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Hepatitis C virus infection affects over 58 million individuals and is responsible for 290,000 annual deaths. The infection spread in the past via blood transfusion and iatrogenic transmission due to the use of non-sterilized glass syringes mostly in developing countries (Cameroon, Central Africa Republic, Egypt) but even in Italy. High-income countries have achieved successful results in preventing certain modes of transmission, particularly in ensuring the safety of blood and blood products, and to a lesser extent, reducing iatrogenic exposure. Conversely, in low-income countries, unscreened blood transfusions and non-sterile injection practices continue to play major roles, highlighting the stark inequalities between these regions. Currently, injection drug use is a major worldwide risk factor, with a growing trend even in low- and middle-income countries (LMICs). Emerging high-risk groups include men who have sex with men (MSM), individuals exposed to tattoo practices, and newborns of HCV-infected pregnant women. The World Health Organization (WHO) has proposed direct-acting antiviral (DAA) therapy as a tool to eliminate infection by interrupting viral transmission from infected to susceptible individuals. However, the feasibility of this ambitious and overly optimistic program generates concern about the need for universal screening, diagnosis, linkage to care, and access to affordable DAA regimens. These goals are very hard to reach, especially in LMICs, due to the cost and availability of drugs, as well as the logistical complexities involved. Globally, only a small proportion of individuals infected with HCV have been tested, and an even smaller fraction of those have initiated DAA therapy. The absence of an effective vaccine is a major barrier to controlling HCV infection. Without a vaccine, the WHO project may remain merely an illusion. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background Data on the prevalence of hepatitis C virus (HCV) infection in Italy are outdated and usually derived from studying residents in small towns. Methods To assess prevalence of and risk factors for HCV infection among Italian residents in 5 metropolitan areas, subjects ≥20 years of age were randomly selected from the list of the general practitioners' registers in 2015. Anti-HCV was tested by a salivary test; HCV-RNA, HCV genotypes, and ALT were determined in positive individuals. Logistic regression analysis evaluated independent risk factors for HCV. Results Of the 4907 enrolled subjects, 112 (2.3%) tested anti-HCV positive. The prevalence of HCV increased with age, from 0.2% in subjects born after the year 1984, to 4.2% in those born before the year 1935 (P < 0.01). The birth-cohort prevalence peaked (7.0%) in elderly. Serum HCV-RNA was detected in 1.7% of the whole population. Nearly 80% of anti-HCV subjects were aware of their status. Age > 70 years, low education level, past use of glass syringes, blood transfusion, intravenous drug use, and cohabitation with an anti-HCV positive subject predicted the HCV positivity. Interpretation In metropolitan areas in Italy, HCV is prevalent in elderly, reflecting a cohort effect determined by modalities of viral transmission no longer operative. The impact of the infection will further diminish in the years to come due to the natural depletion of the reservoir of the virus. This age pattern and the high proportion of subjects aware of their status do not warrant a policy of screening. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 60.3 years, 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). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: Background: In a 1996 survey, prevalence of hepatitis C virus antibodies (anti-HCV) in a southern Italian town was 12.6%. Aims: To identify changes in the epidemiology of hepatitis C virus (HCV) infection. Methods: Anti-HCV, HCV-RNA (PCR, detection limit 15IU/mL), HCV genotype (Innolipa). Were performed in a random 1:4 systematic sample of the general population. Multiple logistic regression analysis was used to estimate factors independently associated with the likelihood of anti-HCV positivity. Results: Of 1012 subjects, 58 (5.7%) were anti-HCV-positive, compared to 12.6% 14 years earlier. Prevalence was 0.4% in individuals <30 years old and 31.8% in those ≥70 years old. Among 139 HCV-negative in 1996 re-sampled in 2010, only one had seroconverted (incidence: 0.05×100 persons/year). Alanine transaminase levels were elevated in 8 (13.8%). HCV-RNA was detected by PCR in 46.5% anti-HCV-positive subjects. In 2010 59% were genotype 2-infected, in 1996 50.7% genotype 1-infected. Previous use of non-disposable glass syringes was a strong independent predictor (OR 3.2; CI 95%=1.4–7.3). Conclusion: Epidemiology of HCV infection in an endemic area of south Italy has changed over 14 years, now largely confined to the oldest age group; this seems to be due to the disappearance of its past main mode of transmission, namely the use of glass syringes. [Copyright &y& Elsevier]

Abstract: Background: The aetiological factors of hepatocellular carcinoma may vary over time. Aims: The study assessed the potential impact of the aetiological factors on the effectiveness of surveillance in real-world patients. Methods: Multicentre, cross-sectional study enrolling consecutive hepatocellular carcinoma cases during a six month period. Results: 1733 cases (1311 prevalent and 422 incident) were recruited (mean age 68.6 years; 46.1% cases over 70 years; 73.9% males; 95.3% with cirrhosis); 63.0% were hepatitis C virus positive and 23.7% were virus negative. Amongst incident HCCs, 34.5% were single ≤3cm and 54.4% met the Milan criteria; 61.6% were diagnosed during surveillance; virus negative patients showed the lowest rate of surveillance (51.0%). Surveillance was an independent predictor of detecting single HCCs ≤2cm (O.R.=5.4; 95% C.I.=2.4–12.4) or HCCs meeting the Milan criteria (O.R.=3.1; 95% C.I.=1.9–5.2). Compared with an earlier Italian survey, there was a higher proportion of elderly subjects (P <0.01), Child-Pugh class A cases (P <0.01), of virus-negative patients (P <0.01) and with single tumours ≤3cm (P <0.01) and a lower prevalence of hepatitis C virus positive individuals (P <0.01). Conclusion: HCC is characterised by a growing prevalence of elderly patients and cases unrelated to hepatitis virus infections. The application of surveillance must be implemented, particularly amongst non-viral patients. [Copyright &y& Elsevier]

Background Autochthonous (locally acquired) cases of acute hepatitis E virus have been recently reported in several developed countries. Aim To evidence cases, if any, and characteristics of acute hepatitis E virus infections in North-East of Italy several years ago. Methods In 2014, stored sera of 165 nonA–nonB acute hepatitis referred to the hospital of Padua during the period 1978–1991 were tested for hepatitis C virus antibodies by EIA III and for anti-hepatitis E virus IgM by Wantai HEV IgM ELISA. Anti-hepatitis E virus IgM positive sera were tested by Real Star HEV RT-PCR kit (Altona Diagnostics, Hamburg, Germany). Results Ninety-six (58.1%) sera resulted anti-HCV positive, and thus classified as acute C hepatitis. None of these subjects was anti-HEV IgM positive. Out of the 69 anti-HCV negative cases, 4 (5.8%) resulted anti-HEV IgM positive (one case hepatitis E virus-RNA positive), with an increasing trend from 2.8% during the years 1978–1984 to 9.1% during the years 1985–1991. All cases occurred in Italian patients with no travel abroad history. Conclusions There is evidence for the presence of autochthonous cases of acute hepatitis E virus infections in Italy since 80s. [ABSTRACT FROM AUTHOR]

Abstract: 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 30years of age (those that had been targeted for compulsory immunization) had been exposed to HBV infection. At multiple logistic regression analysis, age>45years (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 &y& Elsevier]

Abstract: 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 30.2years 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 &y& Elsevier]

The overall situation on viral hepatitis prevention and control in Italy was reviewed and evaluated at a Viral Hepatitis Prevention Board (VHPB) meeting in Catania, Sicily, on 7–8 November 2002. Several specific conclusions, drawn from the presentations and discussions, were considered to constitute an example of how to handle these issues in other European and industrialized countries. [Copyright &y& Elsevier]