Vitamin D and Osteoporosis in HIV/HCV Coinfected Patients: A Literature Review.

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.

The metabolic syndrome and HIV infection.

The metabolic syndrome (MetS), a cluster of risk factors for cardiovascular disease and type 2 diabetes, has become an important public health problem. Considerable differences in the prevalence of the MetS in human immunodeficiency virus (HIV)-infected subjects have been reported, as a consequence of several limitations regarding the diagnostic critera for MetS. New evidence suggests that the use of optimal waist cut-off points specific for the various ethnic populations could represent a step forward in overcoming these limitations. Also the use of specific cut-off points for measuring upper trunk fat as an adjunctive criterion of MetS in HIV patients with lipodystrophy could represent an interesting new research topic. Although metabolic disorders have been associated indirectly with highly active antiretroviral therapy (HAART), directly with HIV infection per se or with host conditions, current circumstances could change the framework of MetS in the HIV setting: For example, the aging HIV population and newer, less metabolically toxic antiretroviral drugs. Lipotoxicity and adipokines have been focused as key issues for explaining MetS in HIV patients. Several studies have investigated the pathophysiology of MetS and cardiovascular complications in HIV infection. Evidence shows that both HIV infection per se and HIV-related chronic immune activation despite antiretroviral therapy are critical factors linking MetS and cardiovascular complications. Current epidemiological and pathogenetic data on MetS in HIV infection, prevention strategies and therapeutic options for all MetS components are reviewed in the light of the recent Adult Treatment Panel IV recommendations and the new antiretroviral drugs.

Non-invasive assessment of liver steatosis and fibrosis in HIV/HCV- and HCV- infected patients.

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.

Occult hepatitis B infection in the immigrant population of Sicily, Italy.

In Italy, about 7 % of the resident population is represented by immigrants originating from geographic regions at high endemicity for hepatitis B virus infection. This study aims to assess the prevalence of occult HBV infection (OBI) including the identification of HBV-genotypes in a population of immigrants serologically negative for hepatitis B surface antigen (HBsAg). Between May 2006 and May 2010, 339 immigrants were tested for markers of HBV, hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections. HBV-DNA was tested by using nested-PCR assays on three different genetic region. HBV-DNA was detected in plasma samples of 11/339 (3.2 %) patients. Most of them had no serological markers of HBV infection, 3/58 (5.2 %) were anti-HBc-alone, and 4/13 (30.8 %) were anti-HIV positive. HIV positivity was the only factor independently associated with the higher probability of observing OBI (OR = 16.5, p < 0.001). No HCV co-infected patients were found. Genotype D was detected in 9/11 (81.8 %) OBI cases, while the remaining two (18.2 %) were classified as genotype E. Although OBI was found at lower rate than expected among immigrants from highly endemic countries, anti-HBc alone positivity was confirmed as a sentinel marker of occult HBV infection. Nevertheless, a marked heterogeneity of HBV markers was found among HBV-DNA positive subjects. Our finding evidenced the predominance of HBV-genotype D viral strains among OBI cases, also in those from geographical areas where overt HBV infections are mainly sustained by viral genotypes other than D.

Chancre of the eyelid as manifestation of primary syphilis, and precocious chorioretinitis and uveitis in an HIV-infected patient: a case report.

BACKGROUND: Ocular syphilis is often difficult to diagnose because of the wide variation in clinical features.HIV co-infection may further complicate the picture. CASE PRESENTATION: Herein the authors report an unusual primary syphilitic ocular lesion in a 45-year-old Italian HIV-infected bisexual man who presented with a unilateral eyelid lesion. Associated precocious signs and symptoms in the posterior segment of both eyes, bilateral chorioretinitis and uveitis, are described. Intravenous penicillin and steroid treatment produced a rapid improvement in clinical status and complete resolution. CONCLUSIONS: Careful questioning about sexual behavior is crucial for unmasking unusual features of ocular syphilis in HIV-infected subjects.

Dairy calcium intake and lifestyle risk factors for bone loss in hiv-infected and uninfected Mediterranean subjects.

BACKGROUND: Despite the reported high prevalence of osteoporosis in the human immunodeficiency virus (HIV)-population, there have been no previous studies examining dairy calcium intake and bone mineral density (BMD) in HIV-subjects. We assessed the prevalence of low BMD in HIV-infected and uninfected subjects and analyzed the effects of calcium intake, lifestyle and HIV-related risk factors on BMD. METHODS: One hundred and twelve HIV-infected subjects were consecutively enrolled. Seventy- six HIV-uninfected subjects matched for age and sex were enrolled as the control group. The HIV-subjects were interviewed about lifestyle habits and completed a weekly food-frequency questionnaire to estimate calcium intake. HIV-RNA, CD4+ T-cell count and data on antiretroviral therapy were also recorded. Both biochemical bone turnover markers and BMD, assessed by dual-energy radiographic absorptiometry (DXA) were recorded in the HIV-cases and controls. We also calculated the 10-year fracture risks using the WHO FRAX equation. RESULTS: Osteoporosis prevalence was significantly higher in the HIV-cases than controls (p < 0.05). BMI values were positively correlated with BMD (p < 0.05). Vitamin D levels were lower in the HIV-subjects (p < 0.02). No correlation was found with daily calcium intake. BMI values were significantly correlated with dairy intake quartiles (p < 0.003). In HIV-subjects, the mean of FRAX score was 1.2 % for hip and 4.7 % for major osteoporotic fractures. On multivariate analysis of the lumbar spine DXA T-score, age (p < 0.005) and HIV/hepatitis C virus co-infection (p < 0.0001) were negatively correlated with BMD, while yogurt intake was a protective predictor of BMD (p < 0.05). In the femur DXA T-score, age (p < 0.01), nadir CD4 + T-cell count < 200 cells/µL (p < 0.05) and drug addiction ( p < 0.0001) were negatively correlated with BMD. CONCLUSIONS: Among the foods rich in calcium, yogurt was a protective predictor of BMD in HIV-subjects. HIV/HCV co-infection, nadir CD4 + T-cell count < 200 cells/µL and drug addiction were independent predictors of severe BMD. Promoting behavioral changes in food intake and lifestyle, aimed at the primary prevention of bone disease in the chronically-infected subjects seems to be essential for implementing medical intervention in these cases.

Prospective evaluation of hepatic steatosis in HIV-infected patients with or without hepatitis C virus co-infection.

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.

Investigation and management of Toxoplasma gondii infection in pregnancy and infancy: a prospective study.

AIM: Toxoplasma gondii infection during pregnancy poses a serious risk to the fetus, therefore timely and accurate diagnosis is essential. The aim of this study was to estimate the frequency of congenital infection via evaluating mother's immunological status and the possibility to improving the diagnostic and therapeutic approaches. METHODS: Eighty five mothers with Toxoplasma seroconversion and their offspring were enrolled (among them, 2 spontaneous abortions were documented in the first trimester). Prenatal PCR diagnosis was carried out on 50 patients (60%), with 7 positive cases (14%). Morphological ultrasound scanning revealed anomalies in one fetus. Long-term follow-up included general physical examinations, serological status tested using Western blot, neuro-radiological, ophthalmologic and neurologic examinations, psychological and developmental tests, visual evoked potential tests and audiology tests, as well as anti-Toxoplasma treatment regimes. RESULTS: Fourteen (17%) of the infants were infected at one-year serological follow-up. Chi-square for linear trend of vertical transmission from the first to the third trimester was significant (P=0.009). Western blot analysis showed IgM and IgA in half of the infected infants. In 69 uninfected infants, anti-Toxoplasma IgG immunoblot analysis excluded infection within the 3 months in 18 infants (26%) and in the others within 6 months of life. The most relevant instrumental findings are described. CONCLUSION: Western blot analysis may help to evaluate infection within the 6 months of life. The accuracy of ultrasound imaging to determine the brain damage in the fetus and newborns is doubtful, and should be combined with MR imaging. Multistep approaches can improve the timing of postnatal follow-up.

Transient elastography: a non-invasive tool for assessing liver fibrosis in HIV/HCV patients.

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 (χ(2)(MH) = 4, P < 0.04). In fact, LS ≥ 9.5 was significantly higher in co-infected than in HIV and HCV mono-infected patients (χ(2) = 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/mm(3) 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.

[Serological screening for Leishmania infantum in asymptomatic blood donors and HIV+ patients living in an endemic area]. / Screening sierologico per Leishmania infantum su donatori di sangue e HIV+ asintomatici residenti in area endemica.

Visceral leishmaniasis (VL) is endemic in Sicily (48 new cases in 2004, of which nine were in Agrigento). In southern Europe between 25-70 per cent of adult VL cases are related to HIV infection. The HIV cases have a high risk (1.5-9%) of developing VL either as a new infection or as the revival of a latent infection. We therefore carried out serologic screening to detect antibodies against L. infantum by IFAT in 1449 blood donors in Agrigento and the surrounding area (May-December 2005) and in 120 HIV+ in western Sicily, all of whom were asymptomatic and had no history of VL. L. DNA was assessed by nested PCR in blood samples of some seropositive donors. Of the 1449 blood donors, 11 (0.75%) were positive by IFAT and three of them were also positive in PCR. L. infantum seropositivity is most probably the expression of recent infection because the clearance of serum antibodies is rather fast (6-12 months) after VL. This is why blood donation by Leishmania seropositive donors, whether positive or negative by PCR, could constitute an infection risk especially for immunosuppressed recipients, who should receive deleukocyted blood. Moreover it could be useful to monitor HIV/Leishmania coinfection cases to avoid the risk of slatentization of L. infection when CD4+ levels are very low.

[Two cases of actinomycosis]. / Due casi di infezione actinomicotica.

Actinomycosis is a bacterial infection due to Gram-positive bacteria of the Actinomyces genus. The authors describe two cases: one of them occurred in a woman with a clinical presentation of a right submandibular indurative mass. After surgery, histological examination showed a granulomatous tissue with many actinomycetes. The second case was observed in a man admitted to hospital with a diagnosis of pulmonary heteroplastic lesion. Also in this case, histological examination showed many actinomycotic colonies. Actinomycosis is an uncommon disease. Establishment of definite diagnosis requires a high index of suspicion in all cases of relapsing cervical lesions. Pulmonary actinomycosis is a rare diagnosis; respiratory physicians should be aware of this important differential when investigating patients for persistent pulmonary shadowing.

[Campylobacter enteritis in Western Sicily. Remarks on 35 cases]. / Il ruolo di Campylobacter spp quale agente di enterite in Sicilia Occidentale. Considerazioni su 35 casi.

INTRODUCTION: Campylobacter spp is the main cause of bacterial gastroenteritis in the developed countries, resulting mainly from the contamination of poultry and animal products. Pathogenesis remains unclear. Various clinical features ranging from watery diarrhoea in apyrexia to dysentery in hyperpyrexia may be the result of differences between strains in the expression of different pathogenetic factors. There are many difficulties in isolating the bacteria in question. METHODS: We processed 540 faecal specimens of children with gastroenteritis. We detected enteropathogen bacteria including Campylobacter spp as well as Rotavirus, Adenovirus and protozoans. For the isolation of Campylobacter we employed the filter membrane technique. The filtrate was plated onto non-selective agar (blood-agar) in microaerophilic atmosphere. RESULTS: The rank order of isolation frequency was: Rotavirus (30.0%), Salmonella (18.5%), Adenovirus (12.6%), Campylobacter (6.5%), Shigella (1.1%), Giardia (0.6%). The Campylobacter strains belonged to C.jejuni in 31 cases and C. coli in 4 cases. The clinical features were: fever (80%), vomitus (31,4%) and diarrhoea in all cases (watery diarrhoea (25.7%), stools more compact with mucus and blood (57.1%) or with mucus alone (17.1%)). CONCLUSIONS: In Western Sicily Campylobacter spp is the second most common agent of bacterial enteritis. We believe that some procedural errors, such as the employment of excessively selective media, could be the cause of the past failure to isolate Campylobacter.