Hepatitis D is Significantly Worse Than Hepatitis B Alone
Hepatitis D virus (HDV) is considered the most aggressive and severe form of viral hepatitis, causing substantially worse outcomes than hepatitis B virus (HBV) monoinfection. 1
Key Clinical Differences in Disease Severity
Progression to Cirrhosis and Liver Failure
HDV coinfection leads to more rapid and frequent progression to cirrhosis compared to HBV alone, with chronic hepatitis D (CHD) patients showing accelerated liver disease. 1
A higher proportion of patients with chronic HBV/HDV coinfection develop cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC) compared to those with chronic HBV infection alone. 1
Approximately 15% of HDV patients progress to cirrhosis in less than 3 years, particularly among people who inject drugs. 1
70-80% of chronic HDV patients develop cirrhosis, compared to lower rates in HBV monoinfection. 2
Mortality and Long-Term Outcomes
More than 50% of patients with chronic hepatitis D die of liver disease within 10 years of diagnosis, though recent studies suggest some patients may have a more indolent course. 3
HDV infection is associated with earlier hepatic decompensation and increased risk of hepatocellular carcinoma compared to HBV alone. 4
Interferon alfa treatment reduces liver-related events (decompensation, HCC, transplant, or mortality) from 8.5% per year to 3.3% per year in HDV patients, highlighting the baseline severity of untreated disease. 3
Acute Infection Severity
Acute HBV/HDV coinfection results in more severe acute hepatitis with a higher mortality rate than acute hepatitis B alone. 1
Acute HDV infection can cause acute liver failure, representing a life-threatening complication. 1
Why HDV is More Pathogenic
HDV is fundamentally a defective virus that requires HBV surface antigen (HBsAg) to complete its life cycle, but once established, it causes independent and severe liver damage. 1
The virus promotes persistent chronic infection through its large delta antigen (L-HDAg), which shuts down viral replication while maintaining infection, leading to ongoing liver injury. 1
HDV superinfection in an HBV carrier almost always results in chronic infection with both viruses (>90% of cases), whereas HBV/HDV coinfection rarely leads to chronicity. 1, 2
Clinical Implications
Screening Recommendations
All HBsAg-positive patients should be screened for HDV given the dramatically worse prognosis when coinfection is present. 1
Initial screening should use anti-HDV antibody testing, followed by quantitative HDV RNA testing if antibodies are detected. 5
Treatment Considerations
HBV nucleos(t)ide analogues (entecavir, tenofovir) are ineffective against HDV, despite their efficacy against HBV. 3, 6
Pegylated interferon alfa remains the primary treatment in most countries, though newer agents like bulevirtide show promise. 3, 6
Important Caveats
While HDV is definitively worse than HBV alone, not all chronic hepatitis D follows a rapidly progressive course—a sizeable proportion of patients may have mild disease, particularly in more recent cohorts. 1, 3 However, even patients with initially mild biochemical activity can develop cirrhosis over time with long-lasting infection. 1
The clinical picture is also influenced by HDV genotype, geographic location, transmission route, and timing of HBV vaccination programs, which affect both prevalence and disease severity. 1
The bottom line: HDV represents a more aggressive, rapidly progressive, and lethal form of viral hepatitis compared to HBV monoinfection, requiring heightened clinical vigilance and different therapeutic approaches. 1, 3, 4