Hepatitis D and Delta Agent
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Direct answer
Hepatitis D, caused by the delta agent, is a defective RNA virus that cannot package its genome without the envelope of hepatitis B virus. Infection therefore occurs only in people who already have hepatitis B, either as a simultaneous coinfection or as a superinfection in a chronic carrier. Superinfection is far more likely to cause severe chronic liver disease, so preventing hepatitis B is the main prevention for hepatitis D.
What you must remember
- Genome: Small circular single-stranded negative-sense RNA of about 1.7 kilobases, encoding only the delta antigen.
- Envelope borrowing: The delta virion is coated with hepatitis B surface antigen, so hepatitis B must be present for assembly.
- Delta antigen: Exists as small and large forms; the large form, produced by RNA editing, is needed for virion assembly.
- Coinfection: Simultaneous hepatitis B and D infection, which is often acute and self-limited.
- Superinfection: Hepatitis D arising in a chronic hepatitis B carrier, which tends to cause chronic hepatitis and rapid progression to cirrhosis.
- Diagnosis: IgM anti-HDV suggests acute infection, while HDV RNA by PCR confirms active replication.
- Treatment: Pegylated interferon alfa has long been the standard therapy, while newer entry inhibitors such as bulevirtide are approved in some countries.
- Prevention: Hepatitis B vaccination protects against hepatitis D, because the delta agent cannot infect without hepatitis B.
Coinfection and superinfection compared
The distinction between coinfection and superinfection drives both prognosis and the serology asked in exams. The two are compared below. Each row can be checked against the timing of the hepatitis B diagnosis. Both modes are worth revising together, since the serology pattern tells them apart.
| Feature | Coinfection | Superinfection |
|---|---|---|
| Timing | Hepatitis B and D acquired together | Hepatitis D added to a chronic hepatitis B carrier |
| Typical course | Often acute and self-limited | Chronic hepatitis with risk of cirrhosis |
| Key serology | IgM anti-HBc and IgM anti-HDV | HBsAg positive with IgM anti-HDV |
| Prognosis | Generally better | Generally worse |
A patient who is HBsAg positive with IgM anti-HDV has acute hepatitis D superimposed on chronic hepatitis B, not a coinfection. Chronic hepatitis B patients with hepatitis D need follow-up for cirrhosis and hepatocellular carcinoma. Serology is read against the clinical history, because the same markers can mean different things in an acute and a chronic setting.
Where the exam tries to catch you
Hepatitis D items usually test dependence on hepatitis B and the difference between the two modes of infection.
- Trap: Thinking hepatitis D can occur alone. Correct: The delta agent needs HBsAg to package its genome, so it never infects a person without hepatitis B.
- Trap: Assuming coinfection always becomes chronic. Correct: Coinfection is usually self-limited, whereas superinfection in a carrier tends to become chronic and severe.
- Trap: Believing hepatitis B vaccination does not help against hepatitis D. Correct: Preventing hepatitis B also prevents hepatitis D, since the delta agent depends on hepatitis B.
Frequently asked questions
Why can hepatitis D not occur without hepatitis B?
Hepatitis D virus lacks its own envelope protein and uses hepatitis B surface antigen to package its genome. Without hepatitis B, the delta agent cannot assemble infectious virions.
What distinguishes hepatitis D coinfection from superinfection?
Coinfection means hepatitis B and D are acquired together, while superinfection means hepatitis D develops in someone already chronically infected with hepatitis B. Superinfection carries a higher risk of chronic and severe liver disease.
Which serological test indicates acute hepatitis D?
IgM anti-HDV in serum indicates acute hepatitis D, and HDV RNA detection by PCR confirms active viral replication. Total anti-HDV reflects past or ongoing infection, so it cannot alone separate acute from chronic disease.
What is the role of the large delta antigen?
The large delta antigen is needed for assembly of infectious virions, because it binds the hepatitis B surface antigen envelope. The small delta antigen supports replication, so both forms are essential to the viral cycle.
Which drug is used for chronic hepatitis D treatment?
Pegylated interferon alfa has long been the standard therapy for chronic hepatitis D, although response is limited. Newer agents such as bulevirtide are approved in some countries, and the choice of treatment depends on local availability.