[General practice and internal medicine. The fighting with shared issues]. / Médecine générale, médecine interne. Des combats aux enjeux partagés.

The training of the primary care physicians has been neglected for long by the French medical faculties that, since 1958, favoured the hyper-specialization of their students. The initiative of a few primary care physicians supported by some academic internal medicine physicians allowed changing this situation gradually. Commitment of a training period in primary care practice and then the involvement of teaching general medicine physicians in the course of the theoretical training were essential to this shift. Following three decades of reforms that lead to recognize general medicine as a sub-specialty, an acknowledged academic course of general medicine is eagerly expected for 2009 with the first appointments of professors of general medicine with tenure. The general internists who share the same objective of global patient care are determined to support this academic course that they will welcome within the French National Council of Universities. This academic course will have to comply with the same teaching and research requirements than the other medical subspecialties.

[Hepatitis C-autoimmune hepatitis overlap syndrome: five new cases]. / Association hépatite auto-immune et hépatite virale C: cinq nouvelles observations.

PURPOSE: The hepatitis C-Autoimmune hepatitis overlap syndrome is an uncommon condition whose management can be difficult in both diagnosis and treatment. PATIENTS AND METHODS: Five cases of hepatitis C and autoimmune hepatitis overlap syndrome, brought by a retrospective study, are reported. Hepatitis C was proven by a positive HCV viral load and the autoimmune hepatitis was proven by characteristic immunological and/or histological features. RESULTS: All patients were female, the mean age at diagnosis was 54.2 years (+/-6.6), only one patient had a history of autoimmune disease (autoimmune thyroiditis). Four patients had significant autoantibodies levels (over 1/320) and 4 had a high serum gammaglobulin level (over 1.5 times the upper normal limit). Liver biopsy showed characteristic features of autoimmune hepatitis in all cases and characteristic features of chronic HCV infection in 3 cases. Corticosteroid and/or immunosuppressive treatment was given as a first line therapy in 4 cases while an antiviral treatment has been tried in 4 cases with a good viral response in 2 of them. Corticosteroid and/or immunosuppressive treatment enhanced HCV viral load in all cases, however a histological improvement was observed in every case in which a control biopsy has been performed (3 cases). CONCLUSION: This study highlights the deciding contribution of the initial histological findings in the diagnosis of such a HCV/autoimmune hepatitis overlap syndrome; it also demonstrates that histological outcome is not necessarily compromised by corticosteroid and/or immunosuppressive treatment.

[Autoimmune hepatitis in a HIV-HCV co-infected patient: diagnostic ant therapeutic difficulties]. / Hépatite auto-immune chez une patiente co-infectée VIH-VHC: difficultés diagnostiques et thérapeutiques.

INTRODUCTION: Autoimmune hepatitis (AIH) is a chronic inflammatory hepatic disorder, characterized by hypergammaglobulinemia and autoantibodies. In some cases, AIH can be associated with another liver disease; such as the hepatitis C-AIH overlap syndrome, which diagnosis and treatment may be delicate. EXEGESE: We report a type 1 AIH case in a HIV-HCV co-infected woman. AIH remission and HCV eradication were obtained with prednisone and interferon plus ribavirine. AIH relapse appeared with corticosteroid withdrawal and a new remission was obtained with immunosuppressive treatment associating prednisone and azathioprine, without opportunistic infection. CONCLUSION: This case illustrates diagnostic and therapeutic difficulties of hepatitis C-AIH overlap syndromes in an HIV-infected patient. To our knowledge, it is the first AIH case report in a HIV-HCV co-infected patient.

[Dilated cardiomyopathy and lipid-lowering drug muscle toxicity revealing late-onset Becker's disease]. / Cardiomyopathie dilatée et toxicité musculaire des hypolipémiants: une maladie de Becker de révélation tardive.

INTRODUCTION: The Becker's muscular dystrophy is a genetic myopathy due to mutations of the dystrophin gene, located in the Xp21 region, with a clinical expression usually occurring in young adults. EXEGESIS: We report an atypical case of late onset Becker's muscular dystrophy diagnosed at the age of 57. The patient suffered from mild skeletal muscle involvement revealed by the use of statins and fibrates, associated with severe dilating cardiomyopathy. The DNA analysis showed a deletion of the exons 11-13 in the Xp21 gene. CONCLUSION: The diagnostic of Becker's muscular dystrophy must be considered in all patients with persistently elevated CPK and/or primitive dilated cardiomyopathy, whatever the age of the patient.

[Portal vein thrombosis in HIV-infected patients: report of four cases]. / Thrombose portale chez des patients infectés par le virus de l'immunodéficience humaine: à propos de quatre observations.

Portal vein thrombosis (PVT) seems rare among HIV infected patients. Even though, the report of such cases is of great interest because it may help to determine the factors of occurrence. We describe cases of PVT in 4 HIV-infected men, aged 32 - 64. Two of them were co-infected with hepatitis C virus (HCV). The four patients had a history of disseminated mycobacterial infection (one case of tuberculosis, 3 cases of mycobacterium avium complex infection) with abdominal lymphadenitis. Despite HAART, their immunodeficiency was profound (CD4: 65 to 216/mm(3)). At the time of diagnosis, two patients were treated with protease-inhibitor containing regimen: indinavir (one case), ritonavir-saquinavir (one case). PVT was revealed by haematemesis (one case), abdominal pain (ome case), anasarca (2 cases). In three patients, the diagnosis of PVT was confirmed by imagery (echo-doppler or angio- RMI), and for the last patient, PVT was found during the transjugular intrahepatic portosystemic shunt setup. A low level of C protein was diagnosed in one case. Cirrhosis was not found in HIV-HCV co-infected patients. Two patients died early after diagnosis, one patient died 3 years after the onset of symptoms. Various factors may cause the development of a PVT in HIV infected patient. Serious immunodeficiency, opportunistic infections such as tuberculosis and mycobacterium avium complex related infection with abdominal lymphadenitis can further the development of PVT. Protease-inhibitor might have facilitated the process. Due to the severe prognosis of advanced cases, early evocation of diagnosis is needed.

Determinants of clinical progression in antiretroviral-naive HIV-infected patients starting highly active antiretroviral therapy. Aquitaine Cohort, France, 1996-2002.

OBJECTIVES: To determine the factors associated with clinical progression (AIDS events and death) in antiretroviral-naive patients who have begun highly active antiretroviral therapy (HAART). METHODS: HIV-infected patients naive to antiretroviral therapy were included in a prospective hospital-based cohort who began HAART between June 1996 and December 2001. Progression was explained by baseline characteristics using Cox proportional hazards models. RESULTS: Overall, data for 709 patients were analysed. In multivariate analysis, factors associated with an increased risk of progression were CD4 count < 50 cells/microL [hazard ratio (HR) = 13.0 (95% confidence interval 3.8-44.3)] and between 50 and 199 cells/microL [HR = 5.1 (1.6-16.3)], when compared with patients with CD4 count>350 cells/microL; AIDS events before HAART prescription [HR = 2.1 (1.2-3.7)]; CD8 count < 400 cells/microL [HR = 1.8 (1.1-3.0)]; and older age (HR = 1.2 by 10 years (1.0-1.5)]. In a second model including CD4 percentage, factors associated with progression were CD4 < 10% [HR = 6.3 (2.2-17.9)] and 10% 20%; CD8 count; AIDS events before HAART prescription; and older age. In a third model including the CD4:CD8 ratio, factors associated with progression were CD4:CD8 < 15% [HR = 8.2 (2.3-28.8)] and 15% < CD4:CD8 < 30% [HR = 4.6 (1.3-16.0)], when compared with patients with CD4:CD8 > 45%; AIDS events before HAART prescription; and older age. The Akaike information criteria for model analysis were 803, 805 and 815, respectively. CONCLUSIONS: Consideration of CD4 level in terms of CD4:CD8 ratio or CD4 percentage can be a good alternative to absolute CD4 count. Other prognostic factors such as older age, CD8 count < 400 cells/microL and AIDS events also have to be considered in the decision to initiate HAART.

[Efficacy and safety of pegylated-interferon plus ribavirin in HIV-infected patients co-infected with hepatitis C virus in clinical practice: a 32 cases observational follow-up]. / Efficacité et tolérance de l'association interféron pégylé-ribavirine chez les patients co-infectés VIH-VHC en pratique clinique: étude observationnelle de 32 patients.

OBJECTIVE: To describe efficacy and safety in clinical practice of pegylated interferon plus ribavirin (INFpeg-Riba) in the treatment of hepatitis C viral infection (HCV) in HIV infected patients. METHODS: Monocentric retrospective study with inclusion of all patients who received at least once INFpeg-Riba before April 1st 2003. All patients were followed up to six months after the end of HCV therapy. RESULTS: Thirty two HIV-positive patients (23 men and 9 women) with chronic hepatitis C treated by INFpeg-Riba were included. The mean age was 43 years. Fourteen patients carried HCV genotype 2 or 3 (43 %) and 18 patients carried genotype 1 or 4 (57%). The Metavir score of fibrosis showed fibrosis F1 (N =3), F2 (N =14), F3 (N =7) and F4 - cirrhosis (N =8). Twenty six patients (81%) were naive for anti hepatitis C drugs. Thirty one per cent of patients were at AIDS stage and 84% were receiving antiretroviral drugs. The mean CD4 cell count was 469 /ml and the plasma RNA HIV was less than 50 copies /ml in 57% of the cases. Adverse events leading to reduction of dose of drugs occurred in 40% and adverse events leading to discontinuation treatment occurred in 12%. A decline of CD4 cell count <200 CD4/ml was observed in 15%. Clearance of HCV-RNA in end of treatment was seen in 46 % and sustained virological response in 34 %. The main predictors of sustained virological response were HCV genotype 2 or 3 (P =0.04) and plasma HIV RNA less than 50 copies/ml (P =0.001). The predictive value of good virological response of a CD4 cell count >350/ml before treatment was very near the statistical significancy (p =0.07). CONCLUSIONS: The efficacy of pegylated interferon plus ribavirin in HIV-HCV co-infected patients is disappointing mainly due to a poor tolerance. In addition to HCV genotype, plasma HIV RNA level and CD4 cell count were essential to predict INFpeg-Riba response and should be taken into account in the process leading to the initiation of such therapy in HIV-HCV co-infected patients.

Risk factors for lactic acidosis in HIV-infected patients treated with nucleoside reverse-transcriptase inhibitors: a case-control study.

A case-control study was undertaken to determine risk factors for lactic acidosis in human immunodeficiency virus-infected patients treated with nucleoside reverse-transcriptase inhibitors (NRTIs). From May 1996 to June 2000, 9 patients with lactic acidosis (defined as a plasma lactic acid level of >5 mM and plasma pH of <7.38) were identified. Control patients were randomly selected from among a large cohort of patients who initiated a dual NRTI regimen in 1996 or after. Two factors were associated with an increased risk of lactic acidosis: first, a creatinine clearance of <70 mL/min before lactic acidosis (OR, 15.8 [range, 3.0-86.5], P<10(-4)), and, second, a low nadir CD4+ T lymphocyte count before the inception of NRTI therapy (OR, 8.4 [range, 1.2-infinity], P=.03). The total cumulative exposure to NRTIs was not associated with an increased risk of lactic acidosis, nor was the cumulative exposure to any of the 4 NRTIs studied. According to these results, monitoring of creatinine clearance, especially in patients with a low nadir CD4+ T lymphocyte count, could lead to modifications in antiretroviral therapy in order to diminish the risk of occurrence of lactic acidosis.

[Amoebic liver abscess. Study of 20 cases with literature review]. / Abcès amibien du foie. Analyse de 20 observations et proposition d'un algorithme thérapeutique.

PURPOSE: The management of amoebic liver abscess includes antiamoebic drugs combined or not with percutaneous puncture or surgical drainage. This study was to suggest a decision tree for the therapeutic approach of such feature. METHODS: We report a retrospective analysis of 20 imported cases with amoebic liver abscesses admitted at the Department of Tropical Diseases during 1995-1999 at the Bordeaux University Hospital Centre, France, and a review of the literature. RESULTS: The twenty patients were 14 males and 6 females, mainly 20 to 40 years old. The clinical presentation was mainly accounting a painful liver enlargement with hyperthermia. The echographic picture was mostly represented by a unique liver element located at the liver right lobe. They were numerous in an HIV infected patient. Thirteen patients have been treated using a medical therapeutic approach. A percutaneous puncture has been necessary for 4 cases. A percutaneous drainage has been realised for two patients as regard to the persistence of the hepatalgia occurrence. A surgical drainage has been experienced by two patients after a lack of efficacy of a percutaneous drainage, after rupture of an abscess treated medically, respectively. A review of the literature and the analysis of the 20 cases history have been used to determine a therapeutic algorithm. CONCLUSION: The occurrence of immediate complications at onset must indicate a first line surgical drainage procedure. Beside this situation, risk factors for rupture must be assessed (high size abscess, pejorative localization), as well as poor prognosis feature (liver failure, bacteraemia). If no pejorative condition occurs, a first-line exclusive medical approach can be undertaken with a clinical efficacy evaluation at H72. Otherwise, the indication of the percutaneous drainage must be discussed.

[Severe lactic acidosis in HIV-infected patients treated with nucleosidic reverse transcriptase analogs: a report of 9 cases]. / Acidose lactique sévère chez les patients infectés par le VIH traités par inhibiteurs nucléosidiques de la reverse transcriptase : 9 cas.

PURPOSE: Symptomatic lactic acidosis requiring intensive care is a rare and severe adverse event related to the mitochondrial toxicity of the nucleoside analog reverse transcriptase inhibitors (NRTIs). METHOD: We retrospectively investigated the clinical and biological features of HIV-infected patients who developed severe lactic acidosis syndrome at the University teaching hospital of Bordeaux and the regional community hospital, during 1996-2000. RESULTS: Nine patients were identified (incidence: 0,9/1000 NRTI treated patient-years), 4 men and 5 women with a median age of 36 years. They had a moderate immunodeficiency (median CD4+ T lymphocyte counts: 197/mm(3)) and only one of them presented a virological failure. The causes of hospital admission were abdominal pain (n = 6), dyspnea (n = 6), asthenia (n = 5), jaundice (n = 4), and vomiting (n = 2). Hepatomegaly was present in 6 patients. Lactic acidosis was found in all cases: median pH: 7.28, bicarbonate: 12 mmol/l, anion gap: 27 mEq/l, plasma lactic acid: 13 mmol/l. Cytolysis (n = 8), cholestasis (n = 6), hepatic failure (n = 4), rhabdomyolysis (n = 4) and pancreatitis (n = 2), were also present. Despite medical intensive care, seven patients died. The only two post-mortem examinations revealed severe hepatic steatosis. Median duration of NRTI therapy was 4 years. At presentation, five patients were receiving lamivudine, five didanosine, four stavudine and three zidovudine. Six patients were coinfected by HCV and/or HBV, four had chronic renal failure and five an immediately preceding infectious disease. CONCLUSION: The prognosis of lactic acidosis is severe. Nucleosid-analog therapy needs clinical and biological monitoring, specially in patients with comorbidities.

A cohort study of nevirapine tolerance in clinical practice: French Aquitaine Cohort, 1997-1999.

We performed a retrospective study to evaluate, under routine circumstances, the tolerance and immunovirological changes associated with antiretroviral regimens that contain nevirapine in 137 patients (88% were antiretroviral experienced). During a mean follow-up of 11 months, 33% of patients reported side effects attributed to nevirapine, and 21% discontinued treatment because of poor tolerance. Administration of antihistamines or corticosteroids at the initiation of treatment was not protective against adverse events (relative risk, 0.82; 95% confidence interval, 0.49-1.38). The proportion of patients with hepatitis C virus (HCV) and/or hepatitis B virus (HBV) coinfection who had alanine aminotransferase levels of >100 IU/L increased from 19.4% at baseline to 42.9% at month 12 of follow-up (P=.02). We noticed a significant increase of the proportion of patients with total cholesterol levels of >5.5 mM (P=.02). We have shown that there is a high level of discontinuation of nevirapine therapy in clinical practice and that side effects were not prevented by administration of antihistamines or corticosteroids. Coinfection with HCV or HBV increased the risk of hepatotoxicity, which lead to the cautious use of nevirapine for such patients.

Causes of death among HIV-infected patients in the era of highly active antiretroviral therapy, Bordeaux, France, 1998-1999.

OBJECTIVES: To describe the causes of death in HIV-infected patients in the era of highly active antiretroviral therapy (HAART). METHOD: A retrospective survey conducted in Bordeaux, France. Medical records of all deaths that had occurred in 1998 and 1999 amongst patients followed within the Aquitaine cohort were reviewed by the same physician. Immediate and underlying causes of death were described, taking into account the morbidity at the time of death. RESULTS: Sixty-six deaths occurred in 1998, and 41 in 1999. Sixty-seven per cent of deceased patients were male. Median age at time of death was 43 years (range 25-71), median CD4 was 162 cells/microL (0-957); 28% of patients had a CD4 count > 200 cells/microL and 7% plasma viral load < 500 HIV-RNA copies/mL. Amongst morbidity present at the time of death, there were 23 bacterial infections, 16 non-Hodgkin's lymphomas, 16 cirrhoses, 15 non HIV-related malignancies, 13 central nervous system diseases and 10 myocardiopathies. The main immediate causes of death were: multiple organ failure (21%), coma (18%), septic shock (15%) and acute respiratory failure (14%). Underlying causes of death were AIDS-defining events (48%), non AIDS HIV-related infection (3%), hepatitis B- or C-associated cirrhosis (14%), non HIV-related malignancies (11%), cardiovascular events (10%), suicide and overdose (6%), treatment-related fatalities (4%), injury (2%) and unknown (2%). Patients dying from AIDS-related events were more often female, had a lower CD4 count, a higher level of HIV-RNA, a shorter history of HIV infection and were less often coinfected with hepatitis B and C viruses than those dying from other underlying causes. CONCLUSIONS: AIDS-related events are no longer the major causes of death of HIV-infected patients in the era of HAART. This evolving mortality pattern justifies an adaptation of both the epidemiological surveillance and the clinical monitoring of HIV-infected patients.

Correlations of soluble interleukin-2 and tumor necrosis factor type II receptors with immunologic and virologic responses under HAART.

We assessed the correlations between some plasma markers of immune activation (soluble receptors of interleukin 2 (sIL2-R) and TNFap75 (sTNFII-R) and usual markers of HIV infection in patients treated with protease-inhibitors (PI). Forty-six PI-naive HIV-1-infected adults were included in a 1-year prospective cohort from the initiation of a P1-containing regimen (M0). Measurements of CD4+cell count, plasma HIV-RNA, sIL2-R and sTNFII-R were performed at M0, M6, and M12. The evolution of sIL2-R from baseline to M12 was significantly different between immunological responders (IR) (CD4+count above 200/mm3 for subject having less than 200 CD4 +/mm3 at inclusion, or increase of at least 50 CD4+/mm3 for others) (58 UI/ml) and non-IR (+28 UI/ml) (P =0.01). The evolution of sTNFII-R between M0 and M12 was significantly different between virological responders (VR) (plasma HIV-1 RNA less than 500 copies/ml at M12) (-2.5 ng/ml) and non-VR (+0.2 ng/ml) (P = 0.02). Our study shows significative correlations between the evolutions of soluble interleukin-2 and TNFR-II receptors and those of CD4+T-lymphocytes or HIV-RNA responses in patients under HAART.

Sarcoidosis-associated hepatitis C virus infection.

Although several reports of sarcoidosis have been reported in hepatitis C virus (HCV)-infected patients treated with interferon-alpha, this association has never been described in nontreated HCV patients. We report two cases of sarcoidosis associated with chronic hepatitis C infection. The patients developed multivisceral sarcoidosis (cutaneous, lungs, nodes) at two and at least six years after the presumed date of infection. One patient obtained remission of sarcoidosis with corticosteroid treatment but the other remained corticodependent. The levels of hepatic enzymes were not significantly modified throughout the course of corticosteroid therapy. In conclusion, these case reports suggest that HCV itself could induce a granulomatous reaction in chronic HCV-infected patients through the stimulation of the cellular immune system. It could be of interest to test for HCV infection all patients diagnosed with sarcoidosis and to watch over every treated or nontreated hepatitis C infected patient for the development of granulomatous lesions.

[Sarcoidosis and comorbidity: retrospective study of 32 cases]. / Sarcoïdose et comorbidité: étude rétrospective de 32 observations.

PURPOSE: A retrospective study was set up to investigate active pathologic processes associated with sarcoidosis diagnosed in 32 patients. METHODS: Eighteen patients had two identified granulomatous localizations (56%) and 14 patients had three localizations or more (27%). Comorbidity was noticed in nine patients (28% of cases). Sarcoidosis was associated with an infectious disease five times (hepatitis C virus [HCV] infection three times, including one case after recombinant interferon alpha therapy, and HIV and HCV co-infection two times). The association of sarcoidosis with a chronic immunologic inflammatory disease was noticed four times (lupus erythematosus two times, myasthenia and primary biliary cirrhosis). Finally, in two cases sarcoidosis was associated with a neoplasia (non-Hodgkin's lymphoma in a co-infected HIV-HCV patient, ovarian cystadenocarcinoma in another patient). Sarcoidosis preceded or revealed the comorbidity four times.