Convenient biological assay for polyethylene glycol-interferons in patients with hepatitis C

The vesicular stomatitis virus cytopathic effect reduction assay is suitable to quantify polyethylene glycol-alpha interferon 2a (PEG-IFN-alpha 2a) and PEG-IFN-alpha 2b. Human serum and ribavirin did not interfere with the assay. This bioassay was successfully used for assaying PEG-IFN-alpha 2a and PEG-IFN-alpha 2b in serum samples from patients undergoing combination therapy.     

Suboccipital tuberculosis: a case report

Suboccipital tuberculosis is an uncommon localization of Pott's disease. The gravity results from the neurological and life threatening risk. We report a case of suboccipital tuberculosis in a 22-year woman who survived. She was given an anti-tuberculosis antibiotic regimen due to pulmonary and pericardal involvement. The patient interrupted her treatment after four months and was admitted six months later for torticolis and spastic tetraplegia without sphincter disorders. Standard x-rays and MRI of the head confirmed suboccipital Pott's disease. Transcranial evacuation was performed and the patient was again given anti-tuberculosis antibiotics. The clinical course was favorable with definitive recovery 45 days later. The patient continued the antibiotic regimen for nine months. An orthopedic supporting device was worn for nine months. The diagnosis of suboccipital tuberculosis can be confirmed on MRI. Appropriate treatment is a subject of debate between exclusive orthopedic or combined orthopedic and surgical treatment. Prognosis depends on the neurological deficit, early diagnosis and prompt treatment.     

Significance of nucleo-cytoplasmic maturation asynchrony in multiple myeloma

Bone marrow samples of 97 patients with multiple myeloma were examined ultrastructurally over a period of eight years, and the degree of nucleo-cytoplasmic maturation asynchrony (NCA) of myeloma plasmocytes was estimated according to the classification scale of Graham and Bernier. One half of the patients showed first degree, 40 percent second and 10 percent third degree of NCA. Clinical classification of the disease according to the staging system of Durie and Salmon and the quantitative staging system of Salmon and Wampler showed some relation to the degree of NCA. The degree of NCA was found to be related to the density of the bone marrow infiltration with myeloma plasmocytes but not to the response to chemotherapy. Some relation was seen to exist between the degree of NCA in myeloma plasmocytes at diagnosis and the prognosis of the disease. The role of electron microscopical analysis in MM diagnostics and its contribution to management of the disease are discussed.     

Mutation in the Hepatitis E Virus Polymerase and Outcome of Ribavirin Therapy

Hepatitis E virus (HEV) can lead to chronic infection in solid-organ transplant patients. Ribavirin is efficient for treatment of chronically infected patients. Recently, the1634R mutation in the HEV polymerase has been associated with treatment failure. However, it is unclear if this mutation can be used as a prognostic marker of treatment outcome. We studied the prevalence of the 1634R mutation in the HEV polymerase of patients starting ribavirin therapy, the influence of the 1634R variants on the viral response, the frequency of the 1634R mutation in patients whose treatment failed, and its impact on ribavirin retreatment. We analyzed pretreatment samples from 63 solid-organ transplant patients with chronic hepatitis E using deep sequencing; 42 patients had a sustained virologic response (SVR), and 21 were non-SVR patients. We detected the 1634R variant by deep sequencing in 36.5% (23/63) of the patients (proportions, 1.3 to 100%). The 1634R variant was detected in 31.0% (13/42) of baseline plasma samples from patients with SVR and in 47.6% (10/21) in the other patients (P = 0.2). The presence of this mutation did not influence the initial decrease in viral RNA. Lastly, a second prolonged ribavirin treatment led to SVR in 70% of the patients who initially did not have SVR, despite the presence of the 1634R variant. We conclude that the presence of the 1634R variant at ribavirin initiation does not lead to absolute ribavirin resistance. Although its proportion increased in patients whose treatment failed, the presence of the 1634R variant did not compromise the response to a second ribavirin treatment.     

Corticosteroid avoidance in adult kidney transplant recipients under rabbit anti‐T‐lymphocyte globulin,mycophenolate mofetil and delayed cyclosporine microemulsion introduction

We conducted the first prospective, randomized, open‐label multicenter study in low‐immunologic risk adult recipients of primary cadaver kidney transplants receiving rabbit anti‐T‐lymphocyte globulin, mycophenolate mofetil, cyclosporine microemulsion introduced on day 5, with and without corticosteroids. Patients were randomly assigned according to age and cold ischemia time to receive corticosteroids for at least 6 months or no corticosteroids at all. The main efficacy evaluation criterion was acute rejection (including all treated episodes and those biopsy‐confirmed) during the first year following transplantation. For this purpose, this report includes the actual results of the whole 12‐month follow‐up of all randomized patients. For efficacy analysis, 98 patients were evaluated in the Steroid avoidance group and 99 in the Steroid maintenance group. Taken as a whole, 81% of the patients (n = 159) never received anti‐rejection treatment. From the 38 patients who received anti‐rejection treatment, 25 (25.5%) were in the Steroid avoidance group and 13 (13.1%) in the Steroid maintenance group (P < 0.031), experiencing respectively 17 (17.3%) and 7 (7.1%) biopsy‐proven first episodes of acute rejection (P < 0.031). Borderline changes (6 vs. 3) were not considered as biopsy‐proven acute rejections. Onset of first rejection was significantly shorter in the Steroid avoidance group (P < 0.027). First‐line anti‐rejection treatment response, need for any rescue therapy, as well as histologic severity of rejection episodes did not statistically differ between the groups. One‐year post‐transplantation analysis showed no differences in delayed graft function, serum creatinine, creatinine clearance, 24‐h proteinuria, as well as serious adverse events between the groups. De novo diabetes (P < 0.07) or dyslipidemia (P < 0.01) as well as newly diagnosed malignancies (P < 0.059) were however more frequently observed in the Steroid maintenance group. At the end of the first post‐transplant year, 99% of patients in the Steroid avoidance group and 97% of patients in the Steroid maintenance group were respectively alive (P = 0.34), with respectively 95% and 93.2% of functioning kidney grafts (P = 0.62). Our results showed that total avoidance of corticosteroids from the day of transplantation was associated with a significantly increased number of clinically diagnosed and treated, and biopsy‐proven acute rejections during the first year of transplantation. Nevertheless, overall outcome, 1‐year patient and graft survival as well as renal function were similar, and the patients in the Steroid avoidance group exhibited a lower incidence of de novo dyslipidemia, diabetes mellitus and malignancies often associated with steroid treatment (Clinical Trials.gov NCT00200551).     

Impact of very early high doses of recombinant erythropoietin on anemia and allograft function in de novo kidney‐transplant patients

After kidney transplantation, occurrence of anemia in the early post‐transplant period (<1 month) is high and arises out of issues that are multifactorial. We performed a retrospective single‐center study to assess whether delivery of high doses of erythropoietin‐stimulating agents (ESA) within the first week of kidney transplantation, translates at 1 month post‐transplant, in to causing less anemia and whether it has an impact on allograft function. Ninety‐nine patients were not given ESA (group I), whereas 82 were (250 IU/kg/week; group II). All patients had similar pretransplant and baseline (day 0) variables. Similar numbers of group II patients were still receiving ESA by day 14 (97.5%) and day 30 (89%). Respective figures for group I were 27% and 27%. Independent factors for anemia at 1 month post‐transplant included: being male subject, treatment for hypertension at pretransplant, anemia at transplant, a higher mean corpuscular volume at transplant, and an induction therapy using antithymocyte globulins. Independent predictive factors for lower creatinine clearance included being female subjects, having a donor aged >50 years, being a recipient aged >50 years, not treated for hypertension at pretransplant, and no post‐transplant ESA therapy. High doses of ESA within the first month of kidney transplantation have no impact on anemia or renal function by 1 month post‐transplant.     

No evidence of occult hepatitis C virus (HCV) infection in serum of HCV antibody‐positive HCV RNA‐negative kidney‐transplant patients

Persistence of hepatitis C virus (HCV) in patients who cleared HCV is still debated. Occult HCV infection is described as the presence of detectable HCV RNA in liver or peripheral blood mononuclear cells (PBMCs) of patients with undetectable plasma HCV‐RNA by conventional PCR assays. We have assessed the persistence of HCV in 26 kidney‐transplant patients, followed up for 10.5 years (range 2–16), after HCV elimination while on hemodialysis. If HCV really did persist, arising out of the loss of immune control caused by institution of the regimen of immunosuppressive drugs after kidney transplantation, HCV reactivation would have taken place. Their immunosuppression relied on calcineurin inhibitors (100%), and/or steroids (62%), and/or antimetabolites (94%). An induction therapy, given to 22 patients, relied on rabbit antithymocyte globulin (59%) or anti‐IL2‐receptor blockers (32%). All patients had undetectable HCV RNA as ascertained by several conventional tests. At the last follow‐up, no residual HCV RNA was detected in the five liver biopsies, the 26 plasma, and in the 37 nonstimulated and 24 stimulated PBMCs tested with an ultrasensitive RT‐PCR assay (detection limit, 2 IU/ml). No biochemical or virologic relapse was seen during follow‐up. The absence of HCV relapse in formerly HCV‐infected immunocompromised patients suggests the complete eradication of HCV after its elimination while on dialysis.