCL-xl. CONCLUSION: The results of this investigation of I/R injury after ITx revealed that rPSGL-Ig treatment led to marked improvement in outcome. The mechanism of action seems to involve the blockade of neutrophil and lymphocyte infiltration leading to a decreased inflammatory response possibly driven by Th2 cytokines. The results not only lend insight into the mechanisms behind I/R injury after ITx but also demonstrate a potential therapeutic modality to ameliorate its consequences.

Animals↗

PubMed2005

MELD fails to measure quality of life in liver transplant candidates.

Previous studies have demonstrated an association between Child Turcotte-Pugh (CTP) class and impaired quality of life. However, the relationship between the model for end-stage liver disease (MELD) score and quality of life (QOL) has not been well studied. In this study, quality of life questionnaires (Medical Outcomes Short Form 36 [SF-36] and the Chronic Liver Disease Questionnaire [CLDQ]) were administered to 150 adult patients awaiting liver transplantation. We also collected demographic data and laboratory results and recorded manifestations of hepatic decompensation. The study found that all domains of the SF-36 and CLDQ were significantly lower in our patient cohort than in normal controls (P < .001). There was a moderate negative correlation between CPT class and physical components of the SF-36 (r = -.30), while there was a weak negative correlation (r = -.10) between CPT class and the mental component. There was a negative moderate correlation between CPT class and overall CLDQ (r = -.39, P < .001) and a weak correlation (r = -.20) between MELD score and overall CLDQ score. Both encephalopathy (correlation coefficient = -.713, P = .004) and ascites (correlation coefficient = -.68, P = .006) were predictive of the QOL using CLDQ (adjusted R(2) = .1494 and f = 0.000). In conclusion, in liver transplant candidates, the severity of liver disease assessed by the MELD score was not predictive of QOL. The presence of ascites and/or encephalopathy was significantly associated with poor quality of life. CTP correlates better to QOL, probably because it contains ascites and encephalopathy.

Female↗

PubMed2005

Inflammatory responses in a new mouse model of prolonged hepatic cold ischemia followed by arterialized orthotopic liver transplantation.

The current models of liver ischemia/reperfusion injury (IRI) in mice are largely limited to a warm ischemic component. To investigate the mechanism of hepatic "cold" IRI, we developed and validated a new mouse model of prolonged cold preservation followed by syngeneic orthotopic liver transplantation (OLT). Two hundred and forty-three OLTs with or without rearterialization and preservation in University of Wisconsin solution at 4 degrees C were performed in Balb/c mice. The 14-day survivals in the nonarterialized OLT groups were 92% (11/12), 82% (9/11), and 8% (1/12) after 1-hour, 6-hour and 24-hour preservation, respectively. In contrast, hepatic artery reconstruction after 1-hour, 6-hour, and 24-hour preservation improved the outcome as evidenced by 2-week survival of 100% (12/12), 100% (10/10), and 33% (4/12), respectively, and diminished hepatocellular damage (serum alanine aminotransferase /histology). Moreover, 24-hour (but not 1-h) cold preservation of rearterialized OLTs increased hepatic CD4+ T-cell infiltration and proinflammatory cytokine (tumor necrosis factor-alpha, interleukin 2, interferon-gamma) production, as well as enhanced local apoptosis, and Toll-like receptor 4/caspase 3 expression. These cardinal features of hepatic IRI validate the model. In conclusion, we have developed and validated a new mouse model of IRI in which hepatic artery reconstruction was mandatory for long-term animal survival after prolonged (24-h) OLT preservation. With the availability of genetically manipulated mouse strains, this model should provide important insights into the mechanism of antigen-independent hepatic IRI and help design much needed refined therapeutic means to combat hepatic IRI in the clinics.

Adenosine↗

PubMed2005

Analysis of long-term outcomes of 3200 liver transplantations over two decades: a single-center experience.

OBJECTIVE: Few studies have evaluated long-term outcomes after orthotopic liver transplantation (OLT). This work analyzes the experience of nearly 2 decades by the same team in a single center. Outcomes of OLT and factors affecting survival were analyzed. METHODS: Retrospective analysis of 3200 consecutive OLTs that were performed at our institution, between February 1984 and December 31, 2001. RESULTS: Of 2662 recipients, 578 (21.7%) and 659 (24.7%) were pediatric and urgent patients, respectively. Overall 1-, 5-, 10-, and 15-year patient and graft survival estimates were 81%, 72%, 68%, 64% and 73%, 64%, 59%, 55%, respectively. Patient survival significantly improved in the second (1992-2001) versus the era I (1984-1991) of transplantation (P < 0.001). Similarly, graft survival was better in the era II of transplantation (P < 0.02). However, biliary and infectious complications increased in era II. When OLT indications were considered, best recipient survival was obtained in children with biliary atresia (82%, 79%, and 78% at 1, 5, and 10 years, respectively), while malignant disease in adult patients resulted in the worst outcomes of 68% and 43% at 1 and 5 years, post-OLT. Further, patients <18 years and nonurgent recipients exhibited superior survival when compared with recipients >18 years (P < 0.001) or urgent patients (P < 0.001). Of 13 donor and recipient variables, era of OLT, recipient age, urgent status, donor age, donor length of hospital stay, etiology of liver disease, retransplantation, warm and cold ischemia, but not graft type (whole, split, living-donor), significantly impacted patient survival. CONCLUSIONS: Long-term benefits of OLT are greatest in pediatric and nonurgent patients. Multiple factors involving the recipient, etiology of liver disease, donor characteristics, operative variables, and surgical experience influence long-term survival outcomes. By balancing and matching these factors with a given recipient, optimum results can be achieved.

Adolescent↗

PubMed2005

Mortality predictors in liver transplant recipients with recurrent hepatitis C cirrhosis.

BACKGROUND/AIM: Recipients of orthotopic liver transplant for hepatitis C (HCV) invariably develop recurrent disease. The risk factors for death and retransplantation following the development of cirrhosis from HCV are unclear. The aim of this study was to identify predictors of survival in liver transplant recipients who develop cirrhosis from recurrent HCV. METHODS: We reviewed records of patients who underwent liver transplantation for cirrhosis due to HCV between January 1990 and December 2001. Prognostic factors of patient survival following the development of recurrent cirrhosis were identified through multivariate analysis. RESULTS: During the study period, 511 patients underwent transplantation for HCV cirrhosis. Of these, 65 patients (13%) developed biopsy proven recurrent cirrhosis from HCV; 43 (8%) were relisted for transplantation, and 24 (5%) underwent retransplantation. The overall Kaplan-Meier patient survival rates after the histologic diagnosis of cirrhosis at 1 and 5 years were 66% and 30%, respectively. A multivariate Cox proportional hazards model showed patients with higher last (i.e. at follow-up or prior to retransplantation) International normalized ratio (INR) values (hazard ratios (HR)=2.02, 95% confidence interval 1.26, 3.24, P<0.01) to have an increased risk of death. CONCLUSION: Our results suggested survival was decreased after the diagnosis of cirrhosis from recurrent HCV. Higher INR was associated with an increased risk of death following the development of cirrhosis.

Adult↗