Hepatitis: Vidal E

Miró JM, Torre-Cisnero J, Moreno A, Tuset M, Quereda C, Laguno M, Vidal E, Rivero A, Gonzalez J, Lumbreras C, Iribarren JA, Fortún J, Rimola A, Rafecas A, Barril G, Crespo M, Colom J, Vilardell J, Salvador JA, Polo R, Garrido G, Chamorro L, Miranda B. · AIDS Study Group (GESIDA) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC). · Enferm Infecc Microbiol Clin. · Pubmed #15970168 links to  free full text

Abstract: Solid organ transplant may be the only therapeutic alternative in some HIV-infected patients. Experience in North America and Europe during the last five years shows that survival at three years after an organ transplant is similar to that observed in HIV-negative patients. The criteria agreed upon to select HIV patients for transplant are: no opportunistic infections (except tuberculosis, oesophageal candidiasis or P. jiroveci -previously carinii- pneumonia), CD4 lymphocyte count above 200 cells/.L (100 cells/.L in the case of liver transplant) and an HIV viral load which is undetectable or suppressible with antiretroviral therapy. Another criterion is a two-year abstinence from heroin and cocaine, although the patient may be in a methadone programme. The main problems in the post-transplant period are pharmacokinetic and pharmacodynamic interactions between antiretorivirals and immunosuppressors, rejection and the management of relapse of HCV infection, which is one of the main causes of post-liver transplant mortality. Up to now, experience with pegylated interferon and ribavirin is scarce in this population. The English version of the manuscript is available at http://www.gesidaseimc.com.

Liozon E, Loustaud V, Jauberteau MO, Jaccard A, Soria P, Bordessoule D, Julia A, Vidal E. · Service de médecine interne A, hôpital Dupuytren, CHU, 2, rue Martin-Luther-King, 87042 Limoges, France. · Rev Med Interne. · Pubmed #11586520 No free full text.

Abstract: OBJECTIVE: We report four cases of non-synchronous antiphospholipid syndrome (APS) and malignant lymphoma, which highlight the complex relationship that seems to exist between these illnesses. METHODS: In a retrospective study conducted in two departments (internal medicine and clinical hematology) of a university hospital, we collected all observations of patients with both APS and malignant lymphoma diagnosed throughout the past decade. RESULTS: An association of APS with malignant lymphoma was recorded in three female and one male patient, median age 42.5 years at the time of diagnosis of the first disease. In each case, the primary APS was diagnosed, with arterial thrombotic events in three cases and venous thrombotic events in one case. One patient had isolated IgG anticardiolipin antibody, whereas the others had a combination of IgG anticardiolipin antibody and lupus anticoagulant with or without IgG anti-beta 2 glycoprotein I antibody. One patient also had an acquired inhibitor to factor VIII:C and a chronic C virus hepatitis. The mean time apparently separating the two illnesses ranged from 18 months to 9 years, but in two cases the diagnosis of APS was delayed due to a progressive, atypical, neurological onset. In two instances, the APS took place at a distance from a cured malignant lymphoma (Hodgkin's disease and nodal large cell B-cell lymphoma), whilst in the others it preceded a B-cell lymphoma (nodal and cutaneous, small cells and primary hepatic, large cells). Treatment resulted in complete haematological response in both cases, with disappearance of anticardiolipin antibody and lupus anticoagulant in the latter following a double autologous peripheral blood stem cell transplantation. In addition, late carcinomas (breast, kidney, thyroid) were seen in two patients. CONCLUSIONS: Our data indicate that the diagnosis of a malignant lymphoma should be considered in patients with a primary APS and peripheral lymph node enlargement or unexplained constitutional symptoms. Conversely, a late onset of arterial or venous thrombotic diathesis after a malignant lymphoma may indicate not only late relapse of malignant lymphoma but also a subsequent APS.

Loustaud-Ratti V, Alain S, Rousseau A, Hubert IF, Sauvage FL, Marquet P, Denis F, Lunel F, Calès P, Lefebvre A, Fauchais AL, Liozon E, Vidal E. · Centre Hospitalier Universitaire (CHU) Limoges, Internal Medicine Department, Limoges, France. · Hepatology. · Pubmed #18435468 No free full text.

Abstract: The impact of ribavirin exposure on sustained virological response (SVR) in patients with chronic hepatitis C is unknown. Preliminary studies showed marked inter-individual variability of ribavirin concentrations despite dose adjustment for body weight (BW) and suggested there was a correlation between single time point concentrations and SVR. None of them evaluated the global exposure to ribavirin. This study was conducted to determine whether early ribavirin global exposure is related with SVR. An exploratory pharmacokinetic-pharmacodynamic (PK-PD) study was conducted in genotype 1 hepatitis C patients treated with peginterferon alfa-2a and ribavirin (dose-adjusted for BW) for 12 weeks, to which amantadine was added for the following 36 weeks. Full and abbreviated ribavirin area under the concentration time curves (AUC(0-12h), AUC(0-4h)) were derived from plasma concentration profiles at day 0 (D0), week 12 (W12), W12 + 1 day, and W24. Virological follow-up was performed at D0 (0, 12, and 24 hours), W2, W4, W6, and monthly until W72 (TaqMan polymerase chain reaction, cut-off 15 international units/mL). Twenty-eight patients were enrolled in the study and 24 completed it. Patients with a SVR had a significantly higher D0 AUC(0-12h) (3695 [1571-6916] versus 2937 [1266-4913] microg/hour/L, P = 0.03) and D0 AUC(0-4h) (2010 [615-3175] versus 1340 [622-2246] microg/hour/L, P = 0.03). Patients with D0 AUCs above the cut-off values defined by receiver operating characteristic curves (3014 microg/hour/L and 1755 microg/hour/L for AUC(0-12h) and AUC(0-4h), respectively) had a significantly better chance of achieving an SVR than patients with AUCs under the thresholds (odds ratio = 16.0, 95% confidence interval 1.54-166.6, P = 0.02 and odds ratio = 8.9, 95% confidence interval, 1.4-56.6; P = 0.02). CONCLUSION: Ribavirin exposure at D0 is significantly related to SVR. To our knowledge, this is the first study to give an early pharmacokinetic predictor of SVR. We propose a minimum AUC(0-4h) threshold of 1755 microg/hour/L at D0 as a target for ribavirin dose adjustment.

Sparsa A, Bonnetblanc JM, Peyrot I, Loustaud-Ratti V, Vidal E, Bédane C. · Service de Dermatologie, CHU Dupuytren, 2, avenue Martin-Luther-King, 87042 Limoges Cedex. · Ann Dermatol Venereol. · Pubmed #17072195 No free full text.

Abstract: BACKGROUND: Scabies is a common parasitic infestation and is very difficult to eradicate from institutions. Ivermectin is used extensively thanks to its efficacy and ease of use through oral administration; it was approved for the treatment of scabies in humans in 2001 in France. Most of the adverse effects noted with this drug have been seen during treatment of onchocerciasis and other filarial disease, but they are rare in the treatment of scabies. We report side effects with ivermectin in two elderly patients with scabies. CASES REPORT: A 72-year-old man was referred for scabies and was treated with benzyl benzoate (Ascabiol) and ivermectin (200 microg/kg) in a single dose. Two days later, the patient presented abdominal pain and nausea. Laboratory tests revealed cytolysis tests for other causes of hepatitis were negative. Within two weeks, liver function had returned to normal. Hepatitis due to ivermectin was diagnosed. An 86-year-old woman hospitalised for scabies was treated with benzyl benzoate and a single dose of ivermectin (200 microg/kg). She developed sinus tachycardia and asthma 3 days later. Screening for embolic, cardiac and infectious origins was found. Toxicity of ivermectin was suspected. DISCUSSION: Since the introduction of ivermectin for the treatment of scabies, reports of adverse events are rare although this drug can cause cardiac dysfunction and liver disease in other indications. In our cases, the causal relationship with ivermectin is probable and care must be taken, particularly in the elderly, the population in which this drug is probably most widely prescribed.

Doffoël-Hantz V, Loustaud-Ratti V, Ramos-Casals M, Alain S, Bezanahary H, Liozon E, Fauchais AL, Vidal E. · Service de médecine interne A, CHU de Limoges, 87000 Limoges, France. · Rev Med Interne. · Pubmed #15710254 No free full text.

Abstract: Hepatitis C virus is one of the most likely candidates as a potential pathogenic agent causing Sjogren's syndrome (SS) in a subset of patients. Nobody has until now described the evolution of SS associated with HCV when chronic hepatitis C is treated with antiviral therapy, interferon being an auto-immunity inductor. This is the purpose of our study. METHODS: Prospective study of 12 patients with a HCV-associated SS defined as certain according to the first european criteria and treated with interferon or interferon/ribavirin for their chronic hepatitis C. RESULTS: More than fifty percent of these patients developed a severe immunological complication especially when they were treated with interferon alone. Ribavirin may have had a protective role on interferon-mediated immunological complications. These complications went on after cessation of therapy. Sicca syndrome was improved only in the patients treated with the association (in 50% of the cases), but these patients also had a sustained virological response. It is difficult to tell if this improvement was due to the hepatitis C virus eradication or ribavirin treatment. CONCLUSION: Hepatitis C virus is implicated in the development of SS in a specific subset of patients for which we can propose the term SS "secondary to HCV" and this disease is not utterly benign especially after the introduction of interferon therapy. Ribavirin when associated with interferon gives a significative sustained virological response and could lower the incidence of immunological interferon-mediated complications with a favorable outcome of sicca syndrome.

Vénat L, Loustaud-Ratti V, Liozon E, Soria P, Nadalon S, Gissot V, Labrousse F, Vidal E. · Service de médecine interne A CHU Dupuytren, Limoges (87). · Presse Med. · Pubmed #12712916 No free full text.

Abstract: OBJECTIVE: Dysmetabolic hepatosiderosis is a recently described entity, which reunites iron overloads associated with polymetabolic syndromes, steatosis and steato-hepatitis. The aim of this study was to specify the relationship between iron overload, polymetabolic syndrome, HFE mutations of primary hemochromatosis and steatosis. METHOD: This was a 5-year retrospective study of 51 patients hospitalised and/or seen in consultation, non-alcoholic, presenting with hyperferritinemia associated with a polymetabolic syndrome and/or hepatic steatosis. RESULTS: Patients mean age was of 53 +/- 12 years with a sex ratio M/F of 5.4. Metabolic disorders were found in 97% of the non-steatosis patients (overweight: 40%, perturbed sugar metabolism: 47%, dyslipidemia: 79.5%). Hyperferritinemia was constant but moderate (513.4 +/- 280.3 ng/ml). Transferrin saturation was predominantly normal (0.44 +/- 0.17). The hepatic enzymes were normal or only slightly perturbed. Steatosis was revealed by sonography in 62% of cases. The hepatic iron overload, documented in 6 patients by hepatic needle biopsy, was discreet (concentration/age ratio of 1.64 +/- 0.19). Among the 59% patients screened for the HFE gene, 40% were positive for C282Y and/or H63D. There was no correlation between ferritin levels and iron parameters, polymetabolic syndrome parameters and hepatic enzymes. The HFE mutations had no influence on the iron parameters. CONCLUSION: Dysmetabolic hepatosiderosis must be know by hospital practitioners because of their prevalence in cases of hyperferritinemia and their therapeutic incidence.

Loustaud-Ratti V, Liozon E, Karaaslan H, Alain S, Paraf F, Le Meur Y, Denis F, Vidal E. · Department of Internal Medicine, Limoges University Hospital, Limoges, France. · Am J Med. · Pubmed #12427502 No free full text.

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Sparsa A, Bédane C, Benazahary H, De Vencay P, Gauthier ML, Le Brun V, Boulinguez S, Loustaud-Ratti V, Soria P, Vidal E, Bonnetblanc JM. · Service de Dermatologie et Vénéréologie, Hôpital Dupuytren, CHRU, Limoges. · Ann Dermatol Venereol. · Pubmed #11907960 links to  free full text

Abstract: BACKGROUND: Fluindione (Previscan) is an oral anticoagulant prescribed in relay to heparin therapy for deep venous thrombosis, pulmonary embolism... The main complications with oral anticoagulants are bleeding. However, severe immuno-allergic complications, especially acute hepatitis, acute renal failure and acute bone marrow failure, have been described with phenindione therapy. OBSERVATIONS: The authors report herein the first five cases of drug-induced hypersensitivity syndrome due to fluindione. Clinical signs included erythroderma and severe systemic manifestations which occurred within 3 to 8 weeks after introducing the molecule. Sex ratio was four males for one female; their ages ranged from 53 to 84 years. Clinical signs included erythroderma (with photosensitivity in two patients), lymphadenopathy and fever evoking severe sepsis. In our observations, marked eosinophilia (5 cases), lymphocytosis, atypical lymphocytes (4 cases), hepatic cytolysis (4 cases), associated in 2 cases with hepatic cholestasis, and pulmonary signs were noted. Cutaneous eruption healed in about 3 to 6 weeks after withdrawal of the drug. In two cases, systemic steroids were required for the severity of systemic manifestations. Long after the acute episode and when steroids were stopped, patch testing with fluindione was still positive. DISCUSSION: To date, acute and/or severe skin diseases due to fluindione, associated or not with multisystemic involvement, have never been reported. This molecule is the most commonly used for the treatment of thromboembolic diseases. Patch testing is easy to perform and can help physicians find the responsible molecule. Moreover, skin manifestations are present only in 87 p. 100 of drug-induced hypersensitivity syndromes. Acute hepatitis and acute renal failure might be drug-induced hypersensitivity syndromes without cutaneous manifestations.

Loustaud-Ratti V, Riche A, Liozon E, Labrousse F, Soria P, Rogez S, Babany G, Delaire L, Denis F, Vidal E. · Department of Internal Medicine, Limoges University Hospital, France. · J Rheumatol. · Pubmed #11669164 No free full text.

Abstract: OBJECTIVE: To describe the prevalence and clinical and laboratory characteristics of sicca syndrome and Sjögren's syndrome (SS) in chronic hepatitis C virus (HCV) infection. METHODS: Forty-five consecutive HCV infected patients referred for liver biopsy were enrolled in a prospective study. Subjective and objective criteria of xerophthalmia or xerostomia were systematically investigated and the patients classified according to 3 sets of criteria (European, Manthorpe, and Fox criteria) for the diagnosis of SS. RESULTS: Sicca syndrome was present in 28 (62%) patients; all had oral dryness and 14 had both oral and ocular dryness. Twenty-four (53%) patients had SS by the European criteria, 25 (56%) by Manthorpe criteria, and 4 (8%) by Fox criteria. Salivary gland biopsy was positive for SS (grade III or IV by Chishom classification) in 21 samples (47%); 9 samples (21%) were classified grade 0, and 15 (32%) grade I or II. No patient had anti-SSA or anti-SSB antibodies. The presence of SS or sicca syndrome was associated with older age and liver disease activity according to the METAVIR scoring system, but not with the presence of other extrahepatic manifestations or with HCV genotype. A high METAVIR activity score was only statistically associated with primary SS. CONCLUSION: HCV infection appears to account for a subgroup of patients with sicca syndrome in which half the cases meet the definition for SS according to European and Manthorpe criteria. This subgroup is characterized by the constant finding of xerostomia, the absence of classical systemic manifestations observed in primary SS, and the absence of anti-SSA or anti-SSB antibodies. Such characteristics delineate a distinctive, virus associated entity that differs from primary SS.

Sparsa A, Loustaud-Ratti V, Liozon E, Denes E, Soria P, Bouyssou-Gauthier ML, Le Brun V, Boulinguez S, Bédane C, Scribbe-Outtas M, Outtas O, Labrousse F, Bonnetblanc JM, Bordessoule D, Vidal E. · Service de médecine interne, hôpital Dupuytren, CHU, Limoges, France. · Rev Med Interne. · Pubmed #11039171 No free full text.

Abstract: PURPOSE: Alpha, beta or gamma interferon (INF) are cytokines produced by cells in response to antigenic stimulation. They are used to treat various hepatic, hematological, oncological and neurological diseases. Cutaneous reactions (rash, alopecia, labial herpes, erythema, or induration at the site of injection, and more rarely cutaneous necrosis) represent 5 to 12% of side-effects observed in patients receiving INF. The authors report six cases of local cutaneous reactions to alpha INF, five of which corresponded to cutaneous necrosis. This makes them question the relevance of INF reintroduction. METHODS: The study included 5 male and 1 female patients (mean age: 59.1 years; range: 42 to 74 years old). Three patients had chronic hepatitis C, while three others presented a blood disease. RESULTS: Cutaneous necrosis occurred after 1 to 10 months of treatment. The mean time to healing was 16.2 weeks. Reintroduction of the drug including injection in other sites did not lead to recurrence of necrosis in five out of the six cases. CONCLUSION: INF-induced cutaneous necrosis does not depend on the type of INF, the site of injection, the dose and may occur 2 months to 9 years after treatment implementation. The exact mechanisms involved in cutaneous necrosis remain unknown. Morbidity is due to a very long time to healing (4 to 6 months). Futhermore, healing sometimes requires prior surgery. Physicians should be aware of the potential occurrence of erythema in patients treated by INF, as it is the first sign of necrosis. The site of injection should then be modified. In case of necrosis, risk factors for thrombophilia, factors reducing microcirculation (DHE, beta-blockers, cigarette smoking) should be investigated. INF injections should be cautiously reintroduced in other sites with the help of a nurse in case of self-injections prior to the occurrence of necrosis. Regarding self-injections patients' training should be emphasized.

Sparsa A, Loustaud-Ratti V, Alain S, Liozon E, Bédane C, Vidal E. · No affiliation provided · Acta Derm Venereol. · Pubmed #15503367 No free full text.

This publication has no abstract.

Alain S, Loustaud-Ratti V, Dubois F, Bret MD, Rogez S, Vidal E, Denis F. · No affiliation provided · Clin Infect Dis. · Pubmed #11823960 No free full text.

This publication has no abstract.