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To the Editor:

We read with interest the letter by Wedemeyer et al.1 who recall the term “vanishing” we had used after a survey on the prevalence of chronic hepatitis Delta virus (HDV) in Italy.2 That paper examined the prevalence of anti-HDV antibodies among 3 cohorts of hepatitis B surface antigen (HbsAg)-positive patients consecutively observed in Italian referral centers in 1987, 1992, and 1997 and found a prevalence of 23%, 14%, and 8.3%, respectively. In younger subjects, the prevalence of anti-HDV dropped from 26% in 1987 to 6.4% in 1997, as a consequence of the drop in newly acquired infections. This phenomenon prompted us to use the term “vanishing”. Unfortunately, this downward trend has stopped. In 2006, we performed a survey in 21 Italian centers in which the prevalence was 8.1% (95 of 1179 patients). The age-specific prevalences (Fig. 1) showed that the proportion of HDV-infected patients was stable in the younger and in the older age classes while slightly increased in the middle age as compared to 1997. Among the 98 patients unaware of their condition and initially diagnosed during 2006 (“incident cases”), anti-HDV antibodies were found in 14.3% of the cases versus 7.5% among 1093 individuals known to have hepatitis B or D (“prevalent cases” P = 0.025). Hence, a new wave of subjects with chronic hepatitis Delta is emerging in very recent years.

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Figure 1. Age-specific prevalences of anti-HDV antibodies in 1997 and in 2006.

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Curiously, in Germany the nadir of anti-HDV prevalence was also reached in 1997 (from 18.6% in 1992 to 6.8% in 1997). What has modified the trend for hepatitis Delta in Europe so suddenly and simultaneously? We can speculate that, beside vaccination programs against hepatitis B virus (HBV), the huge mortality for human immunodeficiency virus (HIV) infection before 1996 has contributed to the rapid reduction of HDV carriers, because HBV, HDV, and HIV share the same modes of transmission, and high prevalences of Delta coinfection were observed in HIV-positive individuals.3 After highly active antiretroviral therapy was introduced in 1996, the mortality related to HIV dropped while morbidity and mortality due to liver disease increased.4 Immigrants from endemic areas are not the sole cause of HDV recrudescence, because they were only 7.3% of the individuals in our series. At present, drug addiction is still strongly associated with acute HDV infection, but other independent risk exposures, such as multiple sexual partners, beauty practices (including tattooing, piercing), household contacts, or uncontrolled medical procedures contribute to maintain the spread of hepatitis Delta in Italy.5

In terms of fraction of liver diseases attributable to HDV, the weight of hepatitis D is still marginal. Indeed, 13% of cirrhosis cases are HBsAg-positive in Italy;6 assuming that 10%-20% of these individuals are infected with HDV, the proportion of cases attributable to HDV ranges from 1%-2%.

Nevertheless, we fully share the conclusions that the attention over HDV infection should not decline. In a recent Italian survey,7 about 30% of HBsAg-positive patients had never been tested for antibodies to HDV, despite the fact that they had a liver disease. There is nothing better than new and effective therapeutical approaches8–10 to stimulate attention for a disease at risk of being forgotten.

References

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Giovanni B. Gaeta*, Tommaso Stroffolini†, Antonina Smedile‡, Grazia Niro?, Alfonso Mele?, * Viral Hepatitis Unit, Department of Infectious Diseases, Second University of Naples, Italy, † Gastroenterology, S. Giacomo Hospital, Rome, Italy, ‡ Gastroenterology, Molinette Hospital and University, Turin, Italy, ? Gastroenterology, CSS Hospital, San Giovanni Rotondo, Italy, ? National Centre of Epidemiology Surveillance and Health Promotion, Istituto Superiore di Sanità, Rome, Italy.