Outcomes in patients who are hepatitis B surface antigen-positive before transplantation: an analysis and study using the joint ISHLT/UNOS thoracic registry.

BACKGROUND: Hepatitis B surface antigenemia (HBsAg) has been considered at least a relative contraindication for heart transplantation, yet patients have undergone liver transplantation for hepatitis B-induced chronic liver disease, albeit with poorer results than for other liver diseases. The impact of asymptomatic hepatitis B infection on heart transplant outcome is not known. METHODS: To examine this question, we queried the Joint International Society for Heart and Lung Transplantation/United Network of Organ Sharing Thoracic Registry for all patients undergoing heart transplantation who had been identified as positive for HBsAg before transplantation. We then sent a 4-question data instrument to the centers responsible for the identified patients. Seventy-eight patients were identified. Of the 78 data forms sent, 53 forms were returned with the requested data. Of the 53 data forms returned, the centers incorrectly identified 23 patients as positive for HBsAg, resulting in 30 patients who were confirmed as HBsAg positive and who served as the final cohort for this analysis. RESULTS: The cohort included 24 males and 6 females, with a mean age of 46 +/- 16 years (range 0 to 68 years). Eleven patients had coronary artery disease, 14 had dilated cardiomyopathy, and 5 patients had a variety of other cardiac diseases. Of those tested at most recent follow-up, 20 of 25 patients continued to be positive for HBsAg, whereas 7 of 21 patients studied had converted and were hepatitis B serum antibody-positive. Approximately 37% of the patients had evidence of active hepatic inflammation or cirrhosis. We found a statistically significant correlation between positivity for hepatitis C antibodies and clinical liver disease (p = 0.0105). No difference in survival could be demonstrated between the study cohort and a reference heart transplant cohort, yet 5 of the 9 deaths were considered to be related to hepatitis B. CONCLUSIONS: These data demonstrate that clinical liver disease is common post-transplantation in HBsAg+ patients who presumably have no overt liver disease at the time of transplantation. Despite the inability to show a survival difference in this cohort, the fact that the majority of deaths were related to hepatitis B should suggest caution in accepting HBsAg+ patients for cardiac transplantation.

Human parvovirus B19 infection presenting as persistent anemia in renal transplant recipients.

BACKGROUND: Immunosuppression cannot be achieved without immunosuppressive effects. Human Parvovirus infection is known to occur after organ transplantation. We present our experience with Parvovirus infection in two cases. METHODS AND RESULTS: Two kidney transplant recipients developed symptomatic anemia requiring blood transfusions. Common causes of anemia, such as gastrointestinal bleeding, iron/vitamin deficiencies, hemolysis, and drug toxicities, were ruled out. A peripheral smear revealed low reticulocyte count. Bone marrow examination showed hypoplastic bone marrow with intranuclear inclusions suggestive of human Parvovirus. This was confirmed by immunohistochemical analysis. Treatment with i.v. immunoglobulin G resulted in a dramatic sustained response. Transplant kidney function remained stable. CONCLUSION: Human Parvovirus infections should be considered in immunosuppressed individuals with anemia with poor bone marrow response. Bone marrow examination can reveal viral inclusions and can be confirmed by immunohistochemical analysis. Intravenous immunoglobulin G results in resolution of anemia.

Homocysteine-induced endoplasmic reticulum stress and growth arrest leads to specific changes in gene expression in human vascular endothelial cells.

Alterations in the cellular redox potential by homocysteine promote endothelial cell (EC) dysfunction, an early event in the progression of atherothrombotic disease. In this study, we demonstrate that homocysteine causes endoplasmic reticulum (ER) stress and growth arrest in human umbilical vein endothelial cells (HUVEC). To determine if these effects reflect specific changes in gene expression, cDNA microarrays were screened using radiolabeled cDNA probes generated from mRNA derived from HUVEC, cultured in the absence or presence of homocysteine. Good correlation was observed between expression profiles determined by this method and by Northern blotting. Consistent with its adverse effects on the ER, homocysteine alters the expression of genes sensitive to ER stress (ie, GADD45, GADD153, ATF-4, YY1). Several other genes observed to be differentially expressed by homocysteine are known to mediate cell growth and differentiation (ie, GADD45, GADD153, Id-1, cyclin D1, FRA-2), a finding that supports the observation that homocysteine causes a dose-dependent decrease in DNA synthesis in HUVEC. Additional gene profiles also show that homocysteine decreases cellular antioxidant potential (glutathione peroxidase, NKEF-B PAG, superoxide dismutase, clusterin), which could potentially enhance the cytotoxic effects of agents or conditions known to cause oxidative damage. These results successfully demonstrate the use of cDNA microarrays in identifying homocysteine-respondent genes and indicate that homocysteine-induced ER stress and growth arrest reflect specific changes in gene expression in human vascular EC.

Homocysteine-dependent alterations in mitochondrial gene expression, function and structure. Homocysteine and H2O2 act synergistically to enhance mitochondrial damage.

Mitochondrial abnormalities have been identified in hepatocytes of patients with hyperhomocysteinemia and in endothelial cells from the aortas of rats with diet-induced hyperhomocysteinemia. However, the mechanism by which homocysteine affects mitochondria is unknown. In this report, homocysteine-induced expression of the mitochondrial electron transport chain gene, cytochrome c oxidase III/ATPase 6,8 (CO3/ATPase 6,8), was identified in a human megakaryocytic cell line DAMI using mRNA differential display. Steady-state mRNA levels of CO3/ATPase 6,8, as well as other mitochondrial transcripts, were increased in DAMI cells by homocysteine in a concentration- and time-dependent manner. Despite an increase in mitochondrial RNA levels and changes in mitochondrial ultrastructure, no effect on either cell growth or mitochondrial respiration rates was observed in DAMI cells exposed to homocysteine at concentrations up to 1 mM. In contrast, 1 mM homocysteine in the presence of Cu2+, which is known to generate H2O2, significantly decreased mitochondrial RNA levels, caused gross morphological changes in mitochondrial ultrastructure, and inhibited both cell growth and mitochondrial respiration rates. However, precursors of cellular glutathione and preexposure to heat shock blocked the decrease in mitochondrial RNA levels caused by homocysteine and Cu2+. The observations that (i) homocysteine and H2O2, but not H2O2 alone, caused a decrease in mitochondrial RNA levels, (ii) intracellular levels of H2O2 were significantly increased in the presence of homocysteine and Cu2+, and (iii) catalase, but not free radical scavengers, prevented a decrease in mitochondrial RNA levels, provide evidence that homocysteine and H2O2 act synergistically to cause mitochondrial damage. Furthermore, our findings suggest that intracellular glutathione and heat shock proteins play a role in protecting mitochondria against the adverse effects elicited by homocysteine and H2O2.

Postoperative mitral valve abscess. A case report.

The authors report a case of a patient with postoperative perimitral bioprosthetic abscess and probable systemic embolization. The location of the abscess is not common and the use of porcine bioprostheses is supposedly associated with a low rate of embolic complications. Because of the high mortality and morbidity, it is stressed that patients with prosthetic valve endocarditis should be managed aggressively with surgery.