Hepatitis D double reflex testing of all hepatitis B carriers in low-HBV- and high-HBV/HDV-prevalence countries

Razavi, Homie; Buti, María; Terrault, Norah A.; Zeuzem, Stefan; Yurdaydın, Cihan; Tanaka, Junko; Aghemo, Alessio; Akarca, Ulus Salih; Masri, Nasser M. Al; Alalwan, Abduljaleel; Aleman, Soo; Alghamdi, Abdullah S; Alghamdi, Saad; Al–Hamoudi, Waleed; Aljumah, Abdulrahman; Altraif, Ibrahim; Asselah, Tarik; Ben‐Ari, Ziv; Berg, Thomas; Biondi, Mia J; Blach, Sarah; Braga, Wornei Silva Miranda; Brandão‐Mello, Carlos Eduardo; Brunetto, M.R.; Cabezas, Joaquín; Cheinquer, Hugo; Chen, Pei‐Jer; Cheon, Myeong-Eun; Chuang, Wan‐Long; Coffin, Carla S.; Coppola, Nicola; Craxı̀, Antonio; Crespo, Javier; Lédinghen, Victor de; Duberg, Ann‐Sofi; Etzion, Ohad; Ferraz, Maria Lúcia Gomes; Ferreira, Paulo Roberto Abrão; Forns, Xavier; Foster, Graham; Gaeta, Giovanni Battista; Gamkrelidze, Ivane; García‐Samaniego, J.; Gheorghe, L.; Gholam, Pierre M.; Gish, Robert G.; Glenn, Jeffrey S.; Hercun, Julian; Hsu, Yao-Chun; Hu, Ching-Chih; Huang, Jee‐Fu; Janjua, Naveed Z.; Jia, Jidong; Kåberg, Martin; Kaita, Kelly; Kamal, Habiba; Kao, Jia‐Horng; Kondili, Loreta A.; Lagging, Martin; Lázaro, Pablo; Lazarus, Jeffrey V.; Lee, Mei-Hsuan; Lim, Young Suk; Marotta, Paul; Navas, María Cristina; Naveira, Marcelo Contardo Moscoso; Orrego, Mauricio; Osiowy, Carla; Pan, Calvin Q.; Raimondo, Giovanni; Ramji, Alnoor; Razavi‐Shearer, Devin; Razavi‐Shearer, Kathryn; Ríos-Hincapié, Cielo Y.; Rodrı́guez, Manuel; Rosenberg, William; Roulot, Dominique; Ryder, Stephen; Safadi, Rifaat; Sanai, Faisal M.; Santantonio, T.; Sarrazin, Christoph; Shouval, Daniel; Tacke, Frank; Tergast, Tammo L.; Villalobos-Salcedo, Juan Miguel; Voeller, Alexis; Yang, Hwai I.; Yu, Ming‐Lung; Zuckerman, Eli

doi:10.1016/j.jhep.2023.02.041

Cited by 24 publications

(11 citation statements)

References 19 publications

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“…Our data support recommendations by several experts, highlighting the need for increased HDV testing and consideration of reflex anti-HDV testing, both in the United States and worldwide. 21 22 23 …”

Section: Discussionmentioning

confidence: 99%

Hepatitis delta testing trends in a US national cohort: An analysis of patient and provider-level predictive factors

John,

Amoli,

Evon

et al. 2024

Hepatology Communications

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Background: The low prevalence of HDV infection in the United States could be attributed to insufficient testing rate, which can result in an underestimation of the true burden of HDV. The primary objective of this study is to quantify the prevalence of and factors associated with HDV antibody (anti-HDV) or RNA testing, among participants with positive HBsAg in the Veterans Health Administration (VHA). Methods: We conducted a retrospective cohort study of participants who tested positive for HBsAg between January 2000 and December 2022 within the VHA. We identified those who were tested for HDV, and patient and provider-level factors associated with HDV testing. Results: Of 41,658 participants with positive HBsAg who had follow-up, 4438 (10.7%) were tested at least once for HDV, of which 135 (3.0%) were positive. Participants in the Northeast (adjusted odds ratio [aOR]: 1.30, 95% CI: 1.17–1.44, p<0.001), and receiving hepatology care (aOR: 1.38, 95% CI: 1.24–1.54, p<0.001) were more likely, while those in the Midwest (aOR: 0.69, 95% CI: 0.60–0.79, p<0.001), under the care of a primary care provider (aOR: 0.61, 95% CI: 0.50–0.74, p<0.001), Blacks (aOR: 0.85, 95% CI: 0.77–0.94, p=0.001), participants who were HCV antibody–positive (aOR: 0.89, 95% CI: 0.81–0.99, p=0.03), and participants who were HIV-positive (aOR: 0.80, 95% CI: 0.71–0.90, p<0.001) were less likely to be tested for HDV. Conclusions: HDV screening rates in the VHA remain low overall. Participants who are Black, living in the Midwest, patients who are HIV-positive, and patients who are HCV-positive are less likely to be tested for HDV. These results suggest that risk-based screening strategies are ineffective in the VHA and highlight the need for refining testing strategies to increase HDV screening rates.

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Section: Discussionmentioning

confidence: 99%

Hepatitis delta testing trends in a US national cohort: An analysis of patient and provider-level predictive factors

John,

Amoli,

Evon

et al. 2024

Hepatology Communications

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“…If universal testing is adopted, yearly retesting is recommended for persons with HBsAg at increased risk of HDV infection . A modeling study suggested that universal screening is cost-effective for countries with low prevalence of HBV or high prevalence of HDV but not for countries where HBV prevalence is high and HDV prevalence is low . An alternative approach is targeted screening as recommended by the American Association for the Study of Liver Diseases .…”

Section: Discussionmentioning

confidence: 99%

Hepatitis D

Negro,

Lok

2023

JAMA

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ImportanceHepatitis D virus (HDV) infection occurs in association with hepatitis B virus (HBV) infection and affects approximately 12 million to 72 million people worldwide. HDV causes more rapid progression to cirrhosis and higher rates of hepatocellular carcinoma than HBV alone or hepatitis C virus.ObservationsHDV requires HBV to enter hepatocytes and to assemble and secrete new virions. Acute HDV-HBV coinfection is followed by clearance of both viruses in approximately 95% of people, whereas HDV superinfection in an HBV-infected person results in chronic HDV-HBV infection in more than 90% of infected patients. Chronic hepatitis D causes more rapidly progressive liver disease than HBV alone. Approximately 30% to 70% of patients with chronic hepatitis D have cirrhosis at diagnosis and more than 50% die of liver disease within 10 years of diagnosis. However, recent studies suggested that progression is variable and that more than 50% of people may have an indolent course. Only approximately 20% to 50% of people infected by hepatitis D have been diagnosed due to lack of awareness and limited access to reliable diagnostic tests for the HDV antibody and HDV RNA. The HBV vaccine prevents HDV infection by preventing HBV infection, but no vaccines are available to protect those with established HBV infection against HDV. Interferon alfa inhibits HDV replication and reduces the incidence of liver-related events such as liver decompensation, hepatocellular carcinoma, liver transplant, or mortality from 8.5% per year to 3.3% per year. Adverse effects from interferon alfa such as fatigue, depression, and bone marrow suppression are common. HBV nucleos(t)ide analogues, such as entecavir or tenofovir, are ineffective against HDV. Phase 3 randomized clinical trials of bulevirtide, which blocks entry of HDV into hepatocytes, and lonafarnib, which interferes with HDV assembly, showed that compared with placebo or observation, these therapies attained virological and biochemical response in up to 56% of patients after 96 weeks of bulevirtide monotherapy and 19% after 48 weeks of lonafarnib, ritonavir, and pegylated interferon alfa treatment.Conclusions and RelevanceHDV infection affects approximately 12 million to 72 million people worldwide and is associated with more rapid progression to cirrhosis and liver failure and higher rates of hepatocellular carcinoma than infection with HBV alone. Bulevirtide was recently approved for HDV in Europe, whereas pegylated interferon alfa is the only treatment available in most countries.

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“…Of the estimated 5 million HDV carriers worldwide, China, Pakistan, and Mongolia are the three countries with the largest number of individuals with chronic hepatitis delta [ 49 ]. Hot spots have been noticed in West-Central Africa, Mongolia, Taiwan, Pakistan, Turkey, and the Amazon basin [ 50 ]. In addition, HDV has spread globally among injection drug users [ 51 ].…”

Section: Hepatitis Delta Superinfectionmentioning

confidence: 99%

Prospects for Controlling Hepatitis B Globally

Soriano,

Moreno-Torres,

Treviño

et al. 2024

Pathogens

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Infection with the hepatitis B virus (HBV) is highly prevalent globally. Over 250 million people suffer from chronic hepatitis B, and more than 800,000 patients die each year due to hepatitis B complications, including liver cancer. Although protective HBV vaccines are recommended for all newborns, global coverage is suboptimal. In adults, sexual transmission is by far the most frequent route of contagion. The WHO estimates that 1.5 million new HBV infections occur annually. Oral nucleos(t)ide analogues entecavir and tenofovir are the most frequent antivirals prescribed as HBV therapy. Almost all patients adherent to the medication achieve undetectable plasma viremia beyond 6 months of monotherapy. However, less than 5% achieve anti-HBs seroconversion, and viral rebound occurs following drug discontinuation. Therefore, nucleos(t)ide analogues need to be lifelong. New long-acting formulations of tenofovir and entecavir are being developed that will maximize treatment benefit and overcome adherence barriers. Furthermore, new antiviral agents are in development, including entry inhibitors, capside assembly modulators, and RNA interference molecules. The use of combination therapy pursues a functional HBV cure, meaning it is negative for both circulating HBV-DNA and HBsAg. Even when this goal is achieved, the cccDNA reservoir within infected hepatocytes remains a signal of past infection, and HBV can reactivate under immune suppression. Therefore, new gene therapies, including gene editing, are eagerly being pursued to silence or definitively disrupt HBV genomes within infected hepatocytes and, in this way, ultimately cure hepatitis B. At this time, three actions can be taken to push HBV eradication globally: (1) expand universal newborn HBV vaccination; (2) perform once-in-life testing of all adults to identify susceptible HBV persons that could be vaccinated (or re-vaccinated) and unveil asymptomatic carriers that could benefit from treatment; and (3) provide earlier antiviral therapy to chronic HBV carriers, as being aviremic reduces the risk of both clinical progression and transmission.

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Hepatitis D double reflex testing of all hepatitis B carriers in low-HBV- and high-HBV/HDV-prevalence countries

Cited by 24 publications

References 19 publications

Hepatitis delta testing trends in a US national cohort: An analysis of patient and provider-level predictive factors

Hepatitis delta testing trends in a US national cohort: An analysis of patient and provider-level predictive factors

Hepatitis D

Prospects for Controlling Hepatitis B Globally

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