Severe evolution of chronic hepatitis C in renal transplantation: a case control study.

BACKGROUND: To evaluate the impact of kidney transplantation on histopathological progression of hepatitis C virus (HCV)-related liver disease. METHODS: In a retrospective study, 28 HCV-positive renal transplant patients, who underwent two sequential liver biopsies with a mean of 7.1+/-4.0 years, were compared with 28 matched immunocompetent controls. RESULTS: According to the Metavir score, the initial and final activity scores (from 0 to 3) increased from 0.2+/-0.4 to 1.4+/-1.1 (P<0.001) and those of fibrosis (from 0 to 4) from 0.5+/-0.5 to 2.0+/-1.4 (P<0.001) in the transplanted group, respectively, whereas the respective differences were not significant in the control group. The yearly progression rate of activity and fibrosis was significantly higher in the renal transplant group as compared with the immunocompetent group: 0.26+/-0.41 vs 0.01+/-0.19 (P<0.01) and 0.26+/-0.35 vs 0.05+/-0.21 (P<0.03), respectively. Twenty (71.5%) and 14 (50.0%) of the renal allograft recipients had activity and fibrosis progression as compared with four (16%) (P<0.001) and four (16%) (P<0.01) in immunocompetent patients; six kidney recipients (21.4%) evolved to cirrhosis vs only one in the control group (3.6%) (P=0.07). Liver-related mortality was significantly higher during the follow-up period in renal transplant patients than in the control group (10 vs 0%) (P<0.05). CONCLUSION: Using conventional immunosuppressive regimen, renal transplantation is associated with a more severe evolution of chronic hepatitis C as compared with HCV-infected immunocompetent subjects. Thus, the histopathological evaluation should be performed and anti-viral therapy discussed before renal transplantation.     

Ketoconazole, an oral antifungal: laboratory and clinical assessment of imidazole drugs

Miconazole, a parenterally administered imidazole antifungal agent has been shown to produce responses in systemic fungal infections in man. Ketoconazole, an analogue, can be given by mouth. It is inhibitory in vitro at low concentrations to most fungi. Blood levels after oral administration to animals and man greatly exceed these inhibitory concentrations for several hours. The efficacy of this drug has been demonstrated in animal models. Initial clinical evaluation has produced responses to therapy with 200-400 mg/day in 13 of 16 evaluable patients with systemic and superficial fungal infections, involving 10 fungal pathogens. No toxicity has been noted to date in these human studies. Ketoconazole is a promising agent needing further extensive evaluation.     

Myocardial macroaggregate uptake on successive lung perfusion scans

In a patient with an Eisenmenger syndrome and multiple intraventricular communications, myocardial uptake of macroaggregated albumin appeared during a perfusion lung scan. This pattern can be explained by an increase of arterial pulmonary hypertension heightening the proportion of the right-to-left shunt.     

CD4+/Leu-7+ large granular lymphocytes in long-term renal allograft recipients. A subset of atypical T cells

In long-term renal allograft recipients on conventional immunosuppression, we have previously reported an abnormal expansion of CD3+/Leu-7+ cells. These cells are large granular lymphocytes without any natural killer activity. About 20% of these CD3+/Leu-7+ cells coexpress the CD4 differentiation antigen. In 65 transplant recipients at risk for more than 6 months, the mean percentage of peripheral blood CD4+/Leu-7+ cells is significantly increased compared with 34 normals (5.0 +/- 0.6% versus 1.0 +/- 0.1%, P less than 0.0001). Patients who never received azathioprine do not show such an abnormality. We carried out this study to further define the phenotype, morphology, and function of these cells. As to phenotype, they coexpress CD2, CD3 but do not coexpress CD1, CD8, CD11, CD16, CD19, CD25, HLA-DR, Leu-M3. Morphologically, CD4+/Leu-7+ cells are typical large granular lymphocytes undistinguishable from CD16+ effector NK cells. CD4+/Leu-7+ cells do not exhibit any natural killer cell activity. In contrast to CD4+/Leu-7- cells, CD4+/Leu-7+ cells do not proliferate when stimulated with either lectins (Con A, PHA) or allogeneic cells. When stimulated for 3 days with PHA, sorted CD4+/Leu-7+ cells do not express IL-2 receptors as detected with a PE-conjugated anti-CD25 monoclonal antibody, whereas 40% of CD4+-Leu-7- cells do so. Finally, when stimulated with PHA, CD4+-Leu-7+ cells are not able to produce detectable levels of IL-2, while CD4+-Leu-7- cells do so. In long-term renal allograft recipients on conventional immunosuppression, Leu-7 antigen identifies a subset of CD4+ cells that do not behave like regular T helper cells. We speculate that these cells represent an alteration in the cellular environment in transplant recipients, perhaps leading to long-term complications such as cancers and chronic viral infections.