D. Palazzo

Interleukin 18: A Biomarker for Differential Diagnosis Between Adult-onset Still’s Disease and Sepsis

Objective. The differential diagnosis between rheumatic diseases and infectious conditions is a great challenge in clinical practice. Adult-onset Still’s disease (AOSD) is a rare systemic inflammatory syndrome that shares several clinical and laboratory variables with sepsis. Interleukin (IL)-18 is overexpressed in AOSD, suggesting a possible role as a disease biomarker. The aim of our study was to detect IL-18 serum levels in a cohort of patients with AOSD and sepsis and to address its possible role as a biomarker for differential diagnosis. Methods. A group of unselected patients with AOSD diagnosed according to the Yamaguchi criteria and consecutive patients with sepsis diagnosed according to the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference criteria were enrolled. The clinical and laboratory data were collected. In the AOSD group, disease activity was assessed by Pouchot’s and Rau’s criteria. IL-18 serum levels were detected by ELISA. Results. Thirty-nine patients with AOSD and 18 patients with sepsis were enrolled. Two out of 18 patients with sepsis (11.1%) also fulfilled the Yamaguchi criteria. A significant difference was found in IL-18 serum levels between patients with active and inactive disease (p < 0.001), and it positively correlated with disease activity (p = 0.0003), ferritin serum level (p = 0.016), and erythrocyte sedimentation rate (p = 0.041). IL-18 was significantly increased in patients with AOSD when compared with sepsis (p = 0.014). For a cutoff of 148.9 pg/ml, this test had a specificity of 78.3% and a sensitivity of 88.6%. Conclusion. We have demonstrated that IL-18 can be a biomarker for differential diagnosis between AOSD and sepsis.

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

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.

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.