Search

Background: In 1991, a mass immunization campaign against the hepatitis B virus (HBV) for children and teenagers was introduced in Italy. This study evaluated the impact of the immunization campaign on the incidence and modes of HBV transmission., Method: Acute HBV cases of viral hepatitis were reported to the National Surveillance System (SEIEVA). Hepatitis A cases reported to the same system were used as controls to calculate the adjusted odds ratios and the population attributable risk for potential risk factors., Results: The incidence of acute HBV declined from 5.0 in 1990 to 0.4 in 2019 per 100,000 population. The fall was almost total in people targeted by the campaign: in 2019, zero cases (100% reduction) in the age-group 0-14 years and 0.1 cases per 100,000 population (99.4% reduction) in the age-group 15-24 years were reported. In the decade 2010-2019, nearly one-fifth (19.3%) of cases occurred in foreigners. Intravenous drug use is no longer a risk factor (OR = 0.7; 95% CI = 0.5-1.02). Beauty treatments, risky sexual exposure, and household contact with an HBsAg carrier were found to be independent predictors of acute hepatitis B., Conclusions: The HB vaccination campaign proved effective in minimising acute HBV in Italy. Control of the infection is close to being reached for the first time in Europe.

Updated incidence data of acute Delta virus hepatitis (HDV) are lacking worldwide. Our aim was to evaluate incidence of and risk factors for acute HDV in Italy after the introduction of the compulsory vaccination against hepatitis B virus (HBV) in 1991. Data were obtained from the National Surveillance System of acute viral hepatitis (SEIEVA). Independent predictors of HDV were assessed by logistic-regression analysis. The incidence of acute HDV per 1-million population declined from 3.2 cases in 1987 to 0.04 in 2019, parallel to that of acute HBV per 100,000 from 10.0 to 0.39 cases during the same period. The median age of cases increased from 27 years in the decade 1991-1999 to 44 years in the decade 2010-2019 (p < .001). Over the same period, the male/female ratio decreased from 3.8 to 2.1, the proportion of coinfections increased from 55% to 75% (p = .003) and that of HBsAg positive acute hepatitis tested for by IgM anti-HDV linearly decreased from 50.1% to 34.1% (p < .001). People born abroad accounted for 24.6% of cases in 2004-2010 and 32.1% in 2011-2019. In the period 2010-2019, risky sexual behaviour (O.R. 4.2; 95%CI: 1.4-12.8) was the sole independent predictor of acute HDV; conversely intravenous drug use was no longer associated (O.R. 1.25; 95%CI: 0.15-10.22) with this. In conclusion, HBV vaccination was an effective measure to control acute HDV. Intravenous drug use is no longer an efficient mode of HDV spread. Testing for IgM-anti HDV is a grey area requiring alert. Acute HDV in foreigners should be monitored in the years to come., (© 2021 John Wiley & Sons Ltd.)

Background: The epidemiology of hepatocellular carcinoma (HCC) is characterized by a dynamical temporal trend of well-established and emerging risk factors., Methods: We evaluated the temporal trend of aetiological factors of HCC over the last two decades in Italy. HCC cases were recruited from two previously published national studies in 1996 and in 2008 and HCC cases were also enlisted from two national surveys in 2001 and in 2014 enrolling consecutive subjects with chronic liver disease (CLD) referring to more than 80 liver units scattered all over the country for a 6-month period., Results: Out of the 9997 subjects with CLD recruited in 2001 and the 2408 recruited in 2014, 3.3% and 5.7% (P < 0.001), respectively, had HCC. The temporal trend of HBsAg -/HCV + HCC cases significantly linearly decreased from 71.1% in 1996 to 57.2% in 2014 (P < 0.001). Conversely, that of virus-negative cases significantly linearly increased from 12.1% to 28.3% (P < 0.001). The proportion of HBV-related HCC cases showed a steady low rate, reflecting the reduced endemicity of the infection in Italy. The proportion of HCC with compensated cirrhosis (i.e., Child-Pugh A) linearly increased over time from 55.6% in 1996 to 76.0% in 2014 (P < 0.001) reflecting the growing effectiveness of semi-annual ultrasound surveillance for early detection of HCC., Conclusion: In conclusion, with decreasing viral aetiology, an overall decrease in the incidence of HCC might be expected in the future. The proportion of metabolic diseases is conversely increasing being considered as an aetiology. The growing prevalence of metabolic disorders in the general population may further increase this trend in the years to come.

Background: There is increasing awareness of HBV reactivation in HCV-RNA-positive/HBV-coinfected patients with chronic liver disease (CLD) treated with oral direct-acting antivirals (DAAs)., Aim: To provide figures on the prevalence of HBV markers in HCV-RNA-positive subjects in Italy, where these findings are lacking., Methods: All subjects aged ≥18 years with CLD consecutively referring to Italian liver units located throughout country were prospectively enrolled in two national surveys in 2001 and 2014., Results: The total number of HCV-RNA-positive cases was 6984; 356 (5.1%) subjects vaccinated against HBV were excluded. A total of 6628 cases were evaluated. The prevalence rates of HBsAg, isolated anti-HBc and anti-HBc/anti-HBs-positivity were 2.9%, 8.1% and 14.7%, respectively. Among the estimated one million HCV-RNA-positive subjects in Italy, a substantial number of subjects are at risk of HBV reactivation due to DAA therapy. The prevalence of liver cirrhosis was higher than that of CLD in HBsAg-positive subjects (4.4% vs. 2.6%, p < 0.01) but not in those positive for other HBV markers., Conclusions: These findings outline the burden of HBV markers among HCV-RNA-positive subjects in Italy, where in 2017 reimbursement for DAA therapy by the National Health System became universal for all patients with chronic HCV infection. HBV vaccination coverage should be greatly extended, since nearly two thirds of subjects in this study resulted negative for any HBV marker., (Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Gender differences in chronic liver disease (CLD) have been partially investigated. To extend the present knowledge, we evaluated 12,263 patients with CLD enrolled in two national surveys (9997 in 2001 and 2557 in 2014)., Methods: The two surveys prospectively recruited patients aged ≥ 18 referring to Italian liver units throughout the country using a similar clinical approach and analytical methods., Results: The overall male to female ratio (M/F) was 1.4 (7138/5124). Compared with females, males were significantly more likely to be younger (52.9 vs. 58.7 yrs.), with HBV infection alone (13.2% vs. 9.2%) and with alcoholic liver disease alone (11.4% vs. 6.9%), but less likely to show HCV infection alone (48.0% vs. 67.9%). A male preponderance was observed in HBV-related cases (1.99) and in alcoholic-related cases (2.3), a preponderance observed both in the 2001 and in 2014 cases. In HCV-related cases, however, females predominated in 2001 (M/F 0.9) and males in 2014 (M/F 1.5).The rate of cirrhosis in alcohol-related etiology was close to 36% in both genders, a finding much higher than that observed for both sexes in HBV and HCV etiologies.Both males and females enrolled in 2014 were older (p < 0.001) and with a higher rate of cirrhosis and/or HCC (p < 0.001) than those investigated in 2001. There was a remarkable increase over time in the proportion of male abstainers (36.7% in 2001 and 64.3% in 2014)., Conclusion: This study highlights important inter- and intra-gender differences in the characteristics and etiological factors of patients with CLD in Italy.

Background: The joint effect of the interaction of alcohol intake, hepatitis B virus (HBV) and hepatitis C virus (HCV) on the risk of cirrhosis is still unexplored because a large sample size is required for this investigation., Objective: Evaluation of interaction of HBV, HCV and alcohol abuse on the risk of cirrhosis., Design: We analysed 12,262 consecutive patients with chronic liver disease of various aetiologies referring to 95 Italian liver units in 2001 or 2014. To evaluate the interaction between alcohol abuse, HBV infection, and HCV infection, patients unexposed to either factors were used as reference category. Adjustment for BMI and age was done by multiple logistic regression analysis., Results: Females were older than males (p<0.01) and less frequently showed HBV and alcoholic aetiology (p<0.01). In both sexes, an overtime increasing age and an increasing proportion of subjects with liver cirrhosis was observed, reflecting a better survival (0.01). An additive interaction is observed in females: the O.R. generated by the simultaneous presence of HBV, HCV, and alcohol (5.09; 95% C.I. 1.06-24.56) exceeds the sum (4.14) of the O.R. generated by a single exposure (O.R. = 0.72 for HBsAg positivity, OR = 1.34 for anti-HCV positivity, and O.R. = 2.08 for alcohol intake). No interaction is observed in male sex., Conclusions: The observed gender difference suggests that the simultaneous presence of HBV/HCV coinfection and risky alcohol intake enhances the mechanism of liver damage to a greater extent in females than in males.

Background: Available data on HBV prevalence in Italy are outdated and assessed with studies conducted in small towns. We aimed to evaluate prevalence of and risk factors for HBV infection in the metropolitan area of Naples, 24 years after the introduction of mass vaccination campaign against Hepatitis B in Italy., Methods: A random systematic sample of the adult general population of Naples was selected from the register of 3 general practitioners in 3 different socio-economic districts. Independent predictors of the likelihood of HBV infection were identified by logistic regression analysis., Results: Among 900 selected subjects, 772 (85.8%) participated in the study. The overall HBsAg and anti-HBc prevalences were 1.7% and 14.4%, respectively. Both markers were more likely detected in the district at low socioeconomic status than in those at medium-high status (p<0.01). Anti-HBc prevalence linearly increased from 0% in subjects 30 years old or younger to 28.0% in those older than 60 years of age (p<0.01). At multivariate analysis, age >60 years (OR3.38; 95%CI:1.98-5.74), low socioeconomic district of residence (OR3.26; 95%CI:1.72-6.18), and low educational qualification (OR2.73; 95%CI:1.45-5.16) were independent predictors of anti-HBc positivity., Conclusion: Differences in socioeconomic conditions have played a major role in the past spread of HBV infection in Naples. Hepatitis B vaccination has resulted very effectively in preventing HBV infection, regardless of the district of residence, as none of the subjects in the vaccinated cohorts was exposed to the infection., (Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Previous cross-sectional studies have shown that hepatitis C virus (HCV) infection had been the main agent associated with liver cirrhosis in Italy., Aim: To assess epidemiological, laboratory and clinical features of liver cirrhosis in Italy in 2014., Patients: Out of the 2557 consecutive subjects evaluated in 16 hospitals located throughout Italy in 2014, 832 (32.6%) had liver cirrhosis and were enrolled in this study., Results: The mean age of subjects was 60.3years, with a male/female ratio of 1.7; 74.9% of cases had Child A cirrhosis and 17.9% superimposed hepatocellular carcinoma. HCV infection, alone or in combination with other aetiologic agents, was responsible of 58.6% of cases, HBV aetiology accounted for the 17.6% and alcohol abuse for the 16.0%. Compared with virus-related cirrhotic patients, those alcohol-related more frequently showed decompensation (p=0.02)., Conclusions: Compared to previous surveys performed in 1992 and in 2001, we observe a statistically significant (p<0.05) decreasing role of both HCV infection and alcohol abuse as aetiologic agents of liver cirrhosis in Italy, explaining, at least in part, the slow, progressive decline of the mortality rate for liver cirrhosis in the last decades in this country (from 34.5 deaths/100,000 inhabitants in1980 to 10.8 in 2012)., (Copyright © 2016 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background: The last Italian prevalence survey on chronic liver diseases (CLD) was performed in 2001. The present study evaluated the changes occurring over thirteen years., Methods: We enrolled 2,557 CLD consecutive patients in 16 Italian liver units in 2014., Results: HBV etiology accounted for 513 (20.2%) cases, alone in 439 and associated with HCV and/or alcohol abuse in 74. Of these 513, 11.9% were anti-HDV-positive and 7.2% HBeAg-positive. HCV alone was responsible for 50.3% of CLD and with alcohol abuse for 5.9%. HCV RNA was detected in 64.0% of the anti-HCV-positive patients tested. HCV genotyping, performed for 899 patients, showed genotype-1a, 1b, 2, 3, 4 and 5 respectively in 16.5%, 45.5%, 15.4%, 8.2%, 15.1% and 0.2%. Alcohol abuse alone was responsible for 6.4% of cases and NAFLD/NASH for 6.3%. Liver cirrhosis (p<0.001) and HCC (p<0.001) were more frequent in alcoholic than viral etiologies. HCV and alcohol etiologies were more frequent in 2001 than 2014 (from 69.9% to 59.9% and from 23.0% to 12.3%, respectively). HBV showed a similar impact. In all etiologies, the 2001 CLD cases were 10 years younger and with a significantly lower rate of cirrhosis than the 2014 cases., Conclusion: The changes in HCV, HBV and alcohol etiologies may help apply more appropriate healthcare strategies., (Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: Hepatitis B virus infection has decreased in Italy. The aims of this study were to identify changes, if any, in the epidemiological pattern of HBV infection in a southern Italian town first surveyed in 1996 and to assess the effectiveness of vaccination campaign against hepatitis B., Methods: In 2010, subjects were selected from the census by a systematic 1:4 random sampling procedure. Hepatitis B surface antigen (HBsAg) and antibodies to hepatitis B core antigen (anti-HBc) were detected by ELISA. Associations (odds ratios) linking exposure to hepatitis B virus infection to potential risk factors were estimated by univariate and multivariate analyses., Results: Of the 1100 eligible subjects, 1020 (92.0%) agreed to participate. The prevalences of HBsAg (0.6%) and anti-HBc (15.2%) were significantly lower than in 1996 (0.8% and 21.5%) (p<0.01). No subject below 30 years of age (those that had been targeted for compulsory immunization) had been exposed to HBV infection. At multiple logistic regression analysis, age>45 years (OR=9.8; 95% CI=5.1-18.7) and past use of glass syringes (OR=1.9; 95% CI=1.2-3.1) independently predicted the likelihood of anti-HBc positivity., Conclusions: These results, albeit obtained in a small town and thus not generalizable, confirm the continuous decreasing trend of HBV infection and demonstrate the effectiveness of the Italian hepatitis B vaccination program., (Copyright © 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background: The epidemiological pattern of hepatitis B virus infection in Italy has greatly changed over the past decades. The aim of the study was to evaluate during time the epidemiological features of acute hepatitis B cases referred to an Infectious Disease Unit in North-East of Italy between 1978 and 1995., Patients and Methods: Stored sera of 183 cases were tested for HBV markers, HBV genotypes, anti-Delta and anti-HCV., Results: Anti-HBcIgM was positive in all cases. Mean age increased from 30.2 years in 1978 to 37.5 in 1995 (P<0.01). Significant increase was observed in proportion of cases reporting intravenous drug use from 11.5% to 29.6% (P<0.03). Chronicity rate was as low as 1.1%. Mean days of hospitalization significantly decreased. HBV genotype determination showed that majority of cases was infected by genotype D, but its prevalence decreased from 88.2% in 1978 to 75.0% in 1995. Delta coinfection was present in 8.2%. The prevalence of HCV in patients with acute HBV was 35.0%; it fluctuated from 26.2% to 44.2%, mostly related (53.1%) to intravenous drug use. Dual infection did not lead to a more severe course of disease., Conclusions: From this retrospective study, remarkable fluctuations in the prevalence of dual HBV-HCV infection before the implementation of HBV vaccination were observed. Presence of anti-HCV did not affect the course of acute HBV., (Copyright © 2012 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate the compliance with the protocol for preventing perinatal hepatitis B infection in Italy, including HBsAg screening of pregnant women and immunization of newborns to infected mothers., Methods: Women consecutively delivering, over 6 months in 2008-2009, in public and private hospitals of 13 Italian regions were recruited. Data on socio-demographic characteristics, HBsAg prenatal screening and newborns immunization were collected., Results: 17,260 pregnant women were enrolled. Of them 16,858 (97.7%) attended prenatal screening. Delivering in a public hospital and in hospitals located in South Italy were both independent predictors of non-adherence to HBsAg screening. Foreign pregnant women were also less likely to be screened. Overall, HBsAg prevalence was 0.86%; it was 0.4% for Italian women and 2.5% for foreign women. Differences in prevalence by country of origin and education were statistically significant. Of 138 newborns from HBsAg positive mothers 131 received passive/active immunization; 7 newborns received just vaccine., Conclusion: In this study compliance with the protocol for preventing perinatal hepatitis B was very good. Further efforts are needed to improve adherence to prenatal screening in public hospitals, in hospital located in southern Italy and among foreign women. HBV spread in Italy is progressively declining, also involving immigrant population., (Copyright © 2010 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Background: Updates on the incidence of and risk factors for acute hepatitis delta virus infection in Italy, as well as in other countries, are lacking, and the impact of the mandatory anti-hepatitis B vaccination has not been evaluated., Methods: We performed a case-control study within a population-based surveillance for acute viral hepatitis., Results: During 1993-2004, 344 cases of acute hepatitis delta virus infection were reported. After a peak in 1993 (2.8 cases per 1 million population), the incidence decreased from 1.7 to 0.5 cases per 1 million population. Coinfections were prevalent. The decrease in incidence particularly affected young adults, and it paralleled the decrease in incidence of acute hepatitis B. In 1993, being an injection drug user (adjusted odds ratio [OR(adj)], 67.9; 95% confidence interval [CI], 18.1-254.5) or being a member of a household with a carrier of hepatitis B surface antigen (OR(adj,) 14.8; 95% CI, 3.0-72.9) were the only independent predictors of infection. During 1994-2004, being an injection drug user (OR(adj), 36.8; 95% CI, 20.7-65.4), cohabitation with an injection drug user (OR(adj), 4.2, 95% CI, 1.7-12.3), hospitalization (OR(adj), 3.5; 95% CI, 1.9-6.6), receipt of dental therapy (OR(adj), 2.3; 95% CI, 1.4-3.6), promiscuous sexual activity (OR(adj), 2.2; 95% CI, 1.4-3.6), and receipt of beauty treatment (OR(adj), 2.0; 95% CI, 1.3-3.2) were independently associated with infection., Conclusions: Incidence of acute hepatitis delta infection is markedly decreasing in Italy. Undergoing invasive medical procedures, engaging in promiscuous sexual activity, and receiving beauty treatments are emerging, in addition to injection drug use, as important risk factors for infection. Further efforts are needed to increase vaccine coverage in high-risk groups and to implement the safety of invasive procedures performed both inside and outside health care facilities.

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.

The aims of the study were to evaluate the role of beauty treatments in the spread of acute viral hepatitis B (HBV) and acute viral hepatitis C (HCV) in Italy. Data from the surveillance system for acute viral hepatitis (SEIEVA) during the period 1997-2002 were used. After exclusion of subjects <15 years or >55 years old and reporting intravenous drug use or blood transfusion, the association of acute HBV and HCV cases with beauty treatments (tattooing, piercing, manicure/chiropody, and barber shop shaving) was estimated comparing 2,964 hepatitis B and 598 hepatitis C cases with 7,221 hepatitis A cases, used as controls, by multiple logistic regression analysis. The population attributable risk (PAR) to beauty treatments was estimated according to Levin's formula. Beauty treatments were associated with acute HBV (OR = 1.8; CI 95% = 1.5-2.1) and acute HCV (OR = 1.7; CI 95% = 1.2-2.3). The strongest association was found with barber shop shaving for HBV (OR = 1.8; CI 95% = 1.5-2.2) and with tattooing for HCV cases (OR = 5.6; CI 95% = 2.8-11.0). The estimates of the population attributable risk (PAR) indicate that nearly 15% of all acute HBV (17.4% in males) and 11.5% of all acute HCV cases (16.4% in males) occurring in 15-55 year old subjects not exposed to intravenous drugs or blood transfusion in Italy are due to beauty treatments. It is concluded that certain beauty treatments play an important role in the spread of HBV and HCV infections in Italy.

The effectiveness in the prevention of perinatally transmitted HBV infection was assessed in 11858 pregnant women consecutively recruited in public and private hospitals in six Italian regions during a 2 months period in 2001. Of them 10881 (91.8%) attended HBsAg antenatal screening. The overall HBsAg prevalence was 1.7% (CI 95%: 1.4-1.9); it was 1.4% (CI 95%: 1.2-1.7) in pregnant women born in Italy but 5.9% (CI 95%: 4.1-8.1) in those born in Asia, Africa, central and south America, and eastern Europe. Results of multiple logistic regression analysis indicate that birth in foreign countries (OR 2.0; CI 95%: 1.3-3.0), family size with more than 4 members in the household (OR 3.5; CI 95%:2.7-4.6), and birth in a private hospital (OR 1.9; CI 95%: 1.3-2.8) were all independent predictors of lack of adherence to HBsAg screening. Out of the 182 new-borns of HBsAg positive mothers 172 (95.0%) were given active plus passive immunisation; this figure was 100% in new-borns of foreign mothers. These findings evidence a good effectiveness in the prevention of perinatally transmitted HBV in Italy. More efforts should be addressed to improve the effectiveness of the programme among foreign pregnant women who have high rate of HBsAg and more likely escape HBsAg screening than Italian pregnant women., (Copyright 2002 Elsevier Science Ltd.)

In Italy, a program of vaccination against hepatitis B targeted at the immunisation of persons at high risk began in 1983. In 1991, vaccination became mandatory for all newborns and adolescents. Since then, the vaccine has been given to more than 10 million children, with an outstanding record of safety and efficacy. The coverage rate is globally around 94%, with differences between the Northern and Southern regions, with the latter having the lower acceptance rate. According to the National Surveillance System (SEIEVA), the incidence of acute hepatitis B per 10(5) inhabitants declined from 5.4 in 1990 to 2 in 2000. The reduction was even greater among 15-24-year-old individuals, where the incidence rate per 10(5) decreased from 17.3 to 2 in the same period. In parallel with the decline of hepatitis B, hepatitis delta has also declined significantly. Catch-up immunisation of unvaccinated adolescents, as well as an effort to improve the vaccination coverage rate in high-risk groups, are required to ameliorate the efficacy of the vaccination campaign. Routine administration of booster doses of vaccine is not considered necessary to sustain immunity in immunocompetent persons., (Copyright 2002 Wiley-Liss, Inc.)

Simple Summary: Hepatitis B virus (HBV) is a potentially life-threatening viral infection that primarily affects the liver. Vaccination against HBV is crucial for preventing the spread of the disease and reducing its associated morbidity and mortality. The introduction of the hepatitis B vaccine has had a significant impact on public health globally, including in Italy. In the 1980s, Italy had one of the highest rates of HBV infection in Europe. The Italian government recognized the importance of vaccination and introduced the hepatitis B vaccine into the national immunization program in 1991, making it freely available. This was a significant step in the fight against HBV infection. By the early 2000s, the prevalence of chronic HBV infection in Italy had decreased to less than 1% among children and adolescents. The introduction of the hepatitis B vaccine in Italy has played a crucial role in reducing the burden of HBV infection and its associated complications. The success of the vaccination program highlights the importance of public health interventions in preventing the spread of infectious diseases. In Italy, Hepatitis B virus (HBV) infection has been characterized by several changes over the last five decades. In 2019, the incidence of acute HBV among subjects targeted by the vaccination campaign was 0 cases in the age group 0–14 years and 0.1/100,000 in the age group 15–24. Nowadays, the burden of different stages of HBV-related chronic liver diseases is minimal. Intravenous drug use is no longer a risk factor (O.R. 0.7; 95% C.I. 0.5–1.02) for acquiring acute HBV; the proportion of cases reporting this exposure fell from 29.8% to 3.3% over the last two decades. The key public health intervention has been the compulsory vaccination campaign started in 1991 for infants 3 months old and 1–2 years old (the latter group for the first 12 years of the campaign). Moreover, non-immunogenic factors and the availability of effective oral antiviral drugs have played and continue to play a prominent role. The potential availability of new oral antiviral drugs with the inherent ability to eliminate the genomic HBV reservoirs may represent a further crucial step in the elimination of the virus in people that are already infected. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepatitis viruses are key actors in the development of hepatocellular carcinoma (HCC), one of the leading causes of death in cancer. From the discovery of hepatitis viruses, many steps in this research field have been made. In this expert narrative review, the pathway leading to the actual public health figures is put in a historical perspective, and future scenarios are imagined for the coming years based on new technology and biological knowledge. Understanding the historical context of the role of hepatitis viruses in the development of HCC is important for improving our comprehension of the mechanisms by which these viruses contribute to cancer development, expanding strategies for prevention and treatment, and improving public health policies to reduce the burden of HCC in populations with high rates of viral hepatitis. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the leading cause of hepatocellular carcinoma (HCC) worldwide. Currently, HBV-related HCC predominates in Sub-Saharan Africa and South-East-Asia, while HCV-related HCC predominates in northern Africa and in the western world. Liver cirrhosis is the underlying condition in most HBV cases and in nearly all HCV cases. Several cofactors, viral and non-viral, play a role in the progression toward HCC: dual HBV/HCV infection, HDV, HIV, alcohol intake, smoking, diabetes mellitus, obesity, and NAFLD/NASH. HBV vaccine is effective in preventing both infection and HCC; antiviral drugs may suppress HBV replication and eradicate HCV infection, halting progression to HCC. Inequalities exist between high- and low-income countries with respect to vaccine availability and access to antivirals. These factors represent barriers to the control of HCC incidence. Lack of an effective vaccine against HCV is also a serious barrier to HCV elimination and HCC prevention. The most crucial steps and knowledge that have arisen over time on the association between the two major hepatotropic viruses and HCC are discussed in this historical review. [ABSTRACT FROM AUTHOR]

Background and rationale of the study. Effect of Long-term nucleoside/nucleotide (NUC) on hepatocellular carcinoma (HCC) incidence in a population of HBeAg-negative genotype D patients has not been adequately studied in real-life cohorts. Our aim was to evaluate the impact of liver fibrosis and other variables on HCC incidence in this population of patients. Of 745 patients with chronic hepatitis B (CHB), 306 HBeAg-negative genotype D were selected and included in this study. All patients received treatment with NUC for at least 18 months. Patients with CHB or compensated cirrhosis were included. Patients with HCC diagnosed before or during the first 18 months of NUC therapy were excluded. Results. HCC was diagnosed in 2 CHB patients (1.0%) and 23 cirrhosis patients (20%) (OR = 24.41, 95% CI 5.40 < OR < 153.2; p < 0.0001). Multivariate analysis revealed that HCC risk was independently associated with age ⩾60 years (OR = 6.45, 95% CI 1.22 to 34.0; p = 0.02) and liver cirrhosis (OR = 12.1, 95% CI 1.39 to 106.2; p = 0.02), but not with virological response (VR), and previous resistance to NUC, or rescue therapy. Multivariate analysis in cirrhosis patients revealed that only age ⩾ 60 years was an independent risk factor associated with HCC (p = 0.003). Conclusions. Liver cirrhosis and age ⩾ 60 years are the stronger risk factors for HCC in genotype D HBeAgnegative patients. Previous resistance to NUC in patients that achieved a VR after rescue therapy was not a predictive factor regarding HCC. VR does not appear to significantly reduce the overall incidence of HCC when a patient has already progressed to liver cirrhosis. [ABSTRACT FROM AUTHOR]

Chronic hepatitis B virus (HBV) infection may be reactivated by immunosuppressive drugs in patients with autoimmune inflammatory rheumatic diseases. This study evaluates HBV serum markers' prevalence in rheumatic outpatients belonging to Spondyloarthritis, Chronic Arthritis and Connective Tissue Disease diagnostic groups in Italy. The study enrolled 302 subjects, sex ratio (M/F) 0.6, mean age ± standard deviation 57 ± 15 years, 167 (55%) of whom were candidates for immunosuppressive therapy. The Spondyloarthritis group included 146 subjects, Chronic Arthritis 75 and Connective Tissue Disease 83 (two patients had two rheumatic diseases; thus, the sum is 304 instead of 302). Ten subjects (3%) reported previous anti-HBV vaccination and tested positive for anti-HBs alone with a titer still protective (>10 IU/mL). Among the remaining 292 subjects, the prevalence of positivity for HBsAg, isolated anti-HBc, anti-HBc/anti-HBs, and any HBV marker was 2%, 4%, 18%, and 24%, respectively. A total of 26/302 (9%) patients with γ-globulin levels ≤0.7 g/dL were more frequently (p = 0.03455) prescribed immunosuppressive therapy, suggesting a more severe rheumatic disease. A not negligible percentage of rheumatic patients in Italy are at potential risk of HBV reactivation related to immunosuppressive therapy. Before starting treatment, subjects should be tested for HBV markers. Those resulting positive should receive treatment or prophylaxis with Nucleos (t) ides analogue (NUCs) at high barrier of resistance, or pre-emptive therapy, according to the pattern of positive markers. HB vaccination is recommended for those who were never exposed to the virus. [ABSTRACT FROM AUTHOR]

Abstract: Hepatitis B reactivation has been widely reported in patients undergoing immunosuppressive therapy in oncohaematological and transplant settings, with a high frequency of hepatic failure. This topic has received growing scientific interest and several studies reported the preventive effect of antiviral agents on hepatitis B reactivation during immunosuppression therapy. Routine prophylaxis is therefore recommended and specific recommendations were elaborated by AASLD, EASL and AISF. On the contrary, few data are available on the risk of HBV reactivation in patients with inflammatory bowel disease (IBD) receiving immunosuppressive therapy, and major questions regarding the optimal management (screening, prophylaxis, therapy, monitoring) of IBD patients with HBV infection remain to be addressed. The aim of this paper is to provide a systematic review of the literature to underline the main aspects of HBV infection and reactivation in patients affected by IBD treated with conventional or biological immunosuppressive drugs. [ABSTRACT FROM AUTHOR]

Background/Aims: This study assess prevalence, risk factors, and clinical and virological features of dual hepatitis B virus (HBV)/hepatitis C virus (HCV) infection.Methods: We evaluated 837 hepatitis B surface antigen positive patients, prospectively enrolled in 14 Italian units.Results: Anti-HCV was present in 59 cases (7%); age specific prevalences were 4.5% (0–30 years), 4.4% (>30–50) and 14% (>50). Independent predictors of dual infection were age >42 years, history of I.V. drug use (IDU), blood transfusion and residence in the South of the country. The strength of the association with IDU was high, but this exposure accounted for five coinfection cases only. Cirrhosis was present in 107 of the 709 patients with HBV alone (15.1%), in 30 of 69 with hepatitis D virus coinfection (43%) and in 17 of 59 with HCV coinfection (28.8%); a light alcohol use was marginally associated with cirrhosis.Of 36 B/C coinfected patients, 16 (44.4%) had only HBV-DNA in serum, (median age=47.5 years) five (13.9%) had both HBV-DNA and HCV-RNA (age=53), nine (25%) had HCV-RNA alone (age=59) and six (16.7%) tested negative for both.Conclusions: This study depicts the epidemiological and clinical burden of dual HBV/HCV infection in Italy. [Copyright &y& Elsevier]