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F Roudot-Thoraval

Publications and source records attributed to F Roudot-Thoraval.

At least 19 recordsLinked to original sources
PubMed2006

Renal allograft biopsies with borderline changes: predictive factors of clinical outcome.

The clinical outcome and appropriate management for patients showing 'borderline changes' on allograft biopsy after renal transplantation is still controversial. In an attempt to identify predictive factors of clinical outcome of patients with such lesions, we reviewed the clinical course of 91 patients with borderline changes. Multivariate analysis revealed significant and independent effects of histological stage (i + t < or = or > 2) and time to borderline changes (< or = or > 3 months after transplant) on serum creatinine levels at 1 year from borderline changes episodes (respectively, p = 0.04 and p = 0.02) and only a significant effect of time to borderline changes on serum creatinine levels at 2 years (p = 0.005). Renal function at 1 year and 2 years as 5- and 8-year graft survival were not significantly different in the group of patients treated with antirejection therapy (T group, n = 49) compared with the untreated group (UT group, n = 42). This study strongly suggests that borderline changes with histological score (i + t) > 2 and late episodes of borderline changes should be considered to be of poor prognosis.

Adult↗
PubMed2005

Changing of hepatitis C virus genotype patterns in France at the beginning of the third millenium: The GEMHEP GenoCII Study.

This cross-sectional study aimed to investigate, during a short period between 2000 and 2001, in a large population of patients with chronic hepatitis C, the epidemiological characteristics of hepatitis C virus (HCV) genotypes in France. Data from 26 referral centres, corresponding to 1769 patients with chronic hepatitis C were collected consecutively during a 6-month period. HCV genotyping in the 5'-non-coding region (NCR) was performed in each center using the line probe assay (LiPA, in 63% of cases), sequencing (25%) or primer-specific polymerase chain reaction (PCR) (12%). HCV genotypes 1a, 1b, 2, 3, 4, 5, non-subtyped 1 and mixed infection were found in 18, 27, 9, 21, 9, 3, 11 and 1% of our population, respectively. HCV genotype distribution was associated with gender, age, source and duration of infection, alanine aminotransferase (ALT) levels, cirrhosis, alcohol consumption, hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection. In multivariate analysis, only the source of infection was the independent factor significantly associated with genotype (P = 0.0001). In conclusion, this study shows a changing pattern of HCV genotypes in France, with i.v. drug abuse as the major risk factor, an increase of genotype 4, and to a lesser extent 1a and 5, and a decrease of genotypes 1b and 2. The modification of the HCV genotype pattern in France in the next 10 years may require new therapeutic strategies, and further survey studies.

Adult↗
PubMed2004

Different mechanisms of steatosis in hepatitis C virus genotypes 1 and 3 infections.

This study reports evidence that hepatocellular steatosis, a frequent histological feature of chronic hepatitis C, is principally metabolic in hepatitis C virus (HCV) genotype 1-infected patients, whereas it is principally virus-induced in HCV genotype 3-infected patients. Multivariate analysis of data on 176 patients with chronic hepatitis C revealed that the severity of steatosis was independently related to HCV RNA load alone in patients infected by HCV genotype 3, whereas it was independently related to the body mass index, daily alcohol intake and histological activity grade (but not viral load) in patients infected by HCV genotype 1. These findings suggest that steatosis is a cytopathic lesion induced by HCV genotype 3, whereas HCV genotype 1 is not steatogenic per se or at the usual in vivo expression levels.

Adult↗
PubMed2004

Clinical features of drusenoid pigment epithelial detachment in age related macular degeneration.

AIM: To analyse clinical features of drusenoid pigment epithelium detachment (PED) in age related macular degeneration. METHODS: 61 eyes of 32 patients with untreated drusenoid PED were followed for an average of 4.6 years (range 1-17 years). Drusenoid PED was defined as (1/2) disc diameter (DD) of confluent soft drusen under the centre of the macula. All patients underwent visual acuity measurement, biomicroscopic fundus examination, stereoscopic colour photograph, and fluorescein and indocyanine green angiography. Optical coherence tomography was performed in selected cases at the last examination. Kaplan Meier survival analysis was performed to estimate the probability of complications. RESULTS: Three different natural outcomes were identified: persistence of drusenoid PED (38%), development of geographic atrophy (49%), and choroidal neovascularisation (CNV) (13%). Based on Kaplan Meier survival analysis, drusenoid PED had a 50% of chance of developing geographic atrophy after 7 years. If the drusenoid PED was greater than 2 DD or was associated with metamorphopsia at initial presentation, progression to atrophy or ingrowth of CNV occurred after 2 years (p<0.01). Indocyanine green angiography confirmed fluorescein angiographic features or ascertained the presence of CNV when fluorescein angiography was equivocal. Optical coherence tomography was helpful in distinguishing coalescent soft drusen from drusenoid PED and disclosed the accumulation of sub or intraretinal fluid in eyes with CNV. CONCLUSION: Drusenoid PED size greater than 2 DD and metamorphopsia were risk factors identified at presentation which affected prognosis. The evaluation of the eyes at risk requires the use of all imaging means in order to ascertain the diagnosis of CNV. At long term (over 10 years), geographic atrophy and CNV had occurred in 75% and 25% respectively, with a poor visual outcome.

Aged↗
PubMed2004

Effect of antiviral treatment on evolution of liver steatosis in patients with chronic hepatitis C: indirect evidence of a role of hepatitis C virus genotype 3 in steatosis.

BACKGROUND AND AIM: Recent studies suggest that liver steatosis in chronic hepatitis C may be the expression of a direct cytopathic effect of hepatitis C virus (HCV), particularly in patients infected with genotype 3. To investigate this hypothesis, we studied the relationship between steatosis evolution and HCV clearance after antiviral treatment in patients with chronic hepatitis C and paired liver biopsies. METHODS: A total of 151 patients (37 with HCV genotype 3; 114 with HCV non-3 genotypes) were selected according to the following criteria: presence of steatosis at initial biopsy; no antiviral treatment prior to the first biopsy; antiviral treatment received between the two biopsies; body mass index (BMI) <28 kg/m(2); absence of excessive alcohol intake; no serum hepatitis B surface antigen or human immunodeficiency virus antibodies; and absence of diabetes mellitus. Evolution of steatosis was examined by comparing steatosis grades between the two biopsies. RESULTS: Twenty five patients (16.5%) were sustained virological responders (SVR) to antiviral treatment. Steatosis evolution after antiviral treatment was as follows: improvement in 36% of cases; stability in 51%; and worsening in 13%. Steatosis improvement was significantly more frequent in SVR than in non-responders (NR) (64% v 31%; p<0.004). This significant difference occurred in patients infected with genotype 3 (91% v 19%; p<0.0001) but not in those infected with non-3 genotypes (43% v 34%; NS). Among the 25 SVR, improvement in steatosis was significantly more frequent in patients infected with genotype 3 than in those infected with non-3 genotypes (91% v 43%; p<0.04) whereas in NR, improvement in steatosis did not differ between those infected with genotype 3 and non-3 genotypes (19% v 34%; NS). In multivariate analysis, four factors were independently associated with steatosis improvement: sustained virological response to antiviral therapy (odds ratio (OR) 6.06 (95% confidence interval (CI) 1.61-22.9); p = 0.01), severe steatosis (OR 5.50 (95% CI 1.54-19.6); p = 0.01), HCV genotype 3 (OR 2.90 (95% CI 0.85-10.0); p = 0.07), and BMI >25 kg/m(2) (OR 0.24 (95% CI 0.08-0.73); p = 0.02). CONCLUSIONS: Our results showed significant improvement in steatosis in patients infected with HCV genotype 3, who achieved sustained viral clearance. This provides further evidence for direct involvement of HCV genotype 3 in the pathogenesis of hepatic steatosis.

Adult↗
PubMed2003

[Observational study of splenectomized patients].

Nearly 4,000 splenectomies are currently performed per year, in France. Few is none about medical practices concerning anti-pneumoccocal immunization and prophylactic antibiotherapy in these patients. The risks of pneumococcal sepsis in splenectomized patients has not been recently reassessed. To address these issues, an observational study of patients undergoing splenectomy, with the enrollment of 600 to 800 patients per year on a 5-year period, is proposed.

Adult↗
PubMed2003

Impact of moderate alcohol consumption on histological activity and fibrosis in patients with chronic hepatitis C, and specific influence of steatosis: a prospective study.

AIM: To evaluate the effects of minimal to moderate alcohol consumption on the severity of histological lesions in patients with chronic hepatitis C. METHODS: Daily alcohol intake (none, 1-20, 21-30, 31-50 g/day) and histological activity and fibrosis were recorded in 260 patients with chronic hepatitis C. RESULTS: The proportion of patients with moderate (A2) or marked (A3) activity increased gradually from 53.8% in abstinent patients to 86.5% for an intake between 31 and 50 g/day (P = 0.003). In multivariate analysis, age > 40 years, alcohol intake between 31 and 50 g/day and moderate or severe steatosis were independently related to histological activity. The proportion of patients with moderate (F2) or marked (F3) fibrosis or cirrhosis (F4) gradually increased from 29.0% in abstinent patients to 67.6% for an intake between 31 and 50 g/day (P < 0.001). Multivariate analysis also showed that alcohol intake between 31 and 50 g/day, moderate or severe steatosis and histological activity were independently related to fibrosis. The deleterious effect of alcohol intake on histological lesions differed according to gender. CONCLUSIONS: This study demonstrates that both activity and fibrosis gradually increase according to the amount of alcohol ingested, and that even moderate alcohol consumption, as low as 31-50 g/day in men and 21-50 g/day in women, may aggravate histological lesions in patients with chronic hepatitis C.

Adult↗
PubMed2003

Impact of smoking on histological liver lesions in chronic hepatitis C.

AIMS AND METHODS: To examine the association between smoking and histological liver lesions in chronic hepatitis C, we studied 244 consecutive patients (152 men, 92 women; mean age 45.9 (12.6) years) with histologically proven chronic hepatitis C. Daily tobacco consumption during the six months preceding liver biopsy was recorded as the number of cigarettes smoked daily. Total lifetime tobacco consumption was recorded as the number of cigarette packs smoked per year (packs-years). Liver biopsy specimens were graded for histological activity and fibrosis according to the METAVIR scoring system. RESULTS: The proportion of patients with moderate (A2) or marked (A3) activity increased gradually from 62.0% in non-smokers to 81.7% in patients who smoked more than 15 cigarettes per day (p<0.009). A similar relationship was observed with total lifetime tobacco consumption: 59.0% of patients who had never smoked had grade A2 or A3 disease activity compared with 84.6% of patients who smoked more than 20 packs per year (p<0.002). Multivariate analysis showed that age over 50 years (odds ratio (OR) 5.4), alcohol intake exceeding 20 g/day (OR 2.75), and tobacco consumption of more than 15 cigarettes/day (OR 3.6) were independently related to the histological activity score. No relationship was found between the severity of fibrosis and either daily tobacco consumption or total lifetime tobacco consumption. Multivariate analysis showed that only age over 50 years (OR 8.8), daily alcohol intake exceeding 30 g/day (OR 3.4), and histological activity score (OR 7.9) were independently related to the fibrosis score. CONCLUSION: This study suggests that smoking, independent of alcohol, could aggravate the histological activity of chronic hepatitis C and that patients with chronic hepatitis C virus infection should be advised to reduce or stop smoking.

Adult↗
PubMed2003

Worsening of steatosis is an independent factor of fibrosis progression in untreated patients with chronic hepatitis C and paired liver biopsies.

BACKGROUND AND AIMS: Steatosis, a frequent histological finding in patients with chronic hepatitis C (CHC), has been suggested to influence liver fibrosis progression. The aim of the present study was to evaluate in patients with CHC and paired liver biopsies the relationship between the evolution of steatosis and that of fibrosis between the two biopsies. METHODS: Ninety six patients were selected according to the following criteria: absence of treatment; absence of cirrhosis at initial biopsy; and serum hepatitis B surface antigen and human immunodeficiency virus antibody negativity. Degrees of necroinflammatory activity, fibrosis, and steatosis grades were assessed in the two biopsies. In addition to histological lesions, parameters studied included the source of infection, duration of infection, body mass index, alcohol intake, alanine aminotransferase levels, hepatitis C virus genotype, and viral load. RESULTS: The mean interval between the two biopsies was 48 (32) months. Steatosis was found in 54% of patients at first biopsy, and was severe in 9%. Worsening of steatosis was observed in 34% of patients, stability in 50%, and improvement in 16%. Worsening of steatosis was significantly associated with hepatic fibrosis progression in patients with (p=0.03) or without (p<0.03) steatosis at diagnosis. Overall, fibrosis progression was observed in 31% of patients and stability in 69%. In a univariate analysis, fibrosis progression was associated with male sex (p=0.05), worsening of histological activity (p=0.04), and worsening of steatosis (p=0.0003). In a multivariate analysis, the only factor independently associated with fibrosis progression was worsening of steatosis (worsening v improvement/stability: odds ratio 4.7 (95% confidence interval 1.3-10.8); p=0.0001). CONCLUSIONS: Our results suggest that in untreated patients with CHC and serial liver biopsies, fibrosis progression is strongly associated with worsening of steatosis.

Adult↗
PubMed2002

Treatment of severe immune thrombocytopenia associated with systemic lupus erythematosus: 59 cases.

OBJECTIVE: To evaluate the response to treatment in a large cohort of patients with systemic lupus erythematosus (SLE) associated with autoimmune thrombocytopenia. METHODS: Response to treatment was assessed retrospectively in 59 patients with SLE, either definite (n = 44) or incomplete (n = 15), associated with frank autoimmune thrombocytopenia (defined as platelet count < 50 x 10(9)/l). Response to treatment was classified as complete (CR: platelet count > 150 x 10(9)/l), partial (PR: platelet count > 50 x 10/l), or failure (FR) in the other cases. RESULTS: Oral prednisone alone was used in 50 of the 59 patients (mean initial dose 1 mg/kg body weight/day). A response was obtained in 80% of cases (CR in 28. PR in 12) but only 11 (22%) had a sustained response (CR, n = 7; PR, n = 4). In contrast, combined treatment with prednisone and either danazol (n = 18) or hydroxychloroquine (n = 11) resulted in 50% (7 CR, 2 PR) and 64% (4 CR, 3 PR) longterm responses, respectively, allowing prednisone to be withdrawn or the dose tapered below 0.2 mg/kg body weight/day. High dose methylprednisolone pulses (n = 10) and intravenous immunoglobulin (IVIG) (n = 31) resulted in positive responses in 60% (4 CR, 2 PR) and 65% (12 CR, 8 PR) of cases, respectively, but the response was transient in each case. Splenectomy (n = 17) resulted in 65% longterm responses (10 CR, 1 PR). Only 2 longterm partial responses were obtained with the 22 immunosuppressant-containing regimens administered to 14 patients. At the end of the study. a response was observed in 52 (88%) patients [CR: 36 (61%), PR: 16 (27%)], mainly as a result of splenectomy or combined treatment with prednisone and either danazol or hydroxychloroquine. CONCLUSION: Longterm remission was obtained in the majority of patients. The major treatments inducing remission were splenectomy and prednisone combined with danazol or hydroxychloroquine.

Adolescent↗
PubMed2001

The nonexpression of CD36 on reticulocytes and mature red blood cells does not modify the clinical course of patients with sickle cell anemia.

It is thought that an increase in the adhesion of circulating reticulocytes to the vascular endothelium may initiate the vascular occlusion underlying the painful crises and organ failures typical of sickle cell disease (SCD). At least 2 receptors, usually present on reticulocytes, seem to be involved in this adhesion process: glycoprotein CD36 (glycoprotein IV) and integrin alpha(4)beta(1) (very late activation antigen--4). Recently, a high frequency of the platelet CD36--deficient phenotype was reported in black Africans. The frequency of this deficiency was similar in subjects with and without SCD. The role of CD36 in vaso-occlusion was then investigated by comparing the clinical course in 2 groups of black Africans homozygous for hemoglobin S, with and without CD36 deficiency, but similar in age, sex, geographical origin, number of alpha-globin genes, and beta-globin gene haplotype. Flow cytometry showed that CD36 was absent from the circulating red blood cells and reticulocytes of platelet CD36--deficient individuals but present on those from patients with normal platelet CD36 expression, and that alpha(4)beta(1) integrin levels were similar on the reticulocytes of the 2 groups. Neither clinical severity, as evaluated by the frequency and characteristics of vaso-occlusive events, nor biological data differed significantly in the 2 groups of patients. Finally, although CD36 has been suggested to play a critical role in the pathogenesis of vaso-occlusion, this study, despite including only a small number of patients, supports the idea that the modulation of expression of a single type of adhesion molecule is insufficient to counteract the pathological process leading to vaso-occlusion in SCD patients. (Blood. 2001;98:966-971)

Adolescent↗
PubMed2001

Predictive factors of post-discharge follow-up care among adolescent suicide attempters.

OBJECTIVE: To study short-term compliance with follow-up care in a sample of adolescent suicide attempters. METHOD: One hundred and sixty-seven adolescents, aged from 13-18 years and hospitalized after a suicide attempt, completed a questionnaire that included the CES-Depression Scale and Zung Anxiety Scale. Physicians assessed the hospital care immediately after the attempt, and post-discharge care plans. Three months later, adolescents were contacted by telephone and asked about follow-up care. RESULTS: After 3 months, 91.6% of the adolescents could be contacted: 25.5% never attended any follow-up; 11.1% went only once; 31.4% missed some appointments; and 32.0% went to all their scheduled appointments. Adolescents who complied with follow-up care differed significantly from those who did not: they showed more depression, anxiety and illicit drug use at the time of the attempt; they had more often planned the attempt; they were hospitalized longer; and they met with a psychiatrist more often while hospitalized. Compliance was also better when the follow-up appointment was scheduled before discharge. CONCLUSION: Compliance with post-discharge follow-up care depends upon the adolescent's psychopathology but may also be improved by the type of hospital care and post-discharge plans.

Adolescent↗
PubMed2001

Seroprevalence of human herpes virus 8 antibody in populations at high or low risk of transfusion, graft, or sexual transmission of viruses.

BACKGROUND: The routes of transmission of human herpes virus 8 (HHV-8) remain unclear. In particular, HHV-8 transmission by blood components and organ transplantation is still debated and raises public health issues. The objective of this study was to determine the prevalence of anti-HHV-8 in selected populations of persons or patients with or without risk factors for the transmission of viral infections, in order to determine the routes of HHV-8 transmission. STUDY DESIGN AND METHODS: A total of 1431 persons or patients at low or high risk of sexually, blood-, or graft-transmitted viral infections were tested by means of a standardized immunofluorescence serologic assay detecting anti-HHV-8. RESULTS: The persons or patients could be classified into three distinct groups according to anti-HHV-8 prevalence: a low prevalence group (0.0% to 5.0%), including healthy blood donors, healthy pregnant women, multiply transfused patients with thalassemia major, and IV drug users; an intermediate prevalence group (5.0% to 20.0%), including organ donors, kidney transplant recipients, and multiply transfused patients with sickle cell disease; a high prevalence group (>20.0%), including HIV-negative persons at high risk of sexually-transmitted viral infections, and HIV-infected homosexual men and heterosexuals. CONCLUSION: The sexual route appears to be the main route of HHV-8 transmission; bloodborne transmission of HHV-8, if it exists, is rare. In contrast, organ transplantation recipients might be exposed to HHV-8 transmission by the transplanted organ, which raises the issue of systematic screening of organ donors.

Adult↗
PubMed2001

Abnormal central complex is a marker of severity in the presence of partial ciliary defect.

BACKGROUND: Ciliary ultrastructural defects with total lack of dynein arms (DA) cause abnormal mucociliary function leading to the chronic infections observed in primary ciliary dyskinesia. The role of partial ciliary ultrastructural defects, especially those involving the central complex, and their relationship with respiratory symptoms have been less thoroughly investigated. OBJECTIVE: In a pediatric population with partial ciliary defects, we determined the relationship(s) between ultrastructural findings, ciliary motility, and clinical and functional features, and evaluated the outcome of this population. DESIGN: We analyzed the clinical presentation and pulmonary function of 43 children with chronic bronchitis and partial ultrastructural defects (from 15% to 90%) of their respiratory cilia demonstrated on bronchial biopsies. The study population was divided into 3 groups according to ciliary ultrastructure: the main ultrastructural defect concerned the central complex in 23 patients (CC group), peripheral microtubules in 8 patients (PMT group), and DA in 12 patients (DA group). RESULTS: The percentage of ciliary defects was lower in the PMT group than in the CC and DA groups. Patients in the PMT group had less severe disease with frequent normal ciliary motility. Patients in the CC group had initially a higher incidence of respiratory tract infections, extensive bronchiectasis frequently requiring surgery, and arguments in favor of a congenital origin (high proportion of sibling form). Partial absence of DA, although of congenital origin, was associated with a good prognosis. In all groups, follow-up showed that the functional prognosis remained good with appropriate treatment. CONCLUSIONS: In children with chronic respiratory infections, presence of situs inversus, sibling form, obstructive pulmonary syndrome, or bronchiectasis required ultrastructural analysis, regardless of ciliary motility. Detection of CC abnormalities is a marker of severity and required intensive therapy and close follow-up.

Adolescent↗
PubMed2001

[Evaluation of the quality drug prescription for patients to be discharged from a university teaching hospital: statutory aspects].

The aim of this work was to assess the quality of written drug prescriptions for patients to be discharged from our hospital. The pharmacological pertinence was not evaluated. Each statutory mention was noted according to a binary system: 1=mention present, 0=mention not present. The total note after analysis of 308 drug prescriptions was 7.3 +/- 1.3 (3.3-10) for a 3.1 +/- 1.0 (1-10) for each prescription. Concerning the "physician" note, the average was 8.1 +/- 1.8. Nevertheless, the function and the name were quite ofently omitted (1/2 and 1/3 respectively). The lowest note was obtained for mentions relating to the patient [5.8 +/- 2.0 (0-10)]. The age and the name were omitted (9/10 and 1/10 respectively). The "drug" note was closed to total note and represented 7.5 +/- 1.8 (2-10). The detailed analysis showed that 1.8% of drug prescriptions presented an illegible drug name. The dosage form was not specified (1/2), the galenic form (1/3), the schedule (1/3) and the posology (1/5). These omissions did not have any serious repercussion as they were rectified in futher control steps. Nevertheless, educational and corrective measures could be aimed to improve the drug prescription.

Documentation↗
PubMed2001

[Hepavir, the first observational study of one cohort of patients treated with alpha-2a interferon, monotherapy. Evaluation of asthenia and its social consequences].

OBJECTIVES: The aim of this observational study in patients with chronic hepatitis C and treated with interferon alpha-2a was to assess 1) monitoring in everyday practice, 2) the acceptability of treatment and 3) the intensity of fatigue. METHODS: Three hundred and fifty four patients were enrolled by physicians in both teaching and general hospitals, or private practice. Before treatment, clinical, epidemiological, and virological data were collected as well as a self-evaluation of fatigue using a visual analogic scale. Clinical follow-up was assessed every 3 months during treatment and 6 months after the end of treatment and included an evaluation of fatigue and the number of workdays missed due to sickness. RESULTS: Two hundred and nineteen men and 135 women, mean age 45 +/- 13, were included. The epidemiological, histological and virological features of this group were similar to those patients usually treated for chronic hepatitis C. Before treatment, the mean measurement of fatigue was 41 on a scale from 0 (perfect form) to 100 (exhausted). Fatigue was unrelated to age, source of infection, biological activity, or histological score. It worsened in patients who stopped interferon after 3 or 6 months, but was stable in patients who continued treatment for 12 months. Fatigue decreased after the end of treatment and was unrelated to treatment response. The need to stop work was strongly related to the intensity of fatigue and the number of workdays missed due to sickness represented nearly two months out of three in 25% of active patients during the first quarter and in 15% of patients thereafter. 61% of patients self-injected interferon (mainly previous drug users) whereas 30% of patients used nurse care throughout treatment. CONCLUSION: This study not only provides a realistic evaluation of fatigue in patients with chronic hepatitis C, before, during and after treatment, but also highlights its social and economic consequences. It shows the need for further cost-effectiveness studies on new therapeutic strategies using combined treatments.

Absenteeism↗
PubMed2000

Identification of MEFV-independent modifying genetic factors for familial Mediterranean fever.

Familial Mediterranean fever (FMF) is a recessively inherited disorder predisposing to renal amyloidosis and associated with mutations in MEFV, a gene encoding a protein of unknown function. Differences in clinical expression have been attributed to MEFV-allelic heterogeneity, with the M694V/M694V genotype associated with a high prevalence of renal amyloidosis. However, the variable risk for patients with identical MEFV mutations to develop this severe complication, prevented by lifelong administration of colchicine, strongly suggests a role for other genetic and/or environmental factors. To overcome the well-known difficulties in the identification of modifying genetic factors, we investigated a relatively homogeneous population sample consisting of 137 Armenian patients with FMF from 127 independent families living in Armenia. We selected the SAA1, SAA2, and APOE genes-encoding serum amyloid proteins and apolipoprotein E, respectively-as well as the patients' sex, as candidate modifiers for renal amyloidosis. A stepwise logistic-regression analysis showed that the SAA1alpha/alpha genotype was associated with a sevenfold increased risk for renal amyloidosis, compared with other SAA1 genotypes (odds ratio [OR] 6. 9; 95% confidence interval [CI] 2.5-19.0). This association, which was present whatever the MEFV genotype, was extremely marked in patients homozygous for M694V (11/11). The risk for male patients of developing renal amyloidosis was fourfold higher than that for female patients (OR=4.0; 95% CI=1.5-10.8). This association, particularly marked in patients who were not homozygous for M694V (34.0% vs. 11.6%), was independent of SAA1-allelic variations. Polymorphisms in the SAA2 or APOE gene did not appear to influence susceptibility to renal amyloidosis. Overall, these data, which provide new insights into the pathophysiology of FMF, demonstrate that susceptibility to renal amyloidosis in this Mendelian disorder is influenced by at least two MEFV-independent factors of genetic origin-SAA1 and sex-that act independently of each other.

Adolescent↗