Hepatitis: Kamar N

Péron JM, Mansuy JM, Vinel JP, Kamar N. · Service d'hépato-gastroentérologie, fédération digestive, hôpital Purpan, CHU de Toulouse, place du Dr-Baylac, TSA 40031, 31059 Toulouse cedex 9, France. · Gastroenterol Clin Biol. · Pubmed #19481395 No free full text.

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Kamar N, Nicot F, Izopet J, Rostaing L. · No affiliation provided · Am J Kidney Dis. · Pubmed #19324484 No free full text.

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Kamar N, Izopet J, Rostaing L. · No affiliation provided · Nephrol Ther. · Pubmed #18272445 No free full text.

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Kamar N, Izopet J, Alric L, Guilbeaud-Frugier C, Rostaing L. · Department of Nephrology, CHU Rangueil,Toulouse University Hospital, Toulouse, France. · Clin Nephrol. · Pubmed #18397713 No free full text.

Abstract: Hepatitis C virus (HCV)-infection leads to chronic liver disease, but also to extra-hepatic manifestations, including kidney disease. We provide an overview of HCV-related kidney diseases in non-transplanted and in kidney transplant patients, and their therapies. Membranoproliferative glomerulonephritis, associated with Type 2 cryoglobulinemia, is the predominant Type of HCV-related glomerulonephritis. Membranous glomerulonephritis and focal segmental glomerular sclerosis are less commonly described. HCV infection seems to be linked to Type 2 diabetes mellitus, and might alter the progression of diabetic-related nephropathy. Patients infected by HCV should be annually screened for markers of kidney disease and, similarly, patients with membranoproliferative or membranous glomerulonephritis should be screened for HCV infection. After transplantation, cryoglobulinemia is frequent and is associated with HCV markers. HCV-related kidney disease requires specific treatment. In non-kidney-transplant patients, treatment relies on either only anti-HCV therapy in cases of moderate renal disease, or combined anti-viral and immunosuppressive therapies in cases of severe renal disease, i.e., nephrotic syndrome and/or progressive renal failure, and in diseases that are refractory to anti-HCV therapy. In kidney transplant patients, ribavirin monotherapy could be used cautiously, whereas rituximab might be a treatment of choice in the presence of cryoglobulinemia. In liver-transplant patients, in addition to anti-HCV therapy, rituximab might be also used.

Camara B, Kamar N, Bonafe JL, Danjoux M, Suc B, Rostaing L. · Service de Néphrologie, Dialyse et Transplantation, CHU de Rangueil, 1, avenue Jean-Poulhès, TSA 50032, 31059 Toulouse cedex 09, France. · Med Mal Infect. · Pubmed #17270378 No free full text.

Abstract: We report a case of secondary syphilis hepatitis in a liver-transplant patient. This homosexual male patient presented, 15 years after orthotopic liver transplantation, with non-squamous papulomacular rash, mild cytolysis, and anicteric cholestasis. Laboratory tests showed syphilis seroconversion with a venereal diseases research laboratory (VDRL) titer of 1/256, a Treponema pallidum hemaglutination assay (TPHA) of 1/5120, and a positive IgM fluorescent Treponemal antibody absorbance (FTA-abs). A liver biopsy performed 13 months after the diagnosis showed low-grade hepatitis with a Metavir score of A1F1; it also showed non-specific portal moderate inflammation consisting primarily of neutrophils, with no evidence of cholestasis. He was given benzathine-penicillin at 2,400,000 IU with a transient increase in prednisolone doses. Cytolysis rapidly, and cholestasis progressively disappeared. IgM FTA-abs became negative, whereas VDRL and TPHA titers decreased slightly over time.

Kamar N, Ribes D, Izopet J, Rostaing L. · Multiorgan Transplant Unit, CHU Rangueil, Toulouse, France. · Transplantation. · Pubmed #17038897 No free full text.

Abstract: Patient survival is significantly lower in hepatitis C virus (HCV)-positive compared to HCV-negative dialysis patients. After renal transplantation, immunosuppressive therapy can result in an increased burden of HCV viremia. Both patient and graft survivals are lower in HCV-positive compared to matched HCV-negative renal-transplant patients. Therefore, it is important to treat HCV infection. At present, after renal transplantation, there is no current safe and efficient therapy. Alpha-interferon (alpha-IFN) does not give a sustained virological response, and is associated with a high rate of renal failure. Ribavirin and amantadine monotherapies are associated with a significant improvement in liver enzymes, but have no impact upon HCV viremia. Ribavirin, however, may be indicated in cases of HCV-related glomerulopathy because it can significantly decrease proteinuria. The combined use of alpha-IFN and ribavirin should only be given to those patients who have developed posttransplant fibrosing cholestatic hepatitis. Therefore, HCV infection needs to be treated pretransplant. In dialysis patients, the only recommended therapy, as yet, is alpha-IFN monotherapy. Pegylated alpha-IFN is under evaluation and ribavirin is contraindicated because it results in severe hemolytic anemia. Twelve months of alpha-IFN therapy results in sustained virological clearance in approximately 40% of patients, regardless of their genotype. HCV RNA, after three months of alpha-IFN therapy, is a predictive factor for a long-term sustained response. Finally, when HCV-positive dialysis patients with a sustained virological response undergo successful renal transplantation, very few suffer a virological relapse, thus emphasizing that these patients were cured.

Kamar N, Rostaing L, Alric L. · Department of Nephrology, Dialysis, and Multiorgan Transplantation, CHU Rangueil, Toulouse University Hospital, Toulouse, France. · Kidney Int. · Pubmed #16514428 No free full text.

Abstract: Membranoproliferative glomerulonephritis (MPGN) associated with type II cryoglobulinemia is the predominant type of hepatitis C virus (HCV)-related glomerulonephritis. The blockade of the renin-angiotensin system, as well as a combined anti-HCV therapy that associates standard or pegylated alpha-interferon with ribavirin, are mandatory in all patients experiencing an HCV-related glomerulonephritis. In patients with nephrotic-range proteinuria and/or progressive renal failure, immunosuppressive therapy is necessary. Rituximab, the monoclonal anti-CD20 antibody that selectively targets the B cells, seems to be as least as efficient as cyclophosphamide. Because it is also better tolerated, it should be preferred to cyclophosphamide. During the acute phase, plasmapheresis and steroid pulses can be used. However, future prospective, controlled, and randomized studies are still required to establish evidence-based guidelines to treat HCV-related glomerulopathies.

Kamar N, Rostaing L, Alric L. · Service de Néphrologie, Hémodialyse et Transplantation d'Organes, Fédération Digestive, CHU Toulouse-Purpan, TSA 40031, 31059 Toulouse Cedex 9. · Gastroenterol Clin Biol. · Pubmed #15060455 No free full text.

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Kamar N, Izopet J, Ribes D, Rostaing L. · Service de néphrologie, dialyse et transplantation, CHU Toulouse-Rangueil. · Nephrologie. · Pubmed #15022868 No free full text.

Abstract: Chronic hepatitis C virus (HCV) infection is the first cause of liver disease after renal transplantation. The prevalence of HCV infection in dialysis and in renal-transplant patients remains high. Mortality of HCV-positive renal-transplant patients is higher than that of HCV-negative ones. Liver disease and sepsis seem to be the main causes of death. Graft survival is also lower in HCV-positive renal-transplant patients. This seems to be due in part to the occurrence of de novo glomerulopathy. The effect of HCV infection upon liver fibrosis in renal-transplant patients receiving immunosuppressive treatment remains controversial. To date, there is no efficient treatment of HCV infection after renal transplantation. Consequently, it is mandatory to treat by alpha-interferon all HCV-positive/RNA-positive dialysis patients waiting for renal transplantation.

Kamar N, Izopet J, Rostaing L. · Service de néphrologie, dialyse et transplantation, CHU Toulouse-Rangueil, Toulouse. · Nephrologie. · Pubmed #12814060 No free full text.

Abstract: In France, the prevalence of hepatitis C virus (HCV) infection in chronic hemodialysis patients is high, about 15 to 42%. Although the incidence and the prevalence of HCV infection decreased during the last decade, de novo cases of HCV infection still occur in hemodialysis units. To date the nosocomial transmission is the principal cause of contamination. The strict application of universal precautions and the separation of chronic hemodialysis patients according to their virological status may decrease the incidence of HCV infection in hemodialysis units. The transaminase level and HCV viremia are lower in chronic hemodialysis patients than that in the general population. Liver disease seems also to be less aggressive. Chronic hemodialysis patients presenting acute hepatitis C infection and those waiting for renal transplantation have to be treated by interferon-alpha (IFN-alpha), since the virological response is elevated and sustained. In case of cirrhosis or severe liver disease, a combined liver-kidney transplantation can be proposed after IFN-alpha therapy. Finally, in chronic hemodialysis who are not candidate for renal transplantation IFN-alpha therapy can be discussed according the patients' age and general health status.

Kamar N, Guitard J, Ribes D, Esposito L, Rostaing L. · Department of Nephrology, Toulouse University Hospital, France. · Exp Clin Transplant. · Pubmed #19338488 links to  free full text

Abstract: OBJECTIVES: Darbepoetin alfa is used to treat renal anemia; however, little information is available concerning its use during the posttransplant period, especially in HCV-positive patients treated with ribavirin for active hepatitis C. MATERIALS AND METHODS: This study investigated the efficacy and safety of using darbepoetin alfa in this population during a 6-month treatment period. All anemic patients were HCV/RNA-positive, treated with ribavirin, and had impaired renal function. Patients (n=7) who had not been treated previously with recombinant human erythropoietin (rHuEPO) were placed in "group no rHuEPO." Patients previously with recombinant human erythropoietin (n=16; "group rHuEPO") were switched to darbepoetin alfa according to the European summary of product characteristics. RESULTS: Seventy-three percent of the patients were men. The mean creatinine clearance at baseline was 58.7 -/+ 21.5 mL/min. All patients received an immunosuppressive treatment. Although mean hemoglobin levels remained stable in group no rHuEPO and increased in group rHuEPO, the difference was not statistically significant. Also, the median darbepoetin-alfa-weighted dose in group no rHuEPO increased while it remained stable in group rHuEPO, as did the median daily dosage of ribavirin; however, these differences were not statistically significant. Creatinine levels and creatinine clearance levels remained stable throughout the study. No significant medical events related to the treatment were reported during the study. CONCLUSIONS: Darbepoetin alfa was found to be efficient and well tolerated in correcting renal anemia in transplant recipients treated with ribavirin for active hepatitis C.

Kamar N, Rostaing L, Sandres-Saune K, Ribes D, Durand D, Izopet J. · Department of Nephrology, Dialysis and Transplantation, CHU Toulouse-Rangueil, TSA 50032, 31059 Toulouse Cedex 9, France. · J Clin Virol. · Pubmed #15072764 No free full text.

Abstract: BACKGROUND: To date, there is no safe and efficient treatment of hepatitis C virus (HCV) infection after renal transplantation. Recently, there were encouraging reports after using amantadine in HCV-positive immunocompetent patients. OBJECTIVES: In an open pilot study, we evaluated the efficacy and the safety of amantadine monotherapy in 8 HCV positive renal-transplant patients with chronic active hepatitis and increased alanine aminotransferase (ALT) levels. RESULTS: After 6 months of amantadine therapy (200 mg per day), there were no decrease in HCV viremia (5.87 +/- 0.37 log copies/ml at M6 versus 5.71 +/- 0.5 log copies/ml at baseline; P > 0.05). However, we found a significant decrease in ALT activity (71 +/- 17 IU/l at M6 versus 100 +/- 9 IU/l at baseline; P = 0.04), whereas the decrease in aspartate aminotransferase activity did not reach statistical significance. There were no significant changes in liver histology. The clinical and biological tolerance was very good. Finally, there were a significant decrease in cyclosporine A whole blood trough levels during therapy. CONCLUSIONS: Our study is the first one to demonstrate that amantadine monotherapy lack of efficacy in HCV renal-transplant patients. It is able to improve liver enzymes but it has no impact neither upon HCV viremia nor upon liver histology.

Kamar N, Sandres-Saune K, Selves J, Ribes D, Cointault O, Durand D, Izopet J, Rostaing L. · Department of Nephrology, Dialysis, and Transplantation, CHU Rangueil, Toulouse, France. · Am J Kidney Dis. · Pubmed #12830471 No free full text.

Abstract: BACKGROUND: Long-term renal transplant (RT) recipient mortality and graft loss increase significantly in hepatitis C virus positive (HCV-[+]ve) patients. Treatment with alpha-interferon in this population is associated with a high rate of acute rejection. The aims of this study were the evaluation of the efficacy and the safety of ribavirin monotherapy in 16 HCV-(+) RT patients (group A) matched to 32 HCV-(+) RT patients (group B) who did not receive ribavirin. METHODS: Ribavirin was started at a daily dose of 1,000 mg and then adapted to hemoglobin level. The study was scheduled for 1 year. RESULTS: Ribavirin monotherapy was associated with a decrease in liver enzymes and serum creatinine levels. When proteinuria was present, this decreased or disappeared. There were no significant changes in HCV viremia. There was a significant progression in liver fibrosis with no improvement in inflammation scores. Hemoglobin levels fall dramatically, despite an important support by recombinant erythropoeitin (median, 20,000 IU/wk). In 3 cases, ribavirin therapy had to be stopped. In the control group, after 1 year of follow-up, there was a significant increase in serum alanine aminotransferase and creatinine values. Proteinuria decreased in only 2 of 12 patients (P = 0.03 as compared with group A). CONCLUSION: One year of ribavirin monotherapy seems to have, at best, no beneficial effect on liver histology, although it improves liver enzyme levels. Despite its efficiency to dramatically decrease proteinuria, its impact on renal function remains unknown.

Garrouste C, Hémery M, Boudat AM, Kamar N. · Department of Nephrology, Tarbes, University Hospital, CHU Rangueil, Toulouse, France. · Clin Nephrol. · Pubmed #19473620 No free full text.

Abstract: Fungi poisoning is quite frequent: in particular, Amanita phalloides has life-threatening toxicity. It is responsible for fulminant hepatitis, and also has renal toxicity. Herein, we report on a patient who developed acute renal failure after ingesting A. phalloides, which required definitive renal replacement therapy, despite rapid liver injury recovery. A kidney biopsy showed massive acute tubular necrosis, mainly in the proximal convoluted tubule, and mild interstitial infiltration by mononuclear cells.

Legrand-Abravanel F, Thevenet I, Mansuy JM, Saune K, Vischi F, Peron JM, Kamar N, Rostaing L, Izopet J. · Laboratoire de Virologie, Institut Fédératif de Biologie, TSA 40031, CHU Toulouse Purpan, Toulouse Cedex, France. · Clin Vaccine Immunol. · Pubmed #19321696 No free full text.

Abstract: We have evaluated three anti-hepatitis E virus (anti-HEV) immunoglobulin M (IgM) assays, the EIAgen HEV IgM assay (Adaltis), the HEV IgM enzyme-linked immunosorbent assay 3.0, and the Assure HEV IgM rapid test (MP Diagnostics), for the routine detection of acute genotype 3 HEV. Their sensitivities were fairly good (90%, 88%, and 82%), and their specificities were excellent (100%, 99.5%, and 100%).

Huyghe E, Kamar N, Wagner F, Capietto AH, El-Kahwaji L, Muscari F, Plante P, Rostaing L. · Department of Urology and Andrology, University Hospital, CHU Rangueil, 31059 Toulouse cedex 9, France. · J Sex Med. · Pubmed #19207273 No free full text.

Abstract: INTRODUCTION: In men, erectile dysfunction (ED) is an important issue. Data concerning ED in men with end-stage liver disease (ESLD) is limited, and the risk factors for ED in this population are still unknown. AIMS: To determine the prevalence, timescale, and risk factors for ED in ESLD patients candidates to liver transplantation. METHODS: Patients candidates for a liver transplantation were asked to participate in a mailed survey about sexual function. Among the 123 eligible men, 98 (84%) agreed to complete the questionnaire. MAIN OUTCOME MEASURES: The quality of erection was evaluated using the five-item International Index of Erectile Function (IIEF-5) score, and satisfaction for sexuality, using the patient-baseline Treatment-Satisfaction Scale (TSS) score. Other questions also focused on patient perception of changes over time. RESULTS: On the overall population, 28 patients (29%) were nonsexually active. Among the 70 patients who were sexually active, 52 patients (74%) had ED. Regarding the development of ED, 50% of the patients perceived that a deterioration of erectile function occurred within the six previous months. The absence of sexual activity was more frequent in hepatitis B or C patients (P = 0.02). The risk factors for ED were alcohol intake (P = 0.03), tobacco use (P = 0.03), and cardiovascular disease (P = 0.004). The significant risk factors for having a low TSS score were having viral hepatitis (P = 0.01), and cardiovascular disease (P = 0.01). CONCLUSION: Population of men with ESLD who are candidates for a liver transplantation is characterized by a high frequency of lack of sexual activity, and by a high prevalence of ED and should be targeted by interventions to improve sexual functioning. These preliminary data need further validation in prospective trial using more comprehensive questionnaires.

Kamar N, Huart A, Tack I, Alric L, Izopet J, Rostaing L. · Nephrology, Dialysis and Multiorgan Transplant Unit, CHU Rangueil, Toulouse, France. · Clin Nephrol. · Pubmed #19203548 No free full text.

Abstract: AIMS: The purpose of this study was to evaluate the renal side-effects of adefovir therapy in kidney-transplant (KT) recipients with chronic hepatitis B virus (HBV) infection, who have become resistant to lamivudine therapy. PATIENTS AND METHODS: 11 kidney-transplant (KT) patients (10 men, 1 woman, median age 54 (46 - 67) years) had lamivudine-resistant chronic HBV infection. With respect to HBV markers, all were HBs Ag-positive, 8 were HBe Ag-negative/HBe antibody- (Ab) positive, i.e. precore mutant, and 3 were HBe Ag-positive/HBe Ab-negative. They were all given adefovir at 10 mg/d (3 cases) or 5 mg/d (6 cases) or 2.5 mg/d (2 cases) according to creatinine clearance. RESULTS: Compared to baseline without adefovir therapy, at last follow-up, adefovir therapy was associated, at 1 and 2 years post therapy, with a significant decrease in aspartate (AST) (28 (17 - 53), 28 (10 - 79) vs. 58 (24 - 1,282) IU/l, p = 0.001), alanine (ALT) (38 (13 - 55), 36 (17 - 92) vs. 72 (31 - 1,594) IU/l, p = 0.0032] aminotransferase levels, and gammaGT (31 (14 - 51), 25 (14 - 196) vs. 44 (25 - 742) IU/l, p = 0.03). With respect to HBV DNA, when compared to baseline, there was a significant decrease at both years 1 and 2 post therapy (p = 0.01). With respect to KT function at 2 years after starting adefovir, there was a significant increase in serum creatinine from 125 (+/- 35) to 141 (+/- 32) micromol/l, (p = 0.02) and a significant increase in 24-h proteinuria. With respect to renal tubular parameters, as compared to baseline without adefovir therapy, one year after adefovir therapy was commenced there was a significant decrease in urinary pH from 6.6 (+0.6) to 5.65 (+/- 0.7); p = 0.03, a significant decrease in bicarbonaturia (from 0.33 +/- 0.7 to 0.1 +/- 0.3 mmol/h, p = 0.01), an increase in urinary excretion of H+ (1.79 (+/- 1.33) to 2.44 (+/- 1.18) mmol/l (p = 0.03)), a significant decrease in phosphatemia (0.82 +/- 0.19 vs. 0.65 +/- 0.13 mmol/l, p = 0.04) and a significant decrease in phosphaturia threshold, a significant decrease in tubular phosphorus reabsorption (75.5 +/- 9.4% vs. 61.8 +/- 16%, p = 0.05), and a significant increase in the phosphorus index of excretion (0.18 +/- 0.114 vs. 0.35 +/- 0.164, p = 0.01). CONCLUSION: We have demonstrated that low-dosage adefovir therapy in kidney-transplant patients is relatively safe as far as renal parameters are concerned, even though we observed a slight impairment of renal proximal-tubular function.

Alric L, Kamar N, Bonnet D, Danjoux M, Abravanel F, Lauwers-Cances V, Rostaing L. · Service de Médecine Interne, Fédération Digestive, CHU Purpan, Toulouse, France. · Transpl Int. · Pubmed #19196449 No free full text.

Abstract: To assess the accuracy of the noninvasive tools, fibrotest (FT) and liver stiffness measurement (LSM) for assessing liver fibrosis in kidney-transplant patients with chronic hepatitis virus B (HBV) or C (HCV) infection. Thirty-eight consecutive kidney-transplant patients with HCV (n = 26) or HBV (n = 12) underwent liver biopsies followed by a FT and LSM. Liver biopsies gave the following fibrosis-grade distribution using METAVIR scores: F0/F1, n = 10 (26.9%); F2, n = 14 (36.8%), F3, n = 7 (18.42%); F4, n = 7 (18.4%). The area under the receiver-operating characteristic curve for mild fibrosis stage <F2 was 0.69 (0.47-0.91) for the FT and 0.68 (0.45-0.90) for LSM; for severe fibrosis stage F3-F4, they were 0.55 (0.35-0.76) for the FT and 0.69 (0.50-0.87) for LSM. Eighty to 90% of patients with no significant liver fibrosis (<F2) were well-classified, with a cut-off value <0.5 for the FT and <7.1 kPa for LSM. Diagnosis of patients with severe liver fibrosis (F3/F4) by FT and LSM differed by 38.4% from the liver biopsy data. The FT and LSM are acceptably accurate for diagnosing mild liver fibrosis in kidney-transplant patients with chronic HCV or HBV infections, but their diagnostic value for predicting severe liver disease needs to be confirmed.

Legrand-Abravanel F, Mansuy JM, Dubois M, Kamar N, Peron JM, Rostaing L, Izopet J. · Institut National de la Santé et de la Recherche Médicale, Toulouse, France · Emerg Infect Dis. · Pubmed #19116067 links to  free full text

Abstract: We characterized 42 hepatitis E virus (HEV) genotype 3 strains from infected patients in France in 3 parts of the genome and sequenced the full-length HEV genotype 3f genome found in Europe. These strains are closely related to swine strains in Europe, which suggests zoonotic transmission of HEV in France.

Mansuy JM, Abravanel F, Miedouge M, Mengelle C, Merviel C, Dubois M, Kamar N, Rostaing L, Alric L, Moreau J, Peron JM, Izopet J. · CHU Toulouse, Hôpital Purpan, Laboratoire de virologie, Institut fédératif de biologie de Purpan, F-31300, France. · J Clin Virol. · Pubmed #18993112 No free full text.

Abstract: BACKGROUND: Hepatitis E was found in people living in industrialized countries who had not travelled to highly endemic areas. OBJECTIVES: To study the cases of acute hepatitis E confirmed thanks to viral genomic detection over a 5 years period in south-west France. STUDY DESIGN: 62 cases of hepatitis E were identified between 2003 and 2007. Their demographic, clinical, and virological features were analyzed. RESULTS: Cases of acute hepatitis E occurred regularly throughout this period. No seasonal variation was found. Patients, usually male (sex ratio=1.95), were adults living in both urban and rural areas. Sixty (96.8%) patients had not travelled abroad during the 6 months before diagnosis. Clinical manifestations ranged from asymptomatic infection to severe hepatitis. HEV was genotyped in 55 specimens. All the patients who had not travelled abroad were infected with genotype 3. CONCLUSION: The incidence of hepatitis E in south-west France was stable from 2003 to 2007, 96.8% of the cases were autochthonous. There was an age-related increase in the disease and patients tended to be men. The predominant genotype and subtype was 3f. However, contaminations pathways involved in hepatitis E in our area remain to clarify.

Garrouste C, Kamar N, Boulestin A, Esposito L, Lavayssiere L, Durand D, Blancher A, Rostaing L. · Nephrology, Dialysis, and Multiorgan Transplant Unit, University Hospital, CHU Rangueil, Toulouse, France. · Exp Clin Transplant. · Pubmed #18954294 links to  free full text

Abstract: OBJECTIVES: To examine the prevalence of cryoglobulinemia and autoimmune markers in stable liver transplant recipients and to determine risk factors and clinical impact. MATERIALS AND METHODS: Ninety-two liver transplant recipients were tested for cryoglobulinemia, hepatitis B and C, complement C3, complement C4, CH50, antinuclear antibodies, anticytoplasmic neutrophil antibodies, anticardiolipid antibodies, rheumatoid factors, and lymphocyte subpopulations. Liver, renal, and hematology tests were done. Immunosuppressive regimens were based on calcineurin inhibitors in 94.6% of the patients. RESULTS: Cryoglobulinemia was present in 18 patients (19.5%) with characteristics of type II in 27.7%, type III in 61.3%, and indeterminate in 11%. Cryoglobulinemia was present in 55.5% of patients with positive hepatitis C virus serology compared with 35.86% of patients with negative hepatitis C virus serology (P = .06). Among those with hepatitis C virus markers, cryoglobulinemia was present in 30%. Anticytoplasmic neutrophil antibodies were positive in 23% of the patients with cryoglobulinemia, but in only 5.4% of the patients without cryoglobulinemia (P = .006). Albuminemia was significantly lower in patients with cryoglobulinemia (38 -/+ 4.2 g/L) than it was in patients without cryoglobulinemia (40.2 -/+ 3.4; P = .05). Cryoglobulinemia was symptomatic in 4 patients (22.2% of all patients). Independent factors associated with cryoglobulinemia were presence of anticytoplasmic neutrophil antibodies, more than 4 HLA incompatibilities, alanine aminotransferase level of 0.68 microkat/L or more, and an albuminemia level greater than 38 g/L. CONCLUSIONS: Cryoglobulinemia is frequent after liver transplant and is symptomatic in approximately 20% of all patients.

Laporte F, Tap G, Jaafar A, Saune-Sandres K, Kamar N, Rostaing L, Izopet J. · Department of Virology, Federal Institute of Biology of Purpan, 330 Avenue de Grande Bretagne-TSA 40031, Toulouse Cedex 9, France. · Am J Infect Control. · Pubmed #18945513 No free full text.

Abstract: BACKGROUND: A deterministic mathematical model is developed to explain nontransfusion nosocomial transmission of hepatitis C virus (HCV) from patient to patient during hemodialysis sessions. METHODS: The model requires 4 sequential steps for cross-transmission: (1) The dialysis session contains at least 1 patient infected with HCV; (2) a hemodialysis staff member connects an uninfected patient to dialysis after having connected an infected patient; (3) the hemodialysis staff member does not change gloves between an infected patient and an uninfected patient; and (4) the uninfected patient is contaminated after exposure to the blood of an infected patient. RESULTS: We tested the model by comparing observed incidences of HCV infection from epidemiologic studies with calculated incidences. Calculated incidences are closed to observed incidences. We assessed the impact of prevalence of HCV infection, no glove change between patients, and nurse:patient ratio on the incidence of HCV infection. We found linear relationships between incidence and prevalence and between incidence and no glove change, and an increasing logarithmic relationship between incidence and nurse:patient ratio. CONCLUSION: Our model should be able to estimate the likely incidence of infection in hemodialysis centers. Compliance with recommended hand hygiene and glove use practices, especially glove changes between patients, is essential to prevent HCV infection in hemodialysis centers, particularly those with high HCV prevalence. Mathematical modeling can used as a tool for control.

Kamar N, Milioto O, Alric L, El Kahwaji L, Cointault O, Lavayssière L, Sauné K, Izopet J, Rostaing L. · Nephrology, Dialysis, and Multiorgan Transplant Unit, University Hospital, CHU Rangueil, 31059 Toulouse Cédex 9, France. · Transplantation. · Pubmed #18724232 No free full text.

Abstract: The aim of our study was to assess the efficacy and safety of entecavir in kidney- and liver-transplant recipients with chronic hepatitis B virus (HBV) infection. Ten male transplant patients with chronic HBV infection (eight kidney- and two liver-transplant patients), who have become adefovir (n=9) or lamivudine-resistant (n=1) were given entecavir at 0.5 to 1 mg/d. All patients were HBs Ag positive: six were HBe Ag(-)/HBe Ab(+), and four were HBe Ag(+)/HBe Ab(-). After a median follow-up of 16.5 months, entecavir therapy was associated with a significant decrease in HBV DNA viral load, that is, 3.86 (2.71-6.46) log10 copies/mL at baseline down to 2.94 (2.15-4) log10 copies/mL at last follow-up (P=0.004). Rate of HBV DNA clearance was 50% in both HBeAg(+) and HBeAg(-) patients. There were no significant changes in renal function or hematological parameters. This study demonstrates that entecavir therapy is safe and efficient in HBV(+) organ-transplant patients.

Kamar N, Mansuy JM, Cointault O, Selves J, Abravanel F, Danjoux M, Otal P, Esposito L, Durand D, Izopet J, Rostaing L. · Department of Nephrology, Dialysis and Multi-Organ Transplantation, and INSERM U858, IFR 31, CHU Rangueil, Toulouse, France. · Am J Transplant. · Pubmed #18557740 No free full text.

Abstract: Hepatitis E virus (HEV) infection was thought to be responsible for acute hepatitis that did not become chronic. However, we have recently reported that HEV infection can evolve to chronic hepatitis, at least in solid-organ transplant patients. We report on two cases of rapidly progressive of HEV-related cirrhosis that occurred in two organ-transplant patients. Case 1: A kidney-pancreas-transplant patient developed acute HEV hepatitis 60 months after transplantation, which evolved to chronicity as defined by persisting elevated liver-enzyme levels and positive serum HEV RNA. At 22 months after the acute phase, she presented with cirrhosis and portal hypertension, that is ascites and esophagus varices. Case 2: A kidney-transplant patient developed acute hepatitis 36 months after transplantation, which persisted and remained unexplained for 38 months. Then, HEV RNA was searched for in their serum and stools, and was found to be positive in both. Retrospective analysis of available stored serum, mainly the serum obtained at the acute phase, confirmed the diagnosis of chronic hepatitis E. In both cases, a liver biopsy showed cirrhosis. We conclude that HEV infection cannot only evolve to chronic hepatitis, but can also be responsible for rapidly progressing cirrhosis in organ-transplant patients.

Canivet C, Böhler T, Galvani S, Péron JM, Muscari F, Alric L, Barange K, Salvayre R, Negre-Salvayre A, Durand D, Suc B, Izopet J, Thomsen M, Rostaing L, Kamar N. · INSERM U858/I2MR, Equipe 10, CHU Rangueil, Toulouse, France. · Transpl Immunol. · Pubmed #18503886 No free full text.

Abstract: The incidence of acute rejection is significantly higher in hepatitis C virus (HCV) liver-transplant patients than in patients who have received a graft for other liver diseases, i.e., mainly alcoholic cirrhosis. The aim of this study was to assess T-cell function, i.e., intralymphocyte cytokine expression (IL-2 and TNF-alpha), T-cell activation [i.e., transferrin receptor (CD71) and interleukin (IL)-2 alpha-chain (CD25) expression], and T-cell proliferation using a flow-cytometry whole-blood assay in patients waiting for a liver transplantation (n=49). Our data suggest that, in mitogen-stimulated T-cells, (i) intra-lymphocyte cytokine expression is significantly higher in patients with liver disease than in healthy volunteers (n=25); (ii) the expression of T-cell activation markers is decreased in patients with liver cirrhosis compared to healthy volunteers, and (iii) the expression of T-cell activation markers and T-cell proliferation are increased in patients with HCV infection (n=15) compared to those without HCV infection (n=34), particularly compared to patients with alcoholic liver disease (n=19). Circulating CD19-positive cells count was also significantly higher in HCV-positive patients. In conclusion, in vitro, mitogen-stimulated T-cell seem to induce a higher immune response in the blood from patients waiting for a liver transplant for HCV-related liver disease than those without HCV infection, and particularly those with alcoholic liver disease.