New review posted on JAMA Network discusses the magnitude of the current hepatitis D virus (HDV) epidemic and its public health implications.
survey: Hepatitis D: an overview. Image credit: Marko Aliaksandr / Shutterstock.com
What is HDV?
HDV is a small ribonucleic acid (RNA) virus that is estimated to affect 12-72 million people worldwide. Compared with HBV or HCV, HDV is associated with a faster rate of development of liver cirrhosis and an increased risk of hepatocellular carcinoma (HCC).
HDV is the smallest single-stranded RNA virus known to cause human disease. HDV RNA encodes only one protein, the HDV antigen (HDAg), which forms a complex with RNA that is subsequently encapsulated by HBV surface antigens (HBsAg).
HDV infects liver cells only in the presence of HBV infection, as its entry into liver cells depends on binding of HBsAg to the cell membrane. HBV is also essential for the production and release of new virions.
HDV transmission and distribution
HDV can be transmitted sexually or by injecting drugs, both of which account for 70% of all cases, in addition to needlestick injuries. The prevalence of HDV infection is unknown in many countries; however, it exceeds 2% in sub-Saharan Africa, Central Asia and Eastern Europe. In Mongolia, HDV prevalence is 40% among people with HBV infection.
Anti-HDV antibodies can be detected in 4-43% of HBsAg-positive American adults. People with late-stage liver disease, those on hemodialysis, men who have sex with men (MSM), sex workers, those who inject drugs, and those who also have human immunodeficiency virus (HIV) infection are more likely to be infected with HDV.
Clinical course of HDV
Acute coinfection with HDV and HBV is diagnosed when HBsAg and immunoglobulin M (IgM) antibodies against HBV core antigen (IgM anti-HBc) are present together with HDV RNA. HDAg is detectable in serum for only a few days.
In about 95% of infected individuals, acute coinfection is followed by rapid clearance of both viruses. When an individual is already infected with HBV, subsequent infection with HDV results in chronic coinfection with both viruses in about 90% of individuals.
HDV infection can become chronic and is likely to progress more rapidly than HBV infection in these individuals. At the time of diagnosis, 30-70% of chronic HDV cases have cirrhosis, while more than half are likely to die within a decade from liver disease.
Persistence of HDV RNA in blood is a major risk factor for progression to cirrhosis and death. Other factors that increase the risk of severe outcomes include the genotype of the virus, as genotype 1 is the most lethal, drinking, obesity, diabetes, and serum HBV-DNA levels.
Diagnosis of HDV
According to the American Association for the Study of Liver Disease HBV Guidelines, the diagnosis of HDV infection should be actively sought in several different situations.
These include when an individual is HBsAg positive, especially if they have active or worsening hepatitis for no apparent reason, or if cirrhosis develops rapidly despite low levels of viral DNA. People from countries with high HDV prevalence, as well as those at high risk of exposure, especially MSM, those with HDV-positive household contacts, or those who inject drugs, should also be screened for HDV.
HDV diagnosis is based on the presence of HDV antibody or HDV RNA, which reflects past/present and current infection, respectively. There is disagreement about whether universal or targeted screening represents the better public health approach, which may vary depending on the prevalence of each infection.
Prevention and treatment of HDV
HBV infection can be prevented by HBV vaccine; however, vaccination is not an option when HBV infection has already occurred.
Therapies for hepatitis D are aimed at depriving the virus of functions necessary to complete its life cycle, which are provided by HBV or by the host.”
Interferon alfa or its pegylated derivative, which has a longer half-life, can be used to prevent the rapid progression of liver disease and the occurrence of severe events because this agent suppresses HDV replication. The use of interferon alfa relieves inflammation of the liver and prevents fibrosis; however, in 70% of patients, these effects eventually disappear.
Interferon alfa is associated with a reduced risk of decompensated liver disease, HCC, liver transplantation, and death from about 8.5% per year to 3.3%. This treatment may cause fatigue, depression and bone marrow suppression.
While HBV therapeutics are ineffective against HDV, drug candidates such as bulevirtide and lonafarnib are currently being investigated in advanced clinical trials. These agents prevent the virus from entering the liver cells and, accordingly, disrupt the assembly of virions. In addition, these agents have been shown to clear the virus and give negative results in almost 60% of HDV-positive patients after 96 weeks on bulevirtide.
Conversely, about 20% of patients experienced improvement after 48 weeks of treatment with lonafarnib in combination with ritonavir and pegylated interferon alfa.
Bulevirtide was recently approved in Europe for the treatment of HDV infection. In other countries, pegylated interferon alfa remains the only therapeutic agent available.
What are the consequences?
Prevention of hepatitis B by vaccination against HBV is the most effective way to prevent hepatitis D. However, no vaccine protects HBV-infected people from HDV superinfection. Therefore, the only preventive measure for patients with chronic HBV infection is to avoid parenteral or sexual exposure to people who are infected with HDV.”
All persons infected with HDV should be advised to keep their personal hygiene items separate to avoid transmission through razors or toothbrushes. Susceptible contacts should be screened and vaccinated against HBV infection as appropriate.
HDV-positive patients with indications for treatment of chronic HBV should receive HBV nucleoside analogues or pegylated interferon alfa, which suppress the replication of both viruses.
