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.
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.
In Italy, the vaccination campaign against hepatitis B virus has been characterized by two phases. In the first phase (1984–1991), vaccination with plasma-derived vaccines was first recommended for ...the high-risk group. In the second phase (1991–nowadays), recombinant vaccine targeted, by law, infants 2 months old and teenagers 12 years old (limited to the first 12 years of campaign); screening for HBsAg became compulsory for all pregnant women during the third trimester of pregnancy. Successful achievements have been attained: No acute HBV case has been observed in the age group targeted by vaccination, the pool of chronic HBsAg carriers is strongly reduced, perinatal HBV transmission is under control, and acute delta virus hepatitis cases are nearly eliminated. The key point of this success has been the peculiar vaccination policy adopted. The combined vaccination of teenagers has generated an early immune cohort of youths, who are no longer at risk of acquiring HBV infection by sources of exposure (i.e., drug use and unsafe sex practices) typical of the young adults. Vaccination of household contacts with HBsAg-positive subjects represents an area of improvement; providing migrants and refugees access to healthcare services is also a focal point. In 2020, Italy became the first country in Europe to achieve the WHO’s regional hepatitis targets.
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.
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.
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.
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.
The aim of this study is to provide updates on the characteristics of chronic HBsAg carriers in Italy before the advent of new drugs eliminating or functionally inactivating the genome HBV ...reservoirs. HBV endemicity has greatly decreased in Italy over the past decades. A not negligible number of chronic HBsAg carriers are still alive in the country. Chronic HBsAg carriers consecutively referring to 9 units in Italy were prospectively enrolled for a 6-month period in 2019. Multiple logistic regression analysis was performed to identify independent predictors of treatment. A total of 894 cases was recruited (sex ratio 1.6; mean age 53.7 ± 13.5 years). The proportion of subjects born abroad was 19.0%; only 1% of cases reported current heavy alcohol intake (> 4 units/day). Chronic HBV infection, chronic HBV hepatitis, and subjects with liver cirrhosis and/or HCC represented 24.8%, 55%, and 19.3% of cases, respectively. After exclusion of the 222 subjects with chronic HBV infection, the proportion of subjects under therapy was as high as 89.3%. A more severe liver disease (OR 2.52; 95% CI = 1.25–5.14) resulted an independent predictor of the likelihood of treatment; male sex was marginally associated (OR 1.67; 95% CI = 1.02–2.76) to the chance of treatment. People born abroad had same chance than Italians native to be treated (OR 2.12; 95% CI = 0.9–4.97). The high proportion of subjects under treatment and the absence of gender and ethnic barrier against treatment sound good news. These updated figures may represent reference data for evaluating the potential impact of forthcoming new therapy against HBV-related disease.
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.
The risk of sexual transmission of hepatitis C virus (HCV) infection was evaluated among 895 monogamous heterosexual partners of HCV chronically infected individuals in a long-term prospective study, ...which provided a follow-up period of 8,060 person-years. Seven hundred and seventy-six (86.7%) spouses were followed for 10 yr, corresponding to 7,760 person-years of observation. One hundred and nineteen (13.3%) spouses (69 whose infected partners cleared the virus following treatment and 50 who ended their relationship or were lost at follow-up) contributed an additional 300 person-years. All couples denied practicing anal intercourse or sex during menstruation, as well as condom use. The average weekly rate of sexual intercourse was 1.8. Three HCV infections were observed during follow-up corresponding to an incidence rate of 0.37 per 1,000 person-years. However, the infecting HCV genotype in one spouse (2a) was different from that of the partner (1b), clearly excluding sexual transmission. The remaining two couples had concordant genotypes, but sequence analysis of the NS5b region of the HCV genome, coupled with phylogenetic analysis showed that the corresponding partners carried different viral isolates, again excluding the possibility of intraspousal transmission of HCV. Our data indicate that the risk of sexual transmission of HCV within heterosexual monogamous couples is extremely low or even null. No general recommendations for condom use seem required for individuals in monogamous partnerships with HCV-infected partners.
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.
Evaluation of interaction of HBV, HCV and alcohol abuse on the risk of cirrhosis.
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.
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.
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.
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