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Ly KN, Yin S, Spradling PR. Disparities in Social Vulnerability and Premature Mortality among Decedents with Hepatitis B, United States, 2010-2019. J Racial Ethn Health Disparities 2025; 12:1344-1356. [PMID: 38472630 PMCID: PMC11390983 DOI: 10.1007/s40615-024-01968-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Revised: 02/27/2024] [Accepted: 03/01/2024] [Indexed: 03/14/2024]
Abstract
BACKGROUND Current US hepatitis B mortality rates remain three times higher than the national target. Mortality reduction will depend on addressing hepatitis B disparities influenced by social determinants of health. OBJECTIVES This study aims to describe characteristics of hepatitis B-listed decedents, which included US birthplace status and county social vulnerability attributes and quantify premature mortality. METHODS We conducted a cross-sectional analysis of 17,483 hepatitis B-listed decedents using the 2010-2019 US Multiple-Cause-of-Death data merged with the county-level Social Vulnerability Index (SVI). Outcomes included the distribution of decedents according to US birthplace status and residence in higher versus lower death burden counties by sociodemographic characteristics, years of potential life lost (YPLL), and SVI quartiles. RESULTS Most hepatitis B-listed decedents were US-born, male, and born during 1945-1965. Median YPLL was 17.2; 90.0% died prematurely. US-born decedents were more frequently White, non-college graduates, unmarried, and had resided in a county with < 500,000 people; non-US-born decedents were more frequently Asian/Pacific Islander, college graduates, married, and had resided in a county with ≥ 1 million people. Higher death burden (≥ 20) counties were principally located in coastal states. US-born decedents more frequently resided in counties in the highest SVI quartile for "Household Characteristics" and "Uninsured," whereas non-US-born decedents more frequently resided in counties in the highest SVI quartile for "Racial/Ethnic Minority Status" and "Housing Type/Transportation." CONCLUSION This analysis found substantial premature hepatitis B mortality and residence in counties ranked high in social vulnerability. Successful interventions should be tailored to disproportionately affected populations and the social vulnerability features of their geographic areas.
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Affiliation(s)
- Kathleen N Ly
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, US Centers for Disease Control and Prevention, 1600 Clifton Rd. NE, Mailstop US12-3, Atlanta, GA, 30333, USA.
| | - Shaoman Yin
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, US Centers for Disease Control and Prevention, 1600 Clifton Rd. NE, Mailstop US12-3, Atlanta, GA, 30333, USA
| | - Philip R Spradling
- Division of Viral Hepatitis, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, US Centers for Disease Control and Prevention, 1600 Clifton Rd. NE, Mailstop US12-3, Atlanta, GA, 30333, USA.
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Jain P, Jain A, Deshmukh R, Samal P, Satapathy T, Ajazuddin. Metabolic dysfunction-associated steatotic liver disease (MASLD): Exploring systemic impacts and innovative therapies. Clin Res Hepatol Gastroenterol 2025; 49:102584. [PMID: 40157567 DOI: 10.1016/j.clinre.2025.102584] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2025] [Revised: 03/24/2025] [Accepted: 03/27/2025] [Indexed: 04/01/2025]
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD), which includes the inflammatory subtype metabolic dysfunction-associated steatohepatitis, is a prominent cause of chronic liver disease with systemic effects. Insulin resistance, obesity, and dyslipidaemia produce MASLD in over 30 % of adults. It is a global health issue. From MASLD to MASH, hepatic inflammation and fibrosis grow, leading to cirrhosis, hepatocellular cancer, and extrahepatic complications such CVD, CKD, and sarcopenia. Effects of MASLD to MASH are mediated through mechanisms that include inflammation, oxidative stress, dysbiosis, and predisposition through genetic makeup. Advances in diagnostic nomenclature in the past few years have moved the emphasis away from NAFLD to MASLD, focusing on the metabolic etiology and away from the stigma of an alcoholic-related condition. Epidemiological data show a large geographical variability and increasing prevalence in younger populations, particularly in regions with high carbohydrate-rich diets and central adiposity. Lifestyle modification is considered as the main management of MASLD currently. This may include dietary intervention, exercise, and weight loss management. Pharmaceutical management is primarily aimed at metabolic dysfunction with promising findings for GLP-1 receptor agonists, pioglitazone and SGLT-2 inhibitors, which can correct both hepatic and systemic outcome. However, it still depends on well-integrated multidisciplinary care models by considering complex relationships between MASLD and its effects on extrahepatic organs. Determining complications at an early stage; developing precision medicine strategies; exploring new therapeutic targets will represent crucial factors in improving their outcomes. This review discuss the systemic nature of MASLD and calls for multiple collaborations to reduce its far-reaching health impacts and our quest for understanding its pathological mechanisms. Thus, collective efforts that are required to address MASLD are under the public health, clinical care, and research angles toward effectively containing its rapidly increasing burden.
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Affiliation(s)
- Parag Jain
- Department of Pharmacology, Rungta College of Pharmaceutical Sciences and Research, Bhilai, C.G., India, 490024.
| | - Akanksha Jain
- Department of Biotechnology, Bharti University, Durg, C.G., India
| | - Rohitas Deshmukh
- Institute of Pharmaceutical Research, GLA University, Mathura, India, 281406
| | - Pradeep Samal
- Department of Pharmacy, Guru Ghasidas Vishwavidyalaya, Bilaspur, C.G., India
| | - Trilochan Satapathy
- Department of Pharmacy, Columbia Institute of Pharmaceutical Sciences, Raipur, C.G., India, 493111
| | - Ajazuddin
- Department of Pharmacology, Rungta College of Pharmaceutical Sciences and Research, Bhilai, C.G., India, 490024
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Lam L, Bourlière M, Pol S, Carrat F. Impact of Nucleos(t)ide Analogs on Major Clinical Outcomes in Patients With Chronic Hepatitis B: A 10-Year French Nationwide Cohort Study. Aliment Pharmacol Ther 2025; 61:865-875. [PMID: 39737762 DOI: 10.1111/apt.18462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Revised: 10/04/2024] [Accepted: 12/17/2024] [Indexed: 01/01/2025]
Abstract
BACKGROUND Conflicting results have been reported on the impact of tenofovir versus entecavir on liver-related outcomes. AIMS To explore trends in clinical outcomes in chronic hepatitis B virus (HBV)-infected patients and compare the impact of tenofovir versus entecavir on the risk of hepatocellular carcinoma (HCC), liver transplantation (LT) and mortality. METHODS We used the French National Health Insurance Databases (SNDS) to identify HBV-infected patients. We quantified the excess clinical burden from 2012 to 2021 by comparing the HBV-infected cohort with a general population cohort, using 1:1 exact matching on birth date, sex, social deprivation index and follow-up start date. The risks of mortality, HCC and LT were compared between patients treated with tenofovir and entecavir using inverse probability weighting. RESULTS A total of 101,740 patients were matched to the general population. From 2012 to 2021, the average annual decreases in excess mortality, incidence of HCC and LT were 3.7%, 8.0% and 11.9%, respectively (p for trend < 0.001). During the same period, the nucleos(t)ide analog (NUC) treatment coverage significantly increased, particularly after 2016 (p < 0.001). Among 14,054 treatment-naïve patients starting tenofovir (n = 7426) or entecavir (n = 6628), we observed no difference in the composite outcome of mortality, LT or HCC (HR, 1.09; 95% CI, 0.95-1.24). Tenofovir was associated with an increased risk of HCC compared with entecavir (HR, 1.31; 95% CI, 1.07-1.62). CONCLUSIONS Tenofovir was associated with a higher risk of HCC compared with entecavir, although no difference in the composite outcome of mortality or liver-related events was observed between the two treatments.
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Affiliation(s)
- Laurent Lam
- Sorbonne Université, INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique, IPLESP, Paris, France
| | - Marc Bourlière
- Department of Hepatology and Gastroenterology, Hôpital Saint Joseph & INSERM, UMR 1252 IRD SESSTIM, Aix Marseille Université, Marseille, France
| | - Stanislas Pol
- AP-HP, Centre Université Paris Centre, Groupe Hospitalier Cochin Port Royal, DMU Cancérologie et spécialités médico-chirurgicales, Service des Maladies du Foie & Université Paris Cité, Paris, France
| | - Fabrice Carrat
- Sorbonne Université, INSERM, Institut Pierre Louis d'Épidémiologie et de Santé Publique, IPLESP, Paris, France
- Sorbonne Université, Department of Public Health, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Antoine, Paris, France
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Wong RJ. Gaps and disparities in the treatment of chronic hepatitis B infection in the USA. Gastroenterol Rep (Oxf) 2025; 13:goaf016. [PMID: 39925941 PMCID: PMC11802464 DOI: 10.1093/gastro/goaf016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Revised: 12/30/2024] [Accepted: 01/13/2025] [Indexed: 02/11/2025] Open
Abstract
Chronic hepatitis B (CHB) infection affects nearly 300 million individuals worldwide and is a leading cause of hepatocellular carcinoma and liver-related mortality. However, major gaps in the CHB cascade of care persist, with the majority of individuals with CHB not diagnosed and not linked to care and treatment. Even among individuals with known CHB, existing studies report on major gaps and disparities in timely linkage to care and timely access to CHB therapies. While the momentum to expand and simplify CHB treatment guidelines is promising, access to treatment still relies on individuals being effectively engaged in clinical care and liver disease monitoring. The contributing factors to the observed gaps and disparities in the CHB cascade of care are complex and multifactorial, and there is no one-size-fits-all solution than can be easily applied across all global regions. However, any serious approach towards addressing the existing gaps in the CHB cascade of care to improve patient outcomes requires a concerted investment from healthcare institutions, governments, policymakers, and industry partners to provide the necessary resources to be able to achieve this goal. Anything less than a comprehensive and collaborative approach that engages all stakeholders to invest effort and resources into tackling the global epidemic of CHB will continue to fall short in making progress towards global viral hepatitis elimination goals.
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Affiliation(s)
- Robert J Wong
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, CA, USA
- Gastroenterology Section, Veterans Affairs Palo Alto Healthcare System, Palo Alto, CA, USA
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Sangro B, Argemi J, Ronot M, Paradis V, Meyer T, Mazzaferro V, Jepsen P, Golfieri R, Galle P, Dawson L, Reig M. EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma. J Hepatol 2025; 82:315-374. [PMID: 39690085 DOI: 10.1016/j.jhep.2024.08.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Accepted: 08/29/2024] [Indexed: 12/19/2024]
Abstract
Liver cancer is the third leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) accounting for approximately 90% of primary liver cancers. Advances in diagnostic and therapeutic tools, along with improved understanding of their application, are transforming patient treatment. Integrating these innovations into clinical practice presents challenges and necessitates guidance. These clinical practice guidelines offer updated advice for managing patients with HCC and provide a comprehensive review of pertinent data. Key updates from the 2018 EASL guidelines include personalised surveillance based on individual risk assessment and the use of new tools, standardisation of liver imaging procedures and diagnostic criteria, use of minimally invasive surgery in complex cases together with updates on the integrated role of liver transplantation, transitions between surgical, locoregional, and systemic therapies, the role of radiation therapies, and the use of combination immunotherapies at various stages of disease. Above all, there is an absolute need for a multiparametric assessment of individual risks and benefits, considering the patient's perspective, by a multidisciplinary team encompassing various specialties.
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Li Y, Hwang N, Snedeker A, Lemon SM, Noe D, Sun L, Clement JA, Zhou T, Tang L, Block T, Du Y. "PROTAC" modified dihydroquinolizinones (DHQs) that cause degradation of PAPD-5 and inhibition of hepatitis A virus and hepatitis B virus, in vitro. Bioorg Med Chem Lett 2024; 102:129680. [PMID: 38428537 DOI: 10.1016/j.bmcl.2024.129680] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Revised: 02/15/2024] [Accepted: 02/27/2024] [Indexed: 03/03/2024]
Abstract
Dihydroquinolizinones (DHQs) that inhibit cellular polyadenylating polymerases 5 and 7 (PAPD5 & 7), such as RG7834, have been shown to inhibit both hepatitis A (HAV) and hepatitis B virus (HBV) in vitro and in vivo. In this report, we describe RG7834-based proteolysis-targeting chimeras (PROTACs), such as compound 12b, (6S)-9-((1-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)-21-oxo-3,6,9,12,15,18-hexaoxa-22-azapentacosan-25-yl)oxy)-6-isopropyl-10-methoxy-2-oxo-6,7-dihydro-2H-pyrido[2,1-a]isoquinoline-3-carboxylic acid. The PROTAC DHQs described here inhibited an HAV reporter virus in vitro with an IC50 of 277 nM. Although the PROTAC DHQs were also inhibitory to HBV, their activities were substantially less potent against HBV in vitro, being in the 10 to 20 µM range, based on the reduction of HBsAg and HBV mRNA levels. Importantly, unlike RG7834, the incubation of cells in vitro with PROTAC DHQ 12b resulted in the degradation of PAPD5, as expected for a PROTAC compound, but curiously not PAPD7. PAPD5 polypeptide degradation was prevented when a proteasome inhibitor, epoxomicin, was used, indicating that proteasome mediated proteolysis was associated with the observed activities of 12b. Taken together, these data show that 12b is the first example of a PROTAC that suppresses both HAV and HBV that is based on a small molecule warhead. The possibility that it has mechanisms that differ from its parent compound, RG7834, and has clinical value, is discussed.
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Affiliation(s)
- You Li
- Division of Infectious Diseases, Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7292, USA
| | - Nicky Hwang
- Baruch S. Blumberg Institute, 3805 Old Easton Road, Doylestown, PA 18902, USA
| | - Andrew Snedeker
- Baruch S. Blumberg Institute, 3805 Old Easton Road, Doylestown, PA 18902, USA
| | - Stanley M Lemon
- Division of Infectious Diseases, Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7292, USA.
| | - Daisy Noe
- Baruch S. Blumberg Institute, 3805 Old Easton Road, Doylestown, PA 18902, USA
| | - Liren Sun
- Baruch S. Blumberg Institute, 3805 Old Easton Road, Doylestown, PA 18902, USA
| | - Jason A Clement
- Baruch S. Blumberg Institute, 3805 Old Easton Road, Doylestown, PA 18902, USA
| | - Tianlun Zhou
- Baruch S. Blumberg Institute, 3805 Old Easton Road, Doylestown, PA 18902, USA
| | - Liudi Tang
- Baruch S. Blumberg Institute, 3805 Old Easton Road, Doylestown, PA 18902, USA
| | - Timothy Block
- Baruch S. Blumberg Institute, 3805 Old Easton Road, Doylestown, PA 18902, USA.
| | - Yanming Du
- Baruch S. Blumberg Institute, 3805 Old Easton Road, Doylestown, PA 18902, USA.
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Lin M, Gao B, Peng M, Chen X, Xiao H, Shi M, Zhang X, Zeng F, Chi X. Metabolic dysfunction-associated steatotic liver disease increases hepatocellular carcinoma risk in chronic hepatitis B patients: a retrospective cohort study. Front Physiol 2024; 15:1347459. [PMID: 38405121 PMCID: PMC10886697 DOI: 10.3389/fphys.2024.1347459] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Accepted: 01/29/2024] [Indexed: 02/27/2024] Open
Abstract
Background: The combined effect of hepatitis B virus infection and metabolic dysfunction-associated steatotic liver disease (MASLD) on hepatocellular carcinoma (HCC) risk remains unclear. The current study sought to elucidate the impact of MASLD on HCC progression in chronic hepatitis B (CHB) patients. Method: This retrospective cohort study included CHB patients who had undergone liver biopsy and abdominal imaging at the Guangdong Provincial Hospital of Chinese Medicine between 2013 and 2019. We investigated the correlation between MASLD and HCC risk, and inverse probability treatment weighting (IPTW) was used to adjust for patient characteristics. Results: A total of 1,613 patients were included, and 483 (29.9%) were diagnosed with MASLD. Over a median follow-up period of 5.02 years, 36 (2.2%) developed HCC, comprising 4.8% (23/483) of those with MASLD and 1.2% (13/1,130) of those without. Those with MASLD had a significantly higher cumulative incidence of HCC than those without (p < 0.001). The presence of MASLD was associated with a higher risk of HCC (adjusted hazard ratio [HR], 3.996; 95% confidence interval [CI], 2.007-7.959; p < 0.001). After adjustment using IPTW, the patients with MASLD retained a higher cumulative incidence of HCC (p < 0.001). Moreover, MASLD was found to be an independent risk factor for the development of HCC (adjusted HR, 10.191; 95% CI, 4.327-24.002; p < 0.001). However, among patients with MASLD, there were no significant differences in the cumulative risk of HCC between patients with and without overweight, between those with <2 and ≥2 cardiometabolic risk factors (CMRFs), between those with <3 and ≥3 CMRFs, or between those with <4 and ≥4 CMRFs (p = 0.110, p = 0.087, p = 0.066, and p = 0.490, respectively). Conclusion: The presence of MASLD is associated with a higher risk of HCC in patients with CHB. Notably, this higher risk is present in patients with MASLD, irrespective of the presence or absence of overweight or the number of CMRFs they have.
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Affiliation(s)
- Ming Lin
- Department of Hepatology, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Bowen Gao
- The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Mengnan Peng
- Community Health Service Center of Tianhenan Street Tianhe District, Guangzhou, China
| | - Xuefang Chen
- Department of Hepatobiliary Surgery, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Huanming Xiao
- Department of Hepatology, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Meijie Shi
- Department of Hepatology, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Xiujuan Zhang
- Department of Hepatology, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Folai Zeng
- Department of Hepatology, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Xiaoling Chi
- Department of Hepatology, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
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Spradling PR, Bocour A, Kuncio DE, Ly KN, Harris AM, Thompson ND. Hepatitis B Care Continuum Models-Data to Inform Public Health Action. Public Health Rep 2024:333549231218277. [PMID: 38205796 PMCID: PMC11569688 DOI: 10.1177/00333549231218277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2024] Open
Abstract
The application of a care continuum model (CCM) can identify gaps in diagnosis, care, and treatment of populations with a common condition, but challenges are inherent in developing a CCM for chronic hepatitis B. In contrast with treatment for HIV or hepatitis C, treatment is not indicated for all people with chronic hepatitis B, clinical endpoints are not clear for those receiving treatment, and those for whom treatment is not indicated remain at risk for complications. This topical review examines the data elements necessary to develop and apply chronic hepatitis B CCMs at the jurisdictional health department level. We conducted a nonsystematic review of US-based publications in Ovid MEDLINE (1946-present), Ovid Embase (1974-present), and Scopus (not date limited) databases, which yielded 724 publications for review. Jurisdictional health departments, if properly supported, could develop locale-specific focused CCMs using person-level chronic hepatitis B registries, updated longitudinally using electronic laboratory reporting data and case reporting data. These CCMs could be applied to identify disparities and improve rates in testing and access to care and treatment, which are necessary to reduce liver disease and chronic hepatitis B mortality. Investments in public health surveillance infrastructure, including substantial enhancements in electronic laboratory reporting and case reporting and the use of supplementary data sources, could enable jurisdictional health departments to develop modified CCMs for chronic hepatitis B that focus, at least initially, on "early" CCM steps, which emphasize optimization of hepatitis B diagnosis, linkage to care, and ongoing clinical follow-up of diagnosed people, all of which can lead to improved outcomes.
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Affiliation(s)
- Philip R. Spradling
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Angelica Bocour
- Viral Hepatitis Program, New York City Department of Health and Mental Hygiene, New York, NY, USA
| | - Danica E. Kuncio
- Division of Disease Control, Philadelphia Department of Public Health, Philadelphia, PA, USA
| | - Kathleen N. Ly
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Aaron M. Harris
- Center for Surveillance, Epidemiology, and Laboratory Services, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Nicola D. Thompson
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA, USA
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Nguyen LBL, Lemoine M, Ndow G, Ward ZJ, Hallet TB, D'Alessandro U, Thursz M, Nayagam S, Shimakawa Y. Treat All versus targeted strategies to select HBV-infected people for antiviral therapy in The Gambia, west Africa: a cost-effectiveness analysis. Lancet Glob Health 2024; 12:e66-e78. [PMID: 38097300 DOI: 10.1016/s2214-109x(23)00467-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 10/04/2023] [Accepted: 10/05/2023] [Indexed: 12/18/2023]
Abstract
BACKGROUND Global elimination of hepatitis B virus (HBV) requires expanded uptake of antiviral therapy, potentially by simplifying testing algorithms, especially in resource-limited countries. We evaluated the effectiveness, cost-effectiveness, and budget impact of three strategies that determine eligibility for anti-HBV treatment, as compared with the WHO 2015 treatment eligibility criteria, in The Gambia. METHODS We developed a microsimulation model of natural history using data from the Prevention of Liver Fibrosis and Cancer in Africa programme (known as PROLIFICA) in The Gambia, for an HBV-infected cohort of individuals aged 20 years. The algorithms included in the model were a conventional strategy using the European Association for the Study of the Liver (EASL) 2017 criteria, a simplified algorithm using hepatitis B e antigen and alanine aminotransferase (the Treatment Eligibility in Africa for the Hepatitis B Virus [TREAT-B] score), a Treat All approach for all HBV-infected individuals, and the WHO 2015 criteria. Outcomes to measure effectiveness were disability-adjusted life years (DALYs) and years of life saved (YLS), which were used to calculate incremental cost-effectiveness ratios (ICERs) with the WHO 2015 criteria as the base-case scenario. Costs were assessed from a modified social perspective. A budget impact analysis was also done. We tested the robustness of results with a range of sensitiviy analyses including probabilistic sensitivity analysis. FINDINGS Compared with the WHO criteria, TREAT-B resulted in 4877 DALYs averted and Treat All resulted in 9352 DALYs averted, whereas the EASL criteria led to an excess of 795 DALYs. TREAT-B was cost-saving, whereas the ICER for Treat All (US$2149 per DALY averted) was higher than the cost-effectiveness threshold for The Gambia (0·5 times the country's gross domestic product per capita: $352). These patterns did not change when YLS was the outcome. In a modelled cohort of 5000 adults (aged 20 years) with chronic HBV infection from The Gambia, the 5-year budget impact was $1·14 million for Treat All, $0·66 million for TREAT-B, $1·03 million for the WHO criteria, and $1·16 million for the EASL criteria. Probabilistic sensitivity analysis indicated that among the Treat All, EASL, and TREAT-B algorithms, Treat All would become the most preferred strategy only with a willingness-to-pay threshold exceeding approximately $72 000 per DALY averted or $110 000 per YLS. INTERPRETATION Although the Treat All strategy might be the most effective, it is unlikely to be cost-effective in The Gambia. A simplified strategy such as TREAT-B might be a cost-saving alternative. FUNDING UK Research and Innovation (Medical Research Council). TRANSLATION For the French translation of the abstract see Supplementary Materials section.
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Affiliation(s)
- Liem B Luong Nguyen
- Institut Pasteur, Université Paris Cité, Unité d'Épidémiologie des Maladies Émergentes, Paris, France; CIC Cochin Pasteur, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Maud Lemoine
- Department of Metabolism, Digestion and Reproduction, Division of Digestive Disease, Liver Unit, St Mary's Hospital, Imperial College London, UK; Medical Research Council Unit, London School of Hygiene & Tropical Medicine, Fajara, The Gambia
| | - Gibril Ndow
- Department of Metabolism, Digestion and Reproduction, Division of Digestive Disease, Liver Unit, St Mary's Hospital, Imperial College London, UK; Medical Research Council Unit, London School of Hygiene & Tropical Medicine, Fajara, The Gambia
| | - Zachary J Ward
- Center for Health Decision Science, Harvard TH Chan School of Public Health, Boston, MA, USA
| | - Timothy B Hallet
- Medical Research Council Centre for Global Infectious Disease Analysis, School of Public Health, Imperial College London, London, UK
| | - Umberto D'Alessandro
- Medical Research Council Unit, London School of Hygiene & Tropical Medicine, Fajara, The Gambia
| | - Mark Thursz
- Department of Metabolism, Digestion and Reproduction, Division of Digestive Disease, Liver Unit, St Mary's Hospital, Imperial College London, UK
| | - Shevanthi Nayagam
- Department of Metabolism, Digestion and Reproduction, Division of Digestive Disease, Liver Unit, St Mary's Hospital, Imperial College London, UK; Medical Research Council Centre for Global Infectious Disease Analysis, School of Public Health, Imperial College London, London, UK
| | - Yusuke Shimakawa
- Institut Pasteur, Université Paris Cité, Unité d'Épidémiologie des Maladies Émergentes, Paris, France.
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10
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Thrift AP, Liu KS, Raza SA, El-Serag HB. Recent Decline in the Incidence of Hepatocellular Carcinoma in the United States. Clin Gastroenterol Hepatol 2023; 21:2418-2420.e3. [PMID: 35944829 DOI: 10.1016/j.cgh.2022.07.034] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Revised: 07/21/2022] [Accepted: 07/25/2022] [Indexed: 02/07/2023]
Affiliation(s)
- Aaron P Thrift
- Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, Texas; Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas.
| | - Kyle S Liu
- Baylor College of Medicine, Houston, Texas
| | - Syed Ahsan Raza
- Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, Texas
| | - Hashem B El-Serag
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas; Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E DeBakey Veterans Affairs Medical Center, Houston, Texas
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Devarbhavi H, Asrani SK, Arab JP, Nartey YA, Pose E, Kamath PS. Global burden of Liver Disease: 2023 Update. J Hepatol 2023:S0168-8278(23)00194-0. [PMID: 36990226 DOI: 10.1016/j.jhep.2023.03.017] [Citation(s) in RCA: 708] [Impact Index Per Article: 354.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Revised: 03/06/2023] [Accepted: 03/09/2023] [Indexed: 03/31/2023]
Abstract
Liver disease accounts for 2 million deaths and is responsible for 4% of all deaths (1 out of every 25 deaths worldwide); approximately 2/3 of all liver related deaths occur in men. Deaths are largely attributable to complications of cirrhosis and hepatocellular carcinoma, with acute hepatitis accounting for a smaller proportion of deaths. The most common causes of cirrhosis worldwide are related to viral hepatitis, alcohol, and nonalcoholic fatty liver disease (NAFLD). Hepatotropic viruses are the etiological factor in most cases of acute hepatitis, but drug-induced liver injury increasingly accounts for a significant proportion of cases. This iteration of the global burden of liver disease is an update of the 2019 version and focuses mainly on areas where significant new information is available like alcohol-associated liver disease, NAFLD, viral hepatitis, and HCC. We also devote a separate section to the burden of liver disease in Africa, an area of the world typically neglected in such documents.
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Affiliation(s)
- Harshad Devarbhavi
- Department of Gastroenterology and Hepatology, St. John's Medical College Hospital, Bangalore, India
| | - Sumeet K Asrani
- Baylor University Medical Center, Baylor Scott and White, Dallas, TX, United States.
| | - Juan Pablo Arab
- Division of Gastroenterology, Department of Medicine, Schulich School of Medicine, Western University & London Health Sciences Centre, London, Ontario, Canada; Departamento de Gastroenterologia, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile
| | - Yvonne Ayerki Nartey
- Department of Internal Medicine, School of Medical Sciences, University of Cape Coast, Cape Coast, Ghana
| | - Elisa Pose
- Liver Unit, Hospital Clinic of Barcelona. Institut D'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)
| | - Patrick S Kamath
- Mayo Clinic College of Medicine and Science, Rochester, MN, United States
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12
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Ward JW, Wanlapakorn N, Poovorawan Y, Shouval D. Hepatitis B Vaccines. PLOTKIN'S VACCINES 2023:389-432.e21. [DOI: 10.1016/b978-0-323-79058-1.00027-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Dieterich D, Graham C, Wang S, Kwo P, Lim YS, Liu CJ, Agarwal K, Sulkowski M. It Is Time for a Simplified Approach to Hepatitis B Elimination. GASTRO HEP ADVANCES 2022; 2:209-218. [PMID: 39132618 PMCID: PMC11307636 DOI: 10.1016/j.gastha.2022.10.004] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Accepted: 10/04/2022] [Indexed: 08/13/2024]
Abstract
Background and Aims Hepatitis B virus (HBV) infection continues to threaten millions of lives across the globe, despite universal vaccination efforts. Current guidelines for screening, vaccination, and treatment are complex and have left too many people undiagnosed or improperly managed. Antiviral therapy has been shown to significantly reduce the incidence of liver-related complications, including liver cancer. However, the complexity of existing guidelines can make it difficult to identify which patients to target for treatment, and recommendations that are difficult to implement in real-world settings pose a barrier to eligible patients to receive therapy and contribute to health disparities in HBV care. The goal of this global expert panel was to gain consensus on a streamlined approach to HBV care to facilitate implementation of HBV intervention and treatment, especially in the primary care setting. Methods A group of 8 liver and infectious disease specialists attended a meeting in January 2021 with the objective of gaining consensus on a streamlined algorithm for HBV care that would encourage implementation of HBV intervention and treatment. Results We have created a comprehensive perspective highlighting screening optimization, diagnostic workup, treatment, and monitoring. This treatment algorithm is designed to provide a streamlined visual pathway for risk stratification and management of patients with HBV that can be adapted in various care settings. Conclusion Simplification of guidelines will be critical to achieving health equity to address this public health threat and achieve HBV elimination.
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Affiliation(s)
- Douglas Dieterich
- Division of Liver Disease, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York
| | - Camilla Graham
- Division of Infectious Disease, Beth Israel Deaconess Medical Center, Boston, Massachusetts
| | - Su Wang
- Center for Asian Health, Saint Barnabas Medical Center, RWJ Barnabas Health, Florham Park, New Jersey
| | - Paul Kwo
- Department of Gastroenterology and Hepatology, Stanford Medical Center, Pleasanton, California
| | - Young-Suk Lim
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Chun-Jen Liu
- Department of Internal Medicine and Hepatitis Research Center at the National Taiwan University Hospital, Taipei, Taiwan
| | - Kosh Agarwal
- Institute of Liver Studies, King’s College Hospital NHS Foundation Trust, London, England
| | - Mark Sulkowski
- Division of Infectious Diseases, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
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Estimating Prevalence of Hepatitis B Virus Coinfection Among Adults With Tuberculosis: A Systematic Review With Meta-analysis. J Clin Gastroenterol 2022; 56:601-617. [PMID: 34009841 DOI: 10.1097/mcg.0000000000001533] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Accepted: 02/15/2021] [Indexed: 01/15/2023]
Abstract
BACKGROUND While patients with hepatitis B virus (HBV) infection and tuberculosis (TB) have similar risk factors, little is known regarding the prevalence of HBV and TB coinfection. We aim to evaluate the prevalence of HBV among patients with TB across world regions. METHODS We systematically reviewed the literature using PubMed from inception through September 1, 2019, to identify studies that provided data to calculate HBV coinfection prevalence among adults with TB infection. Prevalence estimates of HBV coinfection among TB patients were stratified by world regions and calculated using meta-analyses with random-effects models. RESULTS A total of 36 studies met inclusion criteria (4 from the Africa region, 6 from the Americas region, 5 from the Eastern Mediterranean region, 2 from European region, 6 from Southeast Asia region, and 13 from the Western Pacific region). On meta-analysis, overall pooled HBV coinfection prevalence among TB patients was 7.1%, but varied by world region. Region-specific pooled HBV prevalence among TB patients was highest in Africa region [11.4%, 95% confidence interval (CI): 3.45-19.31] and Western Pacific region (10.8%, 95% CI: 8.68-12.84), and was lowest in the Americas (2.2%, 95% CI: 0.78-3.53). Sensitivity analyses yielded similar HBV prevalence estimates across world regions. CONCLUSIONS In this meta-analysis, we observed HBV coinfection prevalence among TB patients to be 38% to 450% higher than published estimates from the Polaris group of region-specific overall HBV prevalence. Timely identification of HBV infection among TB patients will improve patient outcomes by allowing for closer clinical monitoring and management, which may reduce the risk of liver dysfunction and liver failure related to TB treatment.
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Kim WR, Telep LE, Jump B, Lu M, Ramroth H, Flaherty J, Gaggar A, Chokkalingam AP, Gordon SC. Risk of hepatocellular carcinoma in treatment-naïve chronic hepatitis B patients receiving tenofovir disoproxil fumarate versus entecavir in the United States. Aliment Pharmacol Ther 2022; 55:828-835. [PMID: 35137422 DOI: 10.1111/apt.16786] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 09/02/2021] [Accepted: 01/12/2022] [Indexed: 01/27/2023]
Abstract
BACKGROUND Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are the first-line treatment agents for chronic hepatitis B virus (HBV). Recently, whether the degree to which the risk of hepatocellular carcinoma (HCC) may be reduced by ETV vs TDF has been debated. We compared the incidence of HCC among treatment-naïve patients receiving TDF vs ETV in the United States. METHODS From a large administrative medical claims database of commercially insured patients, we identified 166,933 adults with a diagnosis of chronic hepatitis B and a minimum of 12 months of prior enrolment, of whom 3934 and 6127 initiated ETV and TDF respectively. Fine-Gray hazard regression models incorporating treatment propensity scores (PS) were used to estimate the risk of HCC incidence associated with TDF vs ETV; variables considered for adjustment included demographic characteristics, concomitant medication use and baseline comorbidities, as well as competing events including liver transplantation and medication changes. RESULTS After PS weighting, the TDF and ETV groups were well-matched. During the follow-up, 90 patients developed HCC, including 50 receiving ETV and 40 receiving TDF, giving rise to crude incidence rates of 0.62 per 100 person-years (PY) and 0.30 per 100 PY respectively. In PS-weighted, multivariable analysis, TDF was associated with a subdistribution hazard ratio for HCC of 0.58 (95% confidence interval [CI]: 0.38-0.89) compared to ETV. Results were similar when patients ≥40 years and men and women were analysed separately. CONCLUSION Among commercially insured, treatment-naïve patients with chronic hepatitis B in the United States, treatment with TDF was associated with significantly lower risk of HCC than ETV.
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Affiliation(s)
- W Ray Kim
- Stanford University School of Medicine, Stanford, CA, USA
| | | | | | - Mei Lu
- Henry Ford Health System, Detroit, MI, USA
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16
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Low Rates of Hepatitis B Virus Treatment Among Treatment-Eligible Patients in Safety-Net Health Systems. J Clin Gastroenterol 2022; 56:360-368. [PMID: 33780210 DOI: 10.1097/mcg.0000000000001530] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2020] [Accepted: 02/10/2021] [Indexed: 01/05/2023]
Abstract
BACKGROUND Timely initiation of antiviral therapy in chronic hepatitis B virus (CHB) reduces risk of disease progression. We evaluate overall treatment rates and predictors of treatment among treatment-eligible safety-net CHB patients. METHODS We retrospectively evaluated adults with CHB from 2010 to 2018 across 4 large safety-net health systems in the United States. CHB was identified with ICD-9/10 diagnosis coding and confirmed with laboratory data. Treatment eligibility was determined using American Association for the Study of Liver Diseases (AASLD) guidelines. Comparison of CHB treatment rates among treatment-eligible patients were performed using χ2 testing, Kaplan Meier methods and log-rank testing. Adjusted multivariate Cox proportional hazards models evaluated independent predictors of receiving treatment among eligible patients. RESULTS Among 5157 CHB patients (54.7% male, 34.6% African American, 22.3% Asian), 46.8% were treatment-eligible during the study period. CHB treatment rates were 48.4% overall and 37.3% among CHB patients without human immunodeficiency virus. Significantly lower odds of treatment were observed in females versus males (odds ratio: 0.40, 95% confidence interval: 0.33-0.49, P<0.001) and patients age 65 years or above versus age below 45 years (odds ratio: 0.68, 95% confidence interval: 0.51-0.92, P=0.012). Conversely, significantly greater odds of treatment were observed in African American and Asians versus non-Hispanic whites, CHB patients with indigent care versus commercially insured patients, and non-English speaking versus English speaking patients. CONCLUSION Among a large multicentered, safety-net cohort of CHB patients, 46.8% of treatment-eligible CHB patients overall and 37.3% of treatment-eligible CHB patients without human immunodeficiency virus received antiviral therapy. Improving CHB treatment rates among treatment-eligible patients represents "low hanging fruit," given the clear benefits of antiviral therapy in mitigating disease progression.
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17
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Zhou Y, Li J, Gordon SC, Trudeau S, Rupp LB, Boscarino JA, Daida YG, Schmidt MA, Lu M. Laboratory monitoring and antiviral treatment for chronic hepatitis B among routine care patients in the United States. J Viral Hepat 2022; 29:189-195. [PMID: 34905259 DOI: 10.1111/jvh.13639] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Revised: 11/22/2021] [Accepted: 11/30/2021] [Indexed: 12/09/2022]
Abstract
We investigated factors associated with rates of recommended monitoring of chronic hepatitis B (HBV) patients for viral DNA and alanine aminotransferase (ALT), and initiation of antiviral treatment among eligible patients, in a US cohort of patients under routine care. Patients were categorised by treatment indication: definite, equivocal or ineligible. Baseline covariates included demographics, clinical characteristics and specialist care status. 'Recommended monitoring' was defined ≥1 ALT or HBV DNA test per year. Logit models, univariate then multivariable, were used to evaluate factors associated with monitoring and treatment. Among 3,830 patients, treatment was received by 67.5% (788/1168 patients) in the 'definite' category, and 34.1% (208/610 patients) in the 'equivocal' category, of whom 109 moved up to 'definite' status at some point during follow-up. Sex, age and specialist care were independently associated with receipt of treatment in 'definite' patients. Routine monitoring rates were high prior to treatment in 'definite/ treated' patients (ALT: 77%; DNA: 85%) but declined afterwards (ALT 63%; DNA 36%). Rates of monitoring were lower in 'definite/ untreated' patients (ALT: 48%; DNA: 32%). Among 'equivocal/ treated' patients, lower age and comorbidity scores were associated with receipt of treatment; ALT monitoring rates were similar before and after treatment initiation (41% and 46%, respectively), while rates of DNA monitoring declined (55% and 29%). Monitoring among 'treatment ineligible' patients was similar to those in the 'equivocal' and untreated 'definite' groups. A large proportion of US HBV patients under routine care did not receive recommended annual laboratory monitoring, especially after initiation of antiviral treatment, and nearly one-third of patients with 'definite' indications for antiviral therapy remained untreated.
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Affiliation(s)
- Yueren Zhou
- Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan, USA
| | - Jia Li
- Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan, USA
| | - Stuart C Gordon
- Division of Gastroenterology and Hepatology, Henry Ford Health System, Detroit, Michigan, USA.,School of Medicine, Wayne State University, Detroit, Michigan, USA
| | - Sheri Trudeau
- Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan, USA
| | - Loralee B Rupp
- Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, Michigan, USA
| | - Joseph A Boscarino
- Department of Population Health Sciences, Geisinger Clinic, Danville, Pennsylvania, USA
| | - Yihe G Daida
- Center for Integrated Health Care Research, Kaiser Permanente-Hawai'i, Honolulu, Hawaii, USA
| | - Mark A Schmidt
- Center for Health Research, Kaiser Permanente-Northwest, Portland, Oregon, USA
| | - Mei Lu
- Department of Public Health Sciences, Henry Ford Health System, Detroit, Michigan, USA
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18
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Lu M, Li J, Zhou Y, Rupp LB, Moorman AC, Spradling PR, Teshale EH, Boscarino JA, Daida YG, Schmidt MA, Trudeau S, Gordon SC. Trends in Cirrhosis and Mortality by Age, Sex, Race, and Antiviral Treatment Status Among US Chronic Hepatitis B Patients (2006-2016). J Clin Gastroenterol 2022; 56:273-279. [PMID: 33780209 PMCID: PMC10257940 DOI: 10.1097/mcg.0000000000001522] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Accepted: 01/31/2021] [Indexed: 01/05/2023]
Abstract
BACKGROUND Changing US demographics and evolving chronic hepatitis B (CHB) treatments may affect longitudinal trends in CHB-related complications. We studied trends in the prevalence of cirrhosis (past or present) and incidence of all-cause mortality, stratified by patient age, sex, race, and antiviral treatment status, in a sample from US health care systems. METHODS Joinpoint and Poisson regression (univariate and multivariable) were used to estimate the annual percent change in each outcome from 2006 to 2016. RESULTS Among 5528 CHB patients, cirrhosis prevalence (including decompensated cirrhosis) rose from 6.7% in 2006 to 13.7% in 2016; overall mortality was unchanged. Overall rates of cirrhosis and mortality were higher among treated patients, but adjusted annual percent changes (aAPC) were significantly lower among treated than untreated patients (cirrhosis: aAPC +2.4% vs. +6.2%, mortality: aAPC -3.9% vs. +4.0%). Likewise, among treated patients, the aAPC for mortality declined -3.9% per year whereas among untreated patients, mortality increased +4.0% per year. CONCLUSIONS From 2006 to 2016, the prevalence of cirrhosis among CHB patients doubled. Notably, all-cause mortality increased among untreated patients but decreased among treated patients. These results suggest that antiviral treatment attenuates the progression of cirrhosis and the risk of death among patients with CHB.
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Affiliation(s)
- Mei Lu
- Department of Public Health Sciences
| | - Jia Li
- Department of Public Health Sciences
| | | | - Loralee B. Rupp
- Center for Health Policy and Health Services Research, Henry Ford Health System
| | - Anne C. Moorman
- Division of Viral Hepatitis, National Center for HIV, Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA
| | - Philip R. Spradling
- Division of Viral Hepatitis, National Center for HIV, Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA
| | - Eyasu H. Teshale
- Division of Viral Hepatitis, National Center for HIV, Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA
| | - Joseph A. Boscarino
- Department of Epidemiology and Health Research, Geisinger Clinic, Danville, PA
| | - Yihe G. Daida
- Center for Health Research, Kaiser Permanente—Hawaii, Honolulu, HI
| | - Mark A. Schmidt
- Center for Health Research, Kaiser Permanente—Northwest, Portland, OR
| | | | - Stuart C. Gordon
- Division of Gastroenterology and Hepatology, Henry Ford Health System and Wayne State University School of Medicine, Detroit, MI
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He T, Chen T, Liu X, Zhang B, Yue S, Cao J, Zhang G. A Web-Based Prediction Model for Cancer-Specific Survival of Elderly Patients With Early Hepatocellular Carcinoma: A Study Based on SEER Database. Front Public Health 2022; 9:789026. [PMID: 35096742 PMCID: PMC8792840 DOI: 10.3389/fpubh.2021.789026] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Accepted: 12/14/2021] [Indexed: 12/29/2022] Open
Abstract
Background: Primary liver cancer is a common malignant tumor primarily represented by hepatocellular carcinoma (HCC). The number of elderly patients with early HCC is increasing, and older age is related to a worse prognosis. However, an accurate predictive model for the prognosis of these patients is still lacking. Methods: Data of eligible elderly patients with early HCC in Surveillance, Epidemiology, and End Results database from 2010 to 2016 were downloaded. Patients from 2010 to 2015 were randomly assigned to the training cohort (n = 1093) and validation cohort (n = 461). Patients' data in 2016 (n = 431) was used for external validation. Independent prognostic factors were obtained using univariate and multivariate analyses. Based on these factors, a cancer-specific survival (CSS) nomogram was constructed. The predictive performance and clinical practicability of our nomogram were validated. According to the risk scores of our nomogram, patients were divided into low-, intermediate-, and high-risk groups. A survival analysis was performed using Kaplan–Meier curves and log-rank tests. Results: Age, race, T stage, histological grade, surgery, radiotherapy, and chemotherapy were independent predictors for CSS and thus were included in our nomogram. In the training cohort and validation cohort, the concordance indices (C-indices) of our nomogram were 0.739 (95% CI: 0.714–0.764) and 0.756 (95% CI: 0.719–0.793), respectively. The 1-, 3-, and 5-year areas under receiver operating characteristic curves (AUCs) showed similar results. Calibration curves revealed high consistency between observations and predictions. In external validation cohort, C-index (0.802, 95%CI: 0.778–0.826) and calibration curves also revealed high consistency between observations and predictions. Compared with the TNM stage, nomogram-related decision curve analysis (DCA) curves indicated better clinical practicability. Kaplan–Meier curves revealed that CSS significantly differed among the three different risk groups. In addition, an online prediction tool for CSS was developed. Conclusions: A web-based prediction model for CSS of elderly patients with early HCC was constructed and validated, and it may be helpful for the prognostic evaluation, therapeutic strategy selection, and follow-up management of these patients.
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Affiliation(s)
- Taiyu He
- Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing, China
- Institute for Viral Hepatitis, Chongqing Medical University, Chongqing, China
- Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Tianyao Chen
- College of Medical Informatics, Chongqing Medical University, Chongqing, China
| | - Xiaozhu Liu
- Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Biqiong Zhang
- Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing, China
- Institute for Viral Hepatitis, Chongqing Medical University, Chongqing, China
- Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Song Yue
- Department of Gynecology and Obstetrics, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Junyi Cao
- Department of Record Room, Zigong First People's Hospital, Zigong, China
| | - Gaoli Zhang
- Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing, China
- Institute for Viral Hepatitis, Chongqing Medical University, Chongqing, China
- Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
- *Correspondence: Gaoli Zhang
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Liu Z, Zhang Y, Xu M, Li X, Zhang Z. Distribution of hepatitis B virus genotypes and subgenotypes: A meta-analysis. Medicine (Baltimore) 2021; 100:e27941. [PMID: 34918643 PMCID: PMC8678021 DOI: 10.1097/md.0000000000027941] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2019] [Revised: 11/19/2020] [Accepted: 11/04/2021] [Indexed: 02/07/2023] Open
Abstract
Hepatitis B virus (HBV) genotypes and subgenotypes have distinct geographical distributions and influence a number of clinical disease features and responses to treatment. There are many reports on the distribution of HBV genotypes, but great differences are present between studies. What's more, a meta-analysis of HBV genotype- and subgenotype-distribution by country is lacking.A comprehensive literature search was performed in PubMed and a systematic search of full-length HBV sequences and S gene sequences was conducted in the GenBank database. HBV genotypes were checked and subgenotypes were determined by phylogenetic comparison of full-length HBV sequences or S gene sequences. STATA 12.0 was used for the analysis for countries with multiple datasets. BEAST 2.5.2 was used for Bayesian phylogenetic analysis to infer the evolutionary time scales of HBV.This study includes 309 datasets from 110 countries, including 188 relevant studies, 58 full-length gene datasets, and 63 S gene datasets. The meta-analysis was performed on 274 datasets from 75 countries. The distribution of genotypes is more detailed than those described by previous studies. While the overall genotype distribution is similar to that reported in previous studies, some notable aspects were different. The main genotypes present in south-eastern Africa, North Africa, and West Africa are genotypes A, D, and E, respectively. Genotypes G and H are mainly distributed in Mexico. Genotype F is mainly distributed in central and South America, but genotypes A and D are also common in Brazil, Cuba, and Haiti.This study provides a more accurate description of the distribution of HBV genotypes and subgenotypes in different countries and suggests that the differences in genotype distribution may be related to ethnicity and human migration.
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21
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Ezzat R, Eltabbakh M, El Kassas M. Unique situation of hepatocellular carcinoma in Egypt: A review of epidemiology and control measures. World J Gastrointest Oncol 2021; 13:1919-1938. [PMID: 35070033 PMCID: PMC8713321 DOI: 10.4251/wjgo.v13.i12.1919] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 04/17/2021] [Accepted: 10/18/2021] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the sixth most common primary malignancy worldwide, and the third most common cause of death among cancers worldwide. HCC occurs in several pre-existing conditions, including hepatitis C, hepatitis B virus, and non-alcoholic cirrhosis. Egypt used to be the country with the heaviest hepatitis C virus (HCV) burden. The relationship between HCV and HCC is an important research area. In Egypt, HCC is a significant public health problem. A possible cause for the increasing rates of detection of HCC in Egypt is the mass screening program that was carried by the government for detecting and treating HCV. A multidisciplinary approach is now widely applied to HCC management in health centers all over Egypt. Different treatment modalities are available in Egypt, with success rates comparable to global rates. The Egyptian health authorities have made the elimination of HCV from Egypt a special priority, and this approach should lead to a decrease in number of HCC cases in the near future. In this article we review the current situation of HCC in Egypt, including epidemiological aspects, relevant risk factors for HCC development, strategies, and efforts established by health authorities for the screening and prevention of both HCV and HCC in Egypt. We highlight the different modalities for HCC treatment.
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Affiliation(s)
- Reem Ezzat
- Internal Medicine Department, Faculty of Medicine, Assiut University, Assiut 71515, Egypt
| | - Mohamed Eltabbakh
- Tropical Medicine Department, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt
| | - Mohamed El Kassas
- Endemic Medicine Department, Faculty of Medicine, Helwan University, Cairo 11795, Cairo, Egypt
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Wong RJ, Cheung RC. Real-World Safety and Effectiveness of Oral Nucleos(t)ide Analogs in the Treatment of Chronic Hepatitis B Virus Infection. CURRENT HEPATOLOGY REPORTS 2021; 20:144-150. [DOI: 10.1007/s11901-021-00571-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 06/01/2021] [Indexed: 01/03/2025]
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23
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Liu H, Cheng J, Viswanathan U, Chang J, Lu F, Guo JT. Amino acid residues at core protein dimer-dimer interface modulate multiple steps of hepatitis B virus replication and HBeAg biogenesis. PLoS Pathog 2021; 17:e1010057. [PMID: 34752483 PMCID: PMC8604296 DOI: 10.1371/journal.ppat.1010057] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 11/19/2021] [Accepted: 10/22/2021] [Indexed: 12/19/2022] Open
Abstract
The core protein (Cp) of hepatitis B virus (HBV) assembles pregenomic RNA (pgRNA) and viral DNA polymerase to form nucleocapsids where the reverse transcriptional viral DNA replication takes place. Core protein allosteric modulators (CpAMs) inhibit HBV replication by binding to a hydrophobic "HAP" pocket at Cp dimer-dimer interfaces to misdirect the assembly of Cp dimers into aberrant or morphologically "normal" capsids devoid of pgRNA. We report herein that a panel of CpAM-resistant Cp with single amino acid substitution of residues at the dimer-dimer interface not only disrupted pgRNA packaging, but also compromised nucleocapsid envelopment, virion infectivity and covalently closed circular (ccc) DNA biosynthesis. Interestingly, these mutations also significantly reduced the secretion of HBeAg. Biochemical analysis revealed that the CpAM-resistant mutations in the context of precore protein (p25) did not affect the levels of p22 produced by signal peptidase removal of N-terminal 19 amino acid residues, but significantly reduced p17, which is produced by furin cleavage of C-terminal arginine-rich domain of p22 and secreted as HBeAg. Interestingly, p22 existed as both unphosphorylated and phosphorylated forms. While the unphosphorylated p22 is in the membranous secretary organelles and the precursor of HBeAg, p22 in the cytosol and nuclei is hyperphosphorylated at the C-terminal arginine-rich domain and interacts with Cp to disrupt capsid assembly and viral DNA replication. The results thus indicate that in addition to nucleocapsid assembly, interaction of Cp at dimer-dimer interface also plays important roles in the production and infectivity of progeny virions through modulation of nucleocapsid envelopment and uncoating. Similar interaction at reduced p17 dimer-dimer interface appears to be important for its metabolic stability and sensitivity to CpAM suppression of HBeAg secretion.
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Affiliation(s)
- Hui Liu
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
- Baruch S. Blumberg Institute, Doylestown, Pennsylvania, United States of America
| | - Junjun Cheng
- Baruch S. Blumberg Institute, Doylestown, Pennsylvania, United States of America
| | - Usha Viswanathan
- Baruch S. Blumberg Institute, Doylestown, Pennsylvania, United States of America
| | - Jinhong Chang
- Baruch S. Blumberg Institute, Doylestown, Pennsylvania, United States of America
| | - Fengmin Lu
- Department of Microbiology & Infectious Disease Center, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
- * E-mail: (FL); (J-TG)
| | - Ju-Tao Guo
- Baruch S. Blumberg Institute, Doylestown, Pennsylvania, United States of America
- * E-mail: (FL); (J-TG)
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Abstract
Chronic hepatitis B virus (HBV) infection is the leading cause of liver cirrhosis and hepatocellular carcinoma, estimated to be globally responsible for ∼800,000 deaths annually. Although effective vaccines are available to prevent new HBV infection, treatment of existing chronic hepatitis B (CHB) is limited, as the current standard-of-care antiviral drugs can only suppress viral replication without achieving cure. In 2016, the World Health Organization called for the elimination of viral hepatitis as a global public health threat by 2030. The United States and other nations are working to meet this ambitious goal by developing strategies to cure CHB, as well as prevent HBV transmission. This review considers recent research progress in understanding HBV pathobiology and development of therapeutics for the cure of CHB, which is necessary for elimination of hepatitis B by 2030.
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Affiliation(s)
- Timothy M Block
- Baruch S. Blumberg Institute, Doylestown, Pennsylvania 18902, USA;
| | - Kyong-Mi Chang
- The Corporal Michael J. Crescenz VA Medical Center and University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania 19104, USA
| | - Ju-Tao Guo
- Baruch S. Blumberg Institute, Doylestown, Pennsylvania 18902, USA;
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Antiviral Therapy Reduces Risk of Cirrhosis in Noncirrhotic HBV Patients Among 4 Urban Safety-Net Health Systems. Am J Gastroenterol 2021; 116:1465-1475. [PMID: 33661148 DOI: 10.14309/ajg.0000000000001195] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Accepted: 01/22/2021] [Indexed: 12/11/2022]
Abstract
INTRODUCTION To evaluate the impact of chronic hepatitis B virus infection (CHB) treatment on risk of cirrhosis, liver-related outcomes, and death among a diverse CHB cohort with a large proportion of African Americans. METHODS Adults with noncirrhotic CHB without human immunodeficiency virus from 2010 to 2018 were retrospectively evaluated across 4 US safety-net health systems. CHB was identified with International Classification of Diseases, Ninth Revision/Tenth Revision diagnosis coding and confirmatory laboratory data. Propensity-score matching, Kaplan-Meier methods, and adjusted Cox proportional hazards models were used to evaluate impact of CHB treatment on risk of cirrhosis, hepatocellular carcinoma (HCC), death, and composite of cirrhosis, HCC, or death. RESULTS Among 4,064 CHB patients (51.9% female, 42.0% age <45 years, 31.6% African American, 26.6% Asian, 26.7% Hispanic), 23.2% received CHB antiviral therapy and 76.8% did not. Among the propensity score-matched cohort (428 treated and 428 untreated), CHB treatment was associated with lower risk of cirrhosis (hazards ratio 0.65, 95% confidence interval 0.46-0.92, P = 0.015) and composite of cirrhosis, HCC, or death (hazards ratio 0.67, 95% confidence interval 0.49-0.94, P = 0.023). Females vs males and African Americans vs non-Hispanic whites had significantly lower risk of cirrhosis. When treatment effects were stratified by age, sex, and ethnicity, the benefits of antiviral therapies in reducing risk of cirrhosis were seen primarily in CHB patients who were females, age <45 years, and of Asian ethnicity. DISCUSSION Our propensity score-matched cohort of noncirrhotic CHB patients demonstrated significant reductions in risk of cirrhosis due to CHB treatment.
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Ma X, Liu S, Wang M, Wang Y, Du S, Xin Y, Xuan S. Tenofovir Alafenamide Fumarate, Tenofovir Disoproxil Fumarate and Entecavir: Which is the Most Effective Drug for Chronic Hepatitis B? A Systematic Review and Meta-analysis. J Clin Transl Hepatol 2021; 9:335-344. [PMID: 34221919 PMCID: PMC8237148 DOI: 10.14218/jcth.2020.00164] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 01/23/2021] [Accepted: 03/09/2021] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND AND AIMS The therapeutic effect of tenofovir alafenamide fumarate (TAF), tenofovir disoproxil fumarate (TDF) and entecavir (ETV) on chronic hepatitis B (CHB) patients remains inconsistent. The aim of this study was to explore the differences in virological responses to TAF, TDF and ETV in patients with CHB. METHODS Literature searches were conducted of the PubMed, EMBASE, and the Cochrane Library databases to identify randomized controlled trials and observational studies published up to July 21, 2020. Statistical comparisons of virological response between TDF, ETV, and TAF were carried out with pooled odds ratio (OR) values. RESULTS The virological response in TDF-treated CHB patients was notably superior to that of the ETV-treated CHB patients after 12-weeks [OR=1.12, 95% confidence interval (CI): 0.89-1.41], 24-weeks (OR=1.33, 95% CI: 1.11-1.61), 48-weeks (OR=1.62, 95% CI: 1.16-2.25), 72-weeks (OR=1.43, 95% CI: 0.78-2.62), and 96-weeks (OR=1.56, 95% CI: 0.87-2.81) treatment. No significant difference was observed for the virological responses in CHB patients after 48-weeks treatment with TAF or TDF. The virological response in TDF+ETV-treated CHB patients was superior to that of TDF-treated CHB patients after 24-weeks, 48-weeks (OR=1.54, 95% CI: 1.17-2.02), 96-weeks, and 144-weeks. CONCLUSIONS The virological response in TDF-treated CHB patients was superior to that in ETV-treated CHB patients, but there was no significant difference between TAF and TDF. In addition, the therapeutic effect of TDF+ETV was superior to TDF alone.
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Affiliation(s)
- Xuefeng Ma
- Department of Infectious Disease, Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong, China
| | - Shousheng Liu
- Clinical Research Center, Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong, China
- Digestive Disease Key Laboratory of Qingdao, Qingdao, Shandong, China
| | - Mengke Wang
- Department of Infectious Disease, Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong, China
| | - Yifen Wang
- Department of Infectious Disease, Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong, China
| | - Shuixian Du
- Department of Infectious Disease, Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong, China
| | - Yongning Xin
- Department of Infectious Disease, Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong, China
- Digestive Disease Key Laboratory of Qingdao, Qingdao, Shandong, China
- Correspondence to: Yongning Xin, Department of Infectious Disease, Qingdao Municipal Hospital, 1 Jiaozhou Road, Qingdao, Shandong 266011, China. ORCID: https://orcid.org/0000-0002-3692-7655. Tel: +86-532-8278-9463, Fax: +86-532-8596-8434, E-mail: ; Shiying Xuan, Department of Infectious Disease, Qingdao Municipal Hospital, 1 Jiaozhou Road, Qingdao, Shandong 266011, China. ORCID: https://orcid.org/0000-0002-9849-1877. Tel: +86-532-8890-5508, Fax: +86-532-8890-5293, E-mail:
| | - Shiying Xuan
- Department of Infectious Disease, Qingdao Municipal Hospital, Qingdao University, Qingdao, Shandong, China
- Digestive Disease Key Laboratory of Qingdao, Qingdao, Shandong, China
- Correspondence to: Yongning Xin, Department of Infectious Disease, Qingdao Municipal Hospital, 1 Jiaozhou Road, Qingdao, Shandong 266011, China. ORCID: https://orcid.org/0000-0002-3692-7655. Tel: +86-532-8278-9463, Fax: +86-532-8596-8434, E-mail: ; Shiying Xuan, Department of Infectious Disease, Qingdao Municipal Hospital, 1 Jiaozhou Road, Qingdao, Shandong 266011, China. ORCID: https://orcid.org/0000-0002-9849-1877. Tel: +86-532-8890-5508, Fax: +86-532-8890-5293, E-mail:
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Lok AS, Perrillo R, Lalama CM, Fried MW, Belle SH, Ghany MG, Khalili M, Fontana RJ, Sterling RK, Terrault N, Feld JJ, Di Bisceglie AM, Lau DT, Hassan M, Janssen HL, Roberts LR, Lisker‐Melman M, Wong DK, Juan J, Yim C, Patel K, Lee WM, Murakami CS, Do S, Han SB, Tran TT, Cooper SL, Tsai N, Younoszai B, Muir A, Evon D, Darling JM, Carithers RC, Kowdley KV, Wang CC, Luketic VA, Jake Liang T, Hoofnagle JH, Doo E, Chang K, Park J, Wahed A, King WC, Kleiner D. Low Incidence of Adverse Outcomes in Adults With Chronic Hepatitis B Virus Infection in the Era of Antiviral Therapy. Hepatology 2021; 73:2124-2140. [PMID: 32936969 PMCID: PMC8546406 DOI: 10.1002/hep.31554] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Revised: 07/28/2020] [Accepted: 08/19/2020] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND AIMS Outcomes of persons with chronic hepatitis B virus (HBV) infection in the era of antiviral therapy (AVT) are not well characterized. We determined the incidence and factors associated with clinical outcomes in a multiethnic, North American cohort of adults with chronic HBV infection, who were not on AVT at enrollment. APPROACH AND RESULTS Adults with chronic HBV infection, not receiving AVT, and without a history of decompensation, HCC, or liver transplantation (LT), were prospectively followed. Participants with known human immunodeficiency virus (HIV), hepatitis C virus, or hepatitis D virus (HDV) coinfection were excluded. During follow-up, treatment could be initiated per standard of care. Clinical outcomes included: incident cirrhosis, decompensation, HCC, OLT, and HBV-related death. Among 1,418 participants analyzed, 51.5% were women, median age was 41.1 years, 75% were Asian, 10% White, 13% Black, 24% HBeAg(+), and 1.5% cirrhosis at baseline. During the study, 274 started treatment, 83 had an alanine aminotransferase flare, 118 of 330 initially HBeAg(+) became HBeAg(-), and 90 of 1,329 became HBsAg(-). After 6,641 person-years follow-up, 8 participants (4 of 21 with baseline cirrhosis) had 12 clinical outcomes (2 decompensation, 5 HCC, 2 OLT, and 3 HBV-related deaths) and 19 of 1,397 had incident cirrhosis. Twenty-one of 26 participants had first outcome before treatment, none had become HBsAg(-), whereas 5/9 HBeAg(+) had become HBeAg(-) at time of first outcome. Cumulative percentage of clinical outcomes was 16% at year 4 in participants with baseline cirrhosis and 2% (including incident cirrhosis) at year 7 in those without. CONCLUSIONS Incidence of adverse outcomes was low in this closely monitored, large cohort of North American adults with predominantly inactive, chronic HBV without cirrhosis. Our data highlight the benefits of HBsAg loss and the importance of early diagnosis and treatment to prevent cirrhosis and other complications of chronic HBV infection.
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Affiliation(s)
- Anna S. Lok
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA
| | - Robert Perrillo
- Hepatology Division, Baylor Scott and White Medical Center, Dallas, TX
| | | | - Michael W. Fried
- UNC Liver Center, University of North Carolina at Chapel Hill, Chapel Hill, NC
| | - Steven H. Belle
- Epidemiology and Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA
| | | | - Mandana Khalili
- Department of Medicine, Division of Gastroenterology and Hepatology, University of California San Francisco, San Francisco, CA
| | - Robert J. Fontana
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA
| | - Richard K. Sterling
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University, Richmond, VA
| | - Norah Terrault
- Division of Gastrointestinal and Liver Diseases, Keck Medicine of University of Southern California, Los Angeles, CA
| | - Jordan J. Feld
- Toronto Centre for Liver Disease, University Health Network, University of Toronto, Toronto, ON, Canada
| | - Adrian M. Di Bisceglie
- Department of Internal Medicine, Saint Louis University School of Medicine, St. Louis, MO
| | - Daryl T.Y. Lau
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA
| | - Mohamed Hassan
- Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota, Minneapolois, MN
| | - Harry L.A. Janssen
- Toronto Centre for Liver Disease, University of Toronto, Toronto, ON, Canada
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McGlynn KA, Petrick JL, El-Serag HB. Epidemiology of Hepatocellular Carcinoma. Hepatology 2021; 73 Suppl 1:4-13. [PMID: 32319693 PMCID: PMC7577946 DOI: 10.1002/hep.31288] [Citation(s) in RCA: 1277] [Impact Index Per Article: 319.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2020] [Revised: 03/22/2020] [Accepted: 04/10/2020] [Indexed: 02/06/2023]
Abstract
Liver cancer is a major contributor to the worldwide cancer burden. Incidence rates of this disease have increased in many countries in recent decades. As the principal histologic type of liver cancer, hepatocellular carcinoma (HCC) accounts for the great majority of liver cancer diagnoses and deaths. Hepatitis B virus (HBV) and hepatitis C virus (HCV) remain, at present, the most important global risk factors for HCC, but their importance will likely decline in the coming years. The effect of HBV vaccination of newborns, already seen in young adults in some countries, will be more notable as vaccinated cohorts age. In addition, effective treatments for chronic infections with both HBV and HCV should contribute to declines in the rates of viral-associated HCC. Unfortunately, the prevalence of metabolic risk factors for HCC, including metabolic syndrome, obesity, type II diabetes and non-alcoholic fatty liver disease (NAFLD) are increasing and may jointly become the major cause of HCC globally. Excessive alcohol consumption also remains an intractable risk factor, as does aflatoxin contamination of food crops in some parts of the world. While significant efforts in early diagnosis and better treatment are certainly needed for HCC, primary prevention efforts aimed at decreasing the prevalence of obesity and diabetes and controlling mycotoxin growth, are just as urgently required.
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Affiliation(s)
- Katherine A McGlynn
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD
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Chou R, Blazina I, Bougatsos C, Holmes R, Selph S, Grusing S, Jou J. Screening for Hepatitis B Virus Infection in Nonpregnant Adolescents and Adults: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA 2020; 324:2423-2436. [PMID: 33320229 DOI: 10.1001/jama.2020.19750] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Importance A 2014 review for the US Preventive Services Task Force (USPSTF) found antiviral therapy for hepatitis B virus (HBV) infection associated with improved intermediate outcomes, although evidence on clinical outcomes was limited. Objective To update the 2014 HBV screening review in nonpregnant adolescents and adults to inform the USPSTF. Data Sources Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Ovid MEDLINE (2014 to August 2019); with surveillance through July 24, 2020. Study Selection Randomized clinical trials (RCTs) on screening and antiviral therapy; cohort studies on screening, antiviral therapy clinical outcomes, and the association between achieving intermediate outcomes after antiviral therapy and clinical outcomes. Data Extraction and Synthesis One investigator abstracted data; a second investigator checked accuracy. Two investigators independently assessed study quality. Random-effects profile likelihood meta-analysis was performed. Results Thirty trials and 20 cohort studies, with a total of 94 168 participants, were included. No study directly evaluated the effects of screening for HBV infection vs no screening on clinical outcomes such as mortality, hepatocellular carcinoma, or cirrhosis. Screening strategies that focused on risk factors such as ever having immigrated from high-prevalence countries and demographic and behavioral risk factors would identify nearly all HBV infection cases. In 1 study (n = 21 008), only screening immigrants from high-prevalence countries would miss approximately two-thirds of infected persons. Based on 18 trials (n = 2972), antiviral therapy compared with placebo or no treatment was associated with greater likelihood of achieving intermediate outcomes, such as virologic suppression and hepatitis B e-antigen (HBeAg) or hepatitis B surface antigen loss or seroconversion; the numbers needed to treat ranged from 2.6 for virologic suppression to 17 for HBeAg seroconversion. Based on 12 trials (n = 4127), first-line antiviral therapies were at least as likely as nonpreferred therapies to achieve intermediate outcomes. Based on 16 trials (n = 4809), antiviral therapy might be associated with improved clinical outcomes, but data were sparse and imprecise. Nine cohort studies (n = 3893) indicated an association between achieving an intermediate outcome following antiviral therapy and improved clinical outcomes but were heterogeneous (hazard ratios ranged from 0.07 to 0.87). Antiviral therapy was associated with higher risk of withdrawal due to adverse events vs placebo or no antiviral therapy. Conclusions and Relevance There was no direct evidence for the clinical benefits and harms of HBV screening vs no screening. Antiviral therapy for HBV infection was associated with improved intermediate outcomes and may improve clinical outcomes.
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Affiliation(s)
- Roger Chou
- Pacific Northwest Evidence-based Practice Center, Department of Medical Informatics and Clinical Epidemiology; Oregon Health & Science University, Portland
- Division of General Internal Medicine and Geriatrics; Oregon Health & Science University, Portland
| | - Ian Blazina
- Pacific Northwest Evidence-based Practice Center, Department of Medical Informatics and Clinical Epidemiology; Oregon Health & Science University, Portland
| | - Christina Bougatsos
- Pacific Northwest Evidence-based Practice Center, Department of Medical Informatics and Clinical Epidemiology; Oregon Health & Science University, Portland
| | - Rebecca Holmes
- Pacific Northwest Evidence-based Practice Center, Department of Medical Informatics and Clinical Epidemiology; Oregon Health & Science University, Portland
| | - Shelley Selph
- Pacific Northwest Evidence-based Practice Center, Department of Medical Informatics and Clinical Epidemiology; Oregon Health & Science University, Portland
- Department of Family Medicine, Oregon Health & Science University, Portland
| | - Sara Grusing
- Pacific Northwest Evidence-based Practice Center, Department of Medical Informatics and Clinical Epidemiology; Oregon Health & Science University, Portland
| | - Janice Jou
- Pacific Northwest Evidence-based Practice Center, Department of Medical Informatics and Clinical Epidemiology; Oregon Health & Science University, Portland
- Division of Gastroenterology and Hepatology; Oregon Health & Science University, Portland
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Chen K, Chang C, Lee J, Yang C. Tenofovir disoproxil fumarate for patients with chronic hepatitis B who suboptimal response to non‐tenofovir disoproxil fumarate nucleos(t)ide analogs therapy. ADVANCES IN DIGESTIVE MEDICINE 2020. [DOI: 10.1002/aid2.13171] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- Kwei‐Ming Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine Show Chwan Memorial Hospital Changhua Taiwan
| | - Chi‐Hsien Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine Show Chwan Memorial Hospital Changhua Taiwan
| | - Jyong‐Hong Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine Show Chwan Memorial Hospital Changhua Taiwan
| | - Chi‐Chieh Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine Show Chwan Memorial Hospital Changhua Taiwan
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Yang SS, Cai CW, Ma XQ, Xu J, Yu CB. Efficacy and cost-effectiveness of antiviral regimens for entecavir-resistant hepatitis B: A systematic review and network meta-analysis. Hepatobiliary Pancreat Dis Int 2020; 19:507-514. [PMID: 33051132 DOI: 10.1016/j.hbpd.2020.09.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2020] [Accepted: 09/15/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND Chronic hepatitis B (CHB) patients who had exposed to lamivudine (LAM) and telbivudine (LdT) had high risk of developing entecavir (ETV)-resistance after long-term treatment. We aimed to conduct a systematic review and a network meta-analysis on the efficacy and cost-effectiveness on antiviral regimens in CHB patients with ETV-resistance. DATA SOURCES We searched PubMed, EMBASE and Web of Science for studies on nucleos(t)ide analogues (NAs) treatment [including tenofovir disoproxil fumarate (TDF)-based rescue therapies, adefovir (ADV)-based rescue therapies and double-dose ETV therapy] in CHB patients with ETV-resistance. The network meta-analysis was conducted for 1-year complete virological response (CVR) and biological response (BR) rates using GeMTC and ADDIS. A cost-effective analysis was conducted to select an economic and effective treatment regimen based on the 1-year CVR rate. RESULTS A total of 6 studies were finally included in this analysis. The antiviral efficacy was estimated. On network meta-analysis, the 1-year CVR rate in ETV-TDF [odds ratio (OR) = 22.30; 95 % confidence interval (CI): 2.78-241.93], LAM-TDF (OR = 70.67; 95 % CI: 5.16-1307.45) and TDF (OR = 16.90; 95 % CI: 2.28-186.30) groups were significantly higher than that in the ETV double-dose group; the 1-year CVR rate in the LAM-TDF group (OR = 14.82; 95 % CI: 1.03-220.31) was significantly higher than that in the LAM/LdT-ADV group. The 1-year BR rate of ETV-TDF (OR = 28.68; 95 % CI: 1.70-1505.08) and TDF (OR = 21.79; 95 % CI: 1.43-1070.09) therapies were significantly higher than that of ETV double-dose therapy. TDF-based therapies had the highest possibility to achieve the CVR and BR at 1 year, in which LAM-TDF combined therapy was the most effective regimen. The ratio of cost/effectiveness for 1-year treatment was 8 526, 17 649, 20 651 Yuan in the TDF group, TDF-ETV group, and ETV-ADV group, respectively. CONCLUSIONS TDF-based combined therapies such as ETV-TDF and LAM-TDF therapies were the first-line treatment if financial condition is allowed.
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Affiliation(s)
- Si-Si Yang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Cheng-Wei Cai
- Department of Neurosurgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Xue-Qing Ma
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Jia Xu
- Kidney Disease Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
| | - Cheng-Bo Yu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
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Sano T, Amano K, Ide T, Kawaguchi T, Kuwahara R, Arinaga-Hino T, Koga H, Kuromatsu R, Torimura T. Short-term efficacy after switching from adefovir dipivoxil and tenofovir disoproxil fumarate therapy to tenofovir alaferamide for chronic hepatitis B. Biomed Rep 2020; 14:12. [PMID: 33235727 PMCID: PMC7678628 DOI: 10.3892/br.2020.1388] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Accepted: 10/29/2020] [Indexed: 12/17/2022] Open
Abstract
The aim of the present study was to evaluate the effects of switching to tenofovir alafenamide (TAF) in patients who had received a nucleos(t)ide analog (NA) for the treatment of chronic hepatitis B (CHB). The data from 33 Japanese patients with CHB who received TAF therapy after using NA [adefovir dipivoxil (ADV) and/or tenofovir disoproxil fumarate (TDF)] were retrospectively analyzed. Specifically, the biochemical and virological markers from the start of the TAF treatment to 6 months later were assessed. Comparative evaluation was performed by dividing patients into two groups: Long-term (n=19) and short-term administration groups (n=14), with a cutoff administration duration of 10 years. In all 33 patients, the levels of serum hepatitis B surface antigen (HBsAg; 1,126±1,724 to 1,001±1,591 IU/ml; P<0.0001), serum alkaline phosphatase (ALP) (320±126 to 283±124 U/l; P=0.028), serum bone specific alkaline phosphatase (19.7±9.0 to 17.7±8.0 µg/l; P=0.0006) and urine β2-microglobulin-creatinine ratio (U-BMG/Cr; 5,224±17,471 to 3,547±14,652 µg/g·Cre; P=0.002) significantly decreased from baseline after 6 months. Serum HBsAg, serum ALP and U-BMG/Cr showed a significant reduction in both groups. In conclusion, switching from ADV or TDF to TAF resulted in a decrease in serum HBsAg and improvement in serum ALP and U-BMG/Cr after 6 months of treatment in patients regardless of history of treatment with NA.
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Affiliation(s)
- Tomoya Sano
- Division of Gastroenterology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan
| | - Keisuke Amano
- Division of Gastroenterology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan
| | - Tatsuya Ide
- Division of Gastroenterology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan
| | - Toshihiro Kawaguchi
- Division of Gastroenterology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan
| | - Reiichiro Kuwahara
- Division of Gastroenterology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan
| | - Teruko Arinaga-Hino
- Division of Gastroenterology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan
| | - Hironori Koga
- Division of Gastroenterology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.,Division of Liver Cancer Research, Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan
| | - Ryoko Kuromatsu
- Division of Gastroenterology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan
| | - Takuji Torimura
- Division of Gastroenterology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan.,Division of Liver Cancer Research, Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, Kurume, Fukuoka 830-0011, Japan
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Woo HY, Park JY, Bae SH, Kim CW, Jang JY, Tak WY, Kim DJ, Kim IH, Heo J, Ahn SH. Entecavir+tenofovir vs. lamivudine/telbivudine+adefovir in chronic hepatitis B patients with prior suboptimal response. Clin Mol Hepatol 2020; 26:352-363. [PMID: 32460460 PMCID: PMC7364362 DOI: 10.3350/cmh.2019.0044n] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Revised: 04/06/2020] [Accepted: 04/07/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND/AIMS Suboptimal responses to lamivudine or telbivudine plus adefovir (LAM/LdT+ADV) rescue therapy are common in patients with LAM-resistant hepatitis B virus (HBV) infections. We compared patients switched to entecavir plus tenofovir (ETV+TDF) to those maintained on LAM/LdT+ADV. METHODS This prospective randomized controlled trial examined 91 patients whose serum HBV DNA levels were greater than 60 IU/mL after at least 24 weeks of treatment with LAM/LdT+ADV for LAM-resistant HBV. Patients were randomized to receive a new treatment (ETV+TDF, n=45) or maintained on the same treatment (LAM/LdT+ADV, n=46) for 48 weeks. Patients with baseline ADV resistance were excluded. RESULTS Compared to LAM/LdT+ADV group, ETV+TDF group had more patients with a virologic response (42/45 [93.33%] vs. 3/46 [6.52%], P<0.001) and had a greater mean reduction in serum HBV DNA level from baseline (-4.16 vs. -0.37 log10 IU/mL, P<0.001). Multivariate analysis indicated that high baseline HBV DNA level (P=0.005) and LAM/LdT+ADV maintenance therapy (P=0.001) were negatively associated with virologic response. At week 48, additional ADV- or ETV-associated mutations were cleared in ETV+TDF group, but such mutations were present in 4.3% of patients in LAM/LdT+ADV group (P=0.106). The two groups had similar rates of adverse events. CONCLUSION ETV+TDF combination treatment led to a significantly higher rate of virologic response compared to LAM/LdT+ADV combination treatment in patients with LAM-resistant HBV who had suboptimal responses to LAM/LdT+ADV regardless of HBV genotypic resistance profile (NCT01597934).
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Affiliation(s)
- Hyun Young Woo
- Department of Internal Medicine, College of Medicine, Pusan National University, Busan, Korea
- Medical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Si Hyun Bae
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Chang Wook Kim
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jae Young Jang
- Department of Internal Medicine, Institute for Digestive Research, Digestive Disease Center, Soonchunhyang University College of Medicine, Seoul, Korea
| | - Won Young Tak
- Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Korea
| | - Dong Joon Kim
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon, Korea
| | - In Hee Kim
- Department of Internal Medicine, Chonbuk National University Hospital, Chonbuk National University College of Medicine, Chonju, Korea
| | - Jeong Heo
- Department of Internal Medicine, College of Medicine, Pusan National University, Busan, Korea
- Medical Research Institute, Pusan National University Hospital, Busan, Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
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Ogawa E, Nomura H, Nakamuta M, Furusyo N, Koyanagi T, Dohmen K, Ooho A, Satoh T, Kawano A, Kajiwara E, Takahashi K, Azuma K, Kato M, Shimoda S, Hayashi J. Tenofovir alafenamide after switching from entecavir or nucleos(t)ide combination therapy for patients with chronic hepatitis B. Liver Int 2020; 40:1578-1589. [PMID: 32304611 DOI: 10.1111/liv.14482] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2019] [Revised: 03/14/2020] [Accepted: 04/13/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Tenofovir alafenamide (TAF) has been newly approved for the treatment of chronic hepatitis B (CHB). We aimed to assess the effectiveness and renal safety of switching from entecavir (ETV) or nucleos(t)ide analogue (NA) combination therapy to TAF. METHODS This multicentre, retrospective, cohort study included 313 consecutive CHB patients who switched to TAF monotherapy after treatment with ETV or a nucleos(t)ide analogue (NA) combination for over 2 years. Virological/laboratory responses were evaluated for 48 weeks after switchover. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 . Differences in longitudinal parameters were compared by the generalized estimating equation method. RESULTS In the prior ETV group (n = 191), the HBV DNA suppression rate at week 48 was significantly increased, from 75.9% to 96.9% (P < .001). Additionally, mean changes in the HBsAg level at week 48 in HBsAg ≥ 3.0 logIU/mL and < 3.0 logIU/mL groups were -0.09 and -0.13 logIU/mL respectively. In the prior NA combination group (n = 122), the mean changes in HBsAg level at week 48 in the HBsAg ≥ 3.0 logIU/mL and <3.0 logIU/mL groups were -0.08 and -0.11 logIU/mL respectively. For patients with CKD, the eGFR at week 48 was significantly improved compared to those with non-CKD (adjusted slope coefficient difference: 2.75 mL/min/1.73 m2 /48 weeks; P = .001). CONCLUSIONS Switching from ETV or an NA combination to TAF was effective for HBV suppression and continued HBsAg reduction. Moreover, the renal glomerular function of patients in the prior NA combination group with CKD was significantly improved compared to those with non-CKD. LAY SUMMARY Nucleos(t)ide analogues, such as entecavir, tenofovir disoproxil fumarate and tenofovir alafenamide, inhibit hepatitis B virus (HBV) replication and are recommended as first-line oral agents for chronic HBV infection. We evaluated the virological/biochemical effects and renal safety when patients are switched from entecavir or nucleoside-nucleotide analogue combination therapy to tenofovir alafenamide. Our findings suggest that switching to tenofovir alafenamide was effective for HBV suppression and the improvement in renal function for patients with chronic kidney disease.
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Affiliation(s)
- Eiichi Ogawa
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Hideyuki Nomura
- The Center for Liver Disease, Shin-Kokura Hospital, Kitakyushu, Japan.,Department of Medicine, Haradoi Hospital, Fukuoka, Japan
| | - Makoto Nakamuta
- Department of Gastroenterology, Kyushu Medical Center, National Hospital Organization, Fukuoka, Japan
| | - Norihiro Furusyo
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | | | - Kazufumi Dohmen
- Department of Internal Medicine, Chihaya Hospital, Fukuoka, Japan
| | - Aritsune Ooho
- Department of Hepatology, Steel Memorial Yawata Hospital, Kitakyushu, Japan
| | - Takeaki Satoh
- Center for Liver Disease, Kokura Medical Center, Kitakyushu, Japan
| | - Akira Kawano
- Department of Medicine, Kitakyushu Municipal Medical Center, Kitakyushu, Japan
| | | | | | - Koichi Azuma
- Department of Medicine, Kyushu Central Hospital, Fukuoka, Japan
| | - Masaki Kato
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Shinji Shimoda
- Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Jun Hayashi
- Kyushu General Internal Medicine Center, Haradoi Hospital, Fukuoka, Japan
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Abstract
Hepatitis B virus (HBV) reactivation can be a serious complication for patients with chronic or resolved HBV infection when treated with biologics. For HBsAg-positive patients receiving biologics, the risk of HBV reactivation is moderate to high. HBsAg-negative/anti-HBc positive patients are at lower risk of HBV reactivation than HBsAg-positive patients. However, patients taking anti-CD20 agents, such as rituximab, have high risk of HBV reactivation (>10%), so antiviral prophylactic therapies are required. This review provides the different classes of biologics associated with HBV reactivation, stratifies the various reactivation risk levels by HBV status and biologic agent, and discusses management strategies.
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Affiliation(s)
- Eiichi Ogawa
- Department of General Internal Medicine, Kyushu University Hospital, 3-1-1 Maidashi Higashi-ku, Fukuoka 8128582, Japan
| | - Mike T Wei
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, 750 Welch Road, Suite 210, Palo Alto, CA 94304, USA
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, 750 Welch Road, Suite 210, Palo Alto, CA 94304, USA.
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36
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Zhang X, El-Serag HB, Thrift AP. Sex and Race Disparities in the Incidence of Hepatocellular Carcinoma in the United States Examined through Age-Period-Cohort Analysis. Cancer Epidemiol Biomarkers Prev 2019; 29:88-94. [PMID: 31712271 DOI: 10.1158/1055-9965.epi-19-1052] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2019] [Revised: 10/28/2019] [Accepted: 10/29/2019] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Incidence rates for hepatocellular carcinoma (HCC) vary considerably by age, sex, and race/ethnicity. We assessed whether the underlying reasons for variations in HCC among subgroups of the population by age, sex, race/ethnicity, and birth cohort are uniform or whether they interact with one another or have changed over time. METHODS Data were from the U.S. Cancer Statistics registry. We assessed annual trends within population subgroups and examined for secular trends in the male-to-female ratio for HCC incidence. We used joinpoint regression to compute annual percent change and average annual percent change (AAPC) and corresponding 95% confidence intervals (CI). We also used age-period-cohort models to disentangle period and cohort effects. RESULTS Between 2001 and 2015, HCC rates increased in men and women ≥50 years, remained stable among women ages 40 to 49 years, but decreased among males ages 40 to 44 years (AAPC = -2.47%; 95% CI, -3.15% to -1.80%) and 45 to 49 years (AAPC = -3.49%; 95% CI, -4.78% to -2.17%). As a result, the male-to-female incidence rate ratio (IRR) among persons aged <50 years decreased from 4.63 in 2001 to 2.42 in 2015 but remained stable over time among persons aged ≥50 years. HCC rates were lower among successive cohorts of males born after circa 1956, whereas HCC rates among females born circa 1991 were higher than those among females born circa 1956 (IRR = 1.67; 95% CI, 1.05-2.65). CONCLUSIONS As a result of decreasing incidence among males aged <50 years and strong cohort effect, the epidemiology of HCC is changing from a disease with striking male predominance to one with less male predominance. IMPACT The sex and racial disparities and strong birth cohort effect on HCC risk identified in this study have important implications for population-based HCC prevention efforts.
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Affiliation(s)
- Xiaotao Zhang
- Department of Medicine, Section of Epidemiology and Population Sciences, Baylor College of Medicine, Houston, Texas. .,Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas
| | - Hashem B El-Serag
- Department of Medicine, Section of Gastroenterology and Hepatology, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
| | - Aaron P Thrift
- Department of Medicine, Section of Epidemiology and Population Sciences, Baylor College of Medicine, Houston, Texas.,Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas
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Tramontano E, Tarbet B, Spengler JR, Seley-Radtke K, Meier C, Jordan R, Janeba Z, Gowen B, Gentry B, Esté JA, Bray M, Andrei G, Schang LM. Meeting report: 32nd International Conference on Antiviral Research. Antiviral Res 2019; 169:104550. [PMID: 31302149 PMCID: PMC7105345 DOI: 10.1016/j.antiviral.2019.104550] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2019] [Accepted: 07/02/2019] [Indexed: 11/29/2022]
Abstract
The 32nd International Conference on Antiviral Research (ICAR), sponsored by the International Society for Antiviral Research (ISAR), was held in Baltimore, Maryland, USA, on May 12-15, 2019. This report gives an overview of the conference on behalf of the Society. It provides a general review of the meeting and awardees, summarizing the presentations, and their main conclusions from the perspective of researchers active in many different areas of antiviral research and development. As in past years, ICAR promoted and showcased the most recent progress in antiviral research, and continued to foster collaborations and interactions in drug discovery and development. The 33rd ICAR will be held in Seattle, Washington, USA, March 30th-April 3rd, 2020.
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Affiliation(s)
- Enzo Tramontano
- Department of Life and Environmental Sciences, University of Cagliari, Monserrato, Italy
| | - Bart Tarbet
- Department of Animal, Dairy and Veterinary Sciences, Institute for Antiviral Research Utah State University, Logan, UT, USA
| | - Jessica R. Spengler
- Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, GA, USA
| | - Katherine Seley-Radtke
- Department of Chemistry & Biochemistry, University of Maryland, Baltimore County, Baltimore, MD, USA
| | - Chris Meier
- Department of Chemistry, Organic Chemistry, Faculty of Sciences, Universität Hamburg, Martin-Luther-King-Platz 6, 20146, Hamburg, Germany
| | | | - Zlatko Janeba
- Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo Nam. 2, CZ-16610, Prague 6, Czech Republic
| | - Brian Gowen
- Department of Animal, Dairy and Veterinary Sciences, Institute for Antiviral Research Utah State University, Logan, UT, USA
| | - Brian Gentry
- Drake University College of Pharmacy and Health Sciences, Des Moines, IA, USA
| | - José A. Esté
- AIDS Research Institute - Irsicaixa, Hospital Germans Trias I Pujol, Universitat Autónoma de Barcelona, Badalona, Spain
| | | | - Graciela Andrei
- KU Leuven, Rega Institute for Medical Research, Laboratory of Virology and Chemotherapy, B-3000, Leuven, Belgium
| | - Luis M. Schang
- Baker Institute Cornell University, 235 Hungerford Hill Road, Ithaca, NY, USA,Corresponding author
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Zhang Y, Li W, Liu Z, Ye J, Zou G, Zhang Z, Li J. Combination therapy based on pegylated interferon alfa improves the therapeutic response of patients with chronic hepatitis B who exhibit high levels of hepatitis B e-antigen at 24 weeks: A retrospective observational study. Medicine (Baltimore) 2019; 98:e17022. [PMID: 31490387 PMCID: PMC6738969 DOI: 10.1097/md.0000000000017022] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2019] [Revised: 07/31/2019] [Accepted: 08/11/2019] [Indexed: 12/14/2022] Open
Abstract
Pegylated interferon alpha (PEG-IFN-α) is a first-line treatment for patients with chronic hepatitis B (CHB), but its efficacy varies from individual to individual. Early discrimination between responder and non-responder patients is important for optimal clinical management. In addition, low therapeutic efficacy is still a major issue; thus, treatment timing should be optimized.We reviewed our experience with hepatitis B e-antigen (HBeAg)-positive patients treated with PEG-IFN-α, alone or in combination with nucleoside analogues (NAs), from 2009 through 2014. Collected data included both general characteristics of 113 patients and laboratory data at baseline and at treatment weeks 12, 24, 52, and 76. The endpoint was HBeAg seroconversion at week 76.A total of 113 patients with changed to or start of NAs therapy were included in this study. At the end of treatment, 44 (38.9%) patients exhibited HBeAg seroconversion. Patients with HBeAg seroconversion had lower baseline HBeAg (475.5 vs 751.7; P = .007). The incidence of HBeAg seroconversion was significantly higher among patients with HBeAg ≤ 500 signal-to-cutoff ratio (S/CO) (OR = 2.60, 95% CI: 1.16-5.83, P = .02) at baseline, HBeAg S/CO ≤ 20 (OR = 3.37, 95% CI: 1.47-7.73, P = .003), or a higher than 10-fold HBeAg drop (OR = 3.55, 95% CI: 1.50-8.37, P = .003) at week 12 or HBeAg ≤ 15 S/CO (OR = 10.35, 95% CI: 4.09-26.20, P < .001) at week 24. Subgroup analyses demonstrated that in patients with HBeAg >20 S/CO at 24 weeks, the addition of NAs treatment may increase HBeAg seroconversion (23.3% vs 0%, P = .03).HBeAg levels had an impact on the rate of serological conversion in CHB patients receiving PEG-IFN-based treatment. Combination therapy with NAs should be considered in CHB patients maintaining a high HBeAg level after 24 weeks of PEG-IFN monotherapy.
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Affiliation(s)
- Yafei Zhang
- Department of Infectious Diseases, The First Affiliated Hospital, Anhui Medical University
- Department of Infectious Diseases, The Second Affiliated Hospital, Anhui Medical University, Hefei
| | - Wei Li
- Department of Liver Diseases, Fuyang Second People's Hospital, Fuyang, China
| | - Zhongping Liu
- Department of Infectious Diseases, The Second Affiliated Hospital, Anhui Medical University, Hefei
| | - Jun Ye
- Department of Infectious Diseases, The Second Affiliated Hospital, Anhui Medical University, Hefei
| | - Guizhou Zou
- Department of Infectious Diseases, The Second Affiliated Hospital, Anhui Medical University, Hefei
| | - Zhenhua Zhang
- Department of Infectious Diseases, The Second Affiliated Hospital, Anhui Medical University, Hefei
| | - Jiabin Li
- Department of Infectious Diseases, The First Affiliated Hospital, Anhui Medical University
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Zhou H, Xu J, Zhang C, Wen Y. Aberrant histone deacetylase 1 expression upregulates vimentin expression via an NF-κB-dependent pathway in hepatocellular carcinoma. Oncol Lett 2019; 18:339-347. [PMID: 31289505 PMCID: PMC6540068 DOI: 10.3892/ol.2019.10309] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2018] [Accepted: 03/12/2019] [Indexed: 12/14/2022] Open
Abstract
Aberrantly elevated expression levels of histone deacetylase 1 (HDAC1) and vimentin are closely associated with disease progression in hepatocellular carcinoma (HCC). It was previously demonstrated that knocking down expression of HDAC1 resulted in a concurrent decrease in the expression levels of vimentin. However, a causal link between these two proteins has not yet been demonstrated, to the best of our knowledge. In the present study, the association between HDAC1 and vimentin was investigated using an HDAC1 overexpression platform. HDAC1 and vimentin were significantly increased in HCC cells, and HDAC1 overexpression enhanced vimentin mRNA and protein expression levels in an HDAC1 dose-dependent manner. Subsequently, truncation and mutation of a vimentin promoter demonstrated that HDAC1-induced vimentin expression was dependent on a nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) binding site in the vimentin promoter sequence. Furthermore, HDAC1 induced vimentin expression by promoting NF-κB translocation between the cytoplasm and the nucleus, as opposed to modulating the total expression level of vimentin directly. The data in the present study demonstrated that HDAC1 is overexpressed in HCC and that HDAC1 may upregulate vimentin expression through the NF-κB signaling pathway, thus demonstrating a causal link between HDAC1 and vimentin in HCC, and may provide valuable information in understanding the pathogenesis of HCC.
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Affiliation(s)
- Huancheng Zhou
- Department of Hepatobiliary Surgery, Meizhou People's Hospital, Meizhou, Guangdong 514031, P.R. China
| | - Jiwei Xu
- Department of Hepatobiliary Surgery, Meizhou People's Hospital, Meizhou, Guangdong 514031, P.R. China
| | - Caiyun Zhang
- Department of Hepatobiliary Surgery, Meizhou People's Hospital, Meizhou, Guangdong 514031, P.R. China
| | - Yuanzhang Wen
- Department of Hepatobiliary Surgery, Meizhou People's Hospital, Meizhou, Guangdong 514031, P.R. China
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40
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Endeshaw M, Hallowell BD, Razzaghi H, Senkomago V, McKenna MT, Saraiya M. Trends in liver cancer mortality in the United States: Dual burden among foreign- and US-born persons. Cancer 2019; 125:726-734. [PMID: 30480828 PMCID: PMC6681907 DOI: 10.1002/cncr.31869] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Revised: 10/17/2018] [Accepted: 10/23/2018] [Indexed: 12/31/2022]
Abstract
BACKGROUND Since the mid-1980s, the burden of liver cancer in the United States has doubled, with 31,411 new cases and 24,698 deaths occurring in 2014. Foreign-born individuals may be more likely to die of liver cancer than individuals in the general US-born population because of higher rates of hepatitis B infection, a low socioeconomic position, and language barriers that limit the receipt of early cancer detection and effective treatment. METHODS To determine whether liver cancer mortality rates were higher among foreign-born individuals versus US-born individuals in the United States, population-based cancer mortality data were obtained from the National Center for Health Statistics of the Centers for Disease Control and Prevention. Annual population estimates were obtained from the US Census Bureau's American Community Survey. Age-adjusted mortality rates and rate ratios (RRs) for liver cancer stratified by birth place were calculated, and the average annual percent change (AAPC) was used to evaluate trends. RESULTS A total of 198,557 deaths from liver and intrahepatic bile duct cancer were recorded during 2005-2014, and 16% occurred among foreign-born individuals. Overall, foreign-born individuals had a 24% higher risk of liver cancer mortality than US-born individuals (RR, 1.24; 95% confidence interval [CI], 1.22-1.25). Foreign-born individuals did not have any significant changes in liver cancer mortality rates overall, but among US-born individuals, liver cancer mortality rates significantly increased (AAPC, 2.7; 95% CI, 2.1-3.3). CONCLUSIONS Efforts that address the major risk factors for liver cancer are needed to help to alleviate the health disparities observed among foreign-born individuals and reverse the increasing trend observed in the US-born population.
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Affiliation(s)
| | | | - Hilda Razzaghi
- Centers for Disease Control and Prevention, Atlanta, Georgia
| | | | | | - Mona Saraiya
- Centers for Disease Control and Prevention, Atlanta, Georgia
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Tarao K, Nozaki A, Ikeda T, Sato A, Komatsu H, Komatsu T, Taguri M, Tanaka K. Real impact of liver cirrhosis on the development of hepatocellular carcinoma in various liver diseases-meta-analytic assessment. Cancer Med 2019; 8:1054-1065. [PMID: 30791221 PMCID: PMC6434205 DOI: 10.1002/cam4.1998] [Citation(s) in RCA: 106] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2018] [Revised: 12/27/2018] [Accepted: 01/06/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND It is well known that the incidence of developing hepatocelluler carcinoma (HCC) is increased in liver cirrhosis of different etiologies. However, comparison of HCC incidence in various liver diseases has not yet been estimated. We surveyed this comparison. METHODS The PubMed database was examined (1989-2017) for studies published in English language regarding the prospective follow-up results for the development of HCC in various liver diseases. A meta-analysis was performed for each liver disease. RESULTS The annual incidence (%) of HCC in the non-cirrhotic stage and cirrhotic stage, and the ratio of HCC incidence in the cirrhotic stage/non-cirrhotic stage were as follows. (a) hepatitis B virus liver disease: 0.37%→3.23% (8.73-fold), (b) hepatitis C virus liver diseases: 0.68%→4.81% (7.07-fold), (c) primary biliary cholangitis (0.26%→1.79%, 6.88-fold), (d) autoimmune hepatitis (0.19%→0.53%, 2.79-fold), and (e) NASH (0.03%→1.35%, 45.00-fold). Regarding primary hemochromatosis and alcoholic liver diseases, only follow-up studies in the cirrhotic stage were presented, 1.20% and 2.06%, respectively. CONCLUSIONS When the liver diseases advance to cirrhosis, the incidence of HCC is markedly increased. The development of HCC must be closely monitored by ultrasonography, magnetic resonance imaging, and computed tomography, irrespective of the different kinds of liver diseases.
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Affiliation(s)
- Kazuo Tarao
- Tarao’s Gastroenterological ClinicYokohamaJapan
| | - Akito Nozaki
- Gastroenterological Center, Medical CenterYokohama City UniversityYokohamaJapan
| | - Takaaki Ikeda
- Gastroenterology DepartmentYokosuka General Hospital UwamachiYokosukaJapan
| | - Akira Sato
- Division of Gastroenterology, Department of Internal MedicineSt. Marianna University, Yokohama City Seibu HospitalYokohamaJapan
| | - Hirokazu Komatsu
- Department of GastroenterologyYokohama Municipal Citizen’s HospitalYokohamaJapan
| | - Tatsuji Komatsu
- Department Clinical ResearchNational Hospital Organization, Yokohama Medical CenterYokohamaJapan
| | - Masataka Taguri
- Department of Data ScienceYokohama City UniversityYokohamaJapan
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Asrani SK, Devarbhavi H, Eaton J, Kamath PS. Burden of liver diseases in the world. J Hepatol 2019; 70:151-171. [PMID: 30266282 DOI: 10.1016/j.jhep.2018.09.014] [Citation(s) in RCA: 2219] [Impact Index Per Article: 369.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2018] [Revised: 09/10/2018] [Accepted: 09/17/2018] [Indexed: 02/06/2023]
Abstract
Liver disease accounts for approximately 2 million deaths per year worldwide, 1 million due to complications of cirrhosis and 1million due to viral hepatitis and hepatocellular carcinoma. Cirrhosis is currently the 11th most common cause of death globally and liver cancer is the 16th leading cause of death; combined, they account for 3.5% of all deaths worldwide. Cirrhosis is within the top 20 causes of disability-adjusted life years and years of life lost, accounting for 1.6% and 2.1% of the worldwide burden. About 2 billion people consume alcohol worldwide and upwards of 75 million are diagnosed with alcohol-use disorders and are at risk of alcohol-associated liver disease. Approximately 2 billion adults are obese or overweight and over 400 million have diabetes; both of which are risk factors for non-alcoholic fatty liver disease and hepatocellular carcinoma. The global prevalence of viral hepatitis remains high, while drug-induced liver injury continues to increase as a major cause of acute hepatitis. Liver transplantation is the second most common solid organ transplantation, yet less than 10% of global transplantation needs are met at current rates. Though these numbers are sobering, they highlight an important opportunity to improve public health given that most causes of liver diseases are preventable.
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Affiliation(s)
| | | | - John Eaton
- Mayo Clinic College of Medicine, Rochester, MN, USA
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Kulik L, El-Serag HB. Epidemiology and Management of Hepatocellular Carcinoma. Gastroenterology 2019; 156:477-491.e1. [PMID: 30367835 PMCID: PMC6340716 DOI: 10.1053/j.gastro.2018.08.065] [Citation(s) in RCA: 1195] [Impact Index Per Article: 199.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2018] [Revised: 08/22/2018] [Accepted: 08/31/2018] [Indexed: 02/06/2023]
Abstract
The major risk factors for hepatocellular carcinoma (HCC) in contemporary clinical practice are becoming increasingly related to sustained virological response after hepatitis C, suppressed hepatitis B virus during treatment, and alcoholic and nonalcoholic fatty liver disease. We review the emerging data on the risk and determinants of HCC in these conditions and the implications of HCC surveillance. However, from a public health perspective, active hepatitis C and B continue to drive most of the global burden of HCC. In United States, the age-adjusted incidence rates of HCC in Hispanics have surpassed those of HCC in Asians. Prognosis in HCC is complex because of the competing risk imposed by underlying cirrhosis and presence of malignancy. In addition to tumor burden, liver function and performance status; additional parameters including tumor biopsy, serum markers, and subclassification of current staging systems; and taking into account patterns of tumor progression may improve patient selection for therapy. Advancements in the treatment of HCC have included identification of patients who are most likely to derive a clinically significant benefit from the available therapeutic options. Additionally, the combination strategies of locoregional therapies and/or systemic therapy are being investigated.
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Affiliation(s)
- Laura Kulik
- Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University, Chicago, Chicago, Illinois, USA
| | - Hashem B. El-Serag
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine and Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
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Chak E, Taefi A, Li CS, Chen MS, Harris AM, MacDonald S, Bowlus C. Electronic Medical Alerts Increase Screening for Chronic Hepatitis B: A Randomized, Double-Blind, Controlled Trial. Cancer Epidemiol Biomarkers Prev 2018; 27:1352-1357. [PMID: 30089680 DOI: 10.1158/1055-9965.epi-18-0448] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2018] [Revised: 06/30/2018] [Accepted: 08/01/2018] [Indexed: 12/14/2022] Open
Abstract
Background: Implementation of screening recommendations for chronic hepatitis B (CHB) among foreign-born persons at risk has been sub-optimal. The use of alerts and reminders in the electronic health record (EHR) has led to increased screening for other common conditions. The aim of our study was to measure the effectiveness of an EHR alert on the implementation of hepatitis B surface antigen (HBsAg) screening of foreign-born Asian and Pacific Islander (API) patients.Methods: We used a novel technique to identify API patients by self-identified ethnicity, surname, country of origin, and language preference, and who had no record of CHB screening with HBsAg within the EHR. Patients with Medicare and/or Medicaid insurance were excluded due to lack of coverage for routine HBsAg screening at the time of this study. At-risk API patients were randomized to alert activation in their EHR or not (control).Results: A total of 2,987 patients met inclusion criteria and were randomized to the alert (n = 1,484) or control group (n = 1,503). In the alert group, 119 patients were tested for HBsAg, compared with 48 in the control group (odds ratio, 2.64; 95% confidence interval, 1.88-3.73; P < 0.001). In the alert group, 4 of 119 (3.4%) tested HBsAg-positive compared with 5 of 48 (10.4%) in the control group (P = 0.12).Conclusions: An EHR alert significantly increased HBsAg testing among foreign-born APIs.Impact: Utilization of EHR alerts has the potential to improve implementation of hepatitis B-screening guidelines. Cancer Epidemiol Biomarkers Prev; 27(11); 1352-7. ©2018 AACR.
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Affiliation(s)
- Eric Chak
- UC Davis School of Medicine, Division of Gastroenterology and Hepatology, Sacramento, California.
| | - Amir Taefi
- UC Davis School of Medicine, Division of Gastroenterology and Hepatology, Sacramento, California
| | - Chin-Shang Li
- Division of Biostatistics, Department of Public Health Sciences, School of Medicine, University of California, Davis
| | - Moon S Chen
- UC Davis School of Medicine, Division of Hematology and Oncology, Sacramento, California
| | - Aaron M Harris
- Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, Georgia
| | | | - Christopher Bowlus
- UC Davis School of Medicine, Division of Gastroenterology and Hepatology, Sacramento, California
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Li Y, Pan Q, Zhao H. Investigation of the values of CT perfusion imaging and ultrasound elastography in the diagnosis of liver fibrosis. Exp Ther Med 2018; 16:896-900. [PMID: 30116343 PMCID: PMC6090262 DOI: 10.3892/etm.2018.6269] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2017] [Accepted: 06/01/2018] [Indexed: 12/12/2022] Open
Abstract
This study intended to investigate the clinical application values of computed tomography (CT) perfusion imaging and ultrasound elastography in the diagnosis of liver fibrosis, and to analyze the characteristics and diagnostic values of the two methods in liver fibrosis. A total of 320 patients diagnosed with suspected liver fibrosis in Qingdao Municipal Hospital from April 2014 to May 2016 were selected. The patients were diagnosed by ultrasound elastography and CT perfusion imaging, respectively, and the influencing characteristics and diagnostic accuracies of the two methods were compared. Among 320 patients, there were 315 definitely diagnosed with liver fibrosis through liver biopsy. The accuracy of CT perfusion imaging was 95.63% (306/325), while that of ultrasound elastography was 91.88% (294/320); there was a significant difference in accuracy between the two methods (P>0.05). CT perfusion imaging was superior to ultrasound elastography in the degree of liver fibrosis (P<0.05). Receiver operating characteristic (ROC) curve analysis showed that the areas under the curve (AUC) of patients were 0.841 and 0.865 in S1 (P>0.05), 0.830 and 0.887 in S2 (P>0.05), 0.851 and 0.931 in S3 (P>0.05), and 0.951 and 0.970 in S4, respectively (P>0.05). AUC values of ROC curves of CT perfusion imaging and ultrasound elastography in diagnosing liver fibrosis were 0.833 and 0.857, respectively (P>0.05). Both CT perfusion imaging and ultrasound elastography have relatively high accuracies in the clinical diagnosis of liver fibrosis, and they are worth promoting and applying. However, the best imaging method needs to be selected according to the actual situation of patients and research purpose.
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Affiliation(s)
- Yansong Li
- Department of Ultrasound, Qingdao Municipal Hospital, Qingdao, Shandong 266071, P.R. China
| | - Qing Pan
- Department of Ultrasound, Qingdao Municipal Hospital, Qingdao, Shandong 266071, P.R. China
| | - Hong Zhao
- Department of Radiology, Eastern Hospital, Qingdao Municipal Hospital, Qingdao, Shandong 266071, P.R. China
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He W, Peng B, Tang Y, Yang J, Zheng Y, Qiu J, Zou R, Shen J, Li B, Yuan Y. Nomogram to Predict Survival of Patients With Recurrence of Hepatocellular Carcinoma After Surgery. Clin Gastroenterol Hepatol 2018; 16:756-764.e10. [PMID: 29246702 DOI: 10.1016/j.cgh.2017.12.002] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2017] [Revised: 12/04/2017] [Accepted: 12/04/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS We aimed to establish and validate a nomogram to predict survival at 2 and 5 years after recurrence of hepatocellular carcinoma (HCC) in patients who have undergone curative resection. METHODS We developed a nomogram using data from a training cohort of 638 patients (most with hepatitis B virus infection) with recurrence of HCC after curative resection at Sun Yat-sen University Cancer Center, in Guangzhou, China from 2007 through 2013. The median follow-up time was 39.7 months. Patients were evaluated every 3-4 months for the first 2 years after resection and every 3-6 months thereafter. The nomogram was based on variables independently associated with survival after HCC recurrence, including antiviral treatment; albumin-bilirubin grade and alpha-fetoprotein level at recurrence; time from primary resection to recurrence; size, site, number of recurrences; and treatment for recurrence. We validated the nomogram using data from an independent internal cohort of 213 patients treated at the same institution and an external cohort of 127 patients treated at 2 other centers in China, from 2002 through 2009. The predictive accuracy of the nomogram was measured using Harrell's concordance index (C index) and compared with the Barcelona Clinic Liver Cancer staging system of recurrence. RESULTS Our nomogram predicted survival of patients in the training cohort with a C-index of 0.797 (95% CI, 0.765-0.830)-greater than that of the Barcelona Clinic Liver Cancer staging system for recurrence (C-index score, 0.713; 95% CI, 0.680-0.745) (P < .001). This nomogram accurately stratified patients into subgroups with predicted long, medium, and short survival times: the proportions of patients in each group who survived 2 years after HCC recurrence were 91.2%, 67.6%, and 23.8%; the proportions of patients in each group who survived 5 years after HCC recurrence were 74.9%, 53.3%, and 9.1%. Our nomogram predicted patient survival times with C-index scores of 0.756 (95% CI, 0.703-0.808) in the internal validation cohort and 0.747 (95% CI, 0.701-0.794) in the external validation cohorts. CONCLUSIONS We developed a nomogram to determine the probability of survival, at different time points, of patients with recurrence of HCC (most with hepatitis B virus infection), after curative resection and validated it internally and externally.
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Affiliation(s)
- Wei He
- State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China; Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Baogang Peng
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yunqiang Tang
- Department of Surgery, Guangzhou Medical University Cancer Center, Guangzhou, China
| | - Junpin Yang
- State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Yun Zheng
- State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China; Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Jiliang Qiu
- State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China; Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Ruhai Zou
- State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China; Department of Ultrasound, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Jingxian Shen
- State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China; Department of Medical Imaging, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Binkui Li
- State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China; Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
| | - Yunfei Yuan
- State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China; Department of Hepatobiliary Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China.
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Mittal S, Kramer JR, Omino R, Chayanupatkul M, Richardson PA, El-Serag HB, Kanwal F. Role of Age and Race in the Risk of Hepatocellular Carcinoma in Veterans With Hepatitis B Virus Infection. Clin Gastroenterol Hepatol 2018; 16:252-259. [PMID: 28870660 DOI: 10.1016/j.cgh.2017.08.042] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/16/2016] [Revised: 08/20/2017] [Accepted: 08/28/2017] [Indexed: 01/30/2023]
Abstract
BACKGROUND & AIMS Hepatocellular (HCC) surveillance guidelines for patients with chronic hepatitis B virus (HBV) infection are based on race- and age-specific estimates of HCC risk, derived from studies conducted in areas in which HBV is endemic. METHODS We conducted a retrospective cohort study using the national Veterans Administration data to identify patients with chronic HBV infection from 2001 through 2013. We examined the effect of race and age on HCC risk while adjusting for baseline clinical characteristics. RESULTS The study cohort had 8329 patients; 3498 patients (42.0%) were white, 3248 (39%) were African Americans, and 659 (7.9%) were Asian Pacific Islanders. The annual HCC incidence was highest in Asian Pacific Islanders (0.65%), followed by whites (0.57%) and African Americans (0.40%). After adjusting for clinical and viral factors, the risk of HCC was significantly higher in Asian Pacific Islanders compared with whites (adjusted hazard ratio [HR] = 2.04; 95% CI, 1.31-3.17). There was no difference in HCC risk between African Americans and whites (adjusted HR, 0.77; 95% CI, 0.58-1.02). HCC risk increased with age: adjusted HR was 1.97 (95% CI, 0.99-3.87) for 40-49 years; adjusted HR was 3.00 (95% CI, 1.55-5.81) for 50-59 years; and adjusted HR was 4.02 (95% CI, 2.03-7.94) for more than 60 years vs less than 40 years. Patients with cirrhosis had higher risk of HCC than patients without cirrhosis (adjusted HR = 3.69; 95% CI, 2.82-4.83). However, even among patients without cirrhosis, the annual incidence of HCC was more than 0.2% for all patients older than 40 years with high levels of alanine aminotransferase-regardless of race. CONCLUSIONS In a sample of male veterans with chronic HBV infection, risk of HCC is highest among Asian Pacific Islanders, followed by whites and African Americans. Cirrhosis increased HCC risk. Among patients without cirrhosis, male patients who are older than 40 years and have increased levels of alanine aminotransferase might benefit from HCC surveillance, regardless of race.
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Affiliation(s)
- Sahil Mittal
- Center of Innovation, Effectiveness and Quality, Sections of Health Services Research, Section of Gastroenterology and Hepatology, Houston, Texas; Baylor College of Medicine, Houston, Texas.
| | - Jennifer R Kramer
- Center of Innovation, Effectiveness and Quality, Sections of Health Services Research, Section of Gastroenterology and Hepatology, Houston, Texas
| | | | | | - Peter A Richardson
- Center of Innovation, Effectiveness and Quality, Sections of Health Services Research, Section of Gastroenterology and Hepatology, Houston, Texas
| | - Hashem B El-Serag
- Center of Innovation, Effectiveness and Quality, Sections of Health Services Research, Section of Gastroenterology and Hepatology, Houston, Texas; Baylor College of Medicine, Houston, Texas; Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
| | - Fasiha Kanwal
- Center of Innovation, Effectiveness and Quality, Sections of Health Services Research, Section of Gastroenterology and Hepatology, Houston, Texas; Baylor College of Medicine, Houston, Texas; Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas
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Block TM, Locarnini S, McMahon BJ, Rehermann B, Peters MG. Use of Current and New Endpoints in the Evaluation of Experimental Hepatitis B Therapeutics. Clin Infect Dis 2018; 64:1283-1288. [PMID: 28200098 DOI: 10.1093/cid/cix129] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2016] [Accepted: 02/10/2017] [Indexed: 12/15/2022] Open
Abstract
New hepatitis B virus (HBV) therapies are expected to have breakthrough benefit for patients. HBV functional cure is sustained hepatitis B surface antigen loss and anti-HBs gain, with normalization of serum aminotransferases off therapy. Virologic or complete cure additionally includes loss of HBV covalently closed circular DNA. Currently available endpoints of therapy are inadequate to evaluate the efficacy of many of the new therapeutics. Therefore, either new ways of using the existing virologic endpoints and laboratory values or entirely new biomarkers are needed. In this review, we discuss the currently used endpoints, potential new endpoints, as well as what new markers are needed to assess the ability of HBV therapeutics to achieve functional and virologic cure in various phases of HBV infection. In addition, we discuss how patient selection from differing phases of HBV impacts the choice of HBV drug(s) needed to achieve cure.
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Affiliation(s)
- Timothy M Block
- Hepatitis B Foundation and Baruch S. Blumberg Institute, Doylestown, Pennsylvania, USA
| | - Stephen Locarnini
- Victorian Infectious Diseases Reference Laboratory, Doherty Institute, Melbourne, Australia
| | | | - Barbara Rehermann
- Immunology Section, Liver Diseases Branch, National Institutes of Health, Bethesda, Maryland, USA
| | - Marion G Peters
- Department of Medicine, University of California, San Francisco, USA
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Saxena V, Terrault NA. Recurrent Primary Disease After Liver Transplantation. ZAKIM AND BOYER'S HEPATOLOGY 2018:784-815.e14. [DOI: 10.1016/b978-0-323-37591-7.00053-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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