Hepatitis D is an infectious disease of the liver caused by hepatitis D virus, or HDV, a small defective RNA virus that is biologically unusual because it cannot complete its life cycle without hepatitis B virus, or HBV. HDV therefore does not exist as an independent human hepatitis infection in the same way as hepatitis A or hepatitis C. It uses components of HBV, particularly hepatitis B surface antigen, to form infectious particles and spread between liver cells.
A person must have HBV infection to develop hepatitis D. HDV can occur as simultaneous acquisition of HBV and HDV, called coinfection, or as acquisition of HDV by somebody who already has chronic HBV, called superinfection. Chronic HDV occurs only in people who have chronic HBV. WHO estimates that roughly 12 million people living with chronic HBV are infected with HDV globally.
HDV is transmitted primarily through infected blood and other body fluids, broadly following transmission routes associated with HBV. Exposure can occur through contaminated needles or injection equipment, unsafe medical procedures, sexual contact, and, less commonly, transmission around childbirth. Risk is particularly relevant among people who inject drugs, people receiving haemodialysis, some populations in regions where HBV and HDV are endemic, and people with other blood-borne infections. Because HDV depends on HBV, prevention of HBV simultaneously prevents new HDV infection.
Hepatitis B vaccination is therefore the central population-level preventive measure for hepatitis D. It does not, however, eliminate HDV in someone who is already chronically infected with HBV, because vaccination cannot remove established HBV or HDV infection. Blood safety, sterile injection equipment and appropriate infection-control practices further reduce transmission.
Hepatitis D can produce either acute hepatitis or chronic infection, and its clinical course depends partly on whether HBV and HDV are acquired together or whether HDV infects an established HBV carrier. Coinfection can produce an acute hepatitis that ranges from mild illness to severe hepatitis, while superinfection in a person with chronic HBV is more likely to produce severe disease and rapid progression of liver damage.
Symptoms can include fatigue, loss of appetite, nausea, abdominal discomfort, dark urine, pale stools and jaundice, although some infected people have few or no obvious symptoms. The biological severity of HDV is related to its capacity to intensify inflammatory and destructive processes within the liver. Chronic infection can therefore progress towards advanced fibrosis, cirrhosis, liver decompensation and hepatocellular carcinoma more rapidly than many other forms of chronic viral hepatitis. WHO describes chronic HDV as the most severe form of chronic viral hepatitis.
Diagnosis requires establishing both the presence of HBV and evidence of HDV infection. Testing may involve antibodies against HDV as an initial indicator of exposure, followed by molecular testing for HDV RNA to establish active viral replication and help monitor treatment. HBV testing remains essential because HDV cannot establish an independent infection without HBV. Liver enzymes such as alanine aminotransferase and aspartate aminotransferase may be elevated, but enzyme abnormalities are not specific enough to diagnose HDV on their own.
Assessment also considers the extent of liver injury and fibrosis using blood tests, imaging and sometimes elastography or biopsy. A particularly important diagnostic distinction is between previous exposure to HDV and active infection: antibodies demonstrate immune recognition but do not necessarily prove ongoing viral replication, whereas detectable HDV RNA provides evidence of active infection.
Management of hepatitis D is centred on controlling active HDV, managing HBV appropriately, monitoring liver damage and preventing complications. Conventional nucleoside or nucleotide analogues used for HBV can suppress HBV replication but do not directly eliminate HDV because HDV replication has distinct biological requirements. Pegylated interferon alfa has historically been an important treatment for selected patients with chronic HDV, although response rates, tolerability and suitability vary.
Newer HDV-directed approaches have expanded treatment options in some jurisdictions, including bulevirtide, which interferes with viral entry into hepatocytes. Treatment availability and licensing differ by country, so specialist hepatology assessment is important. Patients with advanced liver disease require management of complications and assessment for transplantation when liver function becomes severely compromised.
The relationship between hepatitis D, liver fibrosis and cirrhosis is clinically important because persistent inflammatory injury stimulates wound-healing processes that progressively alter hepatic architecture. Activated hepatic stellate cells produce extracellular matrix proteins, including collagen, which accumulate in the liver. With continued injury, fibrosis can become extensive and eventually form cirrhosis, in which normal hepatic architecture is replaced by bands of scar tissue and regenerative nodules.
Cirrhosis can cause portal hypertension, impaired synthesis of albumin and clotting factors, impaired bilirubin handling, susceptibility to infection and hepatic encephalopathy. HDV also increases the risk of hepatocellular carcinoma in people with chronic HBV infection. Consequently, long-term management is not limited to measuring viral activity; clinicians also monitor liver function, fibrosis, portal-hypertension complications and cancer risk.
A major misconception is that hepatitis D is simply another independent hepatitis virus that can infect anyone. Its defining biological dependency on HBV distinguishes it from the other major human hepatitis viruses. Another important distinction is between coinfection and superinfection: simultaneous acquisition of HBV and HDV is different from HDV infection occurring in an established HBV carrier, and the latter generally carries a greater risk of chronic severe disease.
Hepatitis D should also not be confused with an isolated elevation of liver enzymes, because abnormal enzymes can arise from many hepatic and non-hepatic conditions. Similarly, absence of jaundice does not exclude infection. The disease is geographically uneven, with recognised areas of higher prevalence, but international travel, migration, injection exposure and global movement mean that clinicians outside historically endemic regions may still encounter it.
The public-health importance of hepatitis D arises from its dependence on a preventable co-infection and its potential to accelerate serious liver disease. Expanding hepatitis B vaccination, ensuring safe blood supplies, improving injection safety and identifying people with HBV who may have HDV are therefore interconnected prevention and detection strategies. People with chronic HBV who develop unexplained worsening liver inflammation or progressive fibrosis may require assessment for HDV according to local clinical guidance.
Long-term care can involve repeated viral-load assessment, biochemical monitoring, fibrosis assessment and surveillance for complications of advanced liver disease. The disease also illustrates an important principle in infectious disease biology: a pathogen can depend on another pathogen while still substantially changing the clinical course of the underlying infection. HDV therefore has significance not only as a cause of hepatitis but as a model of viral dependence, co-infection and accelerated organ damage.
