Giovanni Mazzola

Human herpesvirus type 8 DNA sequences in biological samples of HIV-positive and negative individuals in Sicily.

Objective:To evaluate the circulation of a new human herpesvirus (HHV), HHV-8 or Kaposis sarcoma (KS)-associated herpesvirus in a geographical area where a high incidence rate of classical KS was already present before the appearance of the AIDS epidemic. Design and methods:The study was carried out by analysing: (i) bioptic samples from classic, AIDS-associated KS, and controls; (ii) peripheral blood mononuclear cells (PBMC) from classic KS, HIV-positive subjects with and without KS and healthy HIV-negative individuals; (iii) semen samples from heterosexual HIV-positive and HIV-negative individuals affected or not by KS; and (iv) cervical swabs from HIV-negative healthy heterosexual females. All specimens were tested for the presence of HHV-8 DNA sequences by a two-step polymerase chain reaction. Results:Positive results were obtained in 90% of bioptic samples of classic KS and in 100% of AIDS-associated KS. Viral sequences were also present in 50% of PBMC of subjects with classic KS and AIDS-associated KS, in 10% of AIDS patients without the angiosarcoma, and in 11% of healthy HIV-negative individuals. Finally, HHV-8 DNA was detected in 13% of semen of HIV-negative heterosexual individuals and in 10% of AIDS patients without KS. Both PBMC and ejaculates from the same individual gave positive results. No HHV-8 sequences were found in cervical swabs. Conclusions:HHV-8 is widespread in the general population in Sicily since it was detected in PBMC and semen of heterosexual HIV-negative individuals and is not found only in high-risk groups. The viral load appears to be more elevated in a high-risk population and it may be ascribed to a viral reactivation. The higher incidence rates of KS in Sicily compared with northern Italy and other European countries might be related to the presence of HHV-8 in the general population.

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.

Is early recurrence of hepatocellular carcinoma in HCV cirrhotic patients affected by treatment with direct-acting antivirals? A prospective multicentre study

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.

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.

Response-adjusted α-interferon therapy for chronic hepatitis C in HIV-infected patients

In patients with chronic hepatitis C and HIV infection, responsiveness to the standard schedule of a-interferon (IFN) is unsatisfactory. To quantify the effectiveness of tailoring IFN dosage according to HCV viral load under treatment, we enrolled 41 patients (M: F3 2:9) chronically coinfected by HCV and HIV with chronic liver disease. All were former i.v. drug addicts, with a mean age of 3294 years, and had clinical and histological evidence of chronic hepatitis (10% with cirrhosis). The CDC stage was A1 in five, A2 in 14, A3 in eight, B2 in eight, B3 in three and C3 in three. Twenty four patients were on triple therapy with protease inhibitors, 11 were on two-drug anti-HIV regimens and three were untreated. IFN (an1 interferon) was started at 3 MU tiw and increased at 6 MU tiw at 4 weeks if serum HCV-RNA had not dropped by at least 50%. IFN was stopped at 24 weeks in non-responders. Eleven patients received a dose increase (total IFN dose at 24 weeks 396 MU), while 16 did not increase the initial dose (total IFN dose at 24 weeks 216 MU). Fourteen subjects stopped within the first weeks due to relapse of drug abuse (ten) or subjective intolerance (four). ALT and HCV-RNA levels were markedly decreased at week 4, and this reduction lasted up to 24 weeks. However only one patient had a complete biochemical and virological end-of-treatment response, which was maintained over a 24 weeks post-therapy follow-up. All other patients relapsed to baseline ALT and HCV-RNA values after stopping IFN. HIV viral load was slightly reduced under IFN therapy, while CD4 counts were unaffected. We conclude that raising the dose of IFN dose not eradicate HCV in most HIV-infected patients, even when HIV is well controlled by treatment. HCV viraemia and necroinflammation are temporarily suppressed by IFN, but the relevance of these surrogate endpoints to progression of liver disease and to survival cannot be assessed.

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

BackgroundDespite 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.MethodsOne 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.ResultsOsteoporosis 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.ConclusionsAmong 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.

Unusual MRI findings in an immunocompetent patient with EBV encephalitis: a case report

BlackgroundIt is well-known that Epstein-Barr virus (EBV) can affect the central nervous system (CNS).Case presentationHerein 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.ConclusionThis 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.

Rhabdomyolysis associated with the co-administration of daptomycin and pegylated interferon α-2b and ribavirin in a patient with hepatitis C

Rhabdomyolysis is a rare adverse effect reported with daptomy-cin use. Here we report the first case of creatinine phosphokinase (CPK) elevation with rhabdomyolysis developing during the co-administration of daptomycin and pegylated interferon a-2b and ribavirin. We describe the case of a patient with a history of intravenous drug abuse and hepatitis C admitted to our division because of fever and pain in the right gluteal region. The patients general condition was poor, but his physical examination was unremarkable, except for the presence of a right gluteal abscess. The patient had been taking pegylated interferon a-2b and ribavirin for 5 months without reporting side effects. On admission, liver function tests were within normal limits, serum CPK level was slightly elevated (518 U/L; normal values 39 –308 U/L), lactate dehydrogenase (LDH) was 580 U/L (normal values 240–480 U/L), serum creatinine was 1.6 mg/dL and estimated CL CR was 124.8 mL/min. The white blood cell (WBC) count showed neutrophil leucocytosis (WBC 11 580 cells/mm 3 , 87.1% neutrophils) and a low platelet count (72 000 cells/mm 3). All other laboratory findings were within normal limits. Hepatitis C virus (HCV) RNA viral load was undetectable. Blood cultures were performed. The patient was started on empirical antibiotic therapy with levofloxacin (750 mg once daily intravenously) and piperacillin/ tazobactam (4.5 g every 6 h intravenously). Due to lack of improvement of symptoms and fever after 48 h, levofloxacin was switched to daptomycin (500 mg daily intravenously). The second dose was administered, by mistake, 4 h before it should have been. Five days after admission, after only two doses of daptomycin, the patient suddenly complained of weakness and diffuse aches in the proximal thighs and arms. Serum CPK levels were very high (12 933 U/L) and further elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT), 371 and 67 IU/L, respectively, were also noted. A urine drug screen was performed to rule out damage related to illicit substance use, and the results were negative. Blood cultures were positive for methicillin-resistant Staphylococcus aureus (MRSA). Suspecting daptomycin-induced rhabdomyolysis, treatment was switched to linezolid (600 mg twice daily intravenously) and meropenem (1 g every 8 h intravenously). The patient was hydrated (2 L/day) to preserve renal function, and this was strictly monitored throughout the course; urinalysis was positive for myoglobin. Although daptomycin had been interrupted, CPK levels and AST/ALT levels continued to increase for 5 days after and on the …

Diagnostic and vaccine strategies to prevent infections in patients with inflammatory bowel disease

OBJECTIVES The treatment of inflammatory bowel disease (IBD) has been revolutionized by the use of immunomodulatory agents. Although these potent drugs are effective in controlling disease activity, they also cause an increased risk of new infections or reactivation of latent infections. On these premises, we aimed to provide guidance on the definitions of immunocompromised patients, opportunistic infections and the risk factors associated with their occurrence in an IBD context, and to suggest the proper screening tests for infectious diseases and the vaccination schedules to perform before and/or during therapy with immunomodulators. METHODS All the most recent evidences - filtered by the combined work of gastroenterologists and infectious disease experts - were summarized with the aim to provide a practical standpoint for the physician. RESULTS A systematic screening of all infections which may arise during therapy with immunomodulator drugs is necessary in all patients with IBD. CONCLUSIONS The ideal timing to perform screening tests and vaccinations is at the diagnosis of the disease, regardless of its severity at onset, because the course of IBD and its treatment may vary over time, and an immunocompromised status may hamper efficacy and/or possibility to perform all necessary vaccines.

Associated Factors and Liver Disease Severity for Decreased Bone Mineral Density in HIV Mono- and HIV/HCV Co-infected Patients

Objective: We assessed the prevalence and risk factors of decreased bone mineral density (BMD) in patients mono-infected with human immunodeficiency virus (HIV) or co-infected with hepatitis C virus (HIV/HCV). We also evaluated whether bone loss was linked to lipid asset in both groups and to severity of liver fibrosis in the co-infected group. Methods: We consecutively enrolled 194 HIV-patients (129 mono-infected and 65 co-infected). All HIV-patients underwent dual-energy X-ray absorptiometry (DXA), while co-infected patients underwent transient elastography. Advanced liver fibrosis was defined as a median liver stiffness ≥ 9.5 kPa. Fibrosis was also assessed in all the HIVpatients using FIB-4. Results: The overall prevalence of low BMD and osteoporosis was 26.8% and 26.0%, respectively. It was significantly higher among HIV/HCV co-infected than mono-infected patients in lumbar/femoral sites (P<0.04 and P<0.05, respectively). HDL-cholesterol levels correlated independently with lumbar DXA Z-score (P<0.03) in HIV mono-infected subjects. Liver stiffness correlated negatively and independently with femoral Z- and T-scores among co-infected patients (P<0.003; P<0.01, respectively). Stratifying co-infected subjects by sex, liver stiffness and lumbar/ femoral Z-scores (P<0.04) or T-scores (P<0.05; P<0.04, respectively) correlated negatively only in the females. Longer PI exposure was negatively and independently correlated with BMD. Conclusion: Our HIV-infected patients appeared at high risk for low BMD and osteoporosis. Severity of liver fibrosis was an independent predictor of bone loss in co-infection, although other factors could affect the skeletal system in HIV/HCV co-infection. Further research into the impact of liver fibrosis and lipid asset on bone disease in HIV-infection is necessary