Alfonso Mele

Long-term immunogenicity of hepatitis B vaccination and policy for booster: an Italian multicentre study

BACKGROUND Universal anti-hepatitis-B vaccination of infants and adolescents was implemented in Italy in 1991. We undertook a multicentre study in previously vaccinated individuals to assess the duration of immunity and need for booster, over 10 years after vaccination. METHODS In 1212 children and 446 Italian Air Force recruits vaccinated as infants and adolescents, respectively, we measured the concentrations of antibodies to hepatitis-B surface antigen (anti-HBs) and the presence of antibodies to hepatitis-B core antigen (anti-HBc) at enrollment; postimmunisation values were not available. Individuals positive for anti-HBc were tested for hepatitis B surface antigen (HBsAg) and hepatitis B viral DNA. Individuals with anti-HBs concentrations at 10 IU/L or more were regarded as protected; those with antibody less than 10 IU/L were given a booster dose and retested 2 weeks later. Individuals showing postbooster anti-HBs concentrations of less than 10 IU/L were offered two additional vaccine doses and retested 1 month after the third dose. FINDINGS Protective anti-HBs concentrations were retained in 779 (64%, 95% CI 61.6-67) children and 398 (89%, 86.4-92.1) recruits. We recorded antibody amounts of less than 10 IU/L in 433 children (36%, 33-38.4) and 48 (11%, 7.9-13.6) recruits. One child and four recruits were positive for anti-HBc, but negative for HBsAg and hepatitis B viral DNA. Antibody concentrations were higher in recruits than in children (geometric mean titre 234.8 IU/L vs 32.1 IU/L, p=0.0001). 332 (97%) of 342 children and 46 (96%) of 48 recruits who received a booster showed an anamnestic response, whereas ten (3%) children and two (4%) recruits remained negative for anti-HBs or had antibody concentrations of less than 10 IU/L. Prebooster and postbooster antibody titres were strongly correlated with each other in both groups. All individuals given two additional vaccine doses (eight children and two recruits) showed anti-HBs amounts of more than 10 IU/L at 1 month after vaccination. INTERPRETATION Strong immunological memory persists more than 10 years after immunisation of infants and adolescents with a primary course of vaccination. Booster doses of vaccine do not seem necessary to ensure long-term protection.

Hepatitis viruses and non-Hodgkin lymphoma: epidemiology, mechanisms of tumorigenesis, and therapeutic opportunities

Over the past 2 decades considerable evidence has accumulated on the association between hepatitis C virus (HCV) and hepatitis B virus (HBV) and several hematologic malignancies, most notably B-cell non-Hodgkin lymphoma (NHL). In this review we summarize this evidence, address possible mechanisms whereby hepatitis viruses may contribute to lymphomagenesis, and discuss the therapeutic fallouts from this knowledge. Most of this evidence is on HCV, and this is the main focus of the review. Moreover, we mainly address the association with NHL, the most prevalent hematologic malignancy, and the most extensively investigated with regard to an association with hepatitis viruses. Available evidence on the association with other hematologic malignancies is also addressed briefly.

Prevalence and etiology of altered liver tests: a population-based survey in a Mediterranean town.

Serum biochemical liver tests (LTs) (ALT, AST, GGT) and platelet counts are often used to screen for chronic liver disease. Population‐based data on abnormal LTs in Mediterranean areas are lacking. The prevalence and etiology of abnormal LTs were assessed from 2002 to 2003 in a 1 in 5 systematic random sample of the general population who were 12 years of age or older in Cittanova, a southern Italian town with 10,600 inhabitants. LTs, indices of metabolism, and markers of HBV and HCV infection were assayed and alcohol intake was recorded in the selected population. In virus‐free individuals with abnormal LTs, LTs were retested, and upper abdominal echography and tests for other causes of liver damage were undertaken. Among the 1,645 individuals screened, the prevalence of anti‐HCV was 6.5%; the prevalence was particularly high in individuals over 50 years of age. The corresponding prevalence for HBsAg was 0.8%. The overall prevalence of individuals with abnormal LTs was 12.7% (95% CI: 11.1‐14.3). The probable cause of abnormal LTs was excessive alcohol in 45.6%, HCV in 18.6%, HBV in 1%, alcohol plus HCV and/or HBV in 8.8%, and rare diseases in 2%. In 24% of individuals with abnormal LTs, the probable cause was nonalcoholic fatty liver disease (NAFLD); in this subgroup, increased body weight, hypercholesterolemia, and hyperglycemia were common, and 63.3% of them had a bright liver at echography. In conclusion, in southern Italy, a Mediterranean area where dietary habits are different from those in industrialized areas, one eighth of the general population has abnormal LTs suggestive of possible liver damage; NAFLD appears to be emerging as a potentially important etiology of this presumed liver injury. (HEPATOLOGY 2005;41:1151–1159.)

Efficacy of hepatitis A vaccine in prevention of secondary hepatitis A infection: a randomised trial

BACKGROUND Hepatitis A vaccination stops outbreaks of hepatitis A infection, but its efficacy against infection after exposure has not been proven. We investigated the use of hepatitis A vaccine to prevent secondary infections with hepatitis A virus (HAV). METHODS We did a randomised controlled trial of hepatitis A vaccine in household contacts of people with sporadic HAV infection (index cases). Households (index cases and contacts) were randomly assigned to the vaccine group or unvaccinated group, according to the study week in which they were enrolled. All household contacts in the vaccine group received vaccination at the time of entry to the study. FINDINGS During 45 days of follow-up, secondary infection had occurred in ten (13.3%) of 75 households (two families had two cases each) in the untreated group and in two (2.8%) of 71 households in the vaccine group. The protective efficacy of the vaccine was 79% (95% CI 7-95). The number of secondary infections among household contacts was 12 (5.8%) of 207 in the unvaccinated group and two (1.0%) of 197 in the vaccinated group. Therefore, 18 individuals needed to be vaccinated to prevent one secondary infection. INTERPRETATION Hepatitis A vaccine is effective in the prevention of secondary infection of HAV and should be recommended for household contacts of primary cases of HAV infection.

Hepatitis C virus infection and alanine transaminase levels in the general population : a survey in a southern Italian town

BACKGROUND/AIM The aim of the study was to estimate the prevalence, risk factors and genotype distribution of hepatitis C virus (HCV) in the general population older than 5 years of age in a southern Italian town. The positive predictive value of alanine transaminase (ALT) screening in identifying HCV positive subjects was also assessed. METHODS Cluster random sampling from the census of the general population was used. ELISA and RIBA tests assessed the presence of anti-HCV; nested reverse transcription polymerase chain reaction (RT-PCR) was used to identify HCV-RNA; genotyping was performed by INNO-LIPA III. The association linking anti-HCV seropositivity with potential risk factors was assessed by multiple logistic regression analysis. RESULTS Among the 488 subjects enrolled, 79 (16.2%) were anti-HCV positive. The prevalence increased from 1.2% in subjects 6-29 years of age to 42.1% in those > or = 60 years. Forty percent of these positive subjects also had abnormal ALT level and 54.4% were HCV RNA positive by PCR. The positive predictive value of the ALT test in identifying anti-HCV positive subjects was 65%; however, it was 46.7% in subjects younger than 60 years of age and 90.5% in those 60 or older. Genotype 1b was detected in 74% of subjects, type 2c in 23.3%, and type 1a in 2.3%. The only two variables significantly associated with HCV seropositivity in multivariate analysis were age older than 45 years (O.R. 8.5; CI 95%=3.0-24.1) and past use of glass syringes (O.R. 3.4; CI 95%=1.5-7.6). CONCLUSIONS These findings confirm that HCV infection is endemic in southern Italy, particularly among the elderly. Percutaneous exposure, such as injections with nondisposable, multiple-use, glass syringes used in the past for medical purposes may have played a major role in the spread of HCV infection. ALT screening is not useful in detecting HCV positive subjects in the general population, particularly among subjects who could benefit from antiviral therapy.

Prevalence of Infected Patients and Understaffing Have a Role in Hepatitis C Virus Transmission in Dialysis

To assess hepatitis C virus (HCV) incidence rates and identify determinants of infection among hemodialysis patients, a multicenter study was conducted in 58 units in ITALY: An initial seroprevalence survey was conducted among 3,492 patients already on hemodialysis therapy as of January 1997 and among an additional 434 patients who began dialysis up to January 1998. HCV antibodies were assessed by third-generation enzyme immunoassays. Patients testing seronegative at baseline were enrolled into a 1-year incidence study with serological follow-up at 6 and 12 months. For patients who seroconverted, an HCV RNA assay was performed on stored baseline samples to confirm new infection. A nested case-control study was subsequently performed to investigate potential risk factors. For each incident case, three controls negative for both HCV antibodies and HCV RNA were randomly selected. At enrollment, HCV seroprevalence was 30.0%. During follow-up, 23 new HCV cases were documented, with a cumulative incidence of 9.5 cases/1,000 patient-years. By logistic regression analysis, an increased risk for HCV infection emerged for patients attending the dialysis units with a high prevalence of HCV-infected patients at baseline (odds ratio [OR], 4.6) and for those attending units with a low personnel-patient ratio (OR, 5.4). Among extradialysis factors, a history of surgical intervention in the previous 6 months (OR, 16.7) significantly increased HCV risk. These findings suggest that the combination of understaffing and a high level of infected patients in the dialysis setting increases the risk for HCV nosocomial transmission. This is likely related to an increased likelihood for breaks in infection control measures.

Correlation between virus genotype and chronicity rate in acute hepatitis C

BACKGROUND/AIMS Forty-two patients with the diagnosis of acute hepatitis C virus hepatitis were studied to investigate the relationship between hepatitis C virus genotype and progression to chronic infection. METHODS The patients were followed for more than 1 year (mean age 29 years, male/female ratio 2.5). Intravenous drug use was documented in 15 cases, blood transfusion in four, surgical intervention, dental therapy or other parenteral exposure in 15, and unknown factors in the remaining eight. The evolution to chronicity was diagnosed on the basis of a persistent increase in transaminase levels, the presence of HCV-RNA and the histological pattern of chronic hepatitis. RESULTS The majority of cases presented hepatitis C virus infection of subtype 1a (38.1%) or 1b (33.9%). Six cases showed the presence of genotype 3a (14.3%). Subtype 2c was observed in three out of four cases infected with genotype 2. No significant association was demonstrated with documented risk factors. The overall chronicity rate was 59.5%. This value increased to 92% in individuals infected with genotype 1b. By multivariate analysis the age-adjusted odds ratio for infection with genotype 1b as compared with all other genotypes was 14.4 (95% confidence interval; 1.52-137). Moreover, significant differences (p= 0.0002) were present in this group for histological activity index (8.7 as compared with 5-7). CONCLUSIONS The results of this prospective study are consistent with an independent association between hepatitis C virus genotype 1b and a poor prognosis.

Beauty treatments and risk of parenterally transmitted hepatitis : results from the hepatitis surveillance system in Italy

The role of ear-piercing, tattooing, attendance at chiropodist or manicurist and barber shop shaving in transmitting hepatitis B and hepatitis non-A, non-B was evaluated. Data reported here were collected from 1985 to 1993 by the National Viral Hepatitis Surveillance System. The association between parenterally transmitted hepatitis and the considered risk factors was estimated, comparing 6,395 hepatitis B and 2,558 hepatitis non-A, non-B cases with 4,789 hepatitis A cases, using the case-control method. Of the non-A, non-B cases tested from 1991 to 1993, 56.6% were anti-HCV positive. The incidence of parenterally transmitted hepatitis cases reporting specific beauty treatments was also evaluated. Tattooing, ear-piercing and barber shop shaving were associated with both parenterally transmitted hepatitides, while attendance at a chiropodist or manicurist was associated only with hepatitis B. During the study period the incidence of acute hepatitis B and non-A, non-B cases reporting beauty treatments declined by 49%. In spite of this decline, considering that a large part of the general population is exposed to the considered risk factors, the role of beauty treatments in transmitting hepatitis B and hepatitis non-A, non-B should not be underestimated.

Risk of parenterally transmitted hepatitis following exposure to surgery or other invasive procedures: results from the hepatitis surveillance system in Italy

BACKGROUND/AIMS To evaluate the strength of association between parenterally transmitted viral hepatitis and specific types of invasive procedures. METHODS Data from the surveillance system for type-specific acute viral hepatitis (SEIEVA) during the period 1994-1999 were used. The association of acute hepatitis B virus (HBV) and hepatitis C virus (HCV) infection with the potential risk factors (odds ratios (OR)) was estimated comparing 3120 hepatitis B and 1023 hepatitis C cases with 7158 hepatitis A cases, used as controls, by multiple logistic regression analysis. RESULTS Most procedures resulted in being associated with the risk of acquiring acute HBV or HCV. The strongest associations were: for HBV infection, abdominal surgery (adjusted OR = 3.9; 95% confidence intervals (CI) = 2.0-7.5), oral surgery (OR = 2.7; 95% CI = 1.6-4.5) and gynaecological surgery (OR = 2.6; 95% CI = 1.2-5.5); for HCV infection, obstetric/gynaecological interventions (OR = 12.1; 95% CI = 5.6-26.3), abdominal surgery (OR = 7.0; 95% CI = 3.2-14.9) and ophthalmological surgery (OR = 5.2; 95% CI = 1.1-23.2). Biopsy and/or endoscopy were associated with HCV, but not with HBV infection. CONCLUSIONS Invasive procedures represent an important mode of HBV and HCV transmission. Since a large proportion of the adult general population is exposed to these procedures and an effective HCV vaccine is not yet available, non-immunological means of controlling iatrogenic modes of transmission are extremely important.

Effectiveness of Hepatitis B Vaccination in Babies Born to Hepatitis B Surface Antigen-Positive Mothers in Italy

This study examined 522 children born to hepatitis B surface antigen (HBsAg)-positive mothers from 1985 through 1994 and evaluated the protection provided by anti-hepatitis B virus (HBV) immunization at birth. Babies were given hepatitis B immunoglobulin and hepatitis B vaccine at birth. At 5-14 years after immunization, 17 children (3.3%) were anti-HB core antigen positive, and 3 also were HBsAg positive. One carrier child had a double mutation, with substitution of proline-->serine at codons 120 (P120S) and 127 (P127S) within the a determinant of HBsAg. Of the 522 children, 400 (79.2%) of 505 still had protective anti-HBsAg titers > or =10 mIU/mL. Thus, HBV vaccination of children born to HBsAg-positive mothers is effective and confers long-term immunity. There is no evidence that the emergence of HBV escape mutants secondary to the immune pressure against wild-type HBV is of concern.