Liver transplant outcomes in HIV+ haemophilic men.

Hepatitis C virus infection is the major cause of end-stage liver disease and the major indication for transplantation (OLTX), including among HIV-HCV co-infected individuals. The age of HCV acquisition differs between haemophilic and non-haemophilic candidates, which may affect liver disease outcomes. The purpose of the study was to compare rates of pre- and post-OLTX mortality between co-infected haemophilic and non-haemophilic subjects without hepatocellular cancer participating in the Solid Organ Transplantation in HIV Study (HIV-TR). Clinical variables included age, gender, race, liver disease aetiology, BMI, antiretroviral therapy, MELD score, CD4 + cell count, HIV RNA PCR and HCV RNA PCR. Time to transplant, rejection and death were determined. Of 104 HIV-HCV positive subjects enrolled, 34 (32.7%) underwent liver transplantation, including 7 of 15 (46.7%) haemophilic and 27 of 89 (30.3%) non-haemophilic candidates. Although haemophilic subjects were younger, median 41 vs. 47 years, P = 0.01, they were more likely than non-haemophilic subjects to die pre-OLTX, 5 (33.3%) vs. 13 (14.6%), P = 0.03, and reached MELD = 25 marginally faster, 0.01 vs. 0.7 years, P = 0.06. The groups did not differ in baseline BMI, CD4, detectable HIV RNA, detectable HCV RNA, time to post-OLTX death (P = 0.64), graft loss (P = 0.80), or treated rejection (P = 0.77). The rate of rejection was 14% vs. 36% at 1-year and 36% vs. 43% at 3-year, haemophilic vs. non-haemophilic subjects, respectively, and post-OLTX survival, 71% vs. 66% at 1-year and 38% vs. 53% at 3-year. Despite similar transplant outcomes, pretransplant mortality is higher among co-infected haemophilic than non-haemophilic candidates.

Motives and decision making of potential living liver donors: comparisons between gender, relationships and ambivalence.

The motives and decision making of potential living liver donors are critical areas for transplant clinicians evaluating these candidates to understand, yet these topics remain relatively unstudied. Thus, we surveyed 77 prospective living liver donors at the point of donation evaluation using structured instruments to gather more information on their approach to and concerns about donation. We collected information on donation decision making, motives for donation and anticipated social and physical concerns about postdonation outcomes. We examined three additional characteristics of donors: gender, the relationship of the donor to the intended recipient and the presence of ambivalence about donation. Women had more concerns about their family/social responsibilities. Those donating to nonimmediate family were more likely to have been asked to donate but less likely to feel they had to donate. However, ambivalent donors were the most distinct having difficulties and concerns across most areas from their motivations for donating, to deciding to be tested and to donate, to concerns about the postdonation outcomes. We discuss the clinical relevance of these findings to donor evaluation and preparation.

Early trajectories of depressive symptoms after liver transplantation for alcoholic liver disease predicts long-term survival.

Although it is well known that depression is associated with poorer medical outcomes, the association between depression- and liver transplant (LTX)-specific outcomes has not been investigated. We identified three trajectories of depressive symptoms evolving within the first post-LTX year in a cohort of 167 patients transplanted for alcoholic cirrhosis: a group with consistently low depression levels at all time points (group 1, n = 95), a group with initially low depression levels that rose over time (group 2, n = 41), and a group with consistently high depression levels (group 3, n = 31). Controlling for medical factors associated with poorer survival, recipients with increasing depression or persisting depression were more than twice as likely to die (all cause mortality) within the subsequent years. At 10 years post-LTX the survival rate was 66% for the low depression group, but only 46% and 43%, respectively, for the increasing depression and high depression groups. Except for a paradoxically higher percentage of malignancies in the low depression group, the causes of death and other specific LTX outcomes were not different between groups. Whether treatment of depression will improve survival rates is an area for research.

Trajectories of alcohol consumption following liver transplantation.

Any use of alcohol in the years following liver transplantation (LTX) approaches 50% of patients transplanted for alcoholic liver disease (ALD). We collected detailed prospective data on alcohol consumption following LTX for ALD to investigate ongoing patterns of use. Using trajectory modeling we identified four distinct alcohol use trajectories. One group had minimal use over time. Two other groups developed early onset moderate-to-heavy consumption and one group developed late onset moderate use. These trajectories demonstrate that alcohol use varies based on timing of onset, quantity and duration. Using discriminant function analysis, we examine characteristics of recipient's pre-LTX alcohol histories and early post-LTX psychological stressors to identify the profile of those at risk for these specific trajectories. We discuss the relevance of these findings to clinical care and preliminarily to outcomes.

Outcome after liver transplantation for NASH cirrhosis.

Nonalcoholic steatohepatitis (NASH) associated cirrhosis is an increasing indication for liver transplant (LT). The aim of this study was to determine outcome and poor predictive factors after LT for NASH cirrhosis. We analyzed patients undergoing LT from 1997 to 2008 at a single center. NASH was diagnosed on histopathology. LT recipients with hepatitis C, alcoholic or cholestatic liver disease and cryptogenic cirrhosis acted as matched controls. Ninety-eight LT recipients were identified with NASH cirrhosis. Compared to controls, NASH patients had a higher BMI (mean 32.3 kg/m2), and were more likely to be diabetic and hypertensive. Mortality after transplant was similar between NASH patients and controls but there was a tendency for higher earlier mortality in NASH patients (30-day mortality 6.1%, 1-year mortality 21.4%). Sepsis accounted for half of all deaths in NASH patients, significantly higher than controls. NASH patients > or =60 years, BMI > or =30 kg/m2 with diabetes and hypertension (HTN) had a 50% 1-year mortality. In conclusion, patients undergoing LT for NASH cirrhosis have a similar outcome to patients undergoing LT for other indications. The combination of older age, higher BMI, diabetes and HTN are associated with poor outcome after LT. Careful consideration is warranted before offering LT to these high-risk patients.

Safety observations in phase I clinical evaluation of the Excorp Medical Bioartificial Liver Support System after the first four patients.

A Phase I clinical safety evaluation of the Excorp Medical, Inc, Bioartificial Liver Support System (BLSS) is in progress. Inclusion criteria are patients with acute liver failure of any etiology, presenting with encephalopathy deteriorating beyond Parson's Grade 2. The BLSS consists of a blood pump, heat exchanger to control blood temperature, oxygenator to control oxygenation and pH, bioreactor, and associated pressure and flow alarm systems. Patient liver support is provided by 70-100 g of porcine liver cells housed in the hollow fiber bioreactor. A single support period evaluation consists of 12 hour extracorporeal perfusion with the BLSS sandwiched between 12 hours of pre (baseline) and 12 hours of post support monitoring. Blood chemistries and hematologies are obtained every 6 hours during monitoring periods and every 4 hours during perfusion. Physiologic parameters are monitored continuously. The patient may receive a second treatment at the discretion of the clinical physician. Preliminary evaluation of safety considerations after enrollment of the first four patients (F, 41, acetaminophen induced, two support periods; M, 50, Wilson's disease, one support period; F, 53, acute alcoholic hepatitis, two support periods; F, 24, chemotherapy induced, one support period) is presented. All patients tolerated the extracorporeal perfusion well. All patients presented with hypoglycemia at the start of perfusion, treatable by IV dextrose. Transient hypotension at the start of perfusion responded to an IV fluid bolus. Only the second patient required heparin anticoagulation. No serious or unexpected adverse events were noted. Moderate biochemical response to support was noted in all patients. Completion of the Phase I safety evaluation is required to fully characterize the safety of the BLSS.

Zidovudine toxicity to cats infected with feline leukemia virus.

Feline leukemia virus (FeLV) infection of cats is a model for the acquired immunodeficiency syndrome in humans. The toxicity of zidovudine was evaluated in SPF cats experimentally infected with FeLV. At initiation of the zidovudine study, all cats were antibody positive for FeLV antigens but clinically asymptomatic. Four cats were also viremic. Thirteen, 6- to 10-month-old cats were divided into five dosage groups and given zidovudine po at 0, 7.5, 15, 30, or 60 mg/kg daily in three equally divided doses for 32 to 34 days. Titers of circulating virus antigen remained constant; however, three of six cats receiving the higher doses of zidovudine (greater than or equal to 30 mg/kg) showed an increase in antibody titers to FeLV. Administration of zidovudine resulted in a progressive anemia, dependent upon dose and time. Macrocytes were observed prior to the development of anemia and were also found in several nonanemic cats. Repeated measures regression analyses indicated that an increased dose of zidovudine was associated with decreased packed cell volume, red blood cell count, and hemoglobin. As determined from the packed cell volume, the analyses indicate that anemia is induced only by the two highest doses of zidovudine. The regression model indicates that daily doses of 60 and 30 mg/kg are expected to induce anemia by Day 4 and Day 13, respectively. Progressive absolute neutropenia was observed in the greater than or equal to 30 mg/kg groups. Histopathologic lesions consisted of marked bone marrow hypercellularity in cats given greater than or equal to 30 mg/kg zidovudine and splenic extramedullary hematopoiesis in cats given greater than or equal to 15 mg/kg. Thus, oral toxicity of zidovudine in the cat is manifested by a dose-related anemia and neutropenia as observed in humans.