Comparison of liver biopsy and noninvasive techniques for liver fibrosis assessment in patients infected with HCV-genotype 4 in Egypt.

In Egypt, as elsewhere, liver biopsy (LB) remains the gold standard to assess liver fibrosis in chronic hepatitis C (CHC) and is required to decide whether a treatment should be proposed. Many of its disadvantages have led to develop noninvasive methods to replace LB. These new methods should be evaluated in Egypt, where circulating virus genotype 4 (G4), increased body mass index and co-infection with schistosomiasis may interfere with liver fibrosis assessment. Egyptian CHC-infected patients with G4 underwent a LB, an elastometry measurement (Fibroscan(©)), and serum markers (APRI, Fib4 and Fibrotest(©)). Patients had to have a LB ≥15 mm length or ≥10 portal tracts with two pathologists blinded readings to be included in the analysis. Patients with hepatitis B virus co-infection were excluded. Three hundred and twelve patients are reported. The performance of each technique for distinguishing F0F1 vs F2F3F4 was compared. The area under receiver operating characteristic curves was 0.70, 0.76, 0.71 and 0.75 for APRI, Fib-4, Fibrotest© and Fibroscan©, respectively (no influence of schistosomiasis was noticed). An algorithm using the Fib4 for identifying patients with F2 stage or more reduced by nearly 90% the number of liver biopsies. Our results demonstrated that noninvasive techniques were feasible in Egypt, for CHC G4-infected patients. Because of its validity and its easiness to perform, we believe that Fib4 may be used to assess the F2 threshold, which decides whether treatment should be proposed or delayed.

Preexposure prophylaxis (PrEP) of HIV infection in France: a nationwide cross-sectional study (PREVIC study).

Although preliminary studies showed that preexposure prophylaxis (PrEP) lowers the HIV transmission in individuals with HIV, confirmative trials are ongoing and PrEP is not routinely recommended. The aim of this study was to assess whether individuals with HIV share antiretroviral (ARV) drugs for PrEP and to describe awareness and discussion on PrEP in this population. A cross-sectional survey was conducted in France in 23 representative departments of infectious diseases and internal medicine. Physicians administered an anonymous standardized questionnaire to all individuals with HIV receiving ARVs and followed between 24 and 31 October 2011. The questionnaire included items regarding PrEP (awareness; discussion with their close circle, physician or patients' association; experience), personal sociodemographic characteristics, risk behaviors and HIV status of the participants. Five hundred and ninety three participants were recruited: male 74.2% (men who have sex with men 52.4%, heterosexuals 21.6%), member of patient's association 9.8%. Half of them (50.6%) lived with a stable partner and 35.2% with an HIV-negative partner. Almost half (41.8%) were aware and 29.5% had had discussion about PrEP. In logistic regression, awareness and discussion on PrEP were more frequent: (1) among males, in patients' association members (p< 0.001 for both) and in nonheterosexuals (p=0.023 and 0.057, respectively); (2) among women, in those not living with a stable partner (p=0.035 and p=0.03, respectively) or living with an HIV-negative partner (p=0.049 and p=0.083, respectively). One percent of the participants declared having shared ARVs with someone and 8.3% reported PrEP in their close circle. Men reporting PrEP in their close circle shared ARVs more frequently than those who did not (10.3% vs. 0.2%, p < 0.001). Today, individuals with HIV do not seem to widely share personal ARVs for PrEP with seronegative people. A significant number of individuals with HIV are aware of and commonly discuss PrEP.

[Malaria among immigrants, experience of a Parisian hospital (2006-2010)]. / Paludisme chez les migrants, expérience d'un hôpital parisien (2006-2010).

In recent days immigrants represent the main risk group for imported malaria in northern countries. Most of them are migrants returning to their country of origin to visit friends and relatives (VFR). We retrospectively examined the main clinical, biological, and therapeutic data of all malaria cases in immigrants from 2006 to 2010 in Tenon hospital, Paris. The hospital is situated in a Paris district with an important African community. During the study period 239 imported malaria cases were observed in adults of which 199 were immigrants, 186 VFR, and 13 recently arrived. Most cases were from sub-Saharan Africa and Comoro islands. Chimioprophylaxis was not taken in 81.2% of VFR. It was inadequate in 43.7% and not taken correctly in 84.4%. Plasmodium falciparum was the most frequent species identified: 190/199 (95.5%). Severe P. falciparum malaria was observed in 25 cases (13.2%); two of them were recently arrived. One patient, African VFR, died. In this series two high-risk groups were represented: HIV-infected patients and pregnant women. Six of the HIV patients had severe malaria and all pregnant women had anemia. Our results are similar to those observed recently in other European countries. Mean age of VFR is increasing and the risk for severe P. falciparum malaria became identical to the one observed in non-immune travelers. Protection measures remain still insufficient in this population of travelers.

Long-term follow-up of 11 protease inhibitor (PI)-naïve and PI-treated HIV-infected patients harbouring virus with insertions in the HIV-1 protease gene.

OBJECTIVES: Amino acid insertions in the protease gene have been reported rarely, and mainly in patients receiving protease inhibitors (PIs). The aim of the study was to assess the long-term viro-immunological follow-up of HIV-infected patients harbouring virus with protease insertions. METHODS: Cases of virus exhibiting protease insertions were identified in routine resistance genotyping tests. Therapeutic, immunological and virological data were retrospectively collected. RESULTS: Eleven patients harbouring virus with a protease gene insertion were detected (prevalence 0.24%), including three PI-naïve patients. The insertions were mainly located between codons 33 and 39 and associated with surrounding mutations (M36I/L and R41K). The three PI-naïve patients were infected with an HIV-1 non-B subtype. Follow-up of these PI-naïve patients showed that the insert-containing virus persisted for several years, was archived in HIV DNA, and displayed a reduced viral replicative capacity with no impact on resistance level. Of the eight PI-experienced patients, 63% were infected with HIV-1 subtype B; one had been antiretroviral-free for 5 years and seven were heavily PI-experienced (median duration of follow-up 24 months; range 10-62 months). The protease insertion was selected under lopinavir in four patients and under darunavir in one, in the context of major PI-resistance mutations, and following long-term exposure to PIs. The insert-containing virus persisted for a median of 32 months (range 12-62 months) and displayed no specific impact on phenotypic resistance level or viral replicative capacity. CONCLUSION: Our data, obtained during long-term follow-up, show that insertions in the protease gene do not seem to have an impact on resistance level. This finding supports the recommendation of PI-based regimens, although further work is required to confirm it.

Reproducibility of liver stiffness measurements in hepatitis C virus (HCV)-infected patients in Egypt.

Elastometry has demonstrated good accuracy, but little is known about its reproducibility. The aim of this study was to assess the intra- and inter-operator reproducibility of liver stiffness measurement among hepatitis C virus (HCV)-infected patients in Egypt. The study was conducted among HCV-infected patients referred for treatment evaluation in two hepatitis treatment centres of Cairo. Two operators took liver stiffness measurement two times per patient the same day. Intra- and inter-reproducibility were estimated by different methods: Bland and Altman graphics, variation coefficient, intraclass correlation coefficient and Kappa coefficient; 7.1 kPa was used as the threshold of significant (≥F2) fibrosis whenever needed. Fifty-eight patients were included in the study, and 216 measurements were taken. Failure rate was 7% and associated with overweight. For a value of 7.1 kPa, the inter-operator 95% limits of agreement were estimated at ±2.88 kPa. Intra- and inter-operator coefficients of variation ranged between 11% and 15%, intraclass correlation coefficients [95% confidence interval] between 0.94 [0.86-0.97] and 0.97 [0.95-0.99], and Kappa coefficients between 0.65 [0.44-0.88] and 0.92 [0.81-1.00]. The reliability of liver stiffness measurement is questionable when considering the decision to initiate antiviral therapy because of the percentage of discordance between measurements is notable, especially in the intermediate fibrosis stages.

Role of treatment for depressive symptoms in relieving the impact of fatigue in HIV-HCV co-infected patients: ANRS Co13 Hepavih, France, 2006-2008.

Fatigue is a major component of quality of life (QOL) and is associated with depression in HIV-HCV co-infected individuals. We investigated whether treating depressive symptoms (DS) could mitigate the impact of fatigue on daily functioning in co-infected patients, even those at an advanced stage of disease. The analysis was conducted on enrollment data of 328 HIV-HCV co-infected patients recruited in the French nationwide ANRS CO 13 HEPAVIH cohort. Data collection was based on medical records and self-administered questionnaires which included items on socio-behavioural data, the fatigue impact scale (FIS) in three domains (cognitive, physical and social functioning), depressive symptoms (CES-D classification) and use of treatments for depressive symptoms (TDS). After multiple adjustment for gender and unemployment, CD4 cell count <200 per mm(3) was associated with a negative impact of fatigue on the physical functioning dimension (P = 0.002). A higher number of symptoms causing discomfort significantly predicted a higher impact of fatigue on all three dimensions (P < 0.001). This was also true for patients with DS receiving TDS when compared with those with no DS but receiving TDS. A significant decreasing linear trend (P < 0.001) of the impact of fatigue was found across the categories 'DS/TDS', 'DS/no TDS', 'no DS/TDS' and 'no DS/no TDS'. Despite limitations related to the cross-sectional nature of this study, our results suggest that routine screening and treatment for DS can reduce the impact of fatigue on the daily functioning of HIV-HCV co-infected patients and relieve the burden of their dual infection.

Longitudinal evaluation of viral interactions in treated HIV-hepatitis B co-infected patients with additional hepatitis C and D virus.

Virological interactions of hepatitis B (HBV), hepatitis C (HCV) and hepatitis D (HDV) viruses in HIV-infected patients have been poorly characterized especially under treatment influences. Undetection rates of hepatitis viruses were longitudinally analyzed in a 3-year cohort of 308 HIV-HBV co-infected patients and compared using Generalized Estimating Equation models adjusted for age, HIV-RNA, CD4 cell-count and antiviral treatment. Chronic hepatitis co-infection in HIV-infected patients (age years, SD) was: 265 HBV (40.7, 8.2); 19 HBV-HCV (39.7, 4.1); 12 HBV-HDV (35.2, 9.9); 12 HBV-HCV-HDV (39.2, 5.2). At inclusion, treatment with lamivudine/tenofovir was not significantly different between co-infection groups. HBV suppression was significantly associated with HDV (aOR = 3.85, 95%CI 1.13-13.10, P = 0.03) and HCV tri-infection (aOR = 2.65, 95%CI 1.03-6.81, P = 0.04), but marginally associated with HIV-HBV-HCV-HDV (aOR = 2.32, 95%CI 0.94-5.74, P = 0.07). In quad-infection, lower HDV-undetectability (vs HIV-HBV-HDV, P = 0.2) and higher HCV-undetectability (vs HIV-HBV-HCV, P = 0.1) were demonstrated. The degree of HBV suppression varied between visits and co-infection groups [range of aOR during follow-up (vs HIV-HBV co-infection): HIV-HBV-HCV = 2.23-5.67, HIV-HBV-HDV = 1.53-15.17]. In treated co-infected patients, HDV expressed continuous suppression over HCV- and HBV-replications. Peaks and rebounds from undetectable hepatitis B, C and/or D viremia warrant closer follow-up in this patient population. HDV-replication was uncontrolled even with antiviral treatment.

Community-acquired bacteraemic pneumococcal pneumonia in adults: effect of diminished penicillin susceptibility on clinical outcome.

Pneumococcal pneumonia remains a common disease with a high mortality rate. Between 1995 and 2000, we prospectively analyzed 95 consecutive adult cases of community-acquired bacteraemic pneumococcal pneumonia treated in a single centre. The incidence of pneumococcal resistance to penicillin increased from 19 to 50% during the study period. Multivariate analysis showed that only age and recent hospitalization were independently associated with fatal outcome. The proportion of penicillin-resistant strains was slightly but not significantly higher among patients who died before the fourth hospital day than among those who died later. Patients who died before D4 were more likely to have a recent history of hospitalization, cancer and/or chemotherapy. It thus appears that infection by a resistant pneumococcal strain is not in itself a gravity factor in this setting, but that their acquisition is associated with pejorative clinical features.

Portal hypertension due to intrahepatic obstruction in non-Hodgkin's lymphoma.

Portal hypertension is rare in the setting of non-Hodgkin's lymphoma. We report here the case of a 73-year-old man presenting with diffuse high-grade B-cell lymphoma affecting predominantly the liver with large space occupying lesions. Histological examination of liver specimens showed abnormal large lymphoid cells whereas adjacent non-tumoural liver was normal. Portal hypertension was documented by upper gastrointestinal endoscopy that showed grade II oesophageal varices and measurement of portal pressures via transjugular approach showing increased hepatic venous pressure gradient (24 mmHg). We assume that portal hypertension was mainly related to these space occupying lesions.

Cyamamezine-induced acute hepatitis after unique massive intake: a case report.

Hepatotoxicity of cyamamezine, a phenothiazine structurally related to chlorpromazine, has been rarely documented. We report here a case of acute symptomatic hepatitis following a unique massive intake of cyamamezine in a suicide attempt and discuss the mechanisms of such injury.

[Atypical cutaneous leishmaniasis]. / Leishmaniose cutanée de présentation atypique.

French Guyana is an endemic area for American cutaneous leishmaniasis. At the start, the initial red lesion may be mistaken for a whitlow. Twenty percent of developed forms exhibit a sporotrichosis pattern. The notion of travel to an endemic area is very important for diagnosis. We report the case of a young man from French Guyana presenting with a cutaneous lesion of the finger. After numerous surgical treatments for a "whitlow", the final diagnosis of leishmaniasis was difficult because of local-complications and cutaneous rearrangement. Erroneous initial orientation in a unit unaware of tropical diseases can forestall appropriate care of the patients. Epidemiological, clinical and therapeutic data on American tegument leishmaniasis are discussed.

[Febrile pseudotumor lesion of the arm. Atypical presentation of Shulman syndrome]]. / Lésion pseudotumorale fébrile du bras. Présentation atypique d'un syndrome de Shulman.

INTRODUCTION: The diagnostic approach when confronted with a pseudo-tumoral lesion and fever is difficult since it evokes an infectious, rheumatismal inflammatory or even systemic disease. OBSERVATION: A 39 year-old Vietnamese man was hospitalised for polyarthralgia if the arm and fever (39 degrees C). He was treated with non-steroidal anti-inflammatories, which were only partially effective. Biological examinations revealed a severe inflammatory syndrome and cytolysis three-fold higher than normal. Since the infectious, rheumatismal and immunological explorations were negative and in view of the appearance of a pseudo-tumoral inflammatory lesion of the left arm concomitant to infiltration of the underlying muscle revealed on MRI, a muscle biopsy was performed showing eosinophilic fasciitis. Diagnosis of Shulman's syndrome was made and the affection rapidly improved with corticosteroids. COMMENTS: The presentation of our patient was atypical for several reasons: his Vietnamese origin, the initial fever peak at 39 degrees C, the unilateral involvement, the severe inflammatory syndrome, the initial absence of hypereosinophilia, the visceral involvement and notably myositis are all uncommon in Shulman's syndrome. Hence, it is important to rule out its differential diagnosis from local edematous scleroderma, which does not share the same prognosis.

[Predictive ultrasonographic criteria for portal hypertension due to Schistosoma mansoni in a recently established endemiz zone]. / Critères echographiques prédictifs d'hypertension portale due à Schistosoma mansoni dans une zone d'endémie récente.

The first cases of Schistosoma mansoni infection were reported in the Senegal River Basin ten years ago. Today endemicity is so high that prevalence rates exceed 90 p. 100 in some areas. Schistosomiasis sometimes goes undiagnosed until the occurrence of portal hypertension with rupture of esophageal varices. Endoscopy is the gold standard for detection of esophageal varices but it is impractical in remote areas. Ultrasonography has been proposed as a non-invasive alternative. The purpose of this study is to describe the results of simultaneous endoscopic and ultrasonographic assessment in 101 subjects from the Richard-Toll area of the Senegal River Basin. Findings showed that severe forms of schistosomiasis complicated by portal hypertension were already present in the region less 10 years after description of the first case. This study also proposes a diagnostic score for portal hypertension based on ultrasonographic findings. The features included in this score are thickening of portal vessel walls, portal vessel diameter, and collapsed appearance of the splenic vein during inspiration. In our hands this score allowed reliable prediction of the development of esophageal varices. Ultrasonography is a good tool for identifying severe forms of schistosomiasis. It should be useful for routine screening in recently established endemic zones.

Liver stiffness values in HIV-infected patients with isolated anti-hepatitis B core antibodies.

BACKGROUND: Hepatitis B reactivation has been observed in HIV-infected patients with isolated anti-HBc. However, the impact of isolated anti-HBc on liver fibrosis is not known in this population. METHODS: We investigated liver stiffness values (LSV) in a population of HIV-infected patients with isolated anti-HBc, and attempted to identify risk factors for high values. RESULTS: Fifty-one out of 69 patients (74%) had low LSV (≤7.1 kPa). In univariate analysis, high LSV (>7.1 kPa) were associated with HCV coinfection, the duration of HIV infection, the duration of antiretroviral therapy and lipodystrophy. In age-adjusted multivariate analysis, HCV coinfection (OR 11.5; 95% CI, 3.0-62.9; P=0.001) and lipodystrophy (OR 4.6; 95% CI, 1.1-20.7; P=0.031) remained associated with high liver stiffness values. CONCLUSIONS: Lipodystrophy was the only factor associated with high liver stiffness values in our population of HIV-infected patients with isolated anti-Hbc and extensive exposure to antiretroviral drugs active on HBV, apart from HCV coinfection Our study correlates to recent studies the results of which have shown that lipodystrophy, and more generally mitochondrial toxicity, was associated with advanced liver fibrosis in HIV/HCV co-infected patients.