Impact of Prophylaxis vs Pre-emptive Approach for Cytomegalovirus Infection in Kidney Transplant Recipients.

Cytomegalovirus (CMV) is the most common viral infection during the post-transplant period, and it is one of the major causes of morbidity and mortality in kidney transplantation. In this study, the incidence and impact of pre-emptive and prophylactic approaches and long-term effects on graft and patient survival of CMV infection were investigated. Among 493 adult kidney transplant recipients, pretransplant CMV IgG-negative patients and patients with a follow-up shorter than a month were excluded. The patients were divided into 2 groups: pre-emptive group (n = 187, regular screening and acyclovir 400 mg twice daily for 6 months), and prophylaxis group (n = 275, valganciclovir 450 mg/d for 3 months). The pre-emptive group was screened for CMV with either pp65 antigenemia or CMV DNA. There were 462 patients, and mean follow-up was 37.7 months. There were more CMV infections in the pre-emptive group than in the prophylaxis group (n = 56, 30.1% vs n = 12, 4.4%, respectively; P < .001). Late CMV infections were significantly more frequent in the prophylaxis group (10 of 12, 83.3%) than in the pre-emptive group (8 of 56, 14.3%, P < .001). In multivariate analysis, valganciclovir prophylaxis was associated with a lower CMV infection (relative risk [RR]: 0.18, 95% confidence interval [CI] 0.08 to 0.39, P < .001). Delayed graft function was the only independent risk factor for graft loss during the follow-up on multivariate Cox regression analysis (RR: 2.66, 95% GA 1.17 to 6.04, P = .02). Valganciclovir prophylaxis was more protective against CMV infection than the pre-emptive approach. Neither prophylaxis/pre-emptive approaches nor CMV infection had negative effect on graft and patient survival.

The acquisition time of infection: a determinant of the severity of hepatitis C virus-related liver disease in renal transplant patients.

BACKGROUND: The aim of this study was to compare the clinical and histopathological course of HCV infection acquired before and during or after renal transplantation. METHODS: According to HCV status, 197 RT patients were divided into three groups. At the time of RT, anti-HCV antibody was positive in 47 patients (pre-RT HCV group). In 27 patients, in whom anti-HCV negative at the time of RT, anti-HCV and/or HCV RNA was found to be positive following an ALT elevation episode after RT (post-RT HCV group). Both anti-HCV and HCV RNA were negative at all times in remaining 123 patients (control group). RESULTS: Liver biopsy was performed in 31 of 47 patients in pre-RT and 24 of 27 in post-RT HCV group after RT. Duration of follow-up was similar in all groups with a mean of 7.1 +/- 4.0 yr. Ascites and encephalopathy were seen in only post-RT HCV group (22%). Histological grade (6.5 +/- 2.7 vs. 4.1 +/- 1.4) and stage (2.0 +/- 1.5 vs. 0.8 +/- 0.8) was significantly severe in post-RT HCV group (p < 0.01). Three patients died due to liver failure in post-RT HCV group. CONCLUSIONS: HCV infection acquired during or after RT shows a severe and rapidly progressive clinicopathological course, which is significantly different from pre-transplant anti-HCV positive patients.

Nosocomial hepatitis C virus infection in a renal transplantation center.

Nosocomial hepatitis C virus (HCV) infections were recorded in the renal transplantation unit of the university hospital. There were cases of acute HCV infection with aggressive clinical courses diagnosed from a positive HCV RNA test in the early post-transplantation period and which remained anti-HCV negative. Their anti-HCV seronegativity was attributed to them having acquired HCV under intense immunosuppressive therapy and suggested that the aggressive clinical course could be due to the deficient immune response resulting in an inability to limit viral replication. There were also donors diagnosed as having acute HCV infection in the early post-operative period. Genotyping and sequence analysis for HCV were performed on the isolates of eight of these patients who were consecutively transplanted and of three donors whose recipients were infected with HCV prior to transplantation, and who acquired acute HCV infection after transplantation. Of the eight recipients in the first group three were genotype 1a, three were genotype 1b, one was genotype 3a, and the last one was genotype 4 according to Simmond's classification. Of the three donor-recipient couples both the HCV isolates from one couple were genotyped as 1b and the phylogenetic analysis indicated that the patients were infected with a common variant of HCV, but the genotypes of HCV isolates from the other couples were different. Recipients were genotype 1b and the donors were genotype 1a in these couples. Genotype results of the first group and donor-recipient couples, and sequence analysis of genotype 1b and 1a isolates, showed that the source of infection was not a unique strain and there were multiple breaks in universal precautions while managing these patients.

Evaluation of the risk of cervical intraepithelial neoplasia and human papilloma virus infection in renal transplant patients receiving immunosuppressive therapy.

OBJECTIVE: To investigate the risk of cervical intraepithelial neoplasia and the coexistence of human papilloma virus (HPV) infection in renal transplant patients receiving immunosuppressive therapy. MATERIALS AND METHODS: Cervical Papanicolaou (Pap) smear and colposcopic examinations were performed in 48 renal transplant patients receiving immunosuppressive therapy. Microbiological and histopathologic findings were discussed. RESULTS: The patients were evaluated as to cervical neoplasia risk factors and the results were found to be statistically insignificant (p>0.05). Genital neoplasia was encountered in 20 of the 48 renal transplant patients. Koilocytosis developed in 6 out of 8 (75%) patients who were receiving high dose immunosuppressive therapy due to transplant rejection. HPV was found in 2 out of 48 patients; these 2 patients had koilocytosis in their cervical biopsies. The difference between the positive predictive value of colposcopic evaluation and the Pap smear was found to be insignificant (p>0.05). However, if colposcopy had not been performed in two cases of cervical intraepithelial neoplasia class I (CIN-I) and in one case of cervical microinvasive carcinoma, the cases would have been incorrectly diagnosed as normal by the false-negative results of the Pap smear. CONCLUSION: Renal transplant patients who were undergoing immunosuppressive therapy were found to be at increased risk of developing cervical intraepithelial neoplasia. All the patients using immunosuppressive agents should be followed-up by Pap smears every six months and by colposcopic evaluation every year. Avoiding high-risk sexual acts will decrease the risk of HPV transmission and the risk of genital neoplasia as well.

Clinicopathological features of rapidly progressive hepatitis C virus infection in HCV antibody negative renal transplant recipients.

BACKGROUND: Hepatitis C virus (HCV) infection acquired during dialysis treatment generally shows a relatively benign course after renal transplantation (RTx). However, less is known about the course of HCV infection acquired during or after RTx. METHODS: Clinical and histopathological assessment of 15 renal transplant recipients who acquired HCV infection during or after RTx. RESULTS: Alanine aminotransferase levels rose for the first time 1-19 weeks after RTx. HCV RNA was found positive in all patients, but anti-HCV became positive in only nine of them. During a mean follow-up of 21 +/- 12 months, jaundice appeared in 12 patients while ascites and/or hepatic encephalopathy occurred in six. Azathioprine was stopped in all patients. Cyclosporin was also stopped in four patients and in two of them prednisolone was also interrupted for a period of 3-7 weeks. Following this, ascites, hepatic encephalopathy and biochemical disturbances improved, while no deterioration was seen in graft function. Nine of the 15 patients had undergone two consecutive liver biopsies (LB). The first LB revealed cirrhosis in three and chronic hepatitis in six patients; the second LB showed cirrhosis in seven patients. The histological activity index (Knodell's score) progressed from 11.8 +/- 3.5 to 13.8 +/- 3.8. CONCLUSIONS: The results suggest that HCV infection acquired during or after RTx may run an unusual and rapidly progressive clinical and histopathological course at least in some of these patients. Decrease or withdrawal of immunosuppressive drugs may improve early hepatic failure without detrimental effect on graft function during that period.

Screening for human immunodeficiency virus type 1 and 2 in a Turkish blood donor population.

OBJECTIVES: To determine the prevalence of human immunodeficiency virus-1 and -2 infection in voluntary blood donors at a university hospital in the third largest city of Turkey and to evaluate the HIV testing strategy for notifying blood donors. METHODS: Between July 1995 and August 1997, 36,373 voluntary blood donors who met the criteria for donating blood were tested for the presence of HIV-1 and -2 antibodies by using an automated enzyme-linked fluorescent immunoassay. Repeatedly reactive samples were subjected to a different enzyme-linked immunosorbent assay (ELISA) and a line immunoassay (LIA) for the detection of antibodies. RESULTS: Of the 36,373 samples tested 72 were found to be repeatedly reactive or borderline by the first screening enzyme immunoassay (EIA). None of the 72 samples was reactive by the second EIA. These samples were further tested by LIA: 64 were negative on the line immunoassay and 8 were indeterminate. Three of eight donors who had indeterminate results by LIA were tested for HIV-1 DNA by polymerase chain reaction (PCR) and were found to be negative. One additional donor with an indeterminate LIA was found to be negative by EIA and LIA during the 6-month follow-up period. CONCLUSION: Donor questioning, repeat EIA testing, LIA testing, and HIV-1 DNA analysis did not confirm evidence for HIV infection among this blood donor population. Blood donor notification of test results according to the World Health Organization (WHO) strategy III was found to be an appropriate approach.

Rat cytomegalovirus-induced pneumonitis after allogeneic bone marrow transplantation: effective treatment with (S)-1-(3-hydroxy-2-phosphonyl-methoxypropyl)cytosine.

Two antiviral compounds, (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC) and 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG), were evaluated for their effects on rat cytomegalovirus (RCMV)-induced interstitial pneumonitis after allogeneic bone marrow transplantation (BMTx). Eight-week-old Brown Norway rats immunosuppressed by a lethal dose of total body irradiation were inoculated with RCMV and received allogeneic bone marrow cells from Lewis rats. Animals were treated with either HPMPC (20 mg/kg of body weight as a single dose) or DHPG (20 mg/kg as two daily doses for 5 days). The effect of antiviral therapy was monitored by measuring RCMV titers in different organs and the histopathologic changes in lungs at 8 to 10 days postinfection. In RCMV-infected allogeneic BMTx recipients, severe diffuse thickening of alveolar septa (6.02 microns) with a diffuse infiltration of mononuclear cells occurred, whereas in the noninfected allogeneic BMTx recipients, the septal width was on the order of 2 microns (P < 0.01). Treatment with DHPG (20 mg/kg in two daily doses for 5 days) resulted in a decrease in virus titers (log10 PFU per gram of tissue) in lungs and spleens from 3.81 +/- 0.34 and 4.29 +/- 1.07 (untreated animals) to 1.26 +/- 0.53 and 3.22 +/- 0.27 (treated animals), respectively. Treatment with HPMPC (20 mg/kg as a single dose) resulted in a complete reduction of virus titers in all organs to below the detection level (P < 0.01). Furthermore, antiviral treatment resulted in a reduction of the alveolar septal width from 6.02 +/- 1.59 microns (untreated animals) to 4.67 +/- 1.70 and 3.32 +/- 0.63 microns after DHPG and HPMPC treatment, respectively. Treatment with HPMPC (20 mg/kg as a single dose) resulted in a complete reduction of virus titers in all organs to below the detection level (P <0.01). Furthermore, antiviral treatment resulted in a reduction of the alveolar septal width from 6.02 +/- 1.59 micrometre (untreated animals) to 4.67 +/- 0.63 micrometre after DHPG and HPMPC treatment, respectively. Furthermore, the influx of mononuclear cells in the alveolar septa was significantly impaired after treatment with HPMPC (P <0.01). We conclude that in the described rat model, HPMPC is highly effective in suppressing RCMV-induced interstitial pneumonitis after allogeneic BMTx.