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SummaryBackground Data on HCV-related hepatocellular carcinoma (HCC) early recurrence in patients whose HCC was previously cured, and subsequently treated by direct-acting antivirals (DAAs), are equivocal. Aim To assess the risk of HCC early recurrence after DAAs exposure in a large prospective cohort of HCV-cirrhotic patients with previous successfully treated HCC, also looking for risk factors for cancer early recurrence. Methods We enrolled 143 consecutive patients with complete response after curative treatment of HCC, subsequently treated with DAAs and monitored by the web-based RESIST-HCV database. Clinical, biological, and virological data were collected. The primary endpoint was the probability of HCC early recurrence from DAA starting by Kaplan-Meier method. Results Eighty-six per cent of patients were in Child-Pugh class A and 76% of patients were BCLC A. Almost all patients (96%) achieved sustained virological response. Twenty-four HCC recurrences were observed, with nodular or infiltrative pattern in 83% and 17% of patients, respectively. The 6-, 12- and 18-month HCC recurrence rates were 12%, 26.6% and 29.1%, respectively. Main tumour size and history of prior HCC recurrence were independent risk factors for HCC recurrence by Cox multivariate model. Conclusions Probability of HCC early recurrence in patients who had HCC previously cured remains high, despite HCV eradication by DAAs. Risk was comparable but not higher to that reported in literature in DAA-untreated patients. Previous HCC recurrence and tumour size can be used to stratify the risk of HCC early recurrence. Further studies are needed to assess impact of DAAs on late recurrence and mortality.

Many open questions remain to be elucidated about the diagnosis, treatment and prognosis of medullary thyroid cancer (MTC). The most intriguing concerns the outcome of MTC patients after surgery. Great importance is usually given to serum calcitonin (Ct) and carcinoembryonic (CEA) levels. It is commonly believed that the higher are the levels of these tumor markers and their kinetics (double time and velocity of markers levels) the worst is the prognosis. However, this is not the rule, as there are huge MTC metastatic deposits characterized by low serum Ct and CEA levels, and this condition is not closely related to the outcome of the disease during post-surgical follow-up. A series is reported here of patients who have these characteristics, as well as a description of their prognosis and clinical outcome.

Introduction : The increased life expectancy of HIV patients in the era of highly active antiretroviral therapy has had profound consequences for the healthcare systems that provide their care. It is useful to assess whether healthcare resources need to be adapted to the different stages of HIV infection or to patient characteristics [1]. To study how patient features influence utilization of out patient services, we retrospectively analyzed the electronic health record of HIV-positive patients who had followed day-care programs at the AIDS Center of the University of Palermo, Italy. Materials and Methods : 223 HIV-infected subjects were recruited and divided into two groups according to CD4 cell counts (117 with a CD4 count ≤500/mm 3 and 106 with CD4 count ≥500/mm 3 ). Data on age, gender, race, lifestyle habits (including educational level, drug abuse history, smoking status, alcohol consumption, sexual behaviour) BMI, HIV-RNA, CD4+ T-cell count, antiretroviral therapy (ART), comorbidities such as HCV co-infection, osteoporosis biomarker, dyslipidemia, diabetes, renal function and systolic and diastolic blood pressure were recorded in a purposely designed database and were analyzed in relation to AIN by uni- and multivariable logistic regression. Results : Table 1 shows the characteristics of enrolled patients; the average age of the recruited patients was 45.4±9.5 years. 163 individuals were male (73%), 26 were immigrants (12%) and 91 (40%) were treatment-naive. Mean day care access for laboratory tests to evaluate stage of HIV and for treatment monitoring was 6.5 days for CD4 cell count measurements and 9.6 for HIV RNA/drug-resistance testing. When patients were stratified according to CD4 count, mean day care access for laboratory tests to evaluate HIV stage and to monitor treatment was negatively correlated with CD4 cell counts. Conclusions : Only patients with CD4 counts ≤500/mm 3 showed higher rates of healthcare utilization; these data may be useful for monitoring and revising implementation plans for the different phases of HIV disease. (Published: 2 November 2014) Citation : Abstracts of the HIV Drug Therapy Glasgow Congress 2014 Di Carlo P et al. Journal of the International AIDS Society 2014, 17(Suppl 3) :19611 http://www.jiasociety.org/index.php/jias/article/view/19611 | http://dx.doi.org/10.7448/IAS.17.4.19611

Purpose: We aimed to assess the diagnostic reliability of two indirect biomarkers, APRI and FIB-4, for the staging of liver fibrosis using transient elastography (TE) as reference standard, among HIV/HCV co-infected and HCV mono-infected patients. Methods: This is an observational, retrospective study on subjects who had access to the RESIST HCV from October 2013 to December 2016, a regional network encompassing 22 hospitals and academic centers throughout Sicily. Sensitivity, specificity and diagnostic accuracy of indirect biomarkers for liver stiffness measurement (LSM) < 9.5kPa (significant fibrosis) and LSM ≥ 12.5kPa (cirrhosis) were determined by receiver operator characteristics (ROC) curves. Results: 238 HIV/HCV co-infected and 1937 HCV mono-infected patients were included. Performances of FIB-4 and APRI for the detection of significant fibrosis and cirrhosis proved to be unsatisfactory, with very high false negative and false positive rates among both cohorts. No significant differences were found after stratification of HIV/HCV co-infected patients for BMI < or ≥ 25, ALT < or ≥ 40IU/L, ALT < or ≥ 80IU/L, and presence/absence of a bright liver echo pattern on ultrasonography. Conclusions: Differently from other studies, we detected the unreliability of APRI and FIB-4 for the assessment of liver fibrosis in both HCV mono-infected and HIV/HCV co-infected patients.

Background & Aims: Studies have produced conflicting results of the incidence of hepatocellular carcinoma (HCC) in patients with hepatitis C virus–associated cirrhosis treated with direct-acting antivirals (DAAs). Data from clinics are needed to accurately assess the occurrence rate of HCC in patients with cirrhosis in the real world. Methods: We collected data from a large prospective study of 2,249 consecutive patients (mean age = 65.4 years, 56.9% male) with hepatitis C virus–associated cirrhosis (90.5% with Child-Pugh class A and 9.5% with Child-Pugh class B) treated with DAAs from March 2015 through July 2016 at 22 academic and community liver centers in Sicily, Italy. HCC occurrence was evaluated by Kaplan-Meier curves. Cox regression analysis was used to identify variables associated with HCC development. Results: A sustained virologic response (SVR) was achieved by 2,140 patients (total = 95.2%; 95.9% with Child Pugh class A and 88.3% with Child Pugh class B; P

Several studies have demonstrated the efficacy of the oral pre-exposure prophylaxis (PrEP) with tenofovir (with or without emtricitabine) on preventing HIV-negative partners of HIV infected patients to become infected through sexual contacts. PrEP is already available in the United States and now is approved by European Medicine Agency. In this setting we would like to gauge physicians’ knowledge, acquaintance with and attitude to include PrEP in their clinical practice. A cross sectional survey was conducted among Italian physicians expert on antiretroviral therapy. Out of 146 physicians, 35% of participants declared to be familiar with PrEP but only 46% of them believed that, currently, there are not enough reasons to make it available in Italy. 51% of physicians have already been attracted to prescribe it and 63.4% have been openly asked about PrEP. The main concerns noticed were: the risk of acquire other sexual transmitted diseases (STDs) (70% of physicians feared that PrEP could favor STDs spread), the potential harmful of PrEP if not adequately implemented and, especially the risk of possible side effects if not properly used. Nevertheless, 55.9% of participants believed that Health Authorities face an ethical obligation to make PrEP available as part of the strategies to protect from HIV transmission and half of the respondents asked for further researches to better define the role for PrEP. Attitudes regarding PrEP impact on Italian National Health Organization were also very interesting: 57.5% of participants did not believe that investing in PrEP would be an appropriate use of healthcare resources, while 70.6% affirmed that PrEP’s financial coverage should not be funded by the Italian National System of Health (SSN). This survey showed a high awareness of PrEP potential among Italian physicians coupled with a great deal of skepticism about how and if implementing it in clinical practice.

BACKGROUND: Conflicting data have been reported on the prevalence of liver steatosis, its risk factors and its relationship with fibrosis in patients with human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infection or with HCV mono-infection. AIM: The study aims were to assess steatosis prevalence and its risk factors in both HCV groups. We also evaluated whether steatosis was linked with advanced fibrosis. Sixty-eight HIV/HCV co-infected and 69 HCV mono-infected patients were consecutively enrolled. They underwent liver ultrasonography and transient elastography. Bright liver echo-pattern was used to diagnose steatosis; advanced fibrosis was defined as liver stiffness ≥ 9.5 kPa and FIB-4 values ≥ 3.25. The optimal stiffness cut-off according to FIB-4 ≥ 3.25 was evaluated by ROC analysis. RESULTS: No significant difference was found in steatosis-prevalence between mono- and co-infected patients (46.3 vs. 51.4%). Steatosis was associated with triglycerides and impaired fasting glucose/diabetes in HCV mono-infected, with lipodystrophy, metabolic syndrome, total-cholesterol and triglycerides in co-infected patients. Stiffness ≥ 9.5 was significantly more frequent in co-infection (P < 0.003). Advanced fibrosis wasn't significantly associated with steatosis. The area under the ROC curve was 0.85 (95% CI 0.79-0.9). On multivariate analysis steatosis was associated with triglycerides in both HCV mono- and co-infected groups (P < 0.02; P < 0.03). CONCLUSION: Although steatosis was common in both HCV mono- and co-infected patients, it was not linked with advanced fibrosis. Triglycerides were independent predictors of steatosis in either of the HCV-groups. Dietary interventions and lifestyle changes should be proposed to prevent metabolic risk factors.

Vitamin D deficiency further increases the risk of osteoporosis in HIV-positive patients coinfected with hepatitis C virus (HCV); however, it is still unclear whether HCV-related increased fracture risk is a function of the severity of liver disease. The aim of this review was to identify studies on associative vitamin D deficiency patterns in high-risk populations such as HIV/HCV coinfected patients. We did this by searching MEDLINE and EMBASE databases, from inception to August 2014, and included bibliographies. The final 12 articles selected are homogeneous in terms of age but heterogeneous in terms of sample size, participant recruitment, and data source. Most of the HIV/HCV coinfected patients have less than adequate levels of vitamin D. After reviewing the selected articles, we concluded that vitamin D deficiency should be regarded as a continuum and that the lower limit of the ideal range is debatable. We found that vitamin D deficiency might influence liver disease progression in HIV/HCV coinfected patients. Methodological issues in evaluating vitamin D supplementation as a relatively inexpensive therapeutic option are discussed, as well as the need for future research, above all on its role in reducing the risk of HCV-related fracture by modifying liver fibrosis progression.

Background: Limited data are available on hepatic steatosis (HS) in HIV patients who are not infected with hepatitis C virus (HCV). The aims of this study were to assess the prevalence of HS and its risk factors in HIV patients with and without HCV infection, and to evaluate whether HS correlates with advanced liver fibrosis and/or cardiovascular disease risk. Methods: Fifty-seven HIV mono-infected and 61 HIV/HCV co-infected patients were enrolled consecutively. All patients underwent liver ultrasound and transient elastography. The main parameters of liver function, HIV and HCV viral loads, CD4+ cell counts, and data on highly active antiretroviral therapy (HAART) were recorded. Cardiovascular disease risk was evaluated using the 10-year Framingham risk score. Results: HS prevalence in the whole HIV population was 53% (54% in mono-infected patients and 51% in co-infected patients). HS was associated with lipodystrophy and triglyceride values (p < 0.0001), metabolic syndrome (p < 0.0004), and total cholesterol levels (p < 0.001) in both HIV groups. In HIV mono-infected patients, HS was linked with HAART exposure of >1 year (p < 0.01). By multivariate analysis, only triglyceride levels (p < 0.02) and Framingham risk score (p < 0.05) were independently associated with HS in both HIV groups. No correlation was observed between HS and advanced liver fibrosis, measured by transient elastography. Conclusions: HS was common in HIV patients, occurring in about half of the population. HS was found to be linked with the Framingham risk score, but was not correlated with advanced liver fibrosis. We suggest that in our HIV population with HS, the burden of cardiovascular disease risk is greater than that of liver disease progression.

Blackground It is well-known that Epstein-Barr virus (EBV) can affect the central nervous system (CNS). Case presentation Herein the authors report unusual timely Magnetic Resonance Imaging (MRI) brain scan findings in an immunocompetent patient with EBV encephalitis. Diffusion weighted MRI sequence performed during the acute phase of the disease was normal, whereas the Fast Relaxation Fast Spin Echo T2 image showed diffuse signal intensity changes in white matter. The enhancement pattern suggested an inflammatory response restricted to the brain microcirculation. Acyclovir and corticosteroid therapy was administered. After three weeks, all signal intensities returned to normal and the patient showed clinical recovery. Conclusion This report demonstrates that EBV in an immunocompetent adult can present with diffuse, reversible brain white matter involvement in the acute phase of mononucleosis. Moreover, our case suggests that a negative DWI sequence is associated with a favorable improvement in severe EBV CNS infection. More extensive studies are needed to assess what other instrumental data can help to distinguish viral lesions from other causes in the acute phase of disease.

Mediterranean spotted fever (MSF) is a tick-borne acute febrile disease caused by Rickettsia conorii and characterized by fever, maculo-papular rash and a black eschar at the site of the tick bite (‘tache noir’). We describe the case of a 58-year-old man affected by MSF who developed atrial fibrillation. The patient presented himself to the hospital after 7 days of fever, malaise and severe headache. Cardiac auscultation revealed a chaotic heart rhythm and an electrocardiogram confirmed atrial fibrillation with a fast ventricular response. Diagnosis of MSF was made after the appearance of a maculo-papular skin rash, and treatment with oral doxycycline was started. An immunofluorescence antibody test confirmed R. conorii infection. The patient recovered after 7 days of treatment. Cardiac arrhythmia is a rare complication of MSF. Inflammation may play a role in the pathogenesis of atrial fibrillation. R. conorii is an intracellular bacterium which could trigger atrial fibrillation. Our patient was previously healthy and had no reported history of cardiac disease. This suggests that heart function should be monitored in MSF patients even in the absence of underlying risk factors.

AIM: To assess the prevalence of advanced liver fibrosis (ALF) in human immunodeficiency virus (HIV), hepatitis C virus (HCV) and HIV/HCV patients using transient elastography, and to identify factors associated with ALF. METHODS: Between September 2008 and October 2009, 71 HIV mono-infected, 57 HIV/HCV co-infected and 53 HCV mono-infected patients on regular follow-up at our Center were enrolled in this study. Alcohol intake, the main parameters of liver function, presence of HCV-RNA, HIV-RNA, duration of highly active anti-retroviral therapy (HAART) and CD4 cell count were recorded. ALF was defined as liver stiffness (LS) ≥ 9.5 kPa. To estimate liver fibrosis (LF) a further 2 reliable biochemical scores, aspartate aminotransferase platelet ratio index (APRI) and FIB-4, were also used. RESULTS: LS values of co-infected patients were higher than in either HIV or HCV mono-infected patients (c2MH = 4, P < 0.04). In fact, LS ≥ 9.5 was significantly higher in co-infected than in HIV and HCV mono-infected patients (c2 = 5, P < 0.03). Also APRI and the FIB-4 index showed more LF in co-infected than in HIV mono-infected patients (P < 0.0001), but not in HCV mono-infected patients. In HIV⁄HCV co-infected patients, the extent of LS was significantly associated with alcohol intake (P < 0.04) and lower CD4+ cell count (P < 0.02). In HCV patients, LS was correlated with alcohol intake (P < 0.001) and cholesterol levels (P < 0.03). Body mass index, diabetes, HCV- and HIV-viremia were not significantly correlated with LS. In addition, 20% of co-infected patients had virologically unsuccessful HAART; in 50% compliance was low, CD4+ levels were < 400 cells/mm3 and LS was > 9.5 kPa. There was no significant correlation between extent of LF and HAART exposure or duration of HAART exposure, in particular with specific dideoxynucleoside analogues. CONCLUSION: ALF was more frequent in co-infected than mono-infected patients. This result correlated with lower CD4 levels. Protective immunological effects of HAART on LF progression outweigh its hepatotoxic effects.