EXPLORING THE RELATIONSHIP BETWEEN HEPATITIS DELTA VIRUS RNA-BASED SURROGATE ENDPOINTS AND LONG-TERM CLINICAL OUTCOMES IN HEPATITIS DELTA VIRUS INFECTION: A SYSTEMATIC LITERATURE REVIEW
Author(s)
Robert J. Wong, MD, MS, FACG, FAASLD1, Maria Buti, MD2, Arman Papadakis-Sali, MSc3, Pankaj Rai, MS4, Amos Lichtman, MD, MPH5, Celine Der-Torossian, PharmD, AAHIVE5, Chong H Kim, MPH, MS, PhD5, Barinder Singh, MPharm4, Dmitry Manuilov, MD5, Marvin Rock, MPH, DrPH5, Pietro Lampertico, MD, PhD6;
1Stanford University School of Medicine, Division of Gastroenterology and Hepatology, Palo Alto, CA, USA, 2Hospital Universitario Vall d’Hebron, Liver Unit, Barcelona, Spain, 3Gilead Sciences, Inc., LONDON, United Kingdom, 4Pharmacoevidence Private Limited, Mohali, India, 5Gilead Sciences, Inc., Foster City, CA, USA, 6Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy
1Stanford University School of Medicine, Division of Gastroenterology and Hepatology, Palo Alto, CA, USA, 2Hospital Universitario Vall d’Hebron, Liver Unit, Barcelona, Spain, 3Gilead Sciences, Inc., LONDON, United Kingdom, 4Pharmacoevidence Private Limited, Mohali, India, 5Gilead Sciences, Inc., Foster City, CA, USA, 6Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy
OBJECTIVES: Hepatitis delta virus (HDV) infection is associated with significant morbidity and mortality. Evaluation of treatment response through reliable surrogate endpoints is critical for timely treatment decisions. This systematic literature review (SLR) aims to evaluate the association between HDV RNA-based surrogate endpoints and long-term clinical outcomes in adults with HDV.
METHODS: Embase, PubMed, and Cochrane were searched from inception to August 2025 to identify studies evaluating association between HDV RNA-based surrogate endpoints and clinical outcomes using artificial intelligence assisted screening with human in-loop.
RESULTS: Seventeen studies (15 full-text articles and 2 conference abstracts) including 1,572 patients evaluated the association between HDV RNA status and clinical outcomes. Most studies were retrospective (n=14) and conducted in Europe (n=10). Hepatic decompensation (HD, n=5) and hepatocellular carcinoma (HCC, n=5) were the most common clinical endpoints, with most patients receiving interferon- or nucleos(t)ide analogue-based therapies. Overall, patients who achieve or sustain undetectable HDV RNA, were consistently associated with a reduced risk of clinical outcomes (OR: 0.04-0.73; HR: 0.03-0.45), with most studies reporting positive or direct associations across all clinical outcomes. Among studies evaluating the association of HDV RNA with specific clinical outcomes, a statistically significant association (p<0.05) was observed in 4 of 5 studies for HD, 3 of 5 for HCC, 3 of 4 each for cirrhosis and death, and 1 of 2 for liver transplantation.
CONCLUSIONS: This SLR demonstrates that patients who achieve or sustain HDV RNA undetectability are more likely to experience better clinical outcomes than those who do not; whether the strength of this association varies by therapeutic mechanism of action has yet to be elucidated. These findings reinforce the need for enhanced HDV screening in patients with hepatitis B virus to enable early diagnosis, timely care, and initiation of treatment to mitigate liver-related morbidity and mortality.
METHODS: Embase, PubMed, and Cochrane were searched from inception to August 2025 to identify studies evaluating association between HDV RNA-based surrogate endpoints and clinical outcomes using artificial intelligence assisted screening with human in-loop.
RESULTS: Seventeen studies (15 full-text articles and 2 conference abstracts) including 1,572 patients evaluated the association between HDV RNA status and clinical outcomes. Most studies were retrospective (n=14) and conducted in Europe (n=10). Hepatic decompensation (HD, n=5) and hepatocellular carcinoma (HCC, n=5) were the most common clinical endpoints, with most patients receiving interferon- or nucleos(t)ide analogue-based therapies. Overall, patients who achieve or sustain undetectable HDV RNA, were consistently associated with a reduced risk of clinical outcomes (OR: 0.04-0.73; HR: 0.03-0.45), with most studies reporting positive or direct associations across all clinical outcomes. Among studies evaluating the association of HDV RNA with specific clinical outcomes, a statistically significant association (p<0.05) was observed in 4 of 5 studies for HD, 3 of 5 for HCC, 3 of 4 each for cirrhosis and death, and 1 of 2 for liver transplantation.
CONCLUSIONS: This SLR demonstrates that patients who achieve or sustain HDV RNA undetectability are more likely to experience better clinical outcomes than those who do not; whether the strength of this association varies by therapeutic mechanism of action has yet to be elucidated. These findings reinforce the need for enhanced HDV screening in patients with hepatitis B virus to enable early diagnosis, timely care, and initiation of treatment to mitigate liver-related morbidity and mortality.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
CO16
Topic
Clinical Outcomes
Topic Subcategory
Clinical Outcomes Assessment, Relating Intermediate to Long-term Outcomes
Disease
SDC: Infectious Disease (non-vaccine)