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Acknowledgements
Introduction
Recent papers have shown that Interferon-free hepatitis C virus (HCV) therapies with direct-acting antiviral agents (DAAs) can induce a reactivation of SAR131675 receptor virus (HBV) in HCV-treated patients with a concomitant overt or occult HBV infection. This has raised growing interest in the prevalence of HBV serum markers among HCV-RNA-positive subjects, namely hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti-HBs) and antibody to HBV core antigen (anti-HBc). DAA-induced HBV reactivation occurs more frequently in HBsAg-positive individuals than in persons with a resolved HBV infection (HBsAg-negative/anti-HBc-positive with or without anti-HBs) [1], [2].
Several studies have reported the prevalence figures of chronic HCV infection among patients with chronic HBV infection [3], [4], [5], [6], [7], [8], whereas little is known on the prevalence of HBV markers in patients with HCV infection. A study performed in the U.S.A. showed that among 1257 HCV-RNA-positive subjects, 5.8% were HBsAg-positive and 58.8% had evidence of prior exposure to HBV [9].
By pooling the data of two prospective national surveys performed in 2001 [10] and 2014 [11] on subjects referring to several liver units for evaluation of chronic liver disease (CLD), we herein provide figures on the prevalence of HBV markers among HCV-RNA-positive subjects in Italy.
Material and methods
Results
Of the 12,405 subjects enrolled, 8304 resulted anti-HCV-positive, and, of these, 6984 (84.1%) were HCV-RNA-positive. After the exclusion of 356 subjects vaccinated against hepatitis B (presence of isolated anti-HBs positivity), the total number of HCV-RNA-positive subjects evaluated in the present study was 6628. The proportion of chronic hepatitis cases was 76.5%, that of liver cirrhosis 19.9%, and that of HCC 3.7% (data not shown). Of these subjects, 191 (2.9%) resulted HBsAg-positive, 540 (8.1%) HBsAg/anti-HBs-negative and anti-HBc-positive, 972 (14.7%) HBsAg-negative and anti-HBc/anti-HBs-positive, 1703 (26.0%) positive for any HBV marker. All HBV markers showed a decreasing prevalence over time, reaching a statistically significant level only for HBsAg-negative subjects with a presence of both antibodies, and for those positive for any HBV marker (Table 1). None of the 191 subjects with an overt infection (HBsAg positive) was a carrier without HBV induced liver disease.
HBsAg-positive subjects were significantly younger (51.7 vs. 56.6 and 54.4 years; p < 0.01) and with a higher male to female sex ratio (3.5 vs. 1.3 and 1.4; p < 0.01) compared to those with isolated anti-HBc or those with a presence of both antibodies. The prevalence of liver cirrhosis was significantly higher than that of chronic hepatitis in subjects positive for HBsAg (4.4% vs. 2.6%, p < 0.01), but not in those positive for other HBV markers. A statistically significant difference (p < 0.01) in educational level and area of birth was observed only in subjects with isolated anti-HBc positivity (Table 2).
Applying the observed prevalence rates to the estimated one million HCV-RNA-positive subjects living in Italy, a number recently provided by a survey among the general population in five Italian metropolitan areas [13], we can hypothesize the potential number of subjects with HBV markers among HCV-RNA-positive subjects in Italy: nearly 30,000 subjects with overt HBV infection (i.e. presence of HBsAg), almost 80,000 with isolated anti-HBc positivity, and 145,000 with a resolved HBV infection (HBsAg-negative and anti-HBc/anti-HBs-positive) (Table 3).
Discussion
The availability of DAA therapy for chronic HCV infection is a milestone in the cure of this disease. These drugs can eliminate the virus in more than 95% of subjects treated, including those with liver cirrhosis and those with HIV co-infection [15].