Statins and aspirin in the prevention of cardiovascular disease among HIV-positive patients between controversies and unmet needs: review of the literature and suggestions for a friendly use.

BACKGROUND: As in non-infected subjects, statins and aspirin have a pivotal preventive role in reducing the cardiovascular related morbidity and mortality in HIV infected patients. The persistence of immune activation in these subjects, could contribute to accelerate atherosclerosis, therefore, these treatments that reduce inflammation could provide additional cardiovascular protection. However the current guidelines for the use of these drugs in general population are dissimilar, with important differences between American and European ones. Aim of the present position paper is to provide recommendations aimed to overcome the actual differences and limitations among the current ones and to adapt them to the needs of HIV infected patients. RESULTS: We propose to adopt the new ACC/AHA guidelines, simple to use and cost effective, to use the ASCVD score that seems to estimate more accurately the cardiovascular risk among these patients. We suggest to start statin therapy in all patients with a calculated 10-year risk of a cardiovascular event of 10% or greater. Rosuvastatin and atorvastatin should be preferred. LDL-C target may be adopted. Aspirin should be always associated with a statin, in secondary prevention, while in primary prevention it should be reserved only to patients with ≥ 20% 10-year risk particularly adherent to treatments, and with low risk of bleeding. We suggest to start with a dose of 100 mg/day. Finally, management of antiplatelet agents or novel oral anticoagulants may include selecting antiretrovirals with a lower potential for drug interactions or choosing agents least likely to interact with antiretrovirals. CONCLUSIONS: As demonstrated in surveys, HIV physicians are generally highly committed regarding CVD and autonomous in prescribing statins and ASA. Consequently, in the light of the previously discussed discrepancies among the different guidelines and of the incomplete indications regarding HIV-positive persons, the present suggestions could overcome the actual differences and limitations among the current ones.

SERPING1 mRNA overexpression in monocytes from HIV+ patients.

OBJECTIVE: The HIV-1 virus activates the complement system, an essential element of the immune system. SERPING1 is a protease inhibitor that disables C1r/C1s in the C1 complex of the classical complement pathway. METHODS: In this paper, we performed an analysis of several microarrays deposited in GEO dataset to demonstrate that SERPING1 mRNA is modulated in CD14+ monocytes from HIV-1-infected individuals. In addition, data were validated on monocytes isolated from seronegative healthy volunteers, treated with IFNs. RESULTS: Our analysis shows that SERPING1 mRNA is overexpressed in monocytes from HIV-1+ patients and the expression levels correlate positively with viral load and negatively with the CD4+ T-cell count. Of note, anti-retroviral therapy is able to reduce the levels of SERPING1 mRNA, ex vivo. In addition, we found that 30% of the SERPING1 genes network is upregulated in monocytes from HIV-1+ patients. Noteworthy, the expression levels of IFITM1-an antiviral molecule belonging to the genes network-correlate positively with SERPING1 expression. Interestingly, the monocytes treatment with IFN-gamma, IFN-beta and IFN-alpha significantly upregulates the SERPING1 mRNA expression levels. CONCLUSIONS: From the outcome of our investigation, it is possible to conclude that SERPING1 and its network serve as important components of the innate immune system to restrict HIV-1 infection.

Switching regimens in virologically suppressed HIV-1-infected patients: evidence base and rationale for integrase strand transfer inhibitor (INSTI)-containing regimens.

In an era when most individuals with treated HIV infection can expect to live into old age, clinicians should proactively review their patients' current and future treatment needs and challenges. Clinical guidelines acknowledge that, in the setting of virological suppression, treatment switch may yield benefits in terms of tolerability, regimen simplification, adherence, convenience and long-term health considerations, particularly in the context of ageing. In this paper, we review evidence from six key clinical studies on switching virologically suppressed patients to regimens based on integrase strand transfer inhibitors (INSTIs), the antiretroviral class increasingly preferred as initial therapy in clinical guidelines. We review these studies and focus on the virological efficacy, safety, and tolerability of switching to INSTI-based regimens in suppressed HIV-positive individuals. We review the early switch studies SWITCHMRK and SPIRAL [assessing a switch from a ritonavir-boosted protease inhibitor (PI/r) to raltegravir (RAL)-containing regimens], together with data from STRATEGY-PI [assessing a switch to elvitegravir (EVG)-containing regimens; EVG/cobicistat (COBI)/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) vs. remaining on a PI/r-containing regimen], STRATEGY-NNRTI [assessing a switch to EVG/COBI/FTC/TDF vs. continuation of a nonnucleoside reverse transcriptase inhibitor (NNRTI) and two nucleoside reverse transcriptase inhibitors (NRTIs)], STRIIVING [assessing a switch to a dolutegravir (DTG)-containing regimen (abacavir (ABC)/lamivudine (3TC)/DTG) vs. staying on the background regimen], and GS study 109 [assessing a switch to EVG/COBI/FTC/tenofovir alafenamide fumarate (TAF) vs. continuation of FTC/TDF-based regimens]. Switching to INSTI-containing regimens has been shown to support good virological efficacy, with evidence from two studies demonstrating superior virological efficacy for a switch to EVG-containing regimens. In addition, switching to INSTI regimens was associated with improved tolerability and greater reported patient satisfaction and outcomes in some studies. INSTI-based regimens offer an important contemporary switch option that may be tailored to meet and optimize the needs of many patients.

CD4+ T-cell gene expression of healthy donors, HIV-1 and elite controllers: Immunological chaos.

OBJECTIVES: T-cell repertoire dysfunction characterizes human immunodeficiency virus type 1 (HIV-1) infection, but the pathogenic mechanisms remain unclear. Disease progression is probably due to a profound dysregulation of Th1, Th2, Th17 and Treg patterns. The aim of this study was to analyze the features of CD4+ T cells in HIV-positive patients with different viroimmunological profile. METHODS: we used a gene expression dataset of CD4+ T cells from healthy donors, HIV+ naive patients and Elite Controllers (EC), obtained from the NCBI Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo/, accession number GSE18233). RESULTS: Principal Component Analysis (PCA) showed an almost complete overlap between the HIV-infected and EC patients, which cannot easily explain the different responses to HIV infection of these two group of patients. We have found that HIV patients and the EC showed an upregulation of the Th1 pro-inflammatory cytokines and chemokines, compared to the controls. Also, we have surprisingly identified IL28B, which resulted downregulated in HIV and EC compared to healthy controls. We focused attention also on genes involved in the constitution of the immunological synapse and we showed that HLA class I and II genes resulted significantly upregulated in HIV and in EC compared to the control. In addition to it, we have found the upregulation of others syncytial molecules, including LAG3, CTLA4, CD28 and CD3, assisting the formation of syncytia with APC cells. CONCLUSIONS: Understanding the mechanisms of HIV-associated immunological chaos is critical to strategically plan focused interventions.

Vitamin D3 inhibits TNFα-induced latent HIV reactivation in J-LAT cells.

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) is known to suppress NF-kB activity by interfering with its pathways. The aim of this study was to investigate the ability of 1,25(OH)2D3 in reducing the reactivation of the HIV virus J-LAT cells, an established model of latently infected cells, which were treated with TNFalpha (100 ng/ml) for 2 h with or without 24 h 1,25(OH)2D3 (100 nM) pretreatment. Reactivation of HIV RNA in J-LAT was evaluated in terms of green fluorescent protein (GFP) expression. The same experimental setting was repeated on T cells from HIV-infected patients. Treatment with TNFalpha was associated with a 16 % increase in GFP+ cells and a five-fold increase in unspliced HIV RNA expression (p < 0.04). Pretreatment of J-LAT cells with 1,25(OH)2D3 for 24 h followed by TNFalpha (100 ng/ml) for 2 h reduced the percentage of GFP+ cells by 8 %; moreover, a 2.4-fold decrease in unspliced HIV RNA expression was observed (p < 0.002). In T cells from patients, treatment with TNFalpha significantly increased unspliced HIV RNA expression (sixfold increase, p < 0.02), whereas prestimulation with 1,25(OH)2D3 reduced its expression (2.5-fold decrease, p < 0.02) compared to controls.1,25(OH)2D3 is able to reduce the ability of TNFalpha to upregulate the transcription of HIV RNA from latently infected cells. These data provide further understanding of the pathogenic mechanisms regulating viral reactivation from latent reservoirs, along with new insight in viral internalization.

The unwelcome trio: HIV plus cutaneous and visceral leishmaniasis.

Leishmania/Human Immunodeficiency Virus (HIV) coinfection has emerged as an extremely serious and increasingly frequent health problem in the last decades. Considering the insidious and not typical clinical picture in presence of immunosuppressive conditions, the increasing number of people travelling in endemic zones, the ability to survive, within both human and vector bodies, of the parasite, clinicians and dermatologists as the first line should be aware of these kind of "pathologic alliances," to avoid delayed diagnosis and treatment. In this setting, the occurrence of cutaneous lesions can, paradoxically, aid the physician in recognition and approaching the correct staging and management of the two (or three) diseases. Treatment of these unwelcome synergies is a challenge: apart from the recommended anti-retroviral protocols, different anti-leishmanial drugs have been widely used, according with the standard guidelines for visceral leishmaniasis (VL), with no successful treatment regimen still been established.

Tetanus immunity in construction workers in Italy.

BACKGROUND: Tetanus is a serious vaccine-preventable disease that remains a significant health risk in certain occupations. Since 2006, Italy has reported the highest number of cases in Europe. Some professions, such as construction workers, are more exposed to tetanus. AIMS: To evaluate tetanus immunity status and associated factors in construction workers in Italy. METHODS: A cross-sectional study of construction workers attending for periodic occupational health surveillance at one site in Italy between September 2011 and January 2013. Serum tetanus antitoxin levels were measured and analysed according to demographic and clinical variables. RESULTS: All 5275 workers attending for health surveillance between September 2011 and January 2013 agreed to participate. Protective tetanus antitoxin levels (>0.1 IU/ml) were found in 4116 workers (78%). Multivariate logistic regression analysis suggested that the following risk factors were significantly associated with inadequate immunization status: older age (age >58 years, odds ratio [OR] 1.78, 95% confidence intervals [CIs] 1.76-1.84), poor education (no formal education: OR 3.74, 95% CI: 3.69-3.78), unskilled work tasks (OR 2.71, 95% CI: 2.67-2.77) and country of origin (Egypt: OR 1.72, 95% CI: 1.67-1.77; Morocco: OR 1.69, 95% CI: 1.62-1.76). CONCLUSIONS: In this study, a significant proportion of construction workers in Italy were not adequately immunized against tetanus, as required by Italian law. Occupational health professionals should promote and implement vaccination campaigns, especially among migrant workers, for public health and legal reasons.

Lack of clinical and histological progression of chronic hepatitis C in individuals with true persistently normal ALT: the result of a 17-year follow-up.

Thirty to 40% of patients with chronic hepatitis C have persistently normal alanine aminotransferase (PNALT). Even though traditionally considered as healthy people, most PNALT carriers actually have some degree of clinical progression and histological liver damage. We evaluated the clinical and histological outcome of a 17-year follow-up on a cohort of patients with chronic HCV infection and PNALT. Between 1994 and 2011, 70 PNALTs and 55 Hyper-alanine aminotransferase (ALT) subjects underwent a clinical, biochemical, virological and histological follow-up. At the end of the follow-up, all patients were alive. In the PNALT group, none of the patients developed hepatic decompensation, while 14.5% of Hyper-ALTs were diagnosed as affected by decompensated cirrhosis. No significant variation of the Metavir grading and staging scores was observed among PNALTs by comparing pre- and post-follow-up liver specimens. On the contrary, a significant increase in both Metavir grading and staging scores was noticed within the Hyper-ALT group. Finally, the analysis of IL28B single-nucleotide polymorphism rs12979860 revealed no difference between Hyper-ALTs and PNALTs in terms of frequency of C/C genotype. In conclusion, progression of chronic hepatitis C among PNALTs is slow or even absent, because at the end of the 17-year follow-up histological and clinical parameters had not worsened significantly.

Cryptococcal meningitis in an HIV-1-infected person: relapses or IRIS? Case report and review of the literature.

After starting highly active antiretroviral therapy (HAART), HIV-infected patients may experience what is termed immune reconstitution inflammatory syndrome (IRIS). IRIS is characterized by a paradoxical inflammatory response to either previously or recently treated infections or unmasked subclinical infections, when the patient regains the ability to mount a suitable immune response against specific antigens or pathogens. Cryptococcal IRIS (C-IRIS) is thought to be mediated by recovery of Cryptococcus-specific immune responses, resulting in exaggerated host inflammatory responses. In HIV-positive subjects, two distinct modes of presentation of C-IRIS are recognized, "paradoxical" and "unmasking" C-IRIS. "Paradoxical" C-IRIS presents as worsening or recurrence of treated cryptococcal disease following HAART initiation, despite microbiological treatment success. In the "unmasking" form, patients with no prior diagnosis may develop acute symptoms of cryptococcosis, such as meningitis or necrotizing lymphadenopathy, after starting HAART. Here, we present the case of an HIV-positive man, who developed cryptococcal meningitis two months after having started HAART and experienced several meningeal relapses and a "paradoxical" C-IRIS during the following year.

Bone disease in the setting of HIV infection: update and review of the literature.

The advent of highly active antiretroviral therapy (HAART) in the mid-1990s has transformed Human Immunodeficiency Virus (HIV) infection into a chronic disease. HIV-infected patients are living longer and are facing several non-AIDS-associated morbidities related with aging, including diabetes mellitus, cardiovascular disease, osteoporosis, osteopenia and fragility fractures. The prevalence of bone disease is higher among HIV-infected subjects. In addition to traditional risk factors, HAART, chronic inflammation and the virus itself have been suggested to contribute to bone loss in the setting of HIV infection. In the present review, we summarize the current knowledge about risk factors for low bone mineral density in HIV-positive patients as well as current recommendations for fracture screening and treatment in this specific population.

Kaposi' s sarcoma in HIV-positive patients: the state of art in the HAART-era.

Kaposi's sarcoma (KS) is a multicentric angioproliferative cancer of endothelial origin typically occurring in the context of immunodeficiency, i.e. coinfection with Human Immonodeficiency Virus (HIV) or transplantation. The incidence of KS has dramatically decreased in both US and Europe in the Highly Active Antiretroviral Therapy (HAART) era. However, KS remains the second most frequent tumor in HIV-infected patients worldwide and it has become the most common cancer in Sub-Saharan Africa. In 1994, Yuan Chang et al discovered a novel γ-herpesvirus in biopsy specimens of human KS. Epidemiologic studies showed that KS-associated herpesvirus (KSHV) or human herpesvirus-8 (HHV-8) was the etiological agent associated with all subtypes of KS. KS has a variable clinical course ranging from very indolent forms to a rapidly progressive disease. HAART represents the first treatment step for slowly progressive disease. Chemotherapy (CT) plus HAART is indicated for visceral and/or rapidly progressive disease. The current understanding of KS as a convergence of immune evasion, oncogenesis, inflammation and angiogenesis has prompted investigators to develop target therapy, based on anti-angiogenic agents as well as metalloproteinase and cytokine signaling pathway inhibitors. These drugs may represent effective strategies for patients with AIDS-associated KS, which progress despite chemotherapy and/or HAART. In this review, we focus on the current state of knowledge on KSHV epidemiology, pathogenesis and therapeutic options.

Otorrhea in Kawasaki disease diagnosis complicated by an EBV infection: coincidental disease or a true association.

The Authors report on two children affected by Kawasaki disease (KD). The diagnosis of KD was made after exclusion of conditions with similar presentation. At admission these children (cases 1 and 2) presented fever, purulent caseous pharyngotonsillitis, and cervical bilateral lymphadenopathy, as well as an erythematous non-vesicular rash over the face and trunk, and a mild bilateral non-exudative conjunctivitis in case 1. After respectively three and two days corticosteroid therapy was started without any significant improvement of the general condition and any diminutions of the fever. Two days later in case 1 the child presented a clear otorrhea, a cutaneous non vesicular rash, and soon after all the remaining signs of Kawasaki disease, in case 2 otorrhea was found after 4 days and then the other signs of the KD. These patients were treated with intravenous immunoglobulin (2 g/kg day), with an improvement of their general condition. To our knowledge we report the first cases of otorrhea in the setting of Kawasaki disease. We cannot exclude that the presence of Kawasaki disease in the context of otorrhea in children positive for Epstein-Barr virus (EBV) is merely coincidental. Besides, recent acquisitions show that KD is due to a new virus that could cross-react with the EBV. The Authors conclude that the presence of EBV infection or similar condition in a febrile child may not exclude Kawasaki disease and a differential diagnosis has to be performed for a timely commencement of intravenous immunoglobulin therapy.  

Kidney disease in HIV-infected patients.

The introduction of highly active antiretroviral therapy (HAART) has reduced mortality and improved life expectancy of HIV-positive patients. However, increased survival is associated with increased prevalence of comorbidities, such as cardiovascular disease, hepatic and renal disease. Kidney disease, including HIV-associated nephropathy, acute renal failure and chronic kidney disease, represents one of the main causes of morbidity and mortality, especially if associated to other risk factors, i.e. hypertension, diabetes, older age, black race and hepatitis C coinfection. Careful evaluation of renal function may help identifying kidney disease in its early stages. In addition, proper management of hypertension and diabetes is recommended. Even if HAART has changed the natural course of HIV-associated nephropathy, reducing the risk of End-stage Renal Disease (ERDS), some antiretroviral regimens have been related with the development of acute or chronic kidney disease. Further studies are needed to optimize the management of renal disease among HIV-infected patients.

LPS and HIV gp120 modulate monocyte/macrophage CYP27B1 and CYP24A1 expression leading to vitamin D consumption and hypovitaminosis D in HIV-infected individuals.

AIM: Vitamin D deficiency is very common among HIV-infected subjects. We cross-sectionally evaluated the prevalence and risk factors for hypovitaminosis D in 91 HIV-infected Italian patients. PATIENTS AND METHODS: We studied in a cohort of 91 HIV-infected Italian patients the metabolism of Vitamin D by evaluating the in vitro expression of CYP27B1, CYP24A1 and vitamin D receptor (VDR) by monocytes and macrophages stimulated with the viral envelope protein gp120 or lipopolysaccharide (LPS). RESULTS: The prevalence of vitamin D deficiency (25OHD < 10 ng/ml) and vitamin D insufficiency (25OHD 10-30 ng/ml) was 31% and 57%, respectively. In univariate analysis, female sex (p = 0.01), increasing age (p = 0.05), higher highly sensitive-C reactive protein (p = 0.025), higher parathyroid hormone (PTH) (p = 0.043) and lower BMI (p = 0.04) were associated with vitamin D deficiency. In multivariate analysis, the association was still significant only for PTH (p = 0.03) and female sex (p = 0.03). Monocyte stimulation with LPS (100 ng/ml) or gp120 (1 µg/ml) significantly upregulated CYP27B1 mRNA expression. Moreover, gp120 significantly increased VDR mRNA levels. On the contrary, neither LPS nor gp120 modified CYP24A1 levels. Macrophage stimulation with LPS (100 ng/ml) significantly upregulated CYP27B1 and CYP24A1 mRNA expression. When monocytes were cultured in the presence of 25OHD (40 ng/ml) and stimulated with LPS we detected significantly lower levels of 25OHD in the supernatant. CONCLUSIONS: Vitamin D deficiency was very common in our cohort of HIV-infected patients. Chronic inflammation, including residual viral replication, may contribute to hypovitaminosis D, by modulating vitamin D metabolism and catabolism. Systematic screening may help identifying subjects requiring supplementation.

Late presentation of HIV infection: predictors of delayed diagnosis and survival in Eastern Sicily.

OBJECTIVES: Across Europe, more than one third of patients are diagnosed with HIV infection late. Late presentation for care has been associated with higher risk of clinical progression and mortality. In the present study, we evaluated the prevalence, epidemiological characteristics and survival probability of patients with late and very late presentation, newly diagnosed with HIV infection in Catania, Italy, from 1985 to 2010. PATIENTS AND METHODS: According to the European Consensus definition, Late Presenters (LP) were defined as subjects presenting for care with a CD4+ T-cell count below 350 cells/µl or with an AIDS-defining event, regardless of CD4+ T-cell count; patients with advanced HIV disease (Very Late Presenters) (VLP) were those presenting with a CD4+ T-cell count below 200 cells/µl or with an AIDS-defining event, regardless of CD4+ T-cell count. RESULTS: 620 patients were included in the study. 345 (55.6%) subjects were LP, 35% of them were asymptomatic; 246 (39.7%) were VLP. In univariate analysis, late presentation was related to age (p < 0.001), to heterosexual exposure to HIV infection (70% of heterosexual subjects were LP) (p < 0.005) and to being diagnosed during the calendar period from 1991 to 2000 (p < 0.001). Very late presentation was related to age (p < 0.001), male sex (p < 0.01), heterosexual risk (p < 0.001) and to being diagnosed during the calendar period from 1991 to 2000 (p < 0.001). In multivariate analysis, age (p < 0.0001), being older than 50 years old (p = 0.02), years of diagnosis 1991-1995 (p < 0.005) and 1996-2000 (p < 0.05) in the subgroup of late presenters and age (p < 0.0001), being older than 50 years old (p < 0.005), male sex (p < 0.0001), years of diagnosis 1991-1995 (p < 0.05) and 1996-2000 (p < 0.005) in the subgroup of very late presenters maintained statistical significance. The survival probability within LP and VLP group was statistically lower than no LP/VLP (log rank test p < 0.0005 and p < 0.0001, respectively). For both LP (p < 0.002) and VLP (p < 0.0001), survival probability was significantly lower in the pre-HAART era, in comparison with the period of mono/dual therapy and the HAART era. CONCLUSIONS: More than fifty percent of patients in our setting were diagnosed late with HIV infection and, consequently, treated late. Late and very late presentation were associated with lower survival probability. The implementation of strategies focused on targeted prevention efforts and HIV testing programs appears fundamental to diagnose and treat HIV infection as early as possible.

Vitamin D deficiency in HIV infection: an underestimated and undertreated epidemic.

Hypovitaminosis D is a very common disorder, regarding both Western and developing countries. A growing amount of data over the last years have shown vitamin D deficiency to be high prevalent among HIV-positive subjects. In addition to "classic" risk factors, such as female sex, low dietary intake, dark skin pigmentation and low sun exposure, HIV-related factors, including immune activation and antiretroviral adverse effects, may affect vitamin D status. Even if both protease inhibitors and non-nucleoside reverse transcriptase inhibitors have been associated with low vitamin D levels, available evidences have failed to univocally associate hypovitaminosis D with specific antiretroviral class effects. Low vitamin D is known to have a negative impact not only on bone health, but also on neurocognitive, metabolic, cardiovascular and immune functions. Similarly to the general population, several studies conducted on HIV-infected subjects have associated hypovitaminosis D with a greater risk of developing osteopenia/osteoporosis and fragility fractures. Analogously, vitamin D deficiency has been described as an independent risk factor for cardiovascular disease and metabolic disorders, such as insulin resistance and type 2 diabetes mellitus. Last EACS guidelines suggest to screen for hypovitaminosis D every HIV-positive subject having a history of bone disease, chronic kidney disease or other known risk factors for vitamin D deficiency. Vitamin D repletion is recommended when 25-hydroxyvitamin D levels are below 10 ng/ml. Furthermore, it may be indicated in presence of 25OHD values between 10 and 30 ng/ml, if associated with osteoporosis, osteomalacia or increased parathyroid hormone levels. The optimal repletion and maintenance dosing regimens remain to be established, as well as the impact of vitamin D supplementation in preventing comorbidities.

Immuno-modulatory effects of vitamin D3 in human monocyte and macrophages.

Vitamin D3 [1α,25-(OH)(2)D(3)], involved in the regulation of body calcium homeostasis, promotes immature myeloid precursor cells differentiation into monocytes/macrophages. In this study we compared the regulatory interaction between 1α,25-(OH)(2)D(3) and tumor necrosis factor (TNF)-α or lipopolysaccharide (LPS) in the mRNA expression of interleukin (IL)-1ß, (IL)-6, TNF-α, toll like receptors (TLR)-2 and (TLR)-4 in freshly isolated human monocyte (MonoT0) and in macrophages cultured for seven days (MØT7). Additionally, we detected the effect of 1α,25-(OH)(2)D(3) on macrophages chemotaxis. The expression of IL-1ß, IL-6 and TNF-α, as well as TLR-2 and TLR-4 in MonoT0 and in MØT7 was examined by real time RT-PCR. Macrophages chemotaxis was analyzed by using horizontal chemotaxis agarose spot assay. We found that 1α,25-(OH)(2)D(3) influences macrophages chemotaxis and differently modulates the expression of IL-1ß, IL-6, TNF-α and TLRs in the two different stages of monocytes/macrophage maturation. In conclusion our data add new information about the role of 1α,25-(OH)(2)D(3) on the expression of inflammatory mediators in human monocyte/macrophages, underlying the complex function of these cells. Investigating the differences in the pattern of expression of immune-mediators produced by MonoT0 and MØT7 may provide a new way to examine their biochemical and molecular function and may constitute a model system with well-defined behavior with respect to early or tardive events in the innate immune response.

Acoustic Radial Force Impulse as an effective tool for a prompt and reliable diagnosis of hepatocellular carcinoma - preliminary data.

ARFI (Acoustic Radiation Force Impulse) is a novel method based on the use of shear acoustic waves remotely induced by the radiation force of a focused ultrasonic beam. Recently, ARFI has been investigated as a non-invasive method for the assessment of liver fibrosis. The reproducibility of ARFI technology was proved in determining liver fibrosis: in detail, for cirrhosis Fibroscan had its best cut-off at >/= 11 kPa (AUROC of 0.80) whereas ARFI >/= 2.0 m/s (AUROC of 0.89). By pair-wise comparison of AUROC, ARFI was significantly more accurate than TE for a diagnosis of significant and severe fibrosis. Due to the low amount of collagen deposition within hepatocellular carcinoma (HCC) nodules in a context of "hard" cirrhotic parenchyma, ARFI propose itself also as a novel, specific method for an early identification of primitive neoplastic nodules during the follow up of cirrhotic patients. The diagnostic accuracy can be demonstrated either versus the surrounding liver tissue or versus dysplastic or metastatic nodules. Further studies are required to confirm ARFI as a useful tool for HCC follow-up.

The use of peginterferon in monotherapy or in combination with ribavirin for the treatment of acute hepatitis C.

BACKGROUND: Acute hepatitis C becomes chronic in 50% of cases. Early treatment seems to be effective in eradicating HCV infection, although no clear recommendations are available in terms of time of initiation, regimen and duration of therapy. We report a retrospective review of 48 patients with acute HCV infection between January 2006 and December 2007. PATIENTS AND METHODS: This multicenter retrospective study involved three Infectious Disease Units in Sicily and was carried out in three stages: (1) Collection of patients data; (2) Selection of patients according to: elevated ALT (at least 5 times above normal values), seroconversion from negative to positive anti-HCV status; (3) Final selection of patients with a minimum of 12 months follow-up. RESULTS: Out of 60 patients with a diagnosis of acute HCV infection, 48 were eligible for the study. In 13 subjects (52%) of the 25 who were not treated, the disease resolved spontaneously. 23 patients received pegylated interferon in monotherapy or in combination with ribavirin. 95% achieved a sustained virological response (SVR). Of the 22 sustained responders, 17 (70%) negativized HCV RNA within 8 weeks. No difference appeared between patients receiving monotherapy and those treated with combination therapy. Also, no difference was observed, in terms of SVR, between the two different pegylated interferons given for treatment. CONCLUSIONS: The rate of viral clearance was higher in the treated group versus the untreated one (95% versus 52%). The SVR found in our study population (95%) was comparable to that reported in other studies. The combination with ribavirin did not appear to impact our sustained response rate, although ribavirin appeared to induce a faster normalization of ALT levels.