Developments In Hepatitis Delta Research

Abstract

The hepatitis delta virus (HDV) is the smallest human pathogen known so far. Several characteristics of the virus RNA genome resemble that of plant viroids. Since the hepatitis B virus surface antigens are part of the HDV envelope and are necessary for productive infection, HDV may be considered a satellite virus of HBV. Coinfection of the two viruses or superinfection with HDV in HBV carriers increases the risk of fulminant hepatitis and development of liver cirrhosis. At present, there is no specific treatment for hepatitis D. However, vaccination against HBV confers protection against coinfection with HDV. Although the increased rate of vaccination against HBV in developed countries reduced the prevalence of HDV, it is still a threat and remains endemic in many regions of the world. Here, we overview the epidemiology and treatment of hepatitis delta and report recent advances in the research of HDV biology. CLINICAL AND EPIDEMIOLOGICAL FEATURES The hepatitis delta virus (HDV) was discovered by the italian gastroenterologist Mario Rizzetto while studying liver biopsies of hepatitis B virus (HBV) infected patients (Rizzetto et al., 1977). Later, it was shown that HDV infects individuals previously infected with HBV, causing more severe hepatic lesions, and increasing the risk of fulminat hepatitis (Gorinvadarajan et al., 1984; Jacobson et al., 1985). Since the presence of HBV is necessary for the production of infectious HDV particles capable of propagating the infection, the HDV may be considered a HBV satellite virus (Rizzetto et al., 1980; Ponzetto et al, 1988). The clinical association between these two viruses is due to the fact that the genome of HDV does not encode for its own envelope proteins. The HDV envelope consists of HBV surface proteins (HBsAg; Smedile et al., 1994), and as a consequence HDV transmission occurs only in the presence of HBV. HDV replication seems to occur only in the liver, and all pathological abnormalities are limited to this organ. The lesions are similar to those observed during the course of other acute and chronic viral hepatitis. Often they consist of hepatocellular necrosis and inflamation. From the histological point of view, there are no significant differences between lesions caused by HDV and those caused by other hepatitis viruses. The clinical course of HDV infection may be variable. In general, the observed symptoms are more severe than those associated with other hepatitis viruses. The incubation period varies between 3 to 7 weeks. Following this period, the first symptoms can be detected, including fatigue, lethargy, and nausea. It is estimated that 60% to 70% of all hepatitis delta chronic patients will develop chirrosis. This percentage is about three times higher when compared to the percentage that is observed in hepatitis B patients (Rizzetto et al., 1983). The frequency of HDV associated fulminant hepatitis, the more severe form of the acute disease, is 10 times higher than the observed for other viral hepatitis. Fulminant hepatitis is usually associated with hepatic encephalopaties that, in the most severe cases are characterized by somnolence, abnormal behavior, and coma. The mortality associated with fulminant hepatitis is about 80%, independent of the treatment (Purcell and Gerin, 1990). Seroprevalence studies in individuals positive for HBsAg, show a non-uniform worldwide distribution of HDV (Ponzetto et al., 1985; see fig. 1). Developments In Hepatitis Delta Research