Anna Volpe

SCCA antigen combined with alpha-fetoprotein as serologic markers of HCC

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. Because of its increased incidence in the last decade and the estimated further increase in the next 2 decades, HCC is arousing great interest. In Europe and North America, it commonly develops on cirrhotic livers, and surveillance programs have therefore been suggested to identify early HCC, at a stage when it remains suitable for surgical therapy and has a better clinical outcome. The only serologic marker used in clinical practice is α‐fetoprotein (α‐FP), but its sensitivity is poor. In our study, 120 patients with HCC and 90 patients with liver cirrhosis were investigated. We report for the first time to our knowledge that as a marker of HCC, the squamous cell carcinoma (SCCA) antigen has high sensitivity (84.2%) but low specificity (48.9%). However, the combination of α‐FP and SCCA yielded a correct serologic diagnosis in 90.83% of the HCC patients. A small percentage of patients remain undetected, likely because of the low specificity of SCCA. In conclusion, the combined use of α‐FP and SCCA antigen represents a more powerful tool for the serologic detection of HCC.

Anamnestic response to administration of purified non-adsorbed hepatitis B surface antigen in healthy responders to hepatitis B vaccine with long-term non-protective antibody titres

A clinical trial with four groups receiving either 0.6, 3.5, 10 or 20 micro g of purified non-adsorbed hepatitis B surface antigen (HBsAg) was performed to study the kinetics as well as the capacity of the immune memory to respond following exposure to HBsAg in responders to a complete course of hepatitis B vaccine, in whom anti-HBs titres had declined below the seroprotective level. The study population included 64 healthy individuals. All response parameters seropositivity, seroprotection rates, booster response rates and geometric mean titres (GMTs), consistently showed that the immune response was highly satisfactory and dose-dependent. A remarkable immune response was obtained even with a trace amount of HBsAg. This study further supports recent indication that booster hepatitis B vaccine doses may be unnecessary in healthy adult responders to a full course of hepatitis B vaccination.

Long term immunogenicity safety and efficacy of a recombinant hepatitis B vaccine in healthy adults

Two hundred healthy adults seronegative for HBV markers received three 10 or 20 mcg injections of a vaccine formulated from HBsAg produced by a recombinant strain of the yeastSaccharomyces cerevisiae. The vaccine was administered intramuscularly at 0, 1, and 6 months in the deltoid region. The seroconversion rates, expressed in GMT/IU/1 were determined at 1, 2, 6, 7, 12, 24, 36 and 48 months following the initial injection. No severe or serious adverse reactions attributable to the HB vaccines were observed in any subject. The seroconversion rates following the 20 mcg dose of recombinant vaccine were always higher than those observed after the 10 mcg dose, but the differences were not statistically significant. Also the GMT values were lower after the 10 mcg dose of vaccine. Females showed a higher anti-HBs response than males; an age-dependent effect was observed in the anti-HBs response as regards both the percentage of responders and the antibody concentrations in the serum. No adverse reactions to the vaccine were observed. The rDNA vaccine did not induce a response to yeast-derived impurities and did not increase anti-yeast IgE antibody titres. The results of this study have shown that the Amgen rDNA vaccine is safe and clinically well tolerated, and that it provides protection against infection and disease. A vaccination dose of 20 mcg appears more advantageous for healthy adult subjects.

Early Markers of Tubular Dysfunction in Antiretroviral-Experienced HIV-Infected Patients Treated with Tenofovir Versus Abacavir

Tenofovir disoproxil fumerate (TDF) is an effective nucleoside reverse transcriptase inhibitor for HIV infection but it is potentially nephrotoxic. A selective mithochondrial toxicity has been hypothesized. To assess early markers of renal toxicity, we evaluated a cohort of antiretroviral (ARV)-experienced HIV patients who had been switched from a thymidinic backbone to either a TDF/emtricitabine regimen (TDF; 73 patients) or an abacavir/lamivudine (ABV) regimen (28 patients). Markers of mitochondrial toxicity (cytochrome c, Cyc) or cytosolic (α-glutathione S transferase, α-GST) together with common indicators of renal damage were assessed at baseline (T0) and after 1 (T1), 3 (T2), 6 (T3), and 12 (T4) months of patient exposure to therapy. Clinical features of both groups were comparable at T0. There was no significant variation in estimated glomerular filtration rate (eGRF), median urine protein excretion, or microalbuminuria and serum phosphate levels in both groups during the study period. There was a significant increase in urinary excretion of phosphate in patients on TDF compared to those on ABV at T3 and T4. Fractional excretion of uric acid was also altered in the two treatment groups; there was no change in the ABV (constantly less than 0.10), but a progressive increase in TDF patients. Serum potassium levels were significantly lower in ABV than in TDF treated patients. Urine concentrations of α-GST showed a nonsignificant variation in both groups, while Cyc excretion was significantly higher at T1 and T3 in TDF-treated compared to ABV-treated patients. In conclusion, TDF may be associated with subclinical mitochondrial damage, inducing at a later stage increased urinary excretion of phosphate and uric acid, as markers of incipient tubular injury.

Cardiovascular risk factors in patients on long-term treatment with nevirapine- or efavirenz-based regimens

OBJECTIVES The aim of this study was to evaluate the cardiovascular risk among patients treated for more than 5 years with regimens based on nevirapine or efavirenz. PATIENTS AND METHODS A total of 276 patients were retrospectively evaluated, 156 of whom were treated with nevirapine and 120 with efavirenz, by examining traditional risk factors and detecting the presence of subclinical carotid lesions with colour-Doppler ultrasonography. RESULTS When comparing the data at baseline and follow-up in the nevirapine group, total cholesterol, low-density lipoprotein cholesterol (LDLc) and triglycerides showed a significant decrease, while high-density lipoprotein cholesterol increased. Ultrasound data, obtained in a subgroup of 67 patients, did not show significant changes for those treated with nevirapine. In the efavirenz group, total cholesterol, LDLc, triglycerides, glycaemia, body mass index and the number of patients with a pathological ultrasound significantly increased. When comparing the two groups at baseline and follow-up, nevirapine patients had significantly higher values of total cholesterol, LDLc and triglycerides at baseline, while total cholesterol and LDLc differed non-significantly at follow-up; triglycerides became significantly lower in the nevirapine arm with respect to the efavirenz group. Glycaemia was comparable between the two groups at baseline, while it was significantly lower in the nevirapine group at follow-up. The number of pathological ultrasound findings was significantly higher in the efavirenz group at follow-up. CONCLUSIONS Patients treated with nevirapine demonstrated a better lipid and glucose profile and a lower tendency to develop subclinical atherosclerotic lesions.

Pregnancy and Human Herpesvirus 8 Reactivation in Human Immunodeficiency Virus Type 1-Infected Women

ABSTRACT To investigate the impact of pregnancy on human herpesvirus 8 (HHV-8) reactivation in human immunodeficiency virus type 1 (HIV-1)-infected women, the HHV-8 DNA presence and load were analyzed in peripheral blood mononuclear cells (PBMCs) and cervicovaginal secretions (CVSs) from 15 pregnant women coinfected with HIV-1 and HHV-8. HHV-8 detection was analyzed in relation to anti-HHV-8 antibodies and HIV-1-related parameters. Nucleotide sequence analysis of an ORFK1 hypervariable region of the HHV-8 strains was performed. HHV-8 was detected in maternal PBMCs (5/15 women) from the second trimester and in CVSs (5/15 women) mainly from the third trimester. The HHV-8 load significantly increased late in pregnancy in both maternal compartments and was associated with a significant increase in HIV-1 shedding in the genital tract. Antilytic antibodies were significantly more common in HHV-8 DNA-positive women. An elevated HHV-8 load was found in the PBMCs of an infant born to a mother with large amounts of HHV-8 in both compartments at delivery. Different ORFK1 subtypes were found in maternal samples, whereas the same subtype was identified in the mother-child pair. These data suggest that pregnancy may induce HHV-8 replication in HIV-1-infected women. An augmented HHV-8 load may, in turn, influence mother-to-child transmission, since one of the HIV-1-infected mothers with HHV-8 reactivation transmitted her ORFK1 subtype to the infant, who showed a high level of HHV-8 viremia indicative of a primary infection. This finding documents for the first time the perinatal transmission of a specific HHV-8 subtype. Vertical transmission may thus play a role in HHV-8 spread also in areas of subendemicity among HIV-1-infected women.

Hepatitis B virus infection in hospital staff: epidemiology and persistence of vaccine-induced antibodies

To establish the epidemiology of viral hepatitis B (HBV) infection in hospital staff the sera of 2462 workers and 176 professional nursing students were examined. The prevalences of HBsAg and anti-HBs among the workers were 4.5 and 42.2% and among the students were 2.3 and 15.3%, respectively. The risk of infection showed a correlation with the profession of the hospital workers, the various jobs carried out in different departments, age, and the number of working years. The anti-hepatitis vaccination with HBVax and HEVAC-B vaccines was used on 142 professional students and 996 hospital workers. Five years after the beginning of the vaccine cycle the percentage of responders observed among the students was 75 (HBVax) and 79% (HEVAC-B). Among the hospital staff the response registered was 66 and 71%, respectively. The best recorded response among the youngest subjects suggests that the anti-hepatitis vaccination should be obligatory for hospital workers at the beginning of their working period or professional training.

Bone and kidney toxicity induced by nucleotide analogues in patients affected by HBV-related chronic hepatitis: a longitudinal study

OBJECTIVES Nucleotide analogues may promote renal and bone toxicity. The aim of the present study was to evaluate markers of osteorenal toxicity in patients affected by hepatitis B virus-related chronic hepatitis treated with lamivudine plus adefovir who were switched to tenofovir. PATIENTS AND METHODS We evaluated 60 consecutive patients at the time of the switch of treatment and after 1, 3, 6, 9 and 12 months. The mean baseline estimated glomerular filtration rate (eGFR) was 89.3 ± 19.0 mL/min/1.73 m(2). RESULTS During the study period we observed a reduction in mean eGFR up to 6 months after switching to tenofovir, and this remained stable for the last two timepoints. At the end of study, the mean eGFR was 82.6 ± 21.5 mL/min/1.73 m(2), a reduction of 7.5%. The mean baseline proteinuria was 202.6 ± 237.6 mg/24 h. Microhaematuria was observed in 22.6% of patients and hypophosphataemia in 18.6%. After 1 month of tenofovir, we observed a worsening of serum phosphate and parathyroid hormone levels, haemoglobinuria and 24 h proteinuria. After 3 and 12 months of tenofovir, these data tended to recover to baseline levels. A total of 92.6% of patients at baseline had hypovitaminosis D. After supplementation with cholecalciferol, this percentage decreased significantly. We observed a reduced bone mineral density (BMD) in 52.7% of patients at baseline; this increased to 77.8% after 6 months of tenofovir, but at the last timepoint the percentage of patients with a reduced BMD had fallen to a level above the baseline. CONCLUSIONS In conclusion, patients exposed to lamivudine plus adefovir showed relevant osteorenal damage. The switch to tenofovir provoked a slight reduction in eGFR that stabilized after 6 months. The reduced BMD at baseline did not worsen under tenofovir treatment.

Long‐term immunogenicity and safety of an inactivated hepatitis A vaccine in haemophilic patients

Summary. As a consequence of recent outbreaks of HAV infection by blood products, 91 patients, haemophiliacs and subjects with bleeding disorders (10 of whom were also anti‐HIV positive) susceptible to HAV infection received a formalin‐inactivated hepatitis A vaccine (HAVRIX 720 Elisa Units, SmithKline Beecham). Subcutaneous injections were given in the deltoid region at 0, 1 and 6 months. The seroconversion rates and litres, expressed in GMT IU/1, were determined at 1, 2, 6, 7, 12, 18 and 24 months. No adverse reactions to the vaccine were observed. The highest percentage of responders observed was 98.7% in anti‐HIV negative and 71.4% in anti‐HIV positive patients. The anti‐HAV GMT titres were higher in anti‐HIV negative than in anti‐HIV positive patients. The inactivated hepatitis A vaccine is safe, clinically well tolerated, and provides long‐term protection against HAV infection.

Prevalence and risk factors for viral hepatitis in the Kosovarian population: implications for health policy

The prevalence of hepatitis infection among the Kosovarian population is largely unknown. The aim of the study was to evaluate the prevalence and risk factors of hepatitis A, B, C, and D (HAV, HBV, HCV, HDV) infection among the general population and in a group of health care workers in the Kosovo region. Overall, 1,287 participants were recruited, 460 males (36%) and 827 females (64%). Health care workers accounted for 253 individuals (20%), 301 were blood donor candidates (23%), 334 were pregnant women (26%), and 399 (31%) were subjects who had been examined in two clinics for routine laboratory testing. The prevalence of total anti‐HAV was 88.6% (95% CI: 86.69–90.25). Prevalence of anti‐HAV among children up to 10 years was 40.5% (95% CI: 29.6–53.15), reaching 70% (95% CI: 62.25–77.10) in the 11–20 age group. Age, living in rural areas and unemployment were factors associated with higher risk of HAV infection. HBsAg was detected in 2.4% (95% CI: 1.57–3.38%) of the study sample, with a significant age trend (P‐value:0.0110). Positivity for total anti‐HBc was detected in 18.4% (95% CI = 16.27–20.59) of the subjects. Ninety‐three subjects (7.2%) were positive for anti‐HBs alone. An association between age, HSV‐2 positivity, working nurses and HBV infection has been observed. One patient was HDV positive. The prevalence for HCV was 0.5% (95% CI: 0.22–1.12%). HAV infection seems to be high‐intermediate, while HBV shows an intermediate endemicity. It is necessary to highlight the importance of an immunization strategy against HAV and HBV in reducing the incidence of the infection. The prevalence for HCV was very low. J. Med. Virol. 80:833–840, 2008.