Rozenn Esvan

Gender differences in chronic HBsAg carriers in Italy: Evidence for the independent role of male sex in severity of liver disease

It has been shown that sexual hormones have an opposite effect on hepatic fibrosis progression and hepatocellular carcinoma development. Sex differences among 2,762 chronic HBsAg carriers consecutively referring Italian hospitals in 2001 and in 2007 have been evaluated, particularly focusing on the role of gender on severity of liver disease. The overall sex ratio (males/females) was 2.6. Females were more likely born abroad and new diagnosis cases; but less likely HIV coinfected. No sex difference was observed regarding coinfection with other hepatitis viruses. The sex ratio linearly increased with increasing severity of liver disease, being 1.3 in normal ALT, 2.8 in chronic hepatitis, 3.6 in liver cirrhosis, and 6.8 in hepatocellular carcinoma. Adjustment by multiple logistic regression analysis for the confounding effect of age, alcohol intake, HDV infection, HCV infection, and BMI shows that male gender is an independent predictor of the likelihood of more severe liver disease (O.R. 1.7; C.I. 95% = 1.3–2.1). HBV‐DNA levels resulted not associated with the outcome of chronic HBV infection. Despite some potential risk factors associated with liver disease, such as HBV genotype or mutations, not having been controlled for due to lack of availability, the observed sex disparity in the outcome of chronic HBV infection may support biological obervation that HBV infection could be considered a sex hormone–responsive virus. J. Med. Virol. 87:1899–1903, 2015.

Interferon free antiviral treatment of chronic hepatitis C in patients affected by β-thalassemia major

Dear Editor, Chronic hepatitis C (CHC) significantly affects the prognosis of liver disease [1] and health related quality of life (HRQOL) in patients with β-thalassemia major [2, 3]. CHC cure is a crucial event in the prognosis of the disease, since prevents fibrosis progression, decreases the risk of hepatocellular carcinoma (HCC), and improves survival. Standard antiviral therapy with Pegylated Interferon (PEG-IFN) and Ribavirin (RBV) has long been the standard of care, despite its limited efficacy and increased ribavirin induced hematological adverse events in thalassemic patients [4]. Recently, several novel highly effective direct antiviral agents (DAAs) have been approved for HCV treatment, with impressive cure rates, higher than 90%, after 8–12 weeks of therapy and mild adverse events [5], but there are no published reports documenting the efficacy, safety and impact on QOL of available interferon-free antiviral regimens in patients with βthalassemia major. We describe four cases of young patients with βthalassemia major and advanced fibrosis treated with DAAs for CHC (Table 1). HCV genotype was 1b in all p a t i e n t s e x c e p t o n e , wh i c h h a d g en o t y p e 4 . Cryoglobulins were positive in two patients (cryocrit 1.6 and 3.2%) with no organ involvement. All patients were previously non-responders to PEG-IFN ± RBV treatment. Iron chelation drugs included subcutaneous desferrioxamine and/or oral deferasirox. Antiviral therapy with sofosbuvir (SOF) and ledipasvir (LDV) was started for 12 weeks. All patients achieved sustained virologic response (SVR). Treatment was safe and well tolerated, kidney function remained stable, and the only adverse events were mild asthenia and headache. Iron chelation concomitant medications remained unmodified during treatment, as well as the frequency of blood transfusions. Ferritin levels decreased during therapy in three patients, but in two of them returned to baseline levels at FU3. A reduction of liver stiffness, assessed by transient elastography, occurred from baseline to FU3 in all subjects. All SF36 scales related to mental health and to physical health significantly improved at FU6 compared to baseline (Table 2). The present case series suggests that 12-week-combination therapy of SOF/LDV is effective and safe in transfusiondependentβ-thalassemia patients with advanced liver fibrosis. Remarkably, no impact of SOF on kidney function was observed as e-GFR values remained stable during therapy and FU. To our knowledge, no data exist on the interactions between DAAs and iron chelation drugs. We employed SOF and LDV in these patients because this drug combination is associated with limited interactions [6]. Remarkably, in none of the cases, it was necessary to modify iron chelation therapy, and no changes in transfusion requests occurred. Moreover, serum ferritin values, an indirect marker of iron chelation efficacy, showed an improvement during antiviral therapy in all patients but one who reported poor compliance to iron chelation therapy during DAA treatment. A marked improvement of liver stiffness, which correlates with fibrosis stage assessed by liver biopsy [7], was observed in all patients. This result may be partly due to a reduction and control of liver inflammation [8]; however, an initial regression of liver fibrosis might also have occurred, which is an * Elisa Biliotti elisabiliotti@yahoo.it

Impaired flow-mediated dilation in hospitalized patients with community-acquired pneumonia

BACKGROUND Community-acquired pneumonia (CAP) is complicated by cardiovascular events as myocardial infarction and stroke but the underlying mechanism is still unclear. We hypothesized that endothelial dysfunction may be implicated and that endotoxemia may have a role. METHODS Fifty patients with CAP and 50 controls were enrolled. At admission and at discharge, flow-mediated dilation (FMD), serum levels of endotoxins and oxidative stress, as assessed by serum levels of nitrite/nitrate (NOx) and isoprostanes, were studied. RESULTS At admission, a significant difference between patients with CAP and controls was observed for FMD (2.1±0.3 vs 4.0±0.3%, p<0.001), serum endotoxins (157.8±7.6 vs 33.1±4.8pg/ml), serum isoprostanes (341±14 vs 286±10 pM, p=0.009) and NOx (24.3±1.1 vs 29.7±2.2μM). Simple linear correlation analysis showed that serum endotoxins significantly correlated with Pneumonia Severity Index score (Rs=0.386, p=0.006). Compared to baseline, at discharge CAP patients showed a significant increase of FMD and NOx (from 2.1±0.3 to 4.6±0.4%, p<0.001 and from 24.3±1.1 to 31.1±1.5μM, p<0.001, respectively) and a significant decrease of serum endotoxins and isoprostanes (from 157.8±7.6 to 55.5±2.3pg/ml, p<0.001, and from 341±14 to 312±14 pM, p<0.001, respectively). Conversely, no changes for FMD, NOx, serum endotoxins and isoprostanes were observed in controls between baseline and discharge. Changes of FMD significantly correlated with changes of serum endotoxins (Rs=-0.315; p=0.001). CONCLUSIONS The study provides the first evidence that CAP is characterized by impaired FMD with a mechanism potentially involving endotoxin production and oxidative stress.

Occurrence of intestinal parasites among asylum seekers in Italy: A cross-sectional study

BACKGROUND In recent years Europe has experienced a dramatic increase in migration flows. Nevertheless, limited data is available about the occurrence of neglected parasitic diseases among migrant population. The purpose of the present study was to evaluate the prevalence of intestinal and urinary parasites in newly arrived asylum seekers. METHODS A total of 364 newly arrived migrants hosted at the Asylum Seekers Centre of Castelnuovo di Porto (Italy) were screened during 8 months period for intestinal and urinary parasites. Each enrolled subject was interviewed using a standardized questionnaire, with focus on socio-demographical data and risk factors of parasitic infections. RESULTS Stool analysis showed a prevalence of intestinal parasites of 20.6%. The travel route did not affect the prevalence of intestinal parasites (p = 0.096), while a significant negative correlation was found between the length of travel and the prevalence of parasite infection (p = 0.019). No statistically significant correlation between gastrointestinal symptoms and the presence of intestinal parasites was detected. CONCLUSION The prevalence of intestinal parasitosis reported in asylum seekers does not necessarily reflect the prevalence of the parasitosis in the motherland. An anamnestic and syndromic approach may not be sufficient to highlight the problem of intestinal parasitic infestations in a screening setting.

Anti‐HBs seroconversion during treatment with entecavir in a patient with chronic hepatitis B virus infection on hemodialysis

Hepatitis B (HBV) virus infection is one of the most important causes of liver disease in patients with end‐stage renal failure on hemodialysis. The natural history of chronic HBV infection acquired in childhood starts with an immune tolerant phase, followed by an immune clearance phase that may lead to the inactive carrier state or the development of chronic liver disease. Information on antiviral therapy administered very early during the immune clearance phase are lacking and no data exist on the treatment of early immune activation in the hemodialysis setting. This report describes the case of a patient affected by end‐stage renal failure and HBeAg‐positive chronic HBV virus infection treated very early during the immune clearance phase of HBV infection with an adjusted‐dose of nucleoside analogue entecavir. The patient achieved a very rapid HBV‐DNA undetectability, anti‐HBe, and anti‐HBs seroconversion. This is the first report of antiviral therapy with entecavir started during the immune reactive phase of HBV infection in a patient on hemodialysis and it suggests that antiviral treatment can enhance the effects of host immune activation resulting in biochemical, serological, and viral response, even in end‐stage renal failure patients with partial immunodeficiency. Antiviral therapy with entecavir in the setting of hemodialysis was safe and well tolerated. J. Med. Virol. 86:139–143, 2014.