Antonio Aceti

Hepatotoxicity development during antiretroviral therapy containing protease inhibitors in patients with HIV: The role of hepatitis B and C virus infection

&NA; Summary: To evaluate the occurrence of hepatotoxicity in patients during antiretroviral therapy (ART) that contains protease inhibitors and the role of hepatitis viruses in its development, we performed a retrospective study including 1325 HIV‐infected patients treated with ART for at least 6 months. Presence or absence of hepatitis viruses, alanine aminotransferase (ALT), total bilirubin, CD4 cell count, and plasma HIV RNA levels were evaluated. Hepatotoxicity developed in a few study subjects without coinfection, whereas it was significantly higher in coinfected patients. Univariate logistic regression analysis showed that viral hepatitis coinfections are independent risk factors for hepatotoxicity. After 6 months of treatment, ritonavir was associated with higher rates of severe hepatotoxicity in the coinfected group; in fact, ritonavir seems to be the most strongly hepatotoxic agent among coinfected patients. After 12 months of therapy, hepatotoxicity occurred more frequently in patients with hepatitis C virus who did not respond to antiretroviral therapy (ART), whereas patients who did respond to ART showed decreased ALT levels. Hepatotoxicity is not exclusively an effect of drug toxicity, and the presence of hepatitis coinfection is an independent risk factor. Moreover, chronic hepatotoxicity mainly occurs in patients who did not respond to therapy. Conversely, patients who did respond to ART seemed to show improvement of chronic liver infection.

Basophil-bound and serum immunoglobulin E directed against Helicobacter pylori in patients with chronic gastritis.

The immunoglobulin (Ig) E immune response in patients with Helicobacter pylori-associated chronic gastritis has been evaluated. Of 26 patients with H. pylori infection, 22 (84%) tested positive for basophil-bound specific IgE (determined by the histamine release test) and 18 (69%) for serum specific IgE (determined by an enzyme-linked immunosorbent assay). In contrast, only 1 of 17 persons in whom the bacterium was not detected presented cell-bound and serum specific IgE. In the 4 histamine release test--positive but enzyme-linked immunosorbent assay--negative patients, removal of antibody from the basophil surface by acid elution showed that histamine release occurred through an IgE-dependent mechanism. When normal basophils, passively sensitized with serum from IgE-positive patients, were exposed to the H. pylori antigen, a significant release was observed, confirming the class specificity of the response. Inhibition experiments with bacteria other than H. pylori showed that the IgE antibody was specifically directed against this organism. The percentage of antigen-induced histamine release did not correlate with serum specific IgE level. However, the response of basophils to antigenic challenge was proportional to IgE-dependent cellular releasability. This finding suggests that target cell sensitivity may be the most important factor in determining the entity of biological response to the antigenic challenge. The ability of H. pylori to induce a specific IgE immune response could answer key questions regarding the mechanisms inducing gastric inflammation.

Correlation of serum aminotransferases with HCV RNA levels and histological findings in patients with chronic hepatitis C: The role of serum aspartate transaminase in the evaluation of disease progression

Objectives To investigate whether HCV RNA levels can be considered to be predictors of hepatocellular injury in patients with chronic hepatitis C, and whether aminotransferase levels are markers of liver damage. Methods We performed a retrospective study on 112 patients with chronic hepatitis C. For each patient, we considered the baseline alanine aminotransferase (ALT) and serum aspartate transaminase (AST) levels, baseline HCV RNA, HCV genotype, histological evaluation and the mean aminotransferase levels measured in the 6 months following liver biopsy. Results We found a statistically significant correlation between HCV RNA and aminotransferase levels measured during the follow-up (AST: r = 0.24, P = 0.01; ALT: r = 0.27, P = 0.004). We also observed a statistically significant correlation between HCV RNA levels and histological activity index (HAI) (r = 0.25, P = 0.008), as well as between the HAI and both baseline AST (r = 0.34, P = 0.0002) and ALT levels (r = 0.23, P = 0.01). These findings were confirmed by the mean aminotransferase values during follow-up. In the regression analysis, the fibrosis score was significantly and independently associated with baseline AST and ALT values. Conclusions Our results demonstrate a statistically significant correlation of aminotransferase values with the histological parameters, and an even stronger correlation with the AST values. Our study therefore suggests that aminotransferase values, especially AST, may correlate with liver damage.

Hymenolepis diminuta Infection in a Child Living in the Urban Area of Rome, Italy

ABSTRACT We report a case of Hymenolepis diminuta infection in an Italian child affected by tuberous sclerosis. Praziquantel is the drug of choice for the treatment of H. diminuta infection. However, considering the patients neurological disease, we decided to use not praziquantel but niclosamide, which proved equally effective.

IgG subclasses in human hydatid disease : prominence of the IgG4 response

To assess the participation of the four subclasses of IgG in the humoral response to Echinococcus granulosus infection, we determined total and parasite-specific IgG1, IgG2, IgG3 and IgG4 in sera from 46 patients with hydatid disease using an enzyme-linked immunosorbent assay (ELISA). Parasite-specific IgG subclass antibodies were quantitatively measured by means of standard curves obtained by affinity chromatography. Sera from 35 healthy individuals served as controls. The total component of IgG1, IgG2, and IgG3 showed a slight increase in patients with hydatidosis in comparison to normal control subjects with no significant differences. For the IgG4 subclass, however, a marked elevation was found in the patients group (p = 0.001 by analysis of variance). IgG1 and IgG4 subclasses showed a high anti-echinococcus antibody response, whereas there was a low parasite-specific IgG2 and IgG3 response. Indeed IgG-specific antibodies were found to belong mainly to IgG1 (63%) and to IgG4 (30%) and to a lesser extent to IgG2 (5%) and IgG3 (2%). The percentage of the total serum IgG4 antibodies that were specific for hydatid antigen reached a mean level of 18%, significantly higher than that of any of the other three IgG subclasses (p < 0.001 by Students t test). Thus, the continuous antigenic stimulation of hydatidosis may result in an enhanced IgG4 subclass response.

Cellular proviral HIV-DNA decline and viral isolation in naïve subjects with 500 × 106/l CD4 cells treated with highly active antiretroviral therapy

ObjectiveTo evaluate the decay rate of cellular proviral HIV-DNA and viral replication in patients receiving highly active antiretroviral therapy (HAART) in the very early phase of infection.MethodsThirty-four patients treated with HAART and retrospectively selected for progressive decline of plasma

Hepatitis C virus infection of salivary gland epithelial cells. Lack of evidence.

BACKGROUND Hepatitis C virus genome (HCV-RNA) has been detected in whole salivary gland tissue of chronically infected patients. However, contamination of the tissue by plasma or blood cells was not excluded by the previous reports. AIMS To assess whether HCV infects the salivary gland epithelial cells in patients with chronic HCV liver disease. METHODS Twenty unselected patients with chronic active hepatitis (11 cases) or active cirrhosis (nine cases) were examined. Serum and saliva samples were obtained from all patients, 12 of whom (seven, chronic active hepatitis; five, active cirrhosis) underwent salivary gland biopsy. PCR for HCV-RNA was performed on RNA extracted from serum, saliva and salivary gland epithelial cells collected by isokinetic gradient separation after trypsin digestion of whole salivary gland tissue. Saliva samples were also examined for the presence of secretory IgA anti-HCV by gel chromatography and ELISA testing. RESULTS HCV-RNA was detected in all sera with titers ranging from 5.42 x 10(5) genome equivalents/ml to 123.2 x 10(5) genome equivalents/ml. Thirteen patients were infected with genotype 1b, four patients had genotype 1a, two patients had genotype 2a and one patient was unclassifiable. Low titer HCV-RNA (<2 x 10(5) genome equivalents/ml) was detected in 3/20 saliva samples (15%) from highly viremic patients infected with 1b genotype. RNA extracted from salivary gland epithelial cells consistently tested negative for HCV-RNA. In addition, all saliva specimens tested negative for secretory-IgA (S-IgA) anti-HCV, even after a 10-fold concentration of the samples. CONCLUSIONS There was no evidence that HCV infects the salivary gland epithelial cells in our viremic patients with HCV chronic liver disease. Low level HCV-RNA in saliva is most probably due to virus spillover from blood.

Identification of HIV patients with active pulmonary tuberculosis using urine based polymerase chain reaction assay

BACKGROUND Despite the increased dissemination of tuberculosis among HIV infected patients, the diagnosis is difficult to establish. Traditional microbiological methods lack satisfactory sensitivity. We have developed a highly sensitive and specific nested polymerase chain reaction (PCR) capable of detecting Mycobacterium tuberculosis DNA in urine specimens and have used this test to examine urine specimens from HIV patients with active pulmonary tuberculosis. METHODS Urine specimens from 13 HIV infected patients with microbiologically proven active pulmonary tuberculosis, 10 AIDS patients with non-tuberculous mycobacterial infection (documented by blood culture), 53 AIDS patients with no evidence of mycobacterial disease, and 80 healthy subjects (25 with positive skin test to purified protein derivative) were tested forM tuberculosis using PCR, acid fast staining (AFS), and culture. RESULTS Of the urine specimens from patients with active tuberculosis, all tested positive by PCR, two by culture, and none by AFS. No reactivity was observed in urine specimens from patients with non-tuberculous mycobacterial infection. Of the 53 AIDS patients without mycobacterial infection, one had a positive urine PCR. Normal subjects were all negative. CONCLUSIONS Urine based nested PCR for M tuberculosis may be a useful test for identifying HIV patients with pulmonary tuberculosis.

Cortical sources of resting-state EEG rhythms are abnormal in naïve HIV subjects.

OBJECTIVE The aim of the study was to test the hypothesis that cortical sources of resting-state electroencephalographic (EEG) rhythms show peculiar frequency/spatial features in naïve human subjects with human immunodeficiency virus (HIV) compared to healthy control subjects. METHODS Resting-state eyes-closed EEG data were recorded in 18 naïve HIV subjects (15 males; mean age 39 years±2.0 standard error of mean, SEM) and in 18 age-matched cognitively normal subjects (15 males; 38.7years±2.2 SEM). EEG rhythms of interest were delta (2-4Hz), theta (4-8Hz), alpha1 (8-10Hz), alpha2 (10-12Hz), beta1 (13-20Hz) and beta2 (20-30Hz). Cortical EEG sources were estimated by normalised, low-resolution electromagnetic tomography (LORETA). RESULTS Mini Mental State Evaluation (MMSE) score was lower in HIV (26.5 ± 0.7 SEM) than in healthy (29.2 ± 0.5 SEM) subjects (p<0.05). Central and parietal delta sources showed higher amplitude in the HIV than in control subjects. Furthermore, topographically widespread, cortical sources of resting-state alpha rhythms were lower in amplitude in HIV subjects than in control subjects. CONCLUSIONS The present results suggest that topography and frequency of the cortical sources of resting-state EEG rhythms can distinguish groups of HIV and control subjects. SIGNIFICANCE These results encourage future studies in an enlarged cohort of HIV subjects to test the hypothesis that the present methodological approach provides clinically useful information for an early detection of the effect of HIV infection on brain and cognitive functions.

Depression and affective temperaments are associated with poor health-related quality of life in patients with HIV infection

Introduction. Human immunodeficiency virus (HIV) represents one of the most chronic and debilitating infections worldwide. Hopelessness and affective temperaments (mood that is characteristic of an individual’s habitual functioning) may play important roles in the health-related quality of life (HRQoL) of patients with HIV. The purpose of this study was to examine affective temperaments in a sample of patients with HIV, the impact of hopelessness on HRQoL, and associations among HRQoL, hopelessness, and affective temperaments. Methods. The study involved 88 participants who were administered the Short- Form Health Survey (SF-36), the Beck Hopelessness Scale (BHS), the Suicidal History Self-Rating Screening scale (SHSS), the Gotland Male Depression Scale (GMDS), and the Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS-A). Results. Patients with a poorer HRQoL reported more severe depression and hopelessness than patients with a higher HRQoL. Patients with a poorer HRQoL also had higher scores on all dimensions of the TEMPS-A with a depressive component compared to patients with a higher HRQoL. The small sample size in this study limits the generalizability of the findings. Conclusion. Patients with a poorer HRQoL were more depressed and also at an increased risk of suicide as indicated by the more severe hopelessness they reported compared to patients with higher HRQoL. These patients were also more likely to have depressive affective temperaments than those with a higher HRQoL. (Journal of Psychiatric Practice 2013;19:109–117)