An integrative review of the scientific evidence on HDV epidemiology, clinical impact, and emerging treatments in the Brazilian context
In the vast landscape of viral hepatitis, one form stands out for its exceptional severity and mysterious nature: hepatitis Delta virus (HDV). As an "incomplete virus" that only attacks people already living with hepatitis B, HDV accelerates liver disease progression with alarming speed. While global health organizations have increasingly turned their attention to this pathogen, Brazil emerges as a critical hotspot in the Americas—a country with unique viral strains and concerning infection rates that demand closer examination 1 .
HDV is considered the most aggressive form of viral hepatitis
Brazil carries one of the greatest HDV disease burdens worldwide
New treatments are emerging that could transform HDV management
Hepatitis Delta virus possesses a unique biological profile that sets it apart from other hepatitis viruses. Discovered in 1977 by Italian researcher Mario Rizzetto and his team, HDV is classified as a "satellite virus"—it cannot cause infection on its own but requires the presence of hepatitis B virus (HBV) to complete its life cycle 1 2 .
HDV has a genome of approximately 1.7 kilobases, making it the smallest known viral pathogen that infects humans 1
| Infection Type | Definition | Progression to Chronicity | Clinical Severity |
|---|---|---|---|
| Coinfection | Simultaneous infection with HBV and HDV | <5% of cases 2 | Often acute, self-limiting hepatitis; fulminant hepatitis in <5% of cases 2 |
| Superinfection | HDV infection in someone with existing chronic HBV | 70-80% of cases 2 | Typically severe; rapid progression to cirrhosis in 70-80% within 5-10 years 2 4 |
Brazil represents a significant hotspot for HDV infection within the global epidemiology of this virus. While precise nationwide prevalence data remains limited, studies indicate considerable regional variation across this vast country.
| Region/Group | Estimated Prevalence | Contributing Factors |
|---|---|---|
| Amazon Basin | High (up to 20% among HBsAg+ in some areas) 1 | Limited healthcare access, genetic susceptibility, regional HBV endemicity |
| Urban Centers | Variable (likely 5-10% among HBsAg+) | Injection drug use, sexual transmission, migration from endemic areas |
| Indigenous Communities | Disproportionately high 1 | Healthcare disparities, cultural practices, geographical isolation |
| People Who Inject Drugs | Significantly elevated 1 | Sharing of contaminated needles and paraphernalia |
The clinical consequences of hepatitis Delta infection position it as the most severe form of viral hepatitis 3 6 . When HDV superinfects a person already living with chronic hepatitis B, it typically leads to rapid deterioration of liver health through several distinct pathways.
HDV superinfection increases the risk of developing cirrhosis by three-fold and pushes the typical timeline for cirrhosis development forward by at least a decade 4 .
| Liver-Related Event | Reported Cumulative Incidence Range | Timeframe |
|---|---|---|
| Cirrhosis | 0-63% 7 | Variable, typically 5-10 years |
| Hepatic Decompensation | 0-52% 7 | Variable, typically after cirrhosis development |
| Hepatocellular Carcinoma | 0-19% 7 | Long-term follow-up |
| Liver Transplant | 2-43% 7 | Disease course |
| Liver-Related Death | 0-19% 7 | Disease course |
Accurate diagnosis of hepatitis Delta infection remains challenging in Brazil, despite its clinical importance. The current diagnostic approach follows a stepwise process beginning with serological screening followed by confirmatory molecular testing.
The initial diagnostic step involves testing for total anti-HDV antibodies in any HBsAg-positive individual 2 9 . A positive antibody test indicates either past resolved infection or current active infection, necessitating further evaluation.
Confirmatory testing for active infection requires detection of HDV RNA in serum using nucleic acid amplification tests (NAAT) such as PCR 2 9 .
The Centers for Disease Control and Prevention (CDC) includes only these two tests—total anti-HDV and HDV RNA—in its 2025 case definition for HDV infection, explicitly noting that HDV antigen testing is unreliable and that HDV IgM antibody tests suffer from poor specificity 9 .
| Research Tool | Primary Function | Application |
|---|---|---|
| Anti-HDV ELISA/CLIA | Detection of HDV antibodies | Initial serological screening and prevalence studies 2 |
| HDV RNA PCR Assays | Qualitative/quantitative detection of HDV RNA | Confirmatory diagnosis, viral load monitoring 2 9 |
| Next-Generation Sequencing | Comprehensive genomic analysis | HDV genotyping, quasispecies evolution 2 |
| HDV Antigen Immunoassays | Detection of viral antigens | Pathogenesis studies (limited clinical utility) 9 |
The treatment paradigm for hepatitis Delta is undergoing a dramatic transformation, moving from limited options to a promising pipeline of targeted therapies.
| Therapeutic Class | Representative Agents | Mechanism of Action |
|---|---|---|
| Entry Inhibitors | Bulevirtide, HH003, Tobevibart | Block NTCP receptor or HBsAg to prevent viral entry into hepatocytes 4 |
| Prenylation Inhibitors | Lonafarnib (with ritonavir) | Inhibits prenylation of large delta antigen, essential for HDV assembly 1 4 |
| siRNA Therapies | Elebsiran, JNJ-3989 | Silence HBV/HDV RNA, reducing viral replication and HBsAg production 4 5 |
| Nucleic Acid Polymers | REP 2139-Mg | Block HDV envelope formation by targeting HBsAg 4 |
| Novel Interferons | Pegylated interferon-lambda | Activates immune responses with potentially fewer side effects 4 |
The treatment goal in chronic HDV infection is evolving beyond viral suppression to include functional cure, defined as sustained undetectable HDV RNA with normalization of liver enzymes after treatment cessation.
Hepatitis Delta virus represents a significant yet underappreciated public health challenge in Brazil. As this integrative review demonstrates, the country faces a dual burden of established endemic foci in the Amazon region and evolving epidemiological patterns in urban centers.
As scientific advances transform the outlook for hepatitis Delta, Brazil has an opportunity to emerge as a regional leader in confronting this neglected disease.
Through coordinated efforts spanning public health, clinical medicine, and scientific research, the devastating impact of HDV can be mitigated.