Advances in hepatitis D virus biology and disease

Studies over the last decade have defined the natural history and diagnostic features of hepatitis D. Whereas hepatitis D encompasses a wide spectrum of clinical manifestations, patients usually have severe and progressive liver disease. In areas of high endemicity such as Italy, hepatitis D accounts for a significant proportion of requests for liver transplantation. Research interest is now focused on the underlying mechanisms of HDV pathogenesis and identification of the specific interactions of HDV/HBV/host that influence the clinical outcome. Much has been learned about the virology of HDV and its interactions with its helper, HBV. However, little is known about the host response to HDV infection and whether certain immune responses to HDV gene products can modulate the disease course, although there has been some evidence in an animal model that this might be the case. The unique characteristics of HDV replication, eg, autocatalytic self-cleavage and editing of the viral RNA, may influence the disease course and the heterogeneity of HDV genome sequence found in various geographic settings may in part account for the spectrum of disease outcomes by influencing the efficiency of any number of complex interactions. Fortunately, in vitro and in vivo experimental systems are available to address many of these issues and, indeed, further research may identify specific and novel targets for therapeutic intervention. Current medical therapy for hepatitis D is unsatisfactory. The only drug of proven benefit, recombinant interferon, brings relief to only a small proportion of hepatitis D patients. Other antiviral drugs have failed in clinical trials, although studies with some drugs are currently in progress. Fortunately, liver transplantation provides a valid option, because HDV reinfection of the graft occurs much less frequently than does HBV reinfection of HBV transplants and can be adequately prevented by the administration of anti-HBs immunoglobulin. Because of the critical contribution of HBV to the life cycle of HDV, universal immunization against HBV infection represents the ultimate solution for the eradication of hepatitis D. Mass vaccination for HBV and other public health measures for the control of blood-borne pathogens have already resulted in a dramatic decrease in hepatitis D in Italy.