The treatment response of chronically hepatitis C virus-infected patients depends on interferon concentration but not on interferon gene expression in peripheral blood mononuclear cells.

International audienceThe current treatment of chronic hepatitis C is based on pegylated alpha interferon (PEG-IFN-α) and ribavirin. The aim of this study was to identify biological and clinical variables related to IFN therapy that could predict patient outcome. The study enrolled 47 patients treated with PEG-IFN and ribavirin combined therapy. The interferon concentration was measured in serum by a bioassay. The expression of 93 interferon-regulated genes in peripheral blood mononuclear cells was quantified by real-time quantitative reverse transcription-PCR (RT-PCR) before and after 1 month of treatment. The interferon concentration in the serum was significantly lower in nonresponders than in sustained virological responders. Moreover, a significant correlation was identified between interferon concentration and interferon exposition as well as body weight. The analysis of interferon-inducible genes in peripheral blood mononuclear cells among the genes tested did not permit the prediction of treatment outcome. In conclusion, the better option seems to be to treat patients with weight-adjusted PEG-IFN doses, particularly for patients with high weight who are treated with PEG-IFN-α2a. Although the peripheral blood mononuclear cell samples are the easiest to obtain, the measurement of interferon-inducible genes seems not be the best strategy to predict treatment outcome

Serum Neurotrophin Profile in Systemic Sclerosis

International audienceBACKGROUND: Neurotrophins (NTs) are able to activate lymphocytes and fibroblasts; they can modulate angiogenesis and sympathic vascular function. Thus, they can be implicated in the three pathogenic processes of systemic sclerosis (SSc). The aims of this study are to determine blood levels of Nerve Growth Factor (NGF), Brain-Derived Neurotrophic Factor (BDNF) and Neurotrophin-3 (NT-3) in SSc and to correlate them with clinical and biological data.METHODS: Serum samples were obtained from 55 SSc patients and 32 control subjects to measure NTs levels by ELISA and to determine their relationships with SSc profiles. FINDINGS: Serum NGF levels were higher in SSc patients (288.26 ± 170.34 pg/mL) than in control subjects (170.34 ± 50.8 pg/mL, p<0.001) and correlated with gammaglobulins levels and the presence of both anti-cardiolipin and anti-Scl-70 antibodies (p<0.05). In contrast, BDNF levels were lower in SSc patients than in controls (1121.9 ± 158.1 vs 1372.9 ± 190.9 pg/mL, p<0.0001), especially in pulmonary arterial hypertension and diffuse SSc as compared to limited forms (all p<0.05). NT-3 levels were similar in SSc and in the control group (2657.2 ± 2296 vs 2959.3 ± 2555 pg/mL, NS). BDNF levels correlated negatively with increased NGF levels in the SSc group (and not in controls). CONCLUSION: Low BDNF serum levels were not previously documented in SSc, particularly in the diffuse SSc subset and in patients with pulmonary hypertension or anti-Scl-70 antibodies. The negative correlation between NGF and BDNF levels observed in SSc and not in healthy controls could be implicated in sympathic vascular dysfunction in SSc

Manifestations digestives de la Périartérite noueuse, du syndrome de Churg et Strauss et de la Micropolyangéite (étude rétrospective de 21 cas)

LIMOGES-BU Médecine pharmacie (870852108) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Prévalence de la tubulopathie proximale infraclinique chez le patient VHB chronique naïf de tout traitement

LIMOGES-BU Médecine pharmacie (870852108) / SudocSudocFranceF

Reply to: Renal impairment is frequent in chronic hepatitis C patients under triple therapy with telaprevir or boceprevir.

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BDNF levels and liver stiffness in subjects with alcohol use disorder: Evaluation after alcohol withdrawal

International audienceBackground: Brain-derived neurotrophic factor (BDNF) plays a key role in the processes of withdrawal and addiction in alcohol use disorder (AUD), and is also involved in liver homeostasis. The role of BDNF in liver damage and its link with liver stiffness are not known. We hypothesize that serum BDNF levels are linked to changes in hepatic elasticity, both of which depend on variations in alcohol consumption.Objectives: We aimed to study the evolution of BDNF levels and changes in the liver stiffness (LS) of AUD subjects, within two months following withdrawal.Methods: We measured LS by FibroScan® (as an indicator of the degree of liver fibrosis), gamma glutamyl transferase (GGT) levels (as a nonspecific but sensitive marker of liver status) and serum BDNF levels of 62 alcohol-dependent subjects without previously identified liver complications. Measures were obtained at the time of withdrawal (M0) and two months later (M2). Results: BDNF levels increased after alcohol withdrawal and small variations of LS were observed. BDNF values increased significantly according to fibrosis stages measured by LS (p = .028 at M0), and were predicted by GGT levels in a regression model (p = .007 at M0 and p = .003 at M2).Conclusion: In AUD, BDNF levels were associated with measured LS when divided into fibrosis risk categories. Changes in LS and BDNF levels after alcohol withdrawal may be related to changes in homeostatic mechanisms, in addition to those of liver status

Ribavirin in chronic hepatitis C: past and future

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Polyneuropathy with demyelinating features in mixed cryoglobulinemia with hepatitis C virus infection

International audiencePeripheral neuropathy can arise from various mechanisms during hepatitis C virus (HCV) infection, mainly involving associated mixed cryoglobulinemia. The frequency of demyelinating polyneuropathy is probably underestimated in these patients. We report two cases of demyelinating polyneuropathy in HCV-infected patients. The first case concerned a 76-year-old woman followed for hepatitis C associated with a mixed cryoglobulinemia (type II), who developed a chronic progressive distal motor weakness and sensory disturbances concomitant with a raise in serum aspartate aminotransferase (GOT/AST) and alanine aminotransferase (GPT/ALT) levels. Other laboratory studies were normal except for a decrease in the hemolytic fraction of complement to 75 IU (n = 400-520). The second case was a 68-year-old woman followed for hepatitis C associated with a mixed cryoglobulinemia (type II), who had sensory disturbances in the lower limbs. Laboratory studies were otherwise unremarkable. Cerebrospinal fluid studies showed a normal protein content without pleocytosis in both patients. In both cases nerve conduction studies were suggestive of a mixed axonal and demyelinating sensorimotor neuropathy. Sural nerve biopsy showed segmental demyelination and severe loss of large myelinated fibers as well as some onion bulb formation in both cases. The two patients subsequently improved, the first with an antiviral treatment and the second with oral steroids