Anti-HDV positive individuals at ‘significantly higher risk’ for cirrhosis, HCC
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Key takeaways:
- The 5-year cumulative incidences of HCC and liver-related events were 3.8% and 15.6%, respectively.
- Incidences were higher among those with baseline cirrhosis.
Patients who tested positive for hepatitis D virus antibodies were at greater risk for developing hepatocellular carcinoma and other adverse liver-related outcomes, often at a young age, according to study results.
“Chronic hepatitis D is the most severe form of viral hepatitis, often leading to significant liver damage and a rapid progression to cirrhosis and HCC,” Lesley A. Patmore, MD, of the department of gastroenterology and hepatology at Erasmus University Medical Center, told Healio. “Although chronic hepatitis D carries a high risk of advancing to end-stage liver disease and HCC, some individuals may experience a milder disease course. Therefore, risk stratification is essential to identify those who require HCC surveillance and to optimize the use of novel antivirals when available.”
In a retrospective cohort study published in Clinical Gastroenterology and Hepatology, Patmore and colleagues used data from 269 anti-HDV positive patients (median age, 38 years; 58% men) from 10 sites in the Netherlands and United Kingdom to investigate the 5-year cumulative incidences of HCC, liver transplantation and liver-related mortality. They also analyzed predictive tools such as liver stiffness measurement, PAGE-B and fibrosis-4 (FIB-4) index.
At baseline, 34.9% of patients had cirrhosis and 53.9% were HDV RNA positive.
During a median follow-up of 4.3 years, 47 first events occurred, which included 13 incidences of HCC, 27 LTs and seven liver-related deaths. This corresponded with 5-year cumulative incidences of 3.8% (95% CI, 1-6.6) and 15.6% (95% CI, 10.5-20.7) for HCC and liver-related events, respectively. Researchers observed higher incidences of both HCC and liver-related events among patients with cirrhosis (12% and 41.3%) vs. without (0% and 2.1%).
Multivariable Cox regression showed older age (adjusted HR = 1.03; 95% CI, 1.006-1.054) and lower platelet count (aHR = 0.974; 95% CI, 0.967-0.981) were independently associated with HCC development, while cirrhosis (aHR = 13.563; 95% CI, 2.968-61.985), older age (aHR = 1.026; 95% CI, 1.001-1.051) and platelet count (aHR = 0.983; 95% CI, 0.976-0.99) were associated with an increased risk for liver-related events.
Further, anti-HDV positivity was significantly associated with an increased risk for HCC (aHR = 4.2; 95% CI, 1.7-10.8) and liver-related events (aHR = 7.8; 95% CI, 3.8-15.9) in analyses that adjusted for age, platelet count, HBV DNA log10 and cirrhosis at baseline.
“The current study highlights that individuals tested positive for anti-HDV antibodies are at a significantly higher risk of developing liver cirrhosis, HCC and other liver-related complications, often at a relatively young age,” Patmore said. “Two key predictive tools, the PAGE-B score and the FIB-4 score, have been shown to effectively estimate the risk of HCC and other liver-related events in these patients.”
Patmore and colleagues observed higher 5-year cumulative incidences of HCC and other events among those with intermediate (3.2% and 21.2%) and high (25.4% and 45.5%) PAGE-B scores vs. low (0% and 2.1%) scores. Similarly, a higher FIB-4 score correlated with an increased risk for HCC (HR = 1.2; 95% CI, 1.1-1.3) and liver-related events (HR = 1.2; 95% CI, 1.1-1.2).
The researchers reported consistent findings “regardless of cirrhosis or detectable HDV RNA.”
“These risk scores can be valuable in clinical practice for chronic hepatitis D patients, helping to guide strategies for HCC surveillance and prioritize patients who may benefit the most from timely treatment and monitoring,” Patmore said. “New HDV-specific treatment could influence the results, and we hypothesize that novel specific anti-HDV therapies, such as bulevirtide, will result in higher adherence and effectiveness rates.”
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