Hepatitis delta virus infection: open issues.

Hepatitis delta virus (HDV) consists of a circular single-stranded RNA genome which assembles two viral proteins and acquires a lipid envelope in which the hepatitis B surface antigens (HBsAg) are embedded. HDV does not encode its own polymerase, but exploits a cellular enzyme for its replication. A better understanding of the mechanisms of HDV replication mechanism would provide new insights for antiviral strategies. Based on genomic variability, eight major genotypes of HDV have been identified, which differ as much as 40% in the nucleotide sequence. The cloning of HDV-RNA has provided genetic probes for the measurement of HDV-RNA in serum and liver; the sensitivity of HDV-RNA detection improved significantly when the reverse transcriptase-polymerase chain reaction (PCR) technique was introduced. As no commercial test is standardized for viral load detection, home-made assays have been developed in the different referral centers, which may not be comparable. Quantification of HDV in serum by real-time PCR has been recently proposed in the management of chronically infected patients. No specific inhibitors of HDV are available at present and, in spite of the crucial relationship between HDV and HBV, drugs that block HBV have only a theoretical but no sound effect on HDV replication.