HCC and liver-related events in HDV infection

Hepatocellular carcinoma (HCC) and liver-related events (such as decompensation and cirrhosis progression) are significant complications in individuals with hepatitis D virus (HDV) infection. HDV infection is known to cause the most severe form of viral hepatitis, with a high risk of early-onset cirrhosis and HCC. The study summarized in the context provides valuable insights into the predictors, risk factors, and clinical tools for managing these outcomes in anti-HDV–positive individuals.

Key Findings on HCC and Liver-Related Events in HDV Infection:

Incidence of HCC and Liver-Related Events:

• The 5-year cumulative incidence of HCC in anti-HDV–positive individuals was 3.8%, while the incidence of liver-related events was 15.6%.
• Patients with cirrhosis had a markedly higher risk:
• 5-year HCC incidence: 12%.
• 5-year liver-related event rate: 41.3%.
• Non-cirrhotic patients had negligible risks:
• 5-year HCC incidence: 0%.
• 5-year liver-related event rate: 0.9%.

Risk Stratification Using PAGE-B and FIB-4 Scores:

• PAGE-B and FIB-4 scores were validated as effective tools for predicting both HCC and liver-related outcomes in HDV-infected individuals.
• Low-risk groups (PAGE-B <10 or FIB-4 <1.45):
• HCC incidence: 0%.
• Liver-related event rate: 0.9%–2.1%.
• High-risk groups (PAGE-B >17 or FIB-4 >3.25):
• 5-year HCC incidence: 25% and 21%, respectively.
• Liver-related event rate: ~45%–63%.

Independent Predictors of HCC and Liver-Related Events:

• Age and platelet count were independently associated with both HCC and liver-related outcomes in multivariate analyses.
• Detectable HDV RNA doubled the risk of liver-related events (adjusted hazard ratio [aHR]: 2.6; 95% confidence interval [CI]: 1.3–5.0).

Diagnostic and Predictive Tools:

• Liver stiffness measurement (LSM):
• LSM ≥10 kPa: 100% sensitivity for detecting cirrhosis.
• LSM ≥12 kPa: 100% specificity for confirming cirrhosis.
• FIB-4:
• FIB-4 >3.25 had a high positive predictive value (PPV) of 91.7% for advanced fibrosis but poor sensitivity (36.7%).

Comparative Risk:

• Anti-HDV–positive patients had:
• 4.2-fold higher HCC risk compared to HBV mono-infected controls.
• 7.8-fold higher risk of liver-related events compared to HBV mono-infected controls.

Antiviral Therapy and Novel Treatments:

• Only 15.2% of patients received pegylated interferon, reflecting its limited efficacy and tolerability in clinical practice.
• Bulevirtide, an HBV entry inhibitor, represents a promising new therapy for HDV but is costly and requires parenteral administration.

---

Clinical Implications for Management:

1. Risk Stratification:

• PAGE-B and FIB-4 scoring systems allow simple, noninvasive, and cost-effective assessment of HCC and liver-related event risk in HDV-infected individuals.
• These tools can guide personalized care and surveillance strategies.

2. Surveillance Recommendations:

• Low-risk patients (e.g., PAGE-B <10 or FIB-4 <1.45): May require less frequent imaging follow-up due to negligible HCC and minimal liver-related event risk.
• High-risk patients (e.g., PAGE-B >17 or FIB-4 >3.25): Require intensified surveillance, including frequent imaging, strict HCC monitoring, and prioritization for novel antiviral treatments.

3. Therapeutic Considerations:

• The limited use of pegylated interferon highlights the need for more effective and tolerable therapies.
• Bulevirtide offers a new treatment option, but its cost and administration challenges must be considered.

4. Validation Needs:

• The study authors recommend external validation of PAGE-B and FIB-4 scores in bulevirtide-treated and ethnically diverse HDV populations to confirm their utility in broader clinical settings.

---

Conclusion:

HCC and liver-related events are significant risks in HDV-infected individuals, particularly in those with cirrhosis or high-risk scores (PAGE-B >17, FIB-4 >3.25). The use of noninvasive scoring tools like PAGE-B and FIB-4 enables early identification of at-risk patients, guiding surveillance intensity and treatment prioritization. While novel therapies like bulevirtide offer hope, addressing their accessibility and efficacy in diverse populations remains a key challenge.