Louis d'Alteroche

Centre Hospitalier Universitaire de Tours, Tours, Centre, France

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Publications (43)143.38 Total impact

  • [show abstract] [hide abstract]
    ABSTRACT: There is no established therapy for hepatitis E virus (HEV) infection. The aim of this retrospective, multicenter case series was to assess the effects of ribavirin as monotherapy for solid-organ transplant recipients with prolonged HEV viremia. We examined the records of 59 patients who had received a solid-organ transplant (37 kidney-transplant recipients, 10 liver-transplant recipients, 5 heart-transplant recipients, 5 kidney and pancreas-transplant recipients, and 2 lung-transplant recipients). Ribavirin therapy was initiated a median of 9 months (range, 1 to 82) after the diagnosis of HEV infection at a median dose of 600 mg per day (range, 29 to 1200), which was equivalent to 8.1 mg per kilogram of body weight per day (range, 0.6 to 16.3). Patients received ribavirin for a median of 3 months (range, 1 to 18); 66% of the patients received ribavirin for 3 months or less. All the patients had HEV viremia when ribavirin was initiated (all 54 in whom genotyping was performed had HEV genotype 3). At the end of therapy, HEV clearance was observed in 95% of the patients. A recurrence of HEV replication occurred in 10 patients after ribavirin was stopped. A sustained virologic response, defined as an undetectable serum HEV RNA level at least 6 months after cessation of ribavirin therapy, occurred in 46 of the 59 patients (78%). A sustained virologic response was also observed in 4 patients who had a recurrence and were re-treated for a longer period. A higher lymphocyte count when ribavirin therapy was initiated was associated with a greater likelihood of a sustained virologic response. Anemia was the main identified side effect and required a reduction in ribavirin dose in 29% of the patients, the use of erythropoietin in 54%, and blood transfusions in 12%. This retrospective, multicenter study showed that ribavirin as monotherapy may be effective in the treatment of chronic HEV infection; a 3-month course seemed to be an appropriate duration of therapy for most patients.
    New England Journal of Medicine 03/2014; 370(12):1111-20. · 51.66 Impact Factor
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    ABSTRACT: With the growing role of transjugular intrahepatic portosystemic shunt (TIPS) in the management of portal hypertension complications, a number of women of childbearing age are now being treated with TIPS. However, if pregnancy is unusual in patients with cirrhosis, it can occur in the case of noncirrhotic portal hypertension. To our knowledge, there are no data on pregnancy safety after TIPS insertion. We report the first case of a patient with noncirrhotic portal hypertension treated by TIPS who had two successful pregnancies. She presented with HIV-associated obliterative portopathy with recurrent variceal bleeding treated by TIPS. Pregnancies occurred later and progressed normally without maternal or fetal morbidity. There was no effect on TIPS patency, but only a moderate increase in the flow velocity in the portal vein, the stent, and the hepatic artery. Thus, TIPS does not seem to impair progression of pregnancy.
    European journal of gastroenterology & hepatology 02/2014; · 1.66 Impact Factor
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    ABSTRACT: Hepatitis C remains a challenging public health problem worldwide. The identification of viral variants establishing de novo infections and definition of the phenotypic requirements for transmission would facilitate the design of preventive strategies. We explored the transmission of HCV variants in three cases of acute hepatitis following needlestick accidents. We used single-genome amplification of glycoprotein E1E2 gene sequences to map the genetic bottleneck upon transmission accurately. We found that infection was likely established by a single variant in two cases and six variants in the third case. Studies of donor samples showed that the transmitted variant E1E2 amino-acid sequences were identical or closely related to those of variants from the donor virus populations. The transmitted variants harbored a common signature site at position 394, within hyper variable region 1 of E2, together with additional signature amino acids specific to each transmission pair. Surprisingly, these E1E2 variants conferred no greater capacity for entry than the E1E2 derived from non transmitted variants, in lentiviral pseudoparticle assays. Mutants escaping the antibodies of donor sera did not predominate among the transmitted variants either. The fitness parameters affecting the selective outgrowth of HCV variants after transmission in an immunocompetant host may thus be more complex than suggested by mouse models. Human antibodies directed against HCV envelope effectively cross-neutralized the lentiviral particles bearing E1E2 derived from transmitted variants. These findings provide insight into the molecular mechanisms underlying HCV transmission and suggest that viral entry is a potential target for the prevention of HCV infection.
    Journal of Virology 10/2013; · 5.08 Impact Factor
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    ABSTRACT: Most clinical studies suggest that the prevalence and severity of liver steatosis are higher in patients infected with hepatitis C virus (HCV) genotype 3 than in patients infected with other genotypes. This may reflect the diversity and specific intrinsic properties of genotype 3 virus proteins. We analyzed the possible association of particular residues of the HCV core and NS5A proteins known to dysregulate lipid metabolism with steatosis severity in the livers of patients chronically infected with HCV. We used transmission electron microscopy to quantify liver steatosis precisely in a group of 27 patients, 12 of whom were infected with a genotype 3 virus, the other 15 being infected with viruses of other genotypes. We determined the area covered by lipid droplets in liver tissues and analyzed the diversity of the core and NS5A regions encoded by the viral variants circulating in these patients. The area covered by lipid droplets did not differ significantly between patients infected with genotype 3 viruses and those infected with other genotypes. The core and NS5A protein sequences of the viral variants circulating in patients with mild or severe steatosis were evenly distributed throughout the phylogenic trees established from all the collected sequences. Thus, individual host factors seem to play a much greater role than viral factors in the development of severe steatosis in patients chronically infected with HCV, including those infected with genotype 3 viruses.
    PLoS ONE 01/2012; 7(3):e33749. · 3.73 Impact Factor
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    ABSTRACT: Hepatitis E virus (HEV) is an emerging problem amongst transplant recipients. We report a patient with chronic HEV hepatitis after a heart transplant. The patient received a 3-month course of oral ribavirin (17 mg/kg/day). HEV RNA became undetectable in the serum after 1 month of treatment and remained undetectable in serum and stool samples until the last follow-up, 2 months after completion of ribavirin therapy. The values of liver function indicators returned to normal reference ranges. The main ribavirin-induced side effect was a significant but well-tolerated anemia. We confirmed that ribavirin may induce a sustained virologic response (4 months after ribavirin cessation) in heart transplant patients with chronic HEV infection. Liver cytolysis is rather common in patients after heart transplantation. Rapid evolution to liver fibrosis lesions and available anti-viral therapy highlight the need to look for HEV infection in heart transplant recipients with unexplained hepatitis.
    The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 07/2011; 30(7):841-3. · 3.54 Impact Factor
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    ABSTRACT: The epidemic history of HCV genotype 5a is poorly documented in France, where its prevalence is very low, except in a small central area, where it accounts for 14.2% of chronic hepatitis C cases. A Bayesian coalescent phylogenetic investigation based on the E1 envelope gene and a non-structural genomic segment (NS3/4) was carried out to trace the origin of this epidemic using a large sample of genotype 5a isolates collected throughout France. The dates of documented transmissions by blood transfusion were used to calibrate five nodes in the phylogeny. The results of the E1 gene analysis showed that the best-fitting population dynamic model was the expansion growth model under a relaxed molecular clock. The rate of nucleotide substitutions and time to the most recent common ancestors (tMRCA) of genotype 5a isolates were estimated. The divergence of all the French HCV genotype 5a strains included in this study was dated to 1939 [95% HPD: 1921-1956], and the tMRCA of isolates from central France was dated to 1954 [1942-1967], which is in agreement with epidemiological data. NS3/4 analysis provided similar estimates with strongly overlapping HPD values. Phylodynamic analyses give a plausible reconstruction of the evolutionary history of HCV genotype 5a in France, suggesting the concomitant roles of transfusion, iatrogenic route and intra-familial transmission in viral diffusion.
    Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 01/2011; 11(2):496-503. · 3.22 Impact Factor
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    ABSTRACT: Portal vein thromboses are frequent in cirrhotic patients and may be favoured by hypercoagulability in the splanchnic venous system. The coagulation balance and thrombin generation (TG) were evaluated in platelet-free plasma obtained from portal and systemic blood samples in 28 cirrhotic patients while undergoing transjugular intrahepatic porto-systemic shunt. TG assay (TGA) was performed with all samples from cirrhotic patients and with plasma samples from 14 healthy controls, with varying concentrations of tissue factor and phospholipids, with or without thrombomodulin. Screening tests and specific assays were also performed and activated partial thromboplastin time was shorter in portal plasma samples with higher FVIII and lower protein C levels, well correlated with Child-Pugh scores, and higher D-dimers and F1+2 levels However, all TGA parameters were similar in portal and jugular samples, possibly due in part to similar concentrations of factor II and antithrombin in these two sites of plasma sampling. TGA showed lower thrombin peaks and endogenous thrombin potential values in cirrhotic plasma compared to those of healthy controls. Importantly, a resistance to thrombomodulin that well correlated with factor VIII and PC levels, was evidenced in all samples from patients with cirrhosis, and was more significant in those from severely affected cases. This study therefore supports the existence of a relative hypercoagulability in the portal vein of cirrhotic patients that is likely due to protein C/S deficiency and to high FVIII levels.
    Thrombosis and Haemostasis 10/2010; 104(4):741-9. · 6.09 Impact Factor
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    ABSTRACT: We compared 5 non-specific and 2 specific blood tests for liver fibrosis in HCV/HIV co-infection. Four hundred and sixty-seven patients were included into derivation (n=183) or validation (n=284) populations. Within these populations, the diagnostic target, significant fibrosis (Metavir F > or = 2), was found in 66% and 72% of the patients, respectively. Two new fibrosis tests, FibroMeter HICV and HICV test, were constructed in the derivation population. Unadjusted AUROCs in the derivation population were: APRI: 0.716, Fib-4: 0.722, Fibrotest: 0.778, Hepascore: 0.779, FibroMeter: 0.783, HICV test: 0.822, FibroMeter HICV: 0.828. AUROCs adjusted on classification and distribution of fibrosis stages in a reference population showed similar values in both populations. FibroMeter, FibroMeter HICV and HICV test had the highest correct classification rates in F0/1 and F3/4 (which account for high predictive values): 77-79% vs. 70-72% in the other tests (p=0.002). Reliable individual diagnosis based on predictive values > or = 90% distinguished three test categories: poorly reliable: Fib-4 (2.4% of patients), APRI (8.9%); moderately reliable: Fibrotest (25.4%), FibroMeter (26.6%), Hepascore (30.2%); acceptably reliable: HICV test (40.2%), FibroMeter HICV (45.6%) (p<10(-3) between tests). FibroMeter HICV classified all patients into four reliable diagnosis intervals (< or =F1, F1+/-1, > or =F1, > or =F2) with an overall accuracy of 93% vs. 79% (p<10(-3)) for a binary diagnosis of significant fibrosis. Tests designed for HCV infections are less effective in HIV/HCV infections. A specific test, like FibroMeter HICV, was the most interesting test for diagnostic accuracy, correct classification profile, and a reliable diagnosis. With reliable diagnosis intervals, liver biopsy can therefore be avoided in all patients.
    Journal of Hepatology 08/2010; 53(2):238-44. · 9.86 Impact Factor
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    ABSTRACT: Many researchers consider portal thrombosis (PT) as a contraindication to transjugular intrahepatic portosystemic shunt (TIPS). The aim of this retrospective study was to compare the feasibility and long-term prognosis of TIPS in cirrhotic patients, with and without, complete PT. Four hundred and thirty-six consecutive cirrhotic patients with portal hypertension were referred for TIPS, between 1990 and 2004. These patients were divided into two groups according to their portal patency. PT+: 34 patients with complete PT with cavernoma (19) or without (15) cavernoma versus PT-: 402 patients with normal portal patency (308) and partial PT (94). Epidemiological data were compared using the chi and Student's t-tests, and comparative evolution was made from actuarial data using the log-rank test. PT+ patients were more frequently women with viral hepatitis, and TIPS was performed more often for bleeding indications. The TIPS success rate was significantly lower in the PT+ group (79%) than in the PT- group (99.5%) (P<10). Presence of a cavernoma decreased the success rate to 63%. TIPS was always feasible in cases of recent PT and portal cavernoma with an accessible intrahepatic patent portal branch. Early and late outcome and complications were not significantly different between the two groups. Complete PT does not modify TIPS' long-term outcome. Rather than a contraindication, PT should be considered as an indication for TIPS in cirrhotic patients with accessible intrahepatic portal vein. Further randomized studies should be planned in cirrhotic patients with recent PT to better qualify TIPS and anticoagulation indications, respectively.
    European journal of gastroenterology & hepatology 03/2010; 22(9):1093-8. · 1.66 Impact Factor
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    ABSTRACT: The hepatitis C virus genotype is considered to be the most important baseline predictor of a sustained virological response in patients with chronic hepatitis C treated with pegylated interferon and ribavirin. The influence of the subtype on the sustained virological response was investigated in patients infected with genotypes 1, 4, 5, or 6. This study was done on 597 patients with chronic hepatitis C who were given pegylated interferon and ribavirin for 48 weeks. The overall rate of sustained virological response in the 597 patients was 37.8%. Univariate analysis indicated that the sustained virological response of patients infected with subtype 1b (39%) tended to be higher than that of patients infected with subtype 1a (30.6%; P = 0.06) and it was similar to those patients infected with subtypes 4a (51.3%; P = 0.12) or 4d (51.7%; P = 0.16). Multivariate analysis indicated that five factors were independently associated with sustained virological response: the age (OR 0.97; 95% CI = 0.95-0.99), absence of cirrhosis (OR: 2.92; 95% CI = 1.7-5.0; P < 0.01), absence of HIV co-infection (OR: 2.08; 95% CI = 1.2-3.5; P < 0.01), low baseline plasma HCV RNA concentration (OR: 1.74; 95% CI = 1.2-2.6; P < 0.01), and the subtype 1b (OR: 1.61; 95% CI = 1.0-2.5; P = 0.04) or subtypes 4a and 4d (OR: 2.03; 95% CI = 1.1-3.8; P = 0.03). In conclusion, among difficult-to-treat genotypes, the subtype 1a is associated with a lower response to anti-HCV therapy than subtypes 1b, 4a, and 4d.
    Journal of Medical Virology 12/2009; 81(12):2029-35. · 2.37 Impact Factor
  • European Radiology 07/2009; · 3.55 Impact Factor
  • La Presse Médicale 06/2009; 38(7-8):1191-3. · 0.87 Impact Factor
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    Gastroentérologie Clinique et Biologique 05/2009; 33(5):390-1. · 1.14 Impact Factor
  • L d'Alteroche, J-M Perarnau, F Perrotin, Y Bacq
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    ABSTRACT: Pregnancy in patients with portal hypertension is rare but worrying for the clinician. Although the effects of portal hypertension during pregnancy have not been fully elucidated, there is an evident increase in morbidity, especially associated with cirrhosis, which justifies the idea of at-risk pregnancy and requires management by a multidisciplinary team. The prevention and treatment of gastrointestinal haemorrhage is quite similar to that in nonpregnant patients. Investigation and management of portal hypertension before and at the beginning of pregnancy can reduce the risks of foetal loss, restricted intra-uterine growth, premature birth and maternal mortality, which are closely related to gastrointestinal haemorrhage. The risks related to the underlying disease, such as liver failure with cirrhosis and thromboembolic risk with vascular diseases associated with thrombophilia must be taken into consideration. Generally, vaginal delivery with early analgesics for the mother assisted by an extraction device should be preferred to caesarean section, which must be reserved for obstetrical indications.
    Gastroentérologie Clinique et Biologique 06/2008; 32(5 Pt 1):541-6. · 1.14 Impact Factor
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    ABSTRACT: We report a case of a small cell carcinoma of the lung revealed by chronic intestinal pseudo-obstruction associated with achalasia of the lower esophageal sphincter. Tumoral remission was achieved for more than 21 months after chemoradiotherapy but this did not prevent the paraneoplasic syndrome from persisting and medical treatment was not successful in treating the intestinal pseudo-obstruction or the dysphagia, which was not improved by esophageal dilation.
    Gastroentérologie Clinique et Biologique 02/2008; 32(1 Pt. 1):56-8. · 1.14 Impact Factor
  • Gastroentérologie Clinique et Biologique 01/2008; 32(6-7):653-5. · 1.14 Impact Factor
  • Digestive Diseases and Sciences 12/2007; 52(11):3188-90. · 2.26 Impact Factor
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    ABSTRACT: We report a case of autoimmune thrombocytopenia associated with acute reverse seroconversion of hepatitis B in a patient who was initially hepatitis B virus surface antigen negative and hepatitis B virus surface antibody positive. Reactivation occurred 9 months after chemotherapy with anti-CD 20 monoclonal antibodies and autologous hematopoietic stem cell transplantation for lymphoma had been performed. After non specific polyglobulin injections and treatment with adefovir dipivoxil, thrombocytopenia and viral replication were controlled. Seroconversion for both HBe and HBs occurred at 5 months. Adefovir was stopped 4 months later with no relapse during fifteen months of follow-up. This case shows that patients who have had previous contact with hepatitis B virus should be monitored if they become immunosuppressed, even if anti-HBs were initially present.
    Gastroentérologie Clinique et Biologique 02/2007; 31(1):97-9. · 1.14 Impact Factor
  • Gastroentérologie Clinique et Biologique 04/2006; 30(3):492-3. · 1.14 Impact Factor
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    ABSTRACT: Ophthalmologic side effects have been reported during interferon therapy, particularly retinal lesions and neurovisual impairment. The aim of this prospective study was to assess the nature and the frequency of such lesions during alpha-interferon therapy for viral hepatitis. Between 1995 and 2003, 156 patients treated with standard or pegylated alpha-interferon, with or without ribavirin, had a regular ophthalmologic examination before and during treatment. No patient had signs of retinopathy before treatment. Cotton-wool spots were found in 31 patients and retinal hemorrhage in nine patients during treatment (24% of patients). These lesions remained asymptomatic and disappeared in all patients. A previous history of arterial hypertension (RR 4.60, 95% CI 1.95-10.85), age above 45 years (RR 2.80, 95% CI 1.36-5.85), and use of pegylated alpha-interferon (RR 2.75, 95% CI 1.41-5.38) were significantly associated with retinopathy. Neurovisual impairment was present in 31 patients (20%) before treatment and in 74 patients (47%) during treatment. In conclusion, this study showed that signs of retinopathy and neurovisual impairment were common in patients receiving alpha-interferon therapy but were rarely symptomatic. It suggests that alpha-interferon may usually be continued in asymptomatic patients as long as there is careful fundoscopic examination.
    Journal of Hepatology 02/2006; 44(1):56-61. · 9.86 Impact Factor