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.
Background. Hepatitis B vaccination has proven to be very safe and highly effective. This study assessed the proportion of successfully vaccinated individuals among cases with acute hepatitis B, the ...proportion of preventable cases if individuals were vaccinated as recommended, and the reasons for failures. Methods. We analyzed data reported to the Italian Surveillance System for Acute Viral Hepatitis from 1993 to 2014. Results. A total of 362 of 11 311 (3.2%) cases with acute hepatitis B were vaccinated. Of the 277 cases for whom immunization data were available, 50 (18%) received a complete vaccination course according to the correct schedule and before exposure to hepatitis B virus. Molecular characterization of 17 of these cases showed that 6 were infected with S-gene mutants. Among the 10 949 unvaccinated cases, 213 (1.9%) escaped mandatory vaccination and 2821 (25.8%) were not vaccinated despite being at increased risk of infection. Among the latter, the most common risk factors were cohabitation with hepatitis B surface antigen (HBsAg) carriers, intravenous drug use, and homosexual/bisexual practices. Thirty-seven percent of the unvaccinated households with HBsAg carriers were aware of their risk. Lack of trust in the vaccination, negative attitude, and inaccurate beliefs followed by lack of or poor communication and low perceived severity of the disease were the most frequent reasons for vaccine hesitancy. Conclusions. Development of acute disease in successfully vaccinated individuals is a rare event. Further efforts are needed to enhance the vaccine coverage rate in individuals at increased risk of infection.
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.
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 enrolment; 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.
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.
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.
AIM：To evaluate the clinical relevance of each cofactor on clinical presentation of chronic hepatitis B.METHODS：Out of 1366 hepatitis B surface antigen（HBsAg） positive subjects consecutively observed ...in 79 Italian hospitals,53（4.3%） showed as the only cofactor hepatitis D virus（HDV） infection hepatitis B virus（HBV）/HDV group,130（9.5%） hepatitis C virus（HCV）（group HBV/HCV）,6（0.4%） human immunodeficiencyvirus（HIV）（group HBV/HIV）,138（10.2%） alcohol abuse（group HBV/alcohol）;109（8.0%） subjects had at least two cofactors and 924 were in the cofactor-free（CF） group.RESULTS：Compared with patients in group CF those in group HBV/alcohol were older and more frequently had cirrhosis（P 0.001）,those in group HBV/HDV were younger（P 0.001）,more frequently resided in the south of the country and had cirrhosis（P 0.001）,those in group HBV/HCV were older（P 0.001） and more frequently had cirrhosis（P 0.001）.These cofactors were all independent predictors of liver cirrhosis in HBsAg positive patients.Multivariate analysis showed that an older age odds ratio（OR） 1.06,95% CI：1.05-1.08,alcohol abuse with more than 8 drinks daily（OR 2.89,95% CI：1.81-4.62） and anti-HDV positivity（OR 3.48,95% CI：2.16-5.58） are all independently associated with liver cirrhosis.This association was found also for anti-HCV positivity in univariate analysis,but it was no longer associated（OR 1.23,95% CI：0.84-1.80） at multivariate analysis.CONCLUSION：Older age,HDV infection and alcohol abuse are the major determinants of severe liver disease in chronic HBV infection,while HCV replication plays a lesser role in the severity of hepatic damage.
Abstract Objectives Investigating women's knowledge, attitude and practice in relation to menopause and systemic hormone therapy (HT) through a sample survey implemented within the preliminary works ...for the Consensus Conference “Informing women on hormone replacement therapy” that took place in Turin in May 2008 Available at www.partecipasalute.it . Last access 7/8/2008. Methods The survey involved representative samples of women 45–60 years from five Italian regions. Twenty trained interviewers distributed the questionnaires reaching participants at their homes. A total of 969 women were selected from electoral rolls. 720 of them completed the interview (74.3% response rate). Results Participants reported positive attitudes about menopause; more than 90% believed menopause is a normal phase in women's life and more than 40% stated it is a good experience for a woman. Nevertheless, more than half of the sample did not receive any information about menopause and possible therapies, and those who did, often rated it as poor and contrasting. Moreover, clinicians who prescribed HT reported advantages (94%) much more frequently than disadvantages (22%) and risks (39%) in relation to this treatment. Lack of knowledge was associated with women's low educational level and their no or scarce attitude to attend health services. Conclusions More and qualified information should be provided to support women in making informed choices in relation to menopause and the use of systemic HT. Therefore, actions’ should be carried out in order to strengthen the advisory role of clinicians and other sources of information, when taking care of women who may be using or thinking of using HT.
The existence of an association between infection with hepatitis C virus (HCV) and B-cell non-Hodgkin lymphoma (B-NHL) remains controversial, largely because previous studies were based on prevalent ...case series or comparisons with less than optimal control groups. This hospital-based case-control study was conducted from January 1998 through February 2001 to evaluate the association between HCV infection and B-NHL of different types. Cases were consecutive patients with a new diagnosis of B-NHL; controls were patients from other departments of the same hospitals. Both groups were interviewed using a standardized questionnaire. The prevalence of HCV infection was calculated by histologic type of B-NHL and clinical behavior (indolent or aggressive). Adjusted odds ratio (OR) and HCV-attributable risk (AR) were estimated. HCV prevalence was 17.5% among the 400 lymphoma patients and 5.6% among the 396 controls. The OR of B-NHL (patients vs controls), adjusted by age, sex, level of education, and place of birth, was 3.1 (95% confidence interval CI, 1.8-5.2); an OR indicative of positive association was found for indolent and aggressive B-NHL. The estimated AR was 4.6%. This study confirms an association between HCV and B-NHL. In Italy, 1 of 20 instances of B-NHL may be attributable to HCV infection and may, thus, benefit from antiviral treatment.
Abstract In 1992, 620 adolescents were vaccinated against hepatitis B. Anti-HBs concentrations were measured in 480 (77.4%) adolescents 1 month after completion of the primary course of vaccination. ...To assess the persistence of anti-HBs, 347 and 228 of such vaccinees were retested for anti-HBs in 1999 and for anti-HBs and anti-HBc in 2003. More than 10 years after vaccination, individuals with anti-HBs ≥10 mIU/ml were considered protected while those with antibody <10 mIU/ml were given a booster dose and retested 2 weeks later. Check performed in 2003 showed that 208/228 (91.2%) vaccinees retained protective concentrations of anti-HBs. All vaccinees were anti-HBc negative. 11 of the 12 (91.7%) individuals who were given a booster dose of vaccine showed a vigorous anamnestic response while the remaining one showed a weak response (10.6 mIU/ml). These data suggests that hepatitis B vaccination can confer long-term immunity and that immunological memory can outlast the loss of antibody. Hence, the use of routine booster doses of vaccine does not appear necessary to maintain long-term protection in successfully vaccinated immunocompetent individuals.
Caspase-dependent cleavage of antigens associated with apoptotic cells plays a prominent role in the generation of CD8⁺ T cell responses in various infectious diseases. We found that the emergence of ...a large population of autoreactive CD8⁺ T effector cells specific for apoptotic T cell-associated self-epitopes exceeds the antiviral responses in patients with acute hepatitis C virus infection. Importantly, they endow mixed polyfunctional type-1, type-2 and type-17 responses and correlate with the chronic progression of infection. This evolution is related to the selection of autoreactive CD8⁺ T cells with higher T cell receptor avidity, whereas those with lower avidity undergo prompt contraction in patients who clear infection. These findings demonstrate a previously undescribed strict link between the emergence of high frequencies of mixed autoreactive CD8⁺ T cells producing a broad array of cytokines (IFN-γ, IL-17, IL-4, IL-2…) and the progression toward chronic disease in a human model of acute infection.
PDF
