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The International Agency for Research on Cancer (IARC) of the World Health Organization has classified hepatitis D virus (HDV) as carcinogenic, citing sufficient evidence and placing it alongside hepatitis B virus (HBV) and hepatitis C virus (HCV) as a cause of hepatocellular carcinoma (HCC).
Individuals with HBV-HDV coinfection face an elevated risk for liver cancer, highlighting the need for HBV vaccination, systematic screening, and early antiviral treatment to reduce the progression to cirrhosis and HCC.
About 12 million people globally have HBV-HDV coinfection, representing 5% of all chronic HBV cases. The prevalence of this condition varies regionally, with a likely underdiagnosis. True coinfection rates may reach 13%-14%, the highest in Europe’s Mediterranean region.
Virus Biology
HDV is an incomplete virus that infects hepatocytes and requires the envelope protein of hepatitis B surface antigen (HBsAg) for cell exit. Infection occurs only with chronic HBV infection, either as a superinfection or simultaneous acquisition. Humans are the only known natural host.
HDV coinfection worsens HBV-induced hepatic inflammation and prognosis, and up to 80% of patients develop cirrhosis. Triple infection with the HBV virus, HDV, and HIV further increases this risk, and the global prevalence is likely underestimated.
Cancer Risk
HDV infection significantly increases the risk for HCC compared with HBV infection alone. Many patients die from decompensated cirrhosis or HCC, reflecting the aggressive nature of coinfection.
The molecular mechanisms underlying HDV oncogenesis remain unclear. Research conducted over the past 15 years has provided insights that could inform the development of more effective treatments.
Early vaccination prophylaxis is critical for reducing the risk for HCC, despite limited options.
Treatment Options
Randomized controlled trials have demonstrated antiviral efficacy for:
- Pegylated interferon alpha (Peg-IFN) is approved for HBV and is active against HDV.
- Bulevirtide, a synthetic myristoylated lipopeptide entry inhibitor, is used alone or in combination with Peg-IFN.
Suppression of HBV remains central. Nucleoside and nucleotide analogs, such as entecavir, tenofovir alafenamide fumarate, and tenofovir disoproxil fumarate, significantly reduce HCC progression in treated patients compared with untreated patients at risk.
Promising therapeutics include lonafarnib, a farnesyltransferase inhibitor that blocks HDV particle formation, and nucleic acid polymers targeting the host chaperone DNAJB12 to inhibit HBV and HDV replication.
Guideline Updates
The 2023 addendum to the S3 guidelines covers the prophylaxis, diagnosis, and treatment of HBV, including HDV management.
IARC experts also re-evaluated the human cytomegalovirus and Merkel cell polyomavirus. Complete assessments are expected in the next edition of IARC Monographs.
HBV Vaccination
HBV vaccination is the only effective prophylaxis against HBV and HDV. Introduced in 1982 for high-risk groups, it reduced chronic infections, with the WHO expanding its recommendations from 1992 onward.
Infants and young children are at the highest risk of developing this disease. Acute HBV infection often resolves in adults, but infants face up to a 90% risk of developing chronic infection. Newborns of mothers with chronic or undiagnosed HBV infections are particularly vulnerable.
Routine infant immunization includes three doses, with the first dose administered within 12 hours of birth. In Germany, the Standing Committee on Vaccination (STIKO) recommends the administration of combination vaccines, with the hexavalent vaccine administered at 2, 4, and 11 months in a 2 + 1 schedule.
Timely vaccination is crucial because undetected chronic infections often lead to late-stage HCC diagnosis. Adults in high-risk groups should receive HBV vaccination counseling.
STIKO recommends vaccination for close contacts of individuals who are HBsAg-positive, individuals with high-risk sexual contacts, immunocompromised persons, and those with preexisting conditions that increase the risk for severe HBV infection.
Since 2021, insured adults aged 35 years or older in Germany have undergone one-time HBV and HCV screening. HDV testing is recommended for all HBsAg-positive patients. Current frameworks may miss cases, and additional or personalized screening could improve the detection of previously unrecognized infections.
This story was translated from Univadis Germany.
A version of this article appeared on Medscape.com.
The International Agency for Research on Cancer (IARC) of the World Health Organization has classified hepatitis D virus (HDV) as carcinogenic, citing sufficient evidence and placing it alongside hepatitis B virus (HBV) and hepatitis C virus (HCV) as a cause of hepatocellular carcinoma (HCC).
Individuals with HBV-HDV coinfection face an elevated risk for liver cancer, highlighting the need for HBV vaccination, systematic screening, and early antiviral treatment to reduce the progression to cirrhosis and HCC.
About 12 million people globally have HBV-HDV coinfection, representing 5% of all chronic HBV cases. The prevalence of this condition varies regionally, with a likely underdiagnosis. True coinfection rates may reach 13%-14%, the highest in Europe’s Mediterranean region.
Virus Biology
HDV is an incomplete virus that infects hepatocytes and requires the envelope protein of hepatitis B surface antigen (HBsAg) for cell exit. Infection occurs only with chronic HBV infection, either as a superinfection or simultaneous acquisition. Humans are the only known natural host.
HDV coinfection worsens HBV-induced hepatic inflammation and prognosis, and up to 80% of patients develop cirrhosis. Triple infection with the HBV virus, HDV, and HIV further increases this risk, and the global prevalence is likely underestimated.
Cancer Risk
HDV infection significantly increases the risk for HCC compared with HBV infection alone. Many patients die from decompensated cirrhosis or HCC, reflecting the aggressive nature of coinfection.
The molecular mechanisms underlying HDV oncogenesis remain unclear. Research conducted over the past 15 years has provided insights that could inform the development of more effective treatments.
Early vaccination prophylaxis is critical for reducing the risk for HCC, despite limited options.
Treatment Options
Randomized controlled trials have demonstrated antiviral efficacy for:
- Pegylated interferon alpha (Peg-IFN) is approved for HBV and is active against HDV.
- Bulevirtide, a synthetic myristoylated lipopeptide entry inhibitor, is used alone or in combination with Peg-IFN.
Suppression of HBV remains central. Nucleoside and nucleotide analogs, such as entecavir, tenofovir alafenamide fumarate, and tenofovir disoproxil fumarate, significantly reduce HCC progression in treated patients compared with untreated patients at risk.
Promising therapeutics include lonafarnib, a farnesyltransferase inhibitor that blocks HDV particle formation, and nucleic acid polymers targeting the host chaperone DNAJB12 to inhibit HBV and HDV replication.
Guideline Updates
The 2023 addendum to the S3 guidelines covers the prophylaxis, diagnosis, and treatment of HBV, including HDV management.
IARC experts also re-evaluated the human cytomegalovirus and Merkel cell polyomavirus. Complete assessments are expected in the next edition of IARC Monographs.
HBV Vaccination
HBV vaccination is the only effective prophylaxis against HBV and HDV. Introduced in 1982 for high-risk groups, it reduced chronic infections, with the WHO expanding its recommendations from 1992 onward.
Infants and young children are at the highest risk of developing this disease. Acute HBV infection often resolves in adults, but infants face up to a 90% risk of developing chronic infection. Newborns of mothers with chronic or undiagnosed HBV infections are particularly vulnerable.
Routine infant immunization includes three doses, with the first dose administered within 12 hours of birth. In Germany, the Standing Committee on Vaccination (STIKO) recommends the administration of combination vaccines, with the hexavalent vaccine administered at 2, 4, and 11 months in a 2 + 1 schedule.
Timely vaccination is crucial because undetected chronic infections often lead to late-stage HCC diagnosis. Adults in high-risk groups should receive HBV vaccination counseling.
STIKO recommends vaccination for close contacts of individuals who are HBsAg-positive, individuals with high-risk sexual contacts, immunocompromised persons, and those with preexisting conditions that increase the risk for severe HBV infection.
Since 2021, insured adults aged 35 years or older in Germany have undergone one-time HBV and HCV screening. HDV testing is recommended for all HBsAg-positive patients. Current frameworks may miss cases, and additional or personalized screening could improve the detection of previously unrecognized infections.
This story was translated from Univadis Germany.
A version of this article appeared on Medscape.com.
The International Agency for Research on Cancer (IARC) of the World Health Organization has classified hepatitis D virus (HDV) as carcinogenic, citing sufficient evidence and placing it alongside hepatitis B virus (HBV) and hepatitis C virus (HCV) as a cause of hepatocellular carcinoma (HCC).
Individuals with HBV-HDV coinfection face an elevated risk for liver cancer, highlighting the need for HBV vaccination, systematic screening, and early antiviral treatment to reduce the progression to cirrhosis and HCC.
About 12 million people globally have HBV-HDV coinfection, representing 5% of all chronic HBV cases. The prevalence of this condition varies regionally, with a likely underdiagnosis. True coinfection rates may reach 13%-14%, the highest in Europe’s Mediterranean region.
Virus Biology
HDV is an incomplete virus that infects hepatocytes and requires the envelope protein of hepatitis B surface antigen (HBsAg) for cell exit. Infection occurs only with chronic HBV infection, either as a superinfection or simultaneous acquisition. Humans are the only known natural host.
HDV coinfection worsens HBV-induced hepatic inflammation and prognosis, and up to 80% of patients develop cirrhosis. Triple infection with the HBV virus, HDV, and HIV further increases this risk, and the global prevalence is likely underestimated.
Cancer Risk
HDV infection significantly increases the risk for HCC compared with HBV infection alone. Many patients die from decompensated cirrhosis or HCC, reflecting the aggressive nature of coinfection.
The molecular mechanisms underlying HDV oncogenesis remain unclear. Research conducted over the past 15 years has provided insights that could inform the development of more effective treatments.
Early vaccination prophylaxis is critical for reducing the risk for HCC, despite limited options.
Treatment Options
Randomized controlled trials have demonstrated antiviral efficacy for:
- Pegylated interferon alpha (Peg-IFN) is approved for HBV and is active against HDV.
- Bulevirtide, a synthetic myristoylated lipopeptide entry inhibitor, is used alone or in combination with Peg-IFN.
Suppression of HBV remains central. Nucleoside and nucleotide analogs, such as entecavir, tenofovir alafenamide fumarate, and tenofovir disoproxil fumarate, significantly reduce HCC progression in treated patients compared with untreated patients at risk.
Promising therapeutics include lonafarnib, a farnesyltransferase inhibitor that blocks HDV particle formation, and nucleic acid polymers targeting the host chaperone DNAJB12 to inhibit HBV and HDV replication.
Guideline Updates
The 2023 addendum to the S3 guidelines covers the prophylaxis, diagnosis, and treatment of HBV, including HDV management.
IARC experts also re-evaluated the human cytomegalovirus and Merkel cell polyomavirus. Complete assessments are expected in the next edition of IARC Monographs.
HBV Vaccination
HBV vaccination is the only effective prophylaxis against HBV and HDV. Introduced in 1982 for high-risk groups, it reduced chronic infections, with the WHO expanding its recommendations from 1992 onward.
Infants and young children are at the highest risk of developing this disease. Acute HBV infection often resolves in adults, but infants face up to a 90% risk of developing chronic infection. Newborns of mothers with chronic or undiagnosed HBV infections are particularly vulnerable.
Routine infant immunization includes three doses, with the first dose administered within 12 hours of birth. In Germany, the Standing Committee on Vaccination (STIKO) recommends the administration of combination vaccines, with the hexavalent vaccine administered at 2, 4, and 11 months in a 2 + 1 schedule.
Timely vaccination is crucial because undetected chronic infections often lead to late-stage HCC diagnosis. Adults in high-risk groups should receive HBV vaccination counseling.
STIKO recommends vaccination for close contacts of individuals who are HBsAg-positive, individuals with high-risk sexual contacts, immunocompromised persons, and those with preexisting conditions that increase the risk for severe HBV infection.
Since 2021, insured adults aged 35 years or older in Germany have undergone one-time HBV and HCV screening. HDV testing is recommended for all HBsAg-positive patients. Current frameworks may miss cases, and additional or personalized screening could improve the detection of previously unrecognized infections.
This story was translated from Univadis Germany.
A version of this article appeared on Medscape.com.