The role of immunosuppression in malignancies among 351 pediatric renal transplant patients.

The incidence of de novo malignancies over a 38 year experience in 351 children ranging in age from 2 to 18 years was investigated among subjects prescribed various immunosuppressive protocols. There were 14 children (3.98%) who showed de novo malignancies, namely, 4.86 cancers for every 1000 graft-function years (GFYs). Among patients who had grafts functioning for >10 years, 7.4% suffered from cancer. Nine patients survive without a recurrence at a mean of 12.5 +/- 6.6 years including 6 with graft function. Among group I who were treated with pre-calcineurin inhibitor (CNI) therapy 3 (3.8%) children (1 male and 2 females) developed a malignancy at a mean of 15.2 +/- 11.9 years posttransplant (range, 7-35), for 4.65 cancers every 1000 GFYs. Two of them survive with functioning grafts. Among group II, who were treated by CNIs there were 273 children including 24 retransplants. Group II showed 11 malignancies (4.0%), for 5.04 malignancies for every 1000 GFYs. The incidence of cancer was similar in the 2 groups, undergoing different immunosuppressive regimens; however, the malignancies in the CNI- group were more precocious, compared with those of the conventionally-treated cohort.

Malignancies in 2,753 kidney recipients transplanted during a 39-year experience.

An increased development of malignancies has been related to modern potent antirejection drugs. The purpose of this retrospective study was to assess the incidence and risk factors for invasive malignancies among 2753 kidney recipients (KRs), who were transplanted in two periods within our 39-year experience; before (group I) versus after (group II) the introduction of calcineurin inhibitors (CNIs). In group I, formed by 703 KRs under conventional therapy, 45 (6.4%) patients developed a malignancy, while in group II, treated with CNIs, of over 2050 KRs, 182 (8.9%) developed a malignancy different from noninvasive skin cancer. The incidence of malignancies was higher in the group of patients treated with CNIs (8.9% vs 6.4%), despite the shorter follow-up period. Moreover, the malignancy was more precocious in the CNI group, namely a mean time of onset of 75 versus 154 months in the conventionally treated group. The older mean age of recipients in group II affected by malignancies (43.6 years vs 34.6 years of the group I) played a significant (P < .001) role when associated with the more powerful immunosuppressive effect of CNIs, while recipient gender, dialysis period, donor source, and retransplants seemed to have few effects on malignancy development. Recipients over 60 under CNIs showed a 21% incidence of malignancies.

Occult hepatitis B virus infection in dialysis patients: a multicentre survey.

BACKGROUND: The epidemiology and clinical significance of occult hepatitis B virus infection (serum hepatitis B surface antigen-negative patients with detectable hepatitis B virus viraemia in serum) remains controversial with only limited information about its prevalence in patients on long-term dialysis. AIM: To address the epidemiology of occult HBV infection in a large cohort of dialysis patients. METHODS: We screened a large cohort (n = 585) of Italian chronic dialysis patients; from this population, a group of hepatitis B virus surface antigen seronegative patients (n = 213) was tested by Amplicor hepatitis B virus Monitor Test to detect hepatitis B virus viraemia (hepatitis B virus-DNA) in serum. RESULTS: Occult hepatitis B virus infection was absent (zero of 213 = 0%). Persistent hepatitis B virus surface antigen carriage was less frequent than anti-hepatitis B virus core antibody (anti-hepatitis B core antigen) seropositive status in this study group [1.88% (11 of 585) vs. 36% (216 of 585), P = 0.0001]. No dialysis patients seropositive for anti-hepatitis B core antibody in serum (zero of 123 = 0%) had detectable hepatitis B virus-DNA by polymerase chain reaction technology. No significant association between abnormal biochemical liver tests and serum anti-hepatitis B core antibody was noted in our population. Nominal logistic regression analysis demonstrated an independent and significant relationship between anti-HCV antibody and anti-hepatitis B virus core antibody in serum (Wald chi-square 16.06, P = 0.0001). The rate of seropositive patients for anti-hepatitis B virus core antibody was higher among study patients than controls with normal renal function [36.9% (216 of 585) vs. 21.4% (59 of 275), P = 0.0001]; this difference partially persisted after correction for demographic parameters, and viral markers. CONCLUSION: In conclusion, occult hepatitis B virus was absent in our study group. Anti-hepatitis B core antibody was significantly related to presence of anti-HCV antibody supporting shared modes of transmission. Clinical studies based on molecular biology techniques provided with higher sensitivity are planned.

Lamivudine in the treatment of HBV-related liver disease after renal transplantation: an update.

Diminished survival due to hepatitis B has been observed after renal transplantation (RT). Lamivudine, a second-generation nucleoside analogue, has been approved for the treatment of chronic hepatitis B virus (HBV) infection in patients with normal renal function. Numerous clinical experiences with lamivudine after RT have been recently published. Despite numerous shortcomings, all of these reports have shown encouraging results. The rate of clearance of HBV viremia ranged between 67% and 100%, and the frequency of ALT normalization was between 50% and 100% with lamivudine use. Even patients with fibrosing cholestatic hepatitis, a serious form of HBV-related liver disease with ominous course, have been successfully treated with lamivudine. Lamivudine therapy significantly improved the survival of HBsAg positive renal allograft recipients. However, numerous issues concerning the treatment of hepatitis B after RT remain unclear: the optimal time to initiate lamivudine, the appropriate duration of antiviral therapy after RT, and the role for pre-transplantation liver biopsy. Also, the management of lamivudine resistance remains a concern for physicians. Clinical trials are under way.

[Hepatitis C virus and renal transplantation]. / Infezione da virus dell'epatite C (HCV) e trapianto renale.

Liver disease has emerged as an important cause of morbidity and mortality after renal transplantation (RT). Hepatitis C virus (HCV) is the leading cause of liver disease after RT. The impact of HCV infection on patient and graft survival is currently a major concern. Retrospective studies with appropriate follow-up have mainly demonstrated that HCV positive patients have greater mortality compared to HCV negative recipients after RT. Novel investigations by large databases (United States Renal Data Systems (USRDS)) have shown that recipients of donor HCV-positive kidneys are at an independently increased risk of mortality, adjusted hazard ratio 2.12 (95% confidence interval (95% CI), 1.72-2.87, p<0.001); there was no evidence that any subgroup was less affected. With appropriate informed consent, the use of a renal graft from an HCV positive donor could be offered to an HCV infected recipient. Many renal transplant candidates have satisfactory virological responses to antiviral therapy; the persistence of HCV clearance over a prolonged follow-up after RT has been recently noted. Further prospective studies are needed to define better the course of HCV infection among renal allograft recipients.