Martina Spaziante

Pretreatment predictive factors for hepatitis C therapy outcome: relevance of anti-E1E2 antibodies compared to IP-10 and IL28B genotypes.

BACKGROUND Unique serum anti-E1E2 antibodies were shown to be associated with spontaneous recovery or predictive of sustained virological response (SVR) in patients with chronic hepatitis C receiving pegylated interferon/ribavirin (PEG-IFN/RBV) therapy. The objectives were to establish the relationship between pretreatment anti-E1E2 titres and HCV RNA kinetics during PEG-IFN/RBV therapy, and to examine whether the combined determination of interleukin (IL)28B rs12979860 and rs8099917, pretreatment inducible protein (IP)-10 levels and/or anti-E1E2 improved the prediction of SVR. METHODS Sera from 26 treatment-naive consecutive HCV patients treated with PEG-IFN/RBV for 48 weeks were analysed. Serum anti-E1E2 titres and pretreatment IP-10 levels were measured by enzyme-linked immunosorbent assays. The IL28B variants were determined using genotyping real-time polymerase chain reaction method. Viral decline was measured at weeks (W) 4 and 12 and SVR assessed 6 months after the end of therapy. RESULTS Baseline anti-E1E2 titres were correlated with HCV RNA decline at W4 and W12 and were highly predictive of SVR with 100% of patients negative for anti-E1E2 failing to achieve SVR. Receiver operating characteristic curve analyses indicate that the best prediction of SVR (AUC 0.990) was obtained with the combination of anti-E1E2 and IP-10 levels. Predictive values were better than those obtained with IP-10 alone or in combination with IL28B variants. CONCLUSIONS Pretreatment serum anti-E1E2 response predicts HCV RNA clearance kinetics and treatment outcome. The combination of anti-E1E2 and IP-10 significantly improved the prediction of treatment response. This warrants further investigation and validation on larger cohorts of patients in the context of new therapeutic strategies.

Lung Infections in Systemic Rheumatic Disease: Focus on Opportunistic Infections

Systemic rheumatic diseases have significant morbidity and mortality, due in large part to concurrent infections. The lung has been reported among the most frequent sites of infection in patients with rheumatic disease, who are susceptible to developing pneumonia sustained both by common pathogens and by opportunistic microorganisms. Patients with rheumatic disease show a peculiar vulnerability to infectious complications. This is due in part to intrinsic disease-related immune dysregulation and in part to the immunosuppressive treatments. Several therapeutic agents have been associated to a wide spectrum of infections, complicating the management of rheumatic diseases. This review discusses the most frequent pulmonary infections encountered in rheumatic diseases, focusing on opportunistic agents, consequent diagnostic challenges and appropriate therapeutic strategies.

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

Correction to: A challenging case of carbapenemase-producing Klebsiella pneumoniae septic thrombophlebitis and right mural endocarditis successfully treated with ceftazidime/avibactam

IntroductionThe emergence of carbapenemase-producing Klebsiella pneumonia (KPC-Kp) has become a significant problem in terms of public health and clinical outcome in many hospitals in Southern Europe. Treatment options are usually limited and effective treatment of infections caused by these pathogens is a considerable challenge for clinicians. Ceftazidime–avibactam has been recently approved for the treatment of difficult-to-treat infections due to aerobic Gram-negative organisms in patients with limited treatment options.Case reportWe reported the first case of KPC-Kp septic thrombophlebitis and right atrial endocarditis associated with metastatic lung abscesses successfully treated with a prolonged ceftazidime/avibactam plus ertapenem treatment course, suggesting that this combination therapy could be safe and effective for serious Gram-negative infections. Interestingly, we also observed an apparent discrepancy between clinical and microbiological courses: the patient became rapidly afebrile; hemodynamically stable and his procalcitonin levels showed a prompt decreasing trend. Nevertheless, blood cultures remained persistently positive for a prolonged period.ConclusionIn conclusion, ceftazidime–avibactam plus ertapenem was a safe and effective therapy of serious endovascular infection due to KPC-Kp. Moreover, in this setting, follow-up blood cultures might represent an irreplaceable tool to guide the therapy.

Specific dynamic of serum procalcitonin in critically ill patients affected by Gram-negative bacilli septic thrombophlebitis

We read with interest the study by Thomas-Rüddel et al. [1] evaluating the influence of specific pathogens and different foci of infections on serum procalcitonin (PCT) concentrations. The authors concluded that PCT levels were higher in patients with Gram-negative bacteremia compared with patients with Gram-positive or fungal diseases, whereas urogenital and abdominal foci of infection were associated with twofold increased PCT values, independent of causative pathogen. Unfortunately, this study did not provide data on PCT trends in patients affected by endovascular infections. We recently collected a small series of 13 cases of endovascular infections caused by thrombophlebitis due to Gram-negative bacilli (GNB) in the intensive care unit (ICU) of a large University Hospital in Italy. The mean age of patients enrolled was 59.2 ± 13.6 years with a predominance of male sex (61.5%); the mean SAPS II at the admission was 39.7 ± 8.1 points and the most frequent cause of ICU admission was a recent polytrauma (84.6%). All patients had persistent bacteremia despite administration of in vitro active antibiotics and removal of intravascular devices. The diagnosis of septic thrombophlebitis was corroborated by CT scan (53.8%) or echodoppler (46.2%), and thrombus appositions mainly involved aortic trunks (61.5%). The blood isolates were four Klebsiella pneumoniae, four Acinetobacter baumannii, one Enterobacter spp., one Pseudomonas aeruginosa, one Morganella morganii, one Providencia rettgeri, and one Klebsiella oxytoca. Despite the prolonged duration of bacteremia and the appropriate antibiotic therapy, all patients showed an indolent clinical course, with no multi-organ failure, prompt clinical improvement, and rapid decrease of plasma PCT concentrations within normal ranges after the onset of septic episodes (Fig. 1). As previously reported, PCT is produced in response to inflammatory cytokines and bacterial endotoxins [2]. In our cases the rapid decrease of PCT, followed by a stable normalization of serum concentration despite persistence of bacteremia, could be explained with the well-known mechanism of immune tolerance: in fact the selective blocks of some pro-inflammatory pathways, activated by bacterial endotoxins or cytokines, could impact on the production of PCT and favor a long indolent clinical course, even in the face of microbial eradication failure [3]. In conclusion, we think that our data could contribute to complete the results of Thomas-Rüddel et al. and are worthy of being further investigated in a

IL28B Gene Polymorphisms and US Liver Fatty Changes in Patients Who Spontaneously Cleared Hepatitis C Virus Infection

Background Recent clinical studies have shown that the presence of CC genotype in the rs12979860 region of IL28B gene is associated with an increase in the probability of spontaneous clearance of hepatitis C virus (HCV). Moreover, IL28B polymorphism seems to influence the probability of developing liver steatosis in chronic HCV patients. Aims The aims of our clinical study were 1) to verify the distribution of IL28B genotypes (CC, CT or TT) among subjects with spontaneous clearance of HCV infection and 2) to examine the correlation between IL28B polymorphism and hepatic steatosis among these subjects. Methods and patients We enrolled 41 subjects with spontaneous resolution of HCV infection (detectable serum anti-HCV but undetectable HCV-RNA) and 134 healthy controls from the same geographical area. The IL28B single-nucleotide polymorphism (SNP) rs12979860 was genotyped by using a Pyrosequencing™ technique. The presence of steatosis was assessed by liver biopsy or ultrasound examination in the 41 study subjects. Results CC, CT and TT-genotypes of the SNP rs1979860 were found in 66%, 24% and 10% of the subjects who spontaneously cleared HCV and in 31%, 54% and 15% of controls, respectively (p = 0.0003). Among the study subjects, females with CC-genotype were significantly more represented (p = 0.02). Hepatic steatosis did not correlate with IL28B genotype (p = 0,14) but only with a high body mass index (BMI) value (p = 0.03). Conclusions Female subjects carrying IL28B CC-genotype are significantly more represented among Italian patients who spontaneously cleared HCV infection. In addition, among these subjects, the presence of liver steatosis does not correlate with IL28B genotype but is solely related to the occurrence of high BMI. Thus, the association between IL28B polymorphism and steatosis in chronic HCV patients requires the presence of active HCV replication to occur, while in subjects who have cleared the infection, the mechanism(s) inducing liver steatosis are independent from IL28B profile.

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.

Acute hepatitis B in a patient with OLT during treatment with peg-interferon and ribavirin for hepatitis C recurrence

Abstract The course and outcome of acute viral hepatitis in liver transplanted patients with hepatitis C recurrence are unknown. Here we describe a patient who presented with acute hepatitis B infection while on treatment with peg-interferon and ribavirin for hepatitis C recurrence after liver transplantation. A nucleoside analogue was added (entecavir) and the patient cleared hepatitis C virus (HCV) infection and seroconverted to anti-HBs. In this case, the acute hepatitis B virus (HBV) infection might have contributed to the clearance of HCV, the concomitant immunosuppression might have lead to the slow clearance of HBV infection, and the combined antiviral therapy has helped in the resolution of both infections. Hepatitis B vaccination should be recommended in susceptible patients waiting for liver transplantation.