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Li J, Bai H, Gao Z, Gao L, Wang W, Li Y, Lian J, Yao T, Wang K, Hao R, Wang S, Feng Y. Global, regional, and national temporal trends in incidence and mortality for liver cancer due to hepatitis B, 1990-2021: a decomposition and age-period-cohort analysis for the Global Burden of Disease Study 2021. Hepatol Int 2025; 19:368-383. [PMID: 39702656 DOI: 10.1007/s12072-024-10765-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Accepted: 11/30/2024] [Indexed: 12/21/2024]
Abstract
OBJECTIVE This study comprehensively assessed the burden of liver cancer due to hepatitis B (LCHB) from 1990 to 2021, analyzing temporal trends in disease burden and associations with age, period and birth cohort. METHODS Age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR) of LCHB from 1990 to 2021 were collected from the Global Burden of Disease (GBD) 2021. Joinpoint regression analysis estimated long-term trends. Age-period-cohort analysis evaluated the independent effects of age, period and cohort. Decomposition analysis elucidated the impact of population growth, aging and epidemiological changes on the burden. RESULTS Between 1990 and 2019, the ASIR and ASMR of LCHB witnessed an overall declining trend worldwide, with a notably higher burden in males compared to females. The highest ASIR and ASMR were observed in the middle socio-demographic index (SDI) region, while the lowest were in the low-middle SDI region, with substantial differences across countries. Age-period-cohort analysis revealed an initial increase in risk followed by a decline with advancing age, with the burden primarily affecting the elderly. Decomposition analysis indicated that population growth and aging were the primary drivers of the increase in incident cases and deaths. CONCLUSIONS From 1990 to 2021, the ASIR and ASMR of LCHB decreased globally. However, population growth and aging contributed to an increase in the absolute numbers of incident cases and deaths. The risk burden increased with age, and favourable period and cohort effects were found in all SDI regions.
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Affiliation(s)
- Jinbo Li
- School of Public Health, Shanxi Medical University, Taiyuan, 030001, China
- Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan, 030001, China
- Key Laboratory of Coal Environmental Pathogenicity and Prevention, Ministry of Education, Shanxi Medical University, Taiyuan, 030001, China
- Reverse Etiology Research Center Academician Workstation, Shanxi Medical University, Taiyuan, 030001, China
| | - Hongjing Bai
- School of Public Health, Shanxi Medical University, Taiyuan, 030001, China
- Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan, 030001, China
- Key Laboratory of Coal Environmental Pathogenicity and Prevention, Ministry of Education, Shanxi Medical University, Taiyuan, 030001, China
- Reverse Etiology Research Center Academician Workstation, Shanxi Medical University, Taiyuan, 030001, China
| | - Ziyi Gao
- School of Public Health, Shanxi Medical University, Taiyuan, 030001, China
- Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan, 030001, China
- Key Laboratory of Coal Environmental Pathogenicity and Prevention, Ministry of Education, Shanxi Medical University, Taiyuan, 030001, China
- Reverse Etiology Research Center Academician Workstation, Shanxi Medical University, Taiyuan, 030001, China
| | - Linying Gao
- School of Public Health, Shanxi Medical University, Taiyuan, 030001, China
| | - Weigang Wang
- School of Public Health, Shanxi Medical University, Taiyuan, 030001, China
- Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan, 030001, China
- Key Laboratory of Coal Environmental Pathogenicity and Prevention, Ministry of Education, Shanxi Medical University, Taiyuan, 030001, China
- Reverse Etiology Research Center Academician Workstation, Shanxi Medical University, Taiyuan, 030001, China
| | - Yandi Li
- School of Public Health, Shanxi Medical University, Taiyuan, 030001, China
- Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan, 030001, China
- Key Laboratory of Coal Environmental Pathogenicity and Prevention, Ministry of Education, Shanxi Medical University, Taiyuan, 030001, China
- Reverse Etiology Research Center Academician Workstation, Shanxi Medical University, Taiyuan, 030001, China
| | - Jia Lian
- School of Public Health, Shanxi Medical University, Taiyuan, 030001, China
- Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan, 030001, China
- Key Laboratory of Coal Environmental Pathogenicity and Prevention, Ministry of Education, Shanxi Medical University, Taiyuan, 030001, China
- Reverse Etiology Research Center Academician Workstation, Shanxi Medical University, Taiyuan, 030001, China
| | - Tian Yao
- First Hospital of Shanxi Medical University, Taiyuan, 030001, China
| | - Keke Wang
- First Hospital of Shanxi Medical University, Taiyuan, 030001, China
| | - Ruigang Hao
- Taiyuan Center for Disease Control and Prevention, Taiyuan, 030012, China.
| | - Suping Wang
- School of Public Health, Shanxi Medical University, Taiyuan, 030001, China.
- Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan, 030001, China.
- Key Laboratory of Coal Environmental Pathogenicity and Prevention, Ministry of Education, Shanxi Medical University, Taiyuan, 030001, China.
- Reverse Etiology Research Center Academician Workstation, Shanxi Medical University, Taiyuan, 030001, China.
| | - Yongliang Feng
- School of Public Health, Shanxi Medical University, Taiyuan, 030001, China.
- Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan, 030001, China.
- Key Laboratory of Coal Environmental Pathogenicity and Prevention, Ministry of Education, Shanxi Medical University, Taiyuan, 030001, China.
- Reverse Etiology Research Center Academician Workstation, Shanxi Medical University, Taiyuan, 030001, China.
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Tak J, Kim YS, Kim SG. Roles of X-box binding protein 1 in liver pathogenesis. Clin Mol Hepatol 2025; 31:1-31. [PMID: 39355873 PMCID: PMC11791611 DOI: 10.3350/cmh.2024.0441] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Revised: 09/06/2024] [Accepted: 09/27/2024] [Indexed: 10/03/2024] Open
Abstract
The prevalence of drug-induced liver injury (DILI) and viral liver infections presents significant challenges in modern healthcare and contributes to considerable morbidity and mortality worldwide. Concurrently, metabolic dysfunctionassociated steatotic liver disease (MASLD) has emerged as a major public health concern, reflecting the increasing rates of obesity and leading to more severe complications such as fibrosis and hepatocellular carcinoma. X-box binding protein 1 (XBP1) is a distinct transcription factor with a basic-region leucine zipper structure, whose activity is regulated by alternative splicing in response to disruptions in endoplasmic reticulum (ER) homeostasis and the unfolded protein response (UPR) activation. XBP1 interacts with a key signaling component of the highly conserved UPR and is critical in determining cell fate when responding to ER stress in liver diseases. This review aims to elucidate the emerging roles and molecular mechanisms of XBP1 in liver pathogenesis, focusing on its involvement in DILI, viral liver infections, MASLD, fibrosis/cirrhosis, and liver cancer. Understanding the multifaceted functions of XBP1 in these liver diseases offers insights into potential therapeutic strategies to restore ER homeostasis and mitigate liver damage.
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Affiliation(s)
- Jihoon Tak
- College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, Goyang, Korea
| | - Yun Seok Kim
- Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine, Seoul, Korea
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea
| | - Sang Geon Kim
- College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul, Goyang, Korea
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Kang CK, Brennan PN, Dillon JF. How to Effectively Monitor Aging Patients with Chronic Hepatitis B: A Review. Clin Interv Aging 2022; 17:1811-1820. [PMID: 36532948 PMCID: PMC9748119 DOI: 10.2147/cia.s366255] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Accepted: 11/17/2022] [Indexed: 05/11/2024] Open
Abstract
Hepatitis B virus (HBV) infection is a major global public health challenge associated with significant morbidity and mortality. Due to worldwide population aging, HBV infection in the elderly will become increasingly prevalent. Effective universal vaccination programs exist but these are largely targeted towards the younger population. Therefore, the elderly population remains at risk of higher disease burden. New diagnoses of HBV infection in the elderly are usually asymptomatic chronic infections which increases their risk of developing cirrhosis, hepatocellular carcinoma, and liver disease-related mortality, especially if left untreated. Physiological changes and the increasing prevalence of multimorbidity associated with aging also potentially worsen outcomes in elderly patients with chronic HBV infection. Therefore, this cohort of patients should be monitored closely and effectively. Current international clinical practice guidelines unfortunately do not provide hard treatment endpoints specific to elderly patients with chronic HBV infection. Management of these patients is complex and requires an individualized approach. Multiple factors such as physiological changes, comorbidities, compliance, treatment tolerability and efficacy, burden of treatment, and realistic treatment goals need to be considered. Shared decision-making between patient and clinician is essential to ensure that the final decision for or against treatment aligns with the patient's values and preferences. This review article aims to summarize the monitoring and management of chronic HBV infection in the aging population.
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Affiliation(s)
- Chan Keat Kang
- Division of Molecular and Clinical Medicine, School of Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK
| | - Paul N Brennan
- Division of Molecular and Clinical Medicine, School of Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK
| | - John F Dillon
- Division of Molecular and Clinical Medicine, School of Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK
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Cao G, Jing W, Liu J, Liu M. Countdown on hepatitis B elimination by 2030: the global burden of liver disease related to hepatitis B and association with socioeconomic status. Hepatol Int 2022; 16:1282-1296. [PMID: 36048317 DOI: 10.1007/s12072-022-10410-y] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2022] [Accepted: 08/12/2022] [Indexed: 11/28/2022]
Abstract
BACKGROUND AND PURPOSE Hepatitis B virus (HBV) infection causes both acute and chronic liver disease, performing the key driver toward the global elimination of viral hepatitis by 2030. We used data from Global Burden of Disease (GBD) study to quantify the burden of liver disease due to hepatitis B at the global, regional and national levels. METHODS Annual incident cases and age-standardized incidence rates (ASIRs) of liver disease due to hepatitis B between 1990 and 2019 were collected from GBD study 2019. Percentage changes of incident cases and estimated annual percentage changes (EAPCs) of ASIRs were calculated to quantify their temporal trends. Correlations between EAPC and socio-demographic index (SDI) and universal health coverage index (UHCI) were evaluated by Pearson correlation analyses. RESULTS Globally, the incident cases of liver disease due to hepatitis B decreased by 4.51% from 84.45 million in 1990 to 80.65 million in 2019 and ASIR decreased by an average of 1.52% (95%CI - 1.66%, - 1.37%) per year in this period. For the spectrum of liver disease due to hepatitis B, ASIR of cirrhosis and other chronic liver diseases increased by an average of 0.13% (95%CI 0.04%, 0.22%) per year in low SDI region and 0.24% (95%CI 0.04%, 0.34%) per year in low-middle SDI region, and ASIR of liver cancer increased by an average of 0.91% (95%CI 0.37%, 1.46%) per year in high SDI region in 1990-2019. Positive correlations of EAPC in ASIR of liver cancer with SDI and UHCI were observed in nations with SDI ≥ 0.7 or UHCI ≥ 70. CONCLUSION HBV infection remains a global health problem, causing low and low-middle SDI regions with an increasing trend of cirrhosis and other chronic liver diseases, and high SDI region with an increasing trend of liver cancer. Efforts to eliminate hepatitis B by 2030 needs to focus on not only developing regions but also developed regions.
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Affiliation(s)
- Guiying Cao
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, No. 38 Xueyuan Road, Haidian District, Beijing, 100191, China
| | - Wenzhan Jing
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, No. 38 Xueyuan Road, Haidian District, Beijing, 100191, China
| | - Jue Liu
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, No. 38 Xueyuan Road, Haidian District, Beijing, 100191, China
| | - Min Liu
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, No. 38 Xueyuan Road, Haidian District, Beijing, 100191, China.
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Saraf N, Dhampalwar S, Kute V, Bansal SB. Expert Group Opinion for Diagnosis and Management Viral Hepatitis in Solid Organ Transplant Recipients in South Asia. INDIAN JOURNAL OF TRANSPLANTATION 2022; 16:S77-S81. [DOI: 10.4103/ijot.ijot_89_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/18/2023] Open
Abstract
Viral hepatitis is endemic in the South Asia region and is mainly caused by four hepatotropic viruses: hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis E virus (HEV). South Asia region consists of developing countries and HAV and HEV infections are common because of poor sanitary conditions and hygiene practices. HAV and HEV are transmitted person-to-person by fecal[FIGURE DASH]oral route. HBV and HCV are transmitted via permucosal or percutaneous exposure. It is important to know the impact of these viral infections in the setting of transplantation including evaluation and management in pre, peri, and posttransplant periods. This review summarizes the epidemiology, preventive practices, and advisory for travelers to these endemic regions. Furthermore, recommendations for screening donors and recipients in transplant settings are discussed.
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Kinoshita A, Hagiwara N, Osawa A, Akasu T, Matsumoto Y, Ueda K, Saeki C, Oikawa T, Koike K, Saruta M. Poor tolerability of lenvatinib in elderly patients ≥80 years old with hepatocellular carcinoma: A multicenter observational study. J Oncol Pharm Pract 2022; 29:626-636. [PMID: 35112972 DOI: 10.1177/10781552221077039] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
INTRODUCTION Management of elderly patients with cancer has become a global issue. We investigated the safety and tolerability of lenvatinib in hepatocellular carcinoma (HCC) patients ≥80 years old. METHODS We retrospectively evaluated 61 HCC patients and divided them into 2 groups: an elderly group (n = 13, ≥80 years old) and a younger group (n = 48, <80 years old). We compared the adverse events (AEs), administration period, dose intensity, objective response, and progression-free survival (PFS) between the two groups. RESULTS The discontinuation of lenvatinib due to AEs was more frequent in the elderly group (8/13, 61.5%) than in the younger group (10/48, 20.8%) (P = 0.0043). Fatigue and appetite loss accounted for half of the cases discontinued due to AEs in the elderly group. The elderly group had a significantly lower 8-week-delivered dose intensity/body surface area ratio (147.2) and 8-week-relative dose intensity (50.0%) than those in the younger group (267.4, 67%) (P = 0.003, 0.029). The objective response rate was significantly lower in the elderly group (15.4%) than in the younger group (61.5%) (P = 0.021). The PFS in the elderly group tended to be shorter than that in the younger group (P = 0.058, hazard ratio [HR] 1.98). The modified albumin-bilirubin (mALBI) grade (hepatic function) (HR, 2.60; P = 0.01) and objective response (HR, 0.41; P = 0.011) were independently associated with the PFS in the multivariate analysis. CONCLUSION The management of AEs is crucial for adherence and maintaining the dose intensity of lenvatinib in elderly HCC patients.
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Affiliation(s)
- Akiyoshi Kinoshita
- Division of Gastroenterology and Hepatology, 38341the Jikei University Daisan Hospital, Komae, Tokyo, Japan
| | - Noriko Hagiwara
- Division of Gastroenterology and Hepatology, 38341the Jikei University Daisan Hospital, Komae, Tokyo, Japan
| | - Akiyuki Osawa
- Division of Gastroenterology and Hepatology, 38341the Jikei University Daisan Hospital, Komae, Tokyo, Japan
| | - Takafumi Akasu
- Division of Gastroenterology and Hepatology, 26799the Jikei University Kashiwa Hospital, Kashiwa, Chiba, Japan
| | - Yoshihiro Matsumoto
- Division of Gastroenterology and Hepatology, 26799the Jikei University Kashiwa Hospital, Kashiwa, Chiba, Japan
| | - Kaoru Ueda
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine, Minato, Tokyo, Japan
| | - Chisato Saeki
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine, Minato, Tokyo, Japan
| | - Tsunekazu Oikawa
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine, Minato, Tokyo, Japan
| | - Kazuhiko Koike
- Division of Gastroenterology and Hepatology, 38341the Jikei University Daisan Hospital, Komae, Tokyo, Japan
| | - Masayuki Saruta
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine, Minato, Tokyo, Japan
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Cao G, Jing W, Liu J, Liu M. The global trends and regional differences in incidence and mortality of hepatitis A from 1990 to 2019 and implications for its prevention. Hepatol Int 2021; 15:1068-1082. [PMID: 34345993 PMCID: PMC8514357 DOI: 10.1007/s12072-021-10232-4] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Accepted: 07/01/2021] [Indexed: 12/24/2022]
Abstract
BACKGROUND AND PURPOSE Despite decades of improved sanitation and hygiene measures and vaccine introduction, hepatitis A has been spread through numerous outbreaks globally. We used data from the Global Burden of Disease (GBD) study to quantify hepatitis A burden at the global, regional and national levels. METHODS Annual incident cases, deaths, age-standardized incidence rates (ASIRs), and age-standardized mortality rates (ASMRs) of hepatitis A between 1990 and 2019 were derived from the GBD study 2019. Percentage changes of cases and deaths, and estimated annual percentage changes (EAPCs) of ASIRs and ASMRs were calculated to quantify their temporal trends. RESULTS Global hepatitis A incident cases increased by 13.90% from 139.54 million in 1990 to 158.94 million in 2019. ASIR of hepatitis A remained stable (EAPC = 0.00, 95% CI -0.01 to 0.01), whereas ASMR decreased (EAPC = -4.63, 95% CI -4.94 to -4.32) between 1990 and 2019. ASIR increased in low (EAPC = 0.09, 95% CI 0.04 to 0.14) and low-middle (EAPC = 0.04, 95% CI 0.03 to 0.06) socio-demographic index (SDI) regions. For GBD regions, the most significant increases of ASIR were detected in high-income Asia Pacific (EAPC = 0.53, 95% CI 0.41 to 0.66), Oceania (EAPC = 0.31, 95% CI 0.25 to 0.36), and Australasia (EAPC = 0.28, 95% CI 0.13 to 0.44). EAPC of ASIR was positively associated with SDI value in countries and territories with SDI value ≥ 0.7 (ρ = -0.310, p < 0.001). CONCLUSION There is an unfavorable trend that hepatitis A is still pending in hyperendemic regions and is emerging in low endemic regions. These highlight the need of targeted and specific strategies to eliminate hepatitis A, such as sanitation measures and a comprehensive plan for surveillance and vaccination against hepatitis A.
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Affiliation(s)
- Guiying Cao
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Haidian District, No. 38 Xueyuan Road, Beijing, 100191, China.
| | - Wenzhan Jing
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Haidian District, No. 38 Xueyuan Road, Beijing, 100191, China
| | - Jue Liu
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Haidian District, No. 38 Xueyuan Road, Beijing, 100191, China
| | - Min Liu
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Haidian District, No. 38 Xueyuan Road, Beijing, 100191, China.
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Ecarnot F, Maggi S, Michel JP, Veronese N, Rossanese A. Vaccines and Senior Travellers. FRONTIERS IN AGING 2021; 2:677907. [PMID: 35822022 PMCID: PMC9261415 DOI: 10.3389/fragi.2021.677907] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/08/2021] [Accepted: 06/28/2021] [Indexed: 11/18/2022]
Abstract
Background: International tourist travel has been increasingly steadily in recent years, and looks set to reach unprecedented levels in the coming decades. Among these travellers, an increasing proportion is aged over 60 years, and is healthy and wealthy enough to be able to travel. However, senior travellers have specific risks linked to their age, health and travel patterns, as compared to their younger counterparts. Methods: We review here the risk of major vaccine-preventable travel-associated infectious diseases, and forms and efficacy of vaccination for these diseases. Results: Routine vaccinations are recommended for older persons, regardless of whether they travel or not (e.g., influenza, pneumococcal vaccines). Older individuals should be advised about the vaccines that are recommended for their age group in the framework of the national vaccination schedule. Travel-specific vaccines must be discussed in detail on a case-by-case basis, and the risk associated with the vaccine should be carefully weighed against the risk of contracting the disease during travel. Travel-specific vaccines reviewed here include yellow fever, hepatitis, meningococcal meningitis, typhoid fever, cholera, poliomyelitis, rabies, Japanese encephalitis, tick-borne encephalitis and dengue. Conclusion: The number of older people who have the good health and financial resources to travel is rising dramatically. Older travellers should be advised appropriately about routine and travel-specific vaccines, taking into account the destination, duration and purpose of the trip, the activities planned, the type of accommodation, as well as patient-specific characteristics, such as health status and current medications.
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Affiliation(s)
- Fiona Ecarnot
- University Hospital Besancon and University of Franche-Comté, Besancon, France
| | - Stefania Maggi
- CNR, Institute of Neuroscience – Aging Branch, Padua, Italy
| | - Jean-Pierre Michel
- Department of Rehabilitation and Geriatrics, University of Geneva, Geneva, Switzerland
| | - Nicola Veronese
- Geriatrics Section, Department of Medicine, University of Palermo, Palermo, Italy
| | - Andrea Rossanese
- Department of Infectious-Tropical Diseases and Microbiology, IRCCS “Sacro Cuore-Don Calabria,” Verona, Italy
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Castaneda D, Gonzalez AJ, Alomari M, Tandon K, Zervos XB. From hepatitis A to E: A critical review of viral hepatitis. World J Gastroenterol 2021; 27:1691-1715. [PMID: 33967551 PMCID: PMC8072198 DOI: 10.3748/wjg.v27.i16.1691] [Citation(s) in RCA: 71] [Impact Index Per Article: 17.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 03/02/2021] [Accepted: 04/09/2021] [Indexed: 02/06/2023] Open
Abstract
Viral infections affecting the liver have had an important impact on humanity, as they have led to significant morbidity and mortality in patients with acute and chronic infections. Once an unknown etiology, the discovery of the viral agents triggered interest of the scientific community to establish the pathogenesis and diagnostic modalities to identify the affected population. With the rapid scientific and technological advances in the last centuries, controlling and even curing the infections became a possibility, with a large focus on preventive medicine through vaccination. Hence, a comprehensive understanding of hepatitis A, B, C, D and E is required by primary care physicians and gastroenterologists to provide care to these patients. The review article describes the epidemiology, pathogenesis, clinical presentation, diagnostic tools and current medication regimens, with a focus on upcoming treatment options and the role of liver transplantation.
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Affiliation(s)
- Daniel Castaneda
- Digestive Disease Institute, Cleveland Clinic Florida, Weston, FL 33331, United States
| | | | - Mohammad Alomari
- Digestive Disease Institute, Cleveland Clinic Florida, Weston, FL 33331, United States
| | - Kanwarpreet Tandon
- Digestive Disease Institute, Cleveland Clinic Florida, Weston, FL 33331, United States
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Sise ME, Goldberg DS, Kort JJ, Schaubel DE, Alloway RR, Durand CM, Fontana RJ, Brown RS, Friedewald JJ, Prenner S, Landis JR, Fernando M, Phillips CC, Woodle ES, Rike-Shields A, Sherman KE, Elias N, Williams WW, Gustafson JL, Desai NM, Barnaba B, Norman SP, Doshi M, Sultan ST, Aull MJ, Levitsky J, Belshe DS, Chung RT, Reese PP. Multicenter Study to Transplant Hepatitis C-Infected Kidneys (MYTHIC): An Open-Label Study of Combined Glecaprevir and Pibrentasvir to Treat Recipients of Transplanted Kidneys from Deceased Donors with Hepatitis C Virus Infection. J Am Soc Nephrol 2020; 31:2678-2687. [PMID: 32843477 DOI: 10.1681/asn.2020050686] [Citation(s) in RCA: 59] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Accepted: 07/06/2020] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Single-center trials and retrospective case series have reported promising outcomes using kidneys from donors with hepatitis C virus (HCV) infection. However, multicenter trials are needed to determine if those findings are generalizable. METHODS We conducted a prospective trial at seven centers to transplant 30 kidneys from deceased donors with HCV viremia into HCV-uninfected recipients, followed by 8 weeks of once-daily coformulated glecaprevir and pibrentasvir, targeted to start 3 days posttransplant. Key outcomes included sustained virologic response (undetectable HCV RNA 12 weeks after completing treatment with glecaprevir and pibrentasvir), adverse events, and allograft function. RESULTS We screened 76 patients and enrolled 63 patients, of whom 30 underwent kidney transplantation from an HCV-viremic deceased donor (median kidney donor profile index, 53%) in May 2019 through October 2019. The median time between consent and transplantation of a kidney from an HCV-viremic donor was 6.3 weeks. All 30 recipients achieved a sustained virologic response. One recipient died of complications of sepsis 4 months after achieving a sustained virologic response. No severe adverse events in any patient were deemed likely related to HCV infection or treatment with glecaprevir and pibrentasvir. Three recipients developed acute cellular rejection, which was borderline in one case. Three recipients developed polyomavirus (BK) viremia near or >10,000 copies/ml that resolved after reduction of immunosuppression. All recipients had good allograft function, with a median creatinine of 1.2 mg/dl and median eGFR of 57 ml/min per 1.73 m2 at 6 months. CONCLUSIONS Our multicenter trial demonstrated safety and efficacy of transplantation of 30 HCV-viremic kidneys into HCV-negative recipients, followed by early initiation of an 8-week regimen of glecaprevir and pibrentasvir.
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Affiliation(s)
- Meghan E Sise
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
| | - David S Goldberg
- Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, Miami, Florida
| | - Jens J Kort
- Global Medical Affairs Research and Development, AbbVie Inc., North Chicago, Illinois
| | - Douglas E Schaubel
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Rita R Alloway
- Division of Nephrology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Christine M Durand
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Robert J Fontana
- Division of Gastroenterology and Hepatology, University of Michigan Medical School, Ann Arbor, Michigan
| | - Robert S Brown
- Division of Gastroenterology and Hepatology, Weill Cornell Medicine, New York, New York
| | - John J Friedewald
- Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Stacey Prenner
- Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - J Richard Landis
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Melissa Fernando
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - Caitlin C Phillips
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
| | - E Steve Woodle
- Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Adele Rike-Shields
- Division of Transplantation, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio.,The Christ Hospital, Cincinnati, Ohio
| | - Kenneth E Sherman
- Division of Digestive Disease, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Nahel Elias
- Transplant Center and Division of Transplant Surgery, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts
| | - Winfred W Williams
- Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
| | - Jenna L Gustafson
- Gastrointestinal Division, Department of Medicine, Liver Center, Massachusetts General Hospital, Boston, Massachusetts
| | - Niraj M Desai
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Brittany Barnaba
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Silas P Norman
- Division of Nephrology, Michigan Medicine, Ann Arbor, Michigan
| | - Mona Doshi
- Division of Nephrology, Michigan Medicine, Ann Arbor, Michigan
| | - Samuel T Sultan
- Division of Transplant Surgery, New York-Presbyterian/Weill Cornell Medicine, New York, New York
| | - Meredith J Aull
- Division of Transplant Surgery, New York-Presbyterian/Weill Cornell Medicine, New York, New York
| | - Josh Levitsky
- Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois.,Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Dianne S Belshe
- Comprehensive Transplant Center, Northwestern University Feinberg School of Medicine, Chicago, Illinois
| | - Raymond T Chung
- Gastrointestinal Division, Department of Medicine, Liver Center, Massachusetts General Hospital, Boston, Massachusetts
| | - Peter P Reese
- Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.,Renal-Electrolyte and Hypertension Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
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11
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Brandt FP, Spada Júnior V, Yamada R, Wendt GW, Ferreto LED. Caracterização epidemiológica da hepatite B em idosos. REVISTA BRASILEIRA DE GERIATRIA E GERONTOLOGIA 2020. [DOI: 10.1590/1981-22562020023.200119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Resumo Objetivo Caracterizar o perfil e identificar os fatores associados à Hepatite B na população com 60 anos ou mais de idade da região Sudoeste do Paraná, Brasil. Método Trata-se de um estudo epidemiológico descritivo e inferencial que analisou quantitativamente dados secundários obtidos através do Sistema Nacional de Agravos de Notificação (SINAN), entre 2007 a 2017. Resultados A Hepatite B foi mais frequente em homens, com baixa escolaridade e em indivíduos que exerciam atividade ligada à agricultura. A maioria dos casos foi notificada entre 2013 a 2017 e em sujeitos que reportaram exposição a material biológico. No modelo multivariado de regressão logística, as infecções pelos vírus da hepatite B foram associadas à raça/cor não branca (OR: 2,89; IC95% 1,07 – 7,87), ao histórico de realização de transfusão sanguínea (OR: 14,51; IC95% 5,44 – 38,74), em residentes de municípios de 10 a 20 mil habitantes (OR: 4,57; IC95% 1,59 – 13,12) e de municípios entre 20 a 50 mil habitantes (OR: 4,33; IC95% 1,61 – 11,56). Conclusão A caracterização dos possíveis fatores de risco para hepatite B nessa população podem subsidiar ações mais eficazes de prevenção e promoção de saúde, bem como fomentar estudos específicos que possam guiar políticas de atenção integral ao idoso.
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12
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Villani R, Monami M, Di Cosimo F, Fioravanti G, Mannucci E, Vendemiale G, Serviddio G. Direct-acting antivirals for HCV treatment in older patients: A systematic review and meta-analysis. J Viral Hepat 2019; 26:1249-1256. [PMID: 31243849 DOI: 10.1111/jvh.13169] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Revised: 05/14/2019] [Accepted: 05/15/2019] [Indexed: 12/13/2022]
Abstract
The advent of highly effective and well-tolerated direct antiviral antivirals (DAAs) has dramatically changed the landscape of chronic hepatitis C. The effect of DAAs in older adults is difficult to determine since patients aged ≥ 65 years were too few in most clinical trials and data mainly come from observational studies. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of DAAs in patients aged 65 and older. PubMed, Scopus, Web of Science, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, HCV-Trials.com databases were searched for literature published until 1 December 2017. English language articles reporting results of phase 2 or 3 randomized controlled trials (RCTs), single-arm clinical trials (SATs) and observational studies were included in the final analysis. All studies included subgroups of older patients and compared their outcomes with younger individuals. By using a random-effects or fixed-effects model, odds ratio (OR) was calculated for the efficacy and safety. Heterogeneity was tested using I2 statistics. Thirty-seven studies reported data on the DAA efficacy. The OR was 1.66 (95%CI: 1.00-2.75; P = 0.06) in meta-analysis of RCTs, and similar results were found in SATs and observational studies. HCV genotype, stage of fibrosis or HIV co-infection did not affect the rate of SVR in older persons. Prevalence of anaemia (OR 0.26 95%CI: 0.09-0.69; P = 0.007) (OR 0.25 95%CI: 0.09-0.69; P = 0.007) and skin complaints (OR 0.61 95%CI: 0.45-0.83; P = 0.001) was higher in older adults. Finally, geriatric patients affected by chronic HCV infection can be safely treated with DAAs with the same efficacy reported in younger adults.
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Affiliation(s)
- Rosanna Villani
- C.U.R.E. (University Centre for Liver Disease Research and Treatment), Institute of Internal Medicine, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Matteo Monami
- Diabetology, Azienda Ospedaliero Universitaria Careggi and University of Florence, Florence, Italy
| | - Francesca Di Cosimo
- C.U.R.E. (University Centre for Liver Disease Research and Treatment), Institute of Internal Medicine, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Gilda Fioravanti
- C.U.R.E. (University Centre for Liver Disease Research and Treatment), Institute of Internal Medicine, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Edoardo Mannucci
- Diabetology, Azienda Ospedaliero Universitaria Careggi and University of Florence, Florence, Italy
| | - Gianluigi Vendemiale
- C.U.R.E. (University Centre for Liver Disease Research and Treatment), Institute of Internal Medicine, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
| | - Gaetano Serviddio
- C.U.R.E. (University Centre for Liver Disease Research and Treatment), Institute of Internal Medicine, Department of Medical and Surgical Sciences, University of Foggia, Foggia, Italy
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13
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Saleh MI, Bani Melhim S. A time-to-event analysis describing virologic response in patients with chronic hepatitis C infection. J Chemother 2019; 31:274-283. [PMID: 31070545 DOI: 10.1080/1120009x.2019.1609739] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
The objective of this project was to describe longitudinal change in chronic hepatitis C virologic reponse using time-to-event (TTE) analysis and to identify patient characteristics that determine the dynamics of this change. We compiled demographic, clinical, and genetic data from 715 chronic hepatitis C virus (HCV) patients treated with pegylated interferon (PEG-IFN) alfa-2a and ribavirin. TTE modelling described the time between antiviral treatment initiation and the first observation of undetectable HCV RNA. A lognormal TTE model was selected to describe time to first undetectable HCV RNA. The identified predictors of prolonged time to achieve undetectable HCV RNA include HCV genotype 1, low pre-treatment ALT level, older age, or with elevated baseline haemoglobin level. In conclusion, a cohort of patients with low probability of achieving SVR can be identified. This project identifies patients with a low risk of responding to PEG-IFN alfa-2a and ribavirin combination.
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14
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Hemmersbach-Miller M, Wolfe CR, Schmader KE. Solid organ transplantation in older adults. Infectious and other age-related considerations. ACTA ACUST UNITED AC 2019; 3. [PMID: 34113803 PMCID: PMC8189398 DOI: 10.21926/obm.transplant.1901046] [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] [Indexed: 12/11/2022]
Abstract
In the U.S., older adults aged 65 or above comprise nearly one quarter of the solid organ transplant (SOT) waitlists, and the number of transplants performed in this age group continues to increase. There are no specific guidelines for the assessment and follow up of the older SOT candidate or recipient. Older adults are at increased risk of infectious complications after SOT. Despite these complications and even with the use of suboptimal donors, overall outcomes are favorable. We provide an overview to specific consideration as they relate to the older SOT candidate and recipient.
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Affiliation(s)
- Marion Hemmersbach-Miller
- Division of Infectious Diseases, Duke University Medical Center, Durham NC, USA.,Duke Clinical Research Institute, Durham NC, USA
| | - Cameron R Wolfe
- Division of Infectious Diseases, Duke University Medical Center, Durham NC, USA
| | - Kenneth E Schmader
- Division of Geriatrics, Duke University Medical Center, Durham NC, USA.,GRECC, Durham VA, Durham NC. USA
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15
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Kemp L, Clare KE, Brennan PN, Dillon JF. New horizons in hepatitis B and C in the older adult. Age Ageing 2019; 48:32-37. [PMID: 30379991 DOI: 10.1093/ageing/afy170] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2018] [Indexed: 12/23/2022] Open
Abstract
Hepatitis C (HCV) and hepatitis B (HBV), are blood-borne viruses that can cause acute hepatitis; but are clinically relevant because chronic infection is associated with development of cirrhosis and hepatocellular carcinoma. Both these viruses are becoming more common in the older population, due to the ageing of generations exposed to the risk factors associated with infection; intravenous drug use, multiple sexual partners and men who have sex with men. This review will cover the natural history and epidemiology of these infections as well as the revolution in drug therapy that now allows cure of HCV infection and complete control of HBV infection.
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Affiliation(s)
- Linda Kemp
- Gut Group, Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee, Ninewells Hospital and Medical school, Dundee, UK
| | - Kathleen E Clare
- Gut Group, Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee, Ninewells Hospital and Medical school, Dundee, UK
| | - Paul N Brennan
- Gut Group, Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee, Ninewells Hospital and Medical school, Dundee, UK
| | - John F Dillon
- Gut Group, Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee, Ninewells Hospital and Medical school, Dundee, UK
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16
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Michaelis K, Poethko-Müller C, Kuhnert R, Stark K, Faber M. Hepatitis A virus infections, immunisations and demographic determinants in children and adolescents, Germany. Sci Rep 2018; 8:16696. [PMID: 30420608 PMCID: PMC6232152 DOI: 10.1038/s41598-018-34927-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2018] [Accepted: 10/28/2018] [Indexed: 12/17/2022] Open
Abstract
Hepatitis A is a vaccine-preventable disease with a global distribution. It predominantly occurs in regions with inadequate living conditions, but also affects populations in industrialised countries. Children are frequently involved in the transmission of hepatitis A virus (HAV) and thus play a central role in the epidemiology of hepatitis A. Here, we investigated HAV infections, immunisations, and associated demographic determinants in a nationwide, population-based, cross-sectional survey conducted in Germany from 2003-2006. Out of 17,640 children and adolescents, complete data sets (HAV serology, demographic information and vaccination card) were available for 12,249 (69%), all aged 3-17 years. We found protective antibody levels (>=20 IU/L) in 1,755 (14%) individuals, 1,395 (11%) were vaccinated against hepatitis A, 360 (3%) individuals were HAV seropositive without prior hepatitis A vaccination, thus indicating a previous HAV infection. Antibody prevalence (attributable to vaccination or infection) increased significantly with age. Multivariate logistic regression revealed that predominantly children and adolescents with migration background-even if they were born in Germany-are affected by HAV infections. Our results provide a rationale to emphasise existing vaccination recommendations and, moreover, to consider additional groups with a higher risk of infection for targeted vaccination, especially children with a migration background.
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Affiliation(s)
- Kai Michaelis
- Department for Infectious Disease Epidemiology, Unit of Gastrointestinal Infections, Zoonoses, and Tropical Infections, Robert Koch Institute (RKI), D-13353, Berlin, Germany.
| | - Christina Poethko-Müller
- Department of Epidemiology and Health Monitoring, Robert Koch Institute (RKI), D-12101, Berlin, Germany
| | - Ronny Kuhnert
- Department of Epidemiology and Health Monitoring, Robert Koch Institute (RKI), D-12101, Berlin, Germany
| | - Klaus Stark
- Department for Infectious Disease Epidemiology, Unit of Gastrointestinal Infections, Zoonoses, and Tropical Infections, Robert Koch Institute (RKI), D-13353, Berlin, Germany
| | - Mirko Faber
- Department for Infectious Disease Epidemiology, Unit of Gastrointestinal Infections, Zoonoses, and Tropical Infections, Robert Koch Institute (RKI), D-13353, Berlin, Germany
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17
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de Castro TG, Manickavasagan H, Muñoz SJ. Liver Disease in the Elderly. HANDBOOK OF LIVER DISEASE 2018:351-361. [DOI: 10.1016/b978-0-323-47874-8.00026-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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18
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Hepatitis A virus infections and outbreaks in asylum seekers arriving to Germany, September 2015 to March 2016. Emerg Microbes Infect 2017; 6:e26. [PMID: 28442750 PMCID: PMC5457677 DOI: 10.1038/emi.2017.11] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2016] [Revised: 12/16/2016] [Accepted: 01/17/2017] [Indexed: 12/17/2022]
Abstract
From September 2015 to March 2016, hepatitis A notifications in Germany increased by 45% to 699 cases compared to 482 cases in the same period of the previous year. Children aged five to nine years were predominantly affected (22% of all cases in this period). We hypothesized that this increase could be explained by the marked influx of asylum seekers in this time period. We analysed national surveillance data and estimated the number of imported and autochthonous hepatitis A cases in asylum seekers. We also investigated molecular signatures of hepatitis A viruses sampled from asylum seekers to identify chains of transmission. We found that 40% (278 cases) of all 699 hepatitis A cases notified between September 2015 and March 2016 in Germany concerned asylum seekers. Most infections were acquired abroad, but at least 24% accounted for autochthonous infections. Among asylum seekers, children aged five to nine years were overrepresented with 97 of 278 (35%) notified cases. The analysed hepatitis A virus sequences were primarily subgenotype IB strains and clustered with previously isolated samples from the Middle East, Turkey, Pakistan and East Africa. Except one transmission from an asymptomatic child to a nursery nurse working in a mass accommodation, we are not aware of infection chains involving asylum seekers and German residents. We conclude that asylum-seeking children and adolescents are susceptible to hepatitis A virus infections, particularly children aged five to nine years. Measures to prevent secondary infections in asylum seekers such as extended hygiene measures and post-exposure prophylaxis seem advisable.
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19
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Chen CM, Chen SCC, Yang HY, Yang ST, Wang CM. Hospitalization and mortality due to hepatitis A in Taiwan: a 15-year nationwide cohort study. J Viral Hepat 2016; 23:940-945. [PMID: 27386835 DOI: 10.1111/jvh.12564] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2015] [Accepted: 06/07/2016] [Indexed: 12/22/2022]
Abstract
Hepatitis A virus (HAV) is the most common food-borne hepatitis in the world. The study objectives were (i) to describe the epidemiology of HAV-related hospitalizations during 1997-2011 in Taiwan, (ii) to examine the age effect on the length of stay (LOS) in hospital and (iii) to study the factors associated with death. The hospitalized cases were identified from the Taiwan National Health Insurance Research Database between 1997 and 2011 by ICD-9-CM code of 070.0/070.1. Patient sex, birthday, dates of hospitalization and death were analysed. A total of 3990 HAV-hospitalized cases, males 2467 (62%), were identified. The LOS increased as patients' age increased. The overall mortality rate was 16.8 per 1000 hospitalizations. Males had significantly higher case fatality rate than females (20.7 vs 10.5 per 1000 cases). The adjusted odds ratio (aOR) for death rose by age and increased rapidly over 40 years of age. The aOR and 95% confidence interval [95%CI] for aged 40-59 years and aged over 60 years were 7.89 (1.06-58.98) and 14.88 (2.02-109.40) compared to aged 0-19 years, respectively. Patients with chronic liver disease and cirrhosis had significantly higher risk of death (aOR=1.03 [1.01-1.04]), compared to those without liver disease. However, patients with liver disease, but no cirrhosis did not have higher risk of death (aOR=1.00 [0.99-1.01]). The aOR [95%CI] for LOS >9 day was 3.26 (1.96-5.40) compared to cases with LOS ≤9 days. Male sex, age over 40 years, cirrhotic liver and long LOS are significant factors associated with death in HAV-hospitalized cases.
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Affiliation(s)
- C-M Chen
- Department of Pediatrics, St. Joseph Catholic Hospital, Yunlin, Taiwan.,Department of Pediatrics, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan
| | - S C-C Chen
- Department of Pediatrics, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan. .,Heng-Chun Christian Hospital, Pingtung, Taiwan. .,Department of Pediatrics, School of Medicine, Taipei Medical University, Taipei, Taiwan.
| | - H-Y Yang
- Department of Medical Research, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan
| | - S-T Yang
- Department of Pediatrics, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan
| | - C-M Wang
- Department of Pediatrics, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan.,College of Nursing, Chang Gung University of Science and Technology, Chiayi, Taiwan
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20
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Nasr MY, Ali Deeb AS, Badra G, El Sayed IH. Lack of Any Relationship Between Circulating Autoantibodies and Interleukin–6 Levels in Egyptian Patients Infected with the Hepatitis C Virus. Asian Pac J Cancer Prev 2016; 17:4977-4979. [PMID: 28032726 PMCID: PMC5454706 DOI: 10.22034/apjcp.2016.17.11.4977] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Introduction: Elevated serum interleukin (IL) 6 has been reported in patients infected with the hepatitis C virus (HCV), but it remains debatable whether this influences the production of autoantibodies and the biochemical profile of HCV disease. Therefore, this current study was conducted to evaluate the relationship between IL-6 and circulating autoantibody levels in HCV positive patients. Methods: Levels of IL-6 in serum samples from 102 patients with HCV and 103 normal controls were determined by enzyme linked immunosorbent assay (ELISA). Autoantibodies were detected by immunofluorescence. Results: Levels of IL-6 were significantly higher (p=0.028) in patients infected with (HCV) compared with normal group. Autoantibodies were noted in in 43.1% of the patients; of these, 23.5% featured anti-nuclear antibodies (ANA+), 16.7% anti-smooth muscle antibodies (ASMA+), 7.8% anti-mitochondrial antibodies (AMA+), 17.6% anti-parietal cell antibodies (APCA+), 7.8% anti canalicular antibodies, and 2.9% anti reticulin antibodies (ARA+). No patients were found to be positive for anti-brush border antibodies (ABBA) or anti-ribosomal antibodies. (ARiA). No links with IL-6 levels were apparent. Conclusions: IL-6 levels are increased in patients infected with HCV disease and could influence the production of autoantibodies. However, this study did not provide evidence of a specific relationship between IL6 and circulating autoantibodies in such cases.
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Affiliation(s)
- Mohamed Y Nasr
- Molecular Biology department, Genetic Engineering and Biotechnology Research Institute, Sadat City University,Egypt.
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21
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Limited Genetic Diversity of Hepatitis B Virus in the General Population of the Offin River Valley in Ghana. PLoS One 2016; 11:e0156864. [PMID: 27271290 PMCID: PMC4894622 DOI: 10.1371/journal.pone.0156864] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2016] [Accepted: 05/16/2016] [Indexed: 12/14/2022] Open
Abstract
Hepatitis B virus (HBV) infections account for approximately 780,000 deaths per year, most of which occur in the developing world. Co-infection with HBV and hepatitis delta virus (HDV) may lead to the most severe form of viral hepatitis. In Ghana, knowledge on the prevalence of HBV and HDV in the general population is scanty and the few genetic analyses of the prevailing HBV genotypes are dating back more than a decade. In the present study, 1,323 serum samples from individuals living in a rural area (Offin river valley) of Ghana were analyzed for the presence of the hepatitis B surface antigen (HBsAg). Positive sera were subsequently tested for the presence of anti-HDV antibodies. A total of 107 (8%) sera were HBsAg positive with an 8.4% prevalence of anti-HDV antibodies among the HBsAg positives. Phylogenetic analysis based on HBV pre-S/S sequences, attributed all 52 typable samples to genotype E. All belonged to serotype ayw4. While 19 sequences clustered with those from a number of African countries, the other 33 formed a separate cluster distinguished by an intergroup mean distance of 1.5% from the pan-African HBV/E cluster. Successful implementation of HBV vaccination in the region was reflected by the low HBsAg carrier rate of 1.8% among children ≤11 years.
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22
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King A, Bornschlegel K, Johnson N, Rude E, Laraque F. Barriers to Treatment Among New York City Residents with Chronic Hepatitis C Virus Infection, 2014. Public Health Rep 2016; 131:430-7. [PMID: 27252563 PMCID: PMC4869091 DOI: 10.1177/003335491613100309] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
OBJECTIVE New, highly effective hepatitis C virus (HCV) medications recently changed the landscape of HCV treatment. Access to treatment, however, is limited. The New York City Department of Health and Mental Hygiene conducted an enhanced surveillance project to better understand the reasons patients are not treated for HCV. METHODS In June 2014, we randomly selected 300 adults who were reported through routine surveillance as having a positive HCV ribonucleic acid test result and who had seen a medical provider since June 2012. We collected information on demographics, treatment, and barriers to treatment from these 300 patients and their providers by telephone, fax, mail, and medical record review. RESULTS Of 179 providers, 74 (41%) cited co-occurring conditions and 50 (28%) cited patients not keeping follow-up or referral appointments with specialists as common barriers to treatment. Forty providers (22%) reported that they do not prescribe HCV medications and instead refer patients to specialists for treatment. Of 89 patients citing barriers to treatment, 30 (34%) cited co-occurring conditions, 26 (29%) cited concerns about side effects, 21 (24%) indicated not feeling sick, 15 (17%) cited waiting for a better treatment regimen, and 12 (13%) cited medication costs or insurance issues. Only 11 providers and 10 patients denied any barriers to treatment. CONCLUSION Increasing the number of New York City residents with HCV infection who are treated and cured will require programs to increase provider capacity, change provider behavior in treating patients with substance use and medical conditions, improve patient awareness of new medications, provide patient navigation and care coordination support through treatment, and initiate advocacy and policy work.
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Affiliation(s)
- Andrea King
- New York City Department of Health and Mental Hygiene, Queens, NY
| | | | - Nirah Johnson
- New York City Department of Health and Mental Hygiene, Queens, NY
| | - Eric Rude
- New York City Department of Health and Mental Hygiene, Queens, NY
| | - Fabienne Laraque
- New York City Department of Health and Mental Hygiene, Queens, NY
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23
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Kinoshita A, Onoda H, Ueda K, Imai N, Iwaku A, Tanaka K, Fushiya N, Koike K, Nishino H, Tajiri H. Clinical characteristics and survival outcomes of super-elderly hepatocellular carcinoma patients not indicated for surgical resection. Hepatol Res 2016; 46:E5-E14. [PMID: 25753133 DOI: 10.1111/hepr.12514] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2014] [Revised: 02/23/2015] [Accepted: 02/26/2015] [Indexed: 12/17/2022]
Abstract
AIM Considering the dramatic increase in average life expectancy during the 20th century throughout the world, the management of elderly patients with cancer has become a global issue. We herein investigated the clinical characteristics and outcomes of super-elderly hepatocellular carcinoma (HCC) patients over 80 years old not indicated for surgical resection. METHODS We retrospectively evaluated 206 newly diagnosed HCC patients. The patients were divided into two groups according to their age at inclusion; a super-elderly group (n = 37, ≥80 years) and a younger group (n = 169, <80 years). We compared the clinical characteristics, overall survival (OS) and disease-specific survival (DSS) rates among the two groups. Both univariate and multivariate analyses were performed to identify the factors associated with the OS and DSS. RESULTS The proportion of women was higher in the super-elderly group than in the younger group (P = 0.017). There were no significant differences in the OS (P = 0.171) or DSS (P = 0.176) between the two groups. The multivariate analysis revealed that only the Cancer Liver Italian Program score (hazard ratio [HR], 2.972; P < 0.0001; HR, 3.694; P < 0.0001) was independently associated with the OS and DSS. Age was not found to be associated with the OS or DSS according to either the univariate or multivariate analysis. CONCLUSION There were no significant differences in the OS and DSS rates among the super-elderly HCC patients and younger HCC patients not indicated for surgical resection. An advanced age itself does not restrict the therapeutic approach, even in super-elderly HCC patients not indicated for surgical resection.
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Affiliation(s)
- Akiyoshi Kinoshita
- Division of Gastroenterology and Hepatology, Jikei University Daisan Hospital, Tokyo, Japan
| | - Hiroshi Onoda
- Division of Gastroenterology and Hepatology, Jikei University Daisan Hospital, Tokyo, Japan
| | - Kaoru Ueda
- Division of Gastroenterology and Hepatology, Jikei University Daisan Hospital, Tokyo, Japan
| | - Nami Imai
- Division of Gastroenterology and Hepatology, Jikei University Daisan Hospital, Tokyo, Japan
| | - Akira Iwaku
- Division of Gastroenterology and Hepatology, Jikei University Daisan Hospital, Tokyo, Japan
| | - Ken Tanaka
- Division of Gastroenterology and Hepatology, Jikei University Daisan Hospital, Tokyo, Japan
| | - Nao Fushiya
- Division of Gastroenterology and Hepatology, Jikei University Daisan Hospital, Tokyo, Japan
| | - Kazuhiko Koike
- Division of Gastroenterology and Hepatology, Jikei University Daisan Hospital, Tokyo, Japan
| | - Hirokazu Nishino
- Division of Gastroenterology and Hepatology, Jikei University Daisan Hospital, Tokyo, Japan
| | - Hisao Tajiri
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan
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Loustaud-Ratti V, Jacques J, Debette-Gratien M, Carrier P. Hepatitis B and elders: An underestimated issue. Hepatol Res 2016; 46:22-8. [PMID: 25651806 DOI: 10.1111/hepr.12499] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2014] [Revised: 01/17/2015] [Accepted: 02/02/2015] [Indexed: 12/16/2022]
Abstract
As the world's population becomes older, the burden of hepatitis B virus in elderly has to be considered. The liver changes with aging and its function is eventually altered. The prevalence of hepatitis B virus is paradoxically more important in elderly in areas having vaccination programs, because of a loosening of the prevention in older patients. Some differences in hepatitis B presentation must be enhanced in elderly: lower spontaneous hepatitis B surface antigen clearance after a recent contamination, major risk of cirrhosis and hepatocarcinoma. Acute hepatitis B seems to be more often symptomatic, with a great risk of chronicity. Hepatocarcinoma linked to hepatitis B virus has a higher prevalence and a different presentation in elderly. Its treatment is the same as in younger people but is less often possible. Liver transplantation is contraindicated after 70 years old. Hepatitis B treatment panel is the same as in younger people (pegylated interferon, nucleoside or nucleotide agents). It gives identical results with no particular adverse events if the precautions for use are followed. Vaccination is less efficient, as in immunocompromised patients, and needs specific protocols.
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Affiliation(s)
- Véronique Loustaud-Ratti
- Federation of Hepatology, Gastroenterology and Hepatology Unit, CHU Limoges.,INSERM UMR 850, School of Medicine, Limoges, France
| | - Jérémie Jacques
- Federation of Hepatology, Gastroenterology and Hepatology Unit, CHU Limoges
| | | | - Paul Carrier
- Federation of Hepatology, Gastroenterology and Hepatology Unit, CHU Limoges
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Golabi P, Otgonsuren M, Suen W, Koenig AB, Noor B, Younossi ZM. Predictors of Inpatient Mortality and Resource Utilization for the Elderly Patients With Chronic Hepatitis C (CH-C) in the United States. Medicine (Baltimore) 2016; 95:e2482. [PMID: 26817883 PMCID: PMC4998257 DOI: 10.1097/md.0000000000002482] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
New incidents of chronic hepatitis C (CH-C) have stabilized yet the full impact of CH-C is not realized.Assess inpatient mortality and resource utilization for CH-C patients hospitalized in the United States.Adult CH-C patients were identified from The National Inpatient Sample (NIS) 2005 to 2009 database using the International Classification of Disease, Ninth Revision (ICD-9) diagnosis codes (070.51, 070.54, 070.70, 070.71, 070.41, and 070.44) also used to identify comorbidities.324,823 hospitalized CH-C patients were identified. Of these, 13.63% (N = 44,288) were older than 65. The rate of hospitalization for the elderly cohort steadily increased over the study period with Medicare as the payer for the majority (86%). This cohort had higher inpatient charges, approximately a half day longer hospital stay (P < 0.001) and more moderate or severe illness. During the index hospitalization, older CH-C patients were twice more likely to die than the younger age-group (5% versus 2%, P < 0.001). In the adjusted model, older age (OR: 1.02 [95% CI, 1.02-1.03]), severity of illness (OR: 12.06 [95% CI, 10.68-13.62]), and number of diagnoses (OR: 1.10 [95% CI, 1.09-1.11]) were associated with higher in-hospital mortality; severity of illness and having private insurance were significantly associated with charge per hospital stay (P < 0.001).The number of CH-C patients 65 and older increased due to the aging of the baby boomer population. Early treatment of CH-C patients with highly effective, well-tolerated, new anti-HCV regimens may prevent this significant societal burden.
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Affiliation(s)
- Pegah Golabi
- From the Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA (PG, MO, WS, ABK, BN, ZMY); and Center for Liver Diseases, Department of Medicine, Inova Fair Falls Church, VA (WS, ZMY)
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Scarbrough Lefebvre CD, Terlinden A, Standaert B. Dissecting the indirect effects caused by vaccines into the basic elements. Hum Vaccin Immunother 2015; 11:2142-57. [PMID: 26186100 PMCID: PMC4635729 DOI: 10.1080/21645515.2015.1052196] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Vaccination directly protects vaccinated individuals, but it also has the potential for indirectly protecting the unvaccinated in a population (herd protection). Unintended negative consequences such as the re-manifestation of infection, mainly expressed as age shifts, result from vaccination programs as well. We discuss the necessary conditions for achieving optimal herd protection (i.e., high quality vaccine-induced immunity, substantial effect on the force of infection, and appropriate vaccine coverage and distribution), as well as the conditions under which age shifts are likely to occur. We show examples to illustrate these effects. Substantial ambiguity in observing and quantifying these indirect vaccine effects makes accurate evaluation troublesome even though the nature of these outcomes may be critical for accurate assessment of the economic value when decision makers are evaluating a novel vaccine for introduction into a particular region or population group. More investigation is needed to identify and develop successful assessment methodologies for precisely analyzing these outcomes.
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Nelson RE, Hoop R, Korner E, DuVall S, Hayden CL, Knippenberg K, Morgan T, Pandya P, Han J, LaFleur J. Predicting Discontinuation of Pegylated Interferon as a Result of Lack of Efficacy in United States Veterans With Chronic Hepatitis C on Dual Therapy. Ann Pharmacother 2014; 48:826-836. [PMID: 24760408 DOI: 10.1177/1060028014531724] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Many patients with chronic hepatitis C virus (HCV) being treated with pegylated interferon (peg-IFN) plus ribavirin (RBV) do not respond to therapy and do not clear the virus. Standard of care during the era of dual therapy was to discontinue the patient's therapy based on insufficient decreases in viral load after 12 and/or 24 weeks on therapy. OBJECTIVES We identified patient characteristics that were significant predictors of discontinuation as a result of lack of efficacy (LOE) in a national database of US veterans with genotypes 1 and 4. METHODS We identified US veterans who received care at Veterans Affairs medical centers in 2004-2009 and who had lab-confirmed HCV diagnoses and initiated therapy with peg-IFN plus RBV. Patients who discontinued therapy early were classified as either LOE or non-LOE discontinuers based on pharmacy refill patterns and laboratory response data. Predictors of LOE discontinuation were identified using univariate and multivariable Cox proportional hazards modeling. RESULTS Of 321 238 HCV patients with an ICD-9 diagnosis code, 31 215 (9.7%) initiated dual therapy with peg-IFN plus RBV, and 10 333 (3.2%) met all inclusion criteria and were included in the analysis. Overall, 13.6% of the cohort was classified as LOE. Significant predictors of LOE discontinuation included treatment for drug abuse (hazard ratio [HR] = 2.18), age >65 years (HR = 1.75), antiretroviral therapy for HIV (HR = 1.48), black race (HR = 1.47), platelet count >100/mm3 (HR = 1.46), and drug therapy for insomnia (HR = 1.40). CONCLUSIONS We identified risk factors for discontinuation caused by LOE. Future work should focus on determining whether these characteristics are also predictive of triple-therapy LOE discontinuations.
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Affiliation(s)
- Richard E Nelson
- VA Salt Lake City Health Care System IDEAS Center, Salt Lake City, UT, USA
| | | | | | - Scott DuVall
- VA Salt Lake City Health Care System IDEAS Center, Salt Lake City, UT, USA
| | - Candace L Hayden
- VA Salt Lake City Health Care System IDEAS Center, Salt Lake City, UT, USA
| | | | | | | | - Jian Han
- Genentech, South San Francisco, CA, USA
| | - Joanne LaFleur
- VA Salt Lake City Health Care System IDEAS Center, Salt Lake City, UT, USA
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Seña AC, Moorman A, Njord L, Williams RE, Colborn J, Khudyakov Y, Drobenuic J, Xia GL, Wood H, Moore Z. Acute hepatitis B outbreaks in 2 skilled nursing facilities and possible sources of transmission: North Carolina, 2009-2010. Infect Control Hosp Epidemiol 2013; 34:709-16. [PMID: 23739075 PMCID: PMC5675526 DOI: 10.1086/670996] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
OBJECTIVE Acute hepatitis B virus (HBV) infections have been reported in long-term care facilities (LTCFs), primarily associated with infection control breaks during assisted blood glucose monitoring. We investigated HBV outbreaks that occurred in separate skilled nursing facilities (SNFs) to determine factors associated with transmission. DESIGN Outbreak investigation with case-control studies. SETTING Two SNFs (facilities A and B) in Durham, North Carolina, during 2009-2010. PATIENTS Residents with acute HBV infection and controls randomly selected from HBV-susceptible residents during the outbreak period. METHODS After initial cases were identified, screening was offered to all residents, with repeat testing 3 months later for HBV-susceptible residents. Molecular testing was performed to assess viral relatedness. Infection control practices were observed. Case-control studies were conducted to evaluate associations between exposures and acute HBV infection in each facility. RESULTS Six acute HBV cases were identified in each SNF. Viral phylogenetic analysis revealed a high degree of HBV relatedness within, but not between, facilities. No evaluated exposures were significantly associated with acute HBV infection in facility A; those associated with infection in facility B (all odds ratios >20) included injections, hospital or emergency room visits, and daily blood glucose monitoring. Observations revealed absence of trained infection control staff at facility A and suboptimal hand hygiene practices during blood glucose monitoring and insulin injections at facility B. CONCLUSIONS These outbreaks underscore the vulnerability of LTCF residents to acute HBV infection, the importance of surveillance and prompt investigation of incident cases, and the need for improved infection control education to prevent transmission.
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Affiliation(s)
- Arlene C Seña
- Durham County Department of Public Health, Durham, North Carolina, USA.
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Abstract
Liver disease presents with classic symptoms: fatigue, anorexia that progresses to nausea and vomiting, muscle and joint pain, and jaundice. Its most common cause is viral infection (hepatitis) with one of the hepatotropic hepatitis viruses. Although all types of hepatitis cause liver disease, their modes of transmission differ, and treatment may or may not be an option. In all types of hepatitis, people older than 65 years of age tend to develop more severe disease than those who are younger. Hepatitis A is rare in the United States, usually resolves completely with rest and supportive care, and there is no drug treatment. The Food and Drug Administration has approved several medications for hepatitis B, although comorbidities in the elderly may preclude their use. Hepatitis C is generally treated with interferon alpha and ribavirin in patients who can tolerate these agents. Chronic hepatitis D infection is more aggressive than chronic hepatitis B infection, leading to cirrhosis within two years in 10% to 15% of patients. Treatment with interferon for at least one year is recommended, but may not help. Hepatitis E virus infection-typically associated with large waterborne epidemics and endemic in Asia, Africa, and Mexico-is poorly understood and reported only sporadically in the United States. Consultant pharmacists can provide invaluable input concerning management of patients with hepatitis since few guidelines are available. Treatment is complex and often associated with side effects, and it is costly to treat. Complete adherence is critical. Residents, their families, and long-term care staff will need education and support in treating these patients. Pharmacist involvement is especially important as newly approved agents become available; side effects can cause clinicians and patients to abandon treatment.
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