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Hepatitis D Delta Overview; New AASLD 2021 Treatment Studies
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Overview and Statistics
What is hepatitis D?
Hepatitis D is a liver disease caused by the hepatitis D virus (HDV). HDV is known as a "satellite virus," because it can only infect people who are also infected by the hepatitis B virus (HBV). HDV infection can be acute or lead to chronic, long-term illness. The infection can be acquired either simultaneously with HBV as a coinfection or as a superinfection in people who are already chronically infected with HBV.
What is the difference between HBV/HDV coinfection and HDV superinfection?
HBV/HDV coinfection occurs when a person simultaneously becomes infected with both HBV and HDV, whereas HDV superinfection occurs when a person who is already chronically infected with HBV acquires HDV. Although acute HBV/HDV coinfections can resolve, HDV superinfection can lead to rapid progression of the already present HBV infection, resulting in liver cirrhosis and liver failure. These outcomes occur within 5-10 years in 70%-80% and within 1-2 years in 15% of people with chronic HBV/HDV infection (1,2,3,4).
How common is hepatitis D in the United States?
HDV infection is uncommon in the United States, where most cases occur among people who migrate or travel to the United States from countries with high HDV endemicity. Because hepatitis D is not a nationally notifiable condition, the actual number of hepatitis D cases in the United States is unknown (5).
Where is hepatitis D most common?
Hepatitis D is most common in Eastern Europe, Southern Europe, the Mediterranean region, the Middle East, West and Central Africa, East Asia, and the Amazon Basin in South America.
Are there different genotypes of HDV, and where do they circulate?
Eight different HDV genotypes can be found across the globe, all of which share the same transmission routes and risk groups (3). HDV genotype 1 circulates mainly in North America, Europe, the Middle East, and North Africa. HDV genotypes 2 and 4 can be found in East Asia; genotype 3 is found exclusively in the Amazon Basin in South America, and genotypes 5, 6, 7, and 8 are found in West and Central Africa.
Transmission and Exposure
How is the hepatitis D virus transmitted?
HDV is mainly transmitted through activities that involve percutaneous (i.e., puncture through the skin) and to a lesser extent through mucosal contact with infectious blood or body fluids (e.g., semen and saliva), including
• sex with an infected partner;
• injection-drug use that involves sharing needles, syringes, or drug-preparation equipment;
• birth to an infected mother (rare);
• contact with blood from or the open sores of an infected person;
• needle sticks or exposures to sharp instruments; and
• sharing items (e.g., razors and toothbrushes) with an infected person.
HDV is not spread through food or water, sharing eating utensils, breastfeeding, hugging, kissing, hand holding, coughing, or sneezing.
Who is at risk for HDV infection?
The following populations are at increased risk for becoming infected with HDV:
• People chronically infected with HBV
• Infants born to mothers infected with HDV
• Sex partners of persons infected with HDV
• Men who have sex with men
• People who inject drugs
• Household contacts of people with HDV infection
• Health care and public safety workers at risk for occupational exposure to blood or blood-contaminated body fluids
• Hemodialysis patients
Signs and Symptoms
What are the signs and symptoms of acute HDV infection?
HDV causes infection and clinical illness only in HBV-infected people. The signs and symptoms of acute HDV infection are indistinguishable from those of other types of acute viral hepatitis infections. These include:
• Fever
• Fatigue
• Loss of appetite
• Nausea
• Vomiting
• Abdominal pain
• Dark urine
• Clay-colored bowel movements
• Joint pain
• Jaundice
These signs and symptoms typically appear 3-7 weeks after initial infection (6).
Do people who are coinfected with HBV/HDV have different symptoms than those who have HDV superinfection?
Acute hepatitis occurs in HBV/HDV coinfected people, and their symptoms may follow a biphasic course. Symptoms of HBV/HDV coinfection can range from mild to severe (fulminant hepatitis), but for most people, coinfection is self-limited: less than 5% of coinfected people go on to develop chronic infections (2,7). Regardless, acute liver failure is more common among people with HBV/HDV coinfection than among those infected with HBV alone (8).
HDV superinfection accelerates the progression of chronic HBV in 70%-90% of people, regardless of age (2). Although HDV suppresses the replication of HBV, cirrhosis occurs up to a decade earlier in HDV-superinfected persons compared with those infected with HBV alone (2). The mechanisms by which HDV accelerates progression and more severe disease are not clear.
What is the likelihood that HDV infection will become chronic?
The likelihood of progression to chronic HDV infection depends on whether the initial infection occurred by HBV/HDV coinfection or HDV superinfection. Of immunocompetent adults, more than 95% clear both HBV and HDV infections when they are acquired at the same time. On the other hand, HDV becomes chronic in more than 80% of people with HDV superinfection (6).
What health outcomes are associated with chronic HDV infection?
Chronic HDV generally causes a more aggressive and rapid progression of liver disease than chronic HBV infection alone. This is especially evident in patients infected with genotype HDV-3, which is common in the Amazon Basin (9,10). Of people with chronic HDV superinfection, cirrhosis and liver failure occur within 5-10 years in 70%-80% and within 1-2 years in 15% (1,2,3,4). Comparatively, the mean age of onset of cirrhosis for people who acquire chronic hepatitis B in childhood is 40 years (11).
Diagnosis and Treatment
How is hepatitis D diagnosed?
Because cases of hepatitis D are not clinically distinguishable from other types of acute viral hepatitis, diagnosis can be confirmed only by testing for the presence of antibodies against HDV and/or HDV RNA. HDV infection should be considered in any person with a positive hepatitis B surface antigen (HBsAg) who has severe symptoms of hepatitis or acute exacerbations.
How is hepatitis D treated?
No treatment is available for HDV infection specifically. Pegylated interferon alpha has shown some efficacy, but the sustained virologic response rate (a measure of viral clearance) is low (25%) (12). New therapies are being evaluated (12). In cases of fulminant hepatitis and end-stage liver disease, liver transplantation may be considered.
AASLD: EFFICACY OF LONG-TERM TREATMENT OF CHRONIC HEPATITIS D PATIENTS WITH BULEVIRTIDE - RESULTS OF A "REAL WORLD" STUDY (11/23/21)
AASLD: Safety and Efficacy of 2 mg Bulevirtide in Patients with Chronic HBV/HDV Co-Infection: First Real-World Results - (11/17/21)
AASLD: Strong intrahepatic decline of hepatitis D virus RNA and antigen after 48 weeks of treatment with Bulevirtide in chronic HBV/HDV co-infected patients: Interim results from a multicenter, open-label, randomized phase 3 clinical trial (MYR301) - (11/16/21)
AASLD: ETHNIC VARIATIONS IN CLINICAL PRESENTATION AND TREATMENT ELIGIBILITY FOR HEPATITIS DELTA VIRUS INFECTION AT A US REFERRAL CENTER - (11/17/21)
Prevention
How is hepatitis D prevented?
Although no vaccine is available for hepatitis D, vaccination with the hepatitis B vaccine can protect people from HDV infection.
https://www.cdc.gov/hepatitis/hdv/hdvfaq.htm
References
1. National Institute for Health. National Institute of Diabetes and Digestive and Kidney Diseases. United States 2017. Department of Health and Human Services. Available at https://www.niddk.nih.gov/health-information/liver-disease/viral-hepatitis/hepatitis-d#common
2. World Health Organization. Switzerland 2019. Available at
https://www.who.int/news-room/fact-sheets/detail/hepatitis-d
3. Kamili S, Drobeniuc J, Mixson-Hayden T, Kodani M. Delta hepatitis: toward improved diagnostics. Hepatol 2017;66:1716-18.
4. Rizzetto M. Hepatitis D virus: introduction and epidemiology. Cold Spring Harb Persp Med, 2015;5(7): a021576.
5. Paten EU, Thio CL, Boon D, Thomas DL, Tobian AR. Prevalence of hepatitis B and hepatitis D virus infections in the United States, 2011-2016. Clinical Infectious Diseases 2019;69: 4:709-12. Available at: https://doi.org/10.1093/cid/ciz001.
6. Farci P, Niro GA. Clinical features of hepatitis D. Semin Liver Dis 2012;32:22836.
7. Negro F. Hepatitis D virus coinfection and superinfection. Cold Spring Harb Perspect Med 2014;4:a021550.
8. Smedile A, et al. Influence of delta infection on severity of hepatitis B. Lancet 1982; 320:945-7.
9. Casey JL, Niro GA, Engle RE, et al. Hepatitis B virus (HBV)/hepatitis D virus (HDV) coinfection in outbreaks of acute hepatitis in the Peruvian Amazon basin: the roles of HDV genotype III and HBV genotype F. J Infect Dis 1996;174:920-6.
10. Wranke A, Pinheiro Borzacov LM, Parana R, et al. The hepatitis delta international network (HDIN). Liver Int 2018;38:842-50.
11. Guan R, Lui HF. Treatment of hepatitis B in decompensated liver cirrhosis. Int J Hepatol 2011;2011:918017.
12. Farci P, Niro GA. Current and future management of chronic hepatitis D. Gastroenterol Hepatol 2018;14(6):342-51.
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