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Okoli GN, Grossman Moon A, Soos AE, Neilson CJ, Harper DM. Hepatitis B vaccination initiation and vaccination series completion: An in-depth systematic evidence review, with meta-analysis of associations with individual socioeconomic and health-related factors. Vaccine 2025; 55:127051. [PMID: 40154242 DOI: 10.1016/j.vaccine.2025.127051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Revised: 03/14/2025] [Accepted: 03/17/2025] [Indexed: 04/01/2025]
Abstract
BACKGROUND Associations between hepatitis B vaccination and individual socioeconomic/health-related factors have not been summarised. METHODS We conducted a systematic review with meta-analysis (PROSPERO: CRD42023445721) wherein we grouped study populations into a paediatric population (<18-year-olds), community-dwelling adults (≥18-year-olds of average risk), persons at a higher risk of exposure, and persons with a chronic condition(s). We pooled appropriate multivariable-adjusted results using an inverse variance random-effects model, with the pooled results expressed as odds ratios and associated 95% confidence intervals. RESULTS We included 83 cross-sectional studies. Thirty-nine studies reported on vaccination initiation, and 51 reported on vaccination series completion. In the paediatric population, being a child of an Asian versus White mother increased the odds of vaccination initiation, whereas a low versus high mother's socioeconomic status and birth in a health facility versus home birth increased the odds of vaccination series completion. In community-dwelling adults, there were increased odds of vaccination initiation with being younger, a White versus Black/Hispanic person, a health professional, higher education, HIV/hepatitis B screening, influenza vaccination in the past year, health insurance, and health care utilisation. There were increased odds of vaccination series completion with factors like initiation. In persons at a higher risk of exposure, older age, higher education, HIV/hepatitis B screening, influenza vaccination in the past year, being married/cohabiting, and training on infection increased the odds of vaccination initiation. In contrast, drug use, HIV/hepatitis B screening, being married/cohabiting, being female, being a current/former smoker, and having more health worker experience increased the odds of vaccination series completion. In persons with chronic condition(s), younger age was associated with increased odds of vaccination initiation, whereas higher education and being a health professional increased the odds of vaccination series completion. CONCLUSIONS Several individual socioeconomic and health-related factors may influence hepatitis B vaccination, particularly in community-dwelling adults and persons at higher risk of exposure. Our findings may inform targeted messaging to optimise hepatitis B vaccination.
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Affiliation(s)
- George N Okoli
- Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada.
| | | | - Alexandra E Soos
- University of Michigan Medical School, University of Michigan, Michigan, USA
| | - Christine J Neilson
- Neil John Maclean Health Sciences Library, University of Manitoba, Winnipeg, MB, Canada
| | - Diane M Harper
- Departments of Family Medicine and Obstetrics & Gynecology, University of Michigan, Michigan, USA
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Lei Z, Wang L, Gao H, Guo S, Kang X, Yuan J, Lv Z, Jiang Y, Yi J, Chen Z, Wang G. Mechanisms underlying the compromised clinical efficacy of interferon in clearing HBV. Virol J 2024; 21:314. [PMID: 39633459 PMCID: PMC11619119 DOI: 10.1186/s12985-024-02589-3] [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: 09/23/2024] [Accepted: 11/26/2024] [Indexed: 12/07/2024] Open
Abstract
Hepatitis B virus (HBV) is a hepatotropic DNA virus that can cause acute or chronic hepatitis, representing a significant global health concern. By 2019, approximately 296 million individuals were chronically infected with HBV, with 1.5 million new cases annually and 820,000 deaths due to HBV-related cirrhosis and liver cancer. Current treatments for chronic hepatitis B include nucleotide analogs (NAs) and interferons (IFNs), particularly IFN-α. NAs, such as entecavir and tenofovir, inhibit viral reverse transcription, while IFN-α exerts antiviral effects by directly suppressing viral replication, modulating viral genome epigenetics, degrading cccDNA, and activating immune responses. Despite its potential, IFN-α shows limited clinical efficacy, partly due to HBV's interference with the IFN signaling pathway. HBV encodes proteins like HBc, Pol, HBsAg, and HBx that disrupt IFN-α function. For example, HBV Pol inhibits STAT1 phosphorylation, HBsAg suppresses STAT3 phosphorylation, and HBx interferes with IFN-α efficacy through multiple mechanisms. Additionally, HBV downregulates key genes in the IFN signaling pathway, further diminishing IFN-α's antiviral effects. Understanding these interactions is crucial for improving IFN-α-based therapies. Future research may focus on overcoming HBV resistance by targeting viral proteins or optimizing IFN-α delivery. In summary, HBV's ability to resist IFN-α limits its therapeutic effectiveness, highlighting the need for new strategies to enhance treatment outcomes.
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Affiliation(s)
- Zhuoyan Lei
- Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, 8 Shuren St, Gongshu District, Hangzhou, 310015, Zhejiang Province, China
| | - Luye Wang
- Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, 8 Shuren St, Gongshu District, Hangzhou, 310015, Zhejiang Province, China
| | - Hanlin Gao
- Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, 8 Shuren St, Gongshu District, Hangzhou, 310015, Zhejiang Province, China
| | - Shubian Guo
- Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, 8 Shuren St, Gongshu District, Hangzhou, 310015, Zhejiang Province, China
| | - Xinjian Kang
- Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, 8 Shuren St, Gongshu District, Hangzhou, 310015, Zhejiang Province, China
| | - Jiajun Yuan
- Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, 8 Shuren St, Gongshu District, Hangzhou, 310015, Zhejiang Province, China
| | - Ziying Lv
- Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, 8 Shuren St, Gongshu District, Hangzhou, 310015, Zhejiang Province, China
| | - Yuxin Jiang
- Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, 8 Shuren St, Gongshu District, Hangzhou, 310015, Zhejiang Province, China
| | - Jinping Yi
- Department of Clinical Laboratory, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Zhi Chen
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, National Clinical Research Center for Infectious Diseases, Zhejiang University, Hangzhou, China
| | - Gang Wang
- Key Laboratory of Artificial Organs and Computational Medicine of Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, 8 Shuren St, Gongshu District, Hangzhou, 310015, Zhejiang Province, China.
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Sharma B, Bodh V, Sharma N, Sharma R, Sachdeva A, Gupta A, Kanga A, Sharma D, Chauhan A. Hepatitis B in Trans-Himalayan Tribal Population: High Prevalence, High Pediatric Burden, Virologic Patterns, and Implications for Public Health Interventions. J Clin Exp Hepatol 2024; 14:101336. [PMID: 38283704 PMCID: PMC10809090 DOI: 10.1016/j.jceh.2023.101336] [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: 07/11/2023] [Accepted: 12/17/2023] [Indexed: 01/30/2024] Open
Abstract
Background/Aims The prevalence of hepatitis B is higher in tribal populations, compared to non-tribal populations in India. Therefore, this study aimed to investigate the risk factors, virological and biochemical profile of patients with hepatitis B in a tribal population. Methods This study analyzed data collected from a community-based project conducted in Spiti, Himachal Pradesh, from July 2015 to 2017. The study included adults and children inhabiting 40 cluster villages out of 82 villages in the subdivision. The blood samples were collected for liver panel, hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), Anti-HBe antibody (anti-HBe Ab) and Hepatitis B virus DNA (HBV-DNA). Results HBsAg was positive in 23.08% of the population (968/4201), with a prevalence of 13.51% in children under 5 years of age. HBeAg positivity was seen in 22.4% of the participants, while anti-HBe Ab positivity was seen in 59.03% of the participants. HBeAg positive infection, HBeAg positive hepatitis, HBeAg negative hepatitis and HBeAg negative infection were seen in 18.06%, 1.98%, 6.17% and 74.01% of the participants, respectively. HBeAg positivity was highest in 2nd decade (40.83% vs 22% overall). Patients with HBeAg positivity exhibited higher levels of HBV DNA [1960 (IQR: 0-108) IU/ml vs 97.2 (IQR: 0-2090) IU/ml, P < 0.001] and alanine transaminase (ALT) [22.5 (IQR: 16-33) U/L vs 19 (IQR: 14-26) U/L, P = 0.003] levels compared to HBeAg negative patients. Conclusion This study shows a high prevalence of hepatitis B in tribal population, particularly among children under 5 years of age.
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Affiliation(s)
- Brij Sharma
- Department of Gastroenterology, Indira Gandhi Medical College, Shimla, India
| | - Vishal Bodh
- Department of Gastroenterology, Indira Gandhi Medical College, Shimla, India
| | - Neetu Sharma
- Department of Physiology, Indira Gandhi Medical College, Shimla, India
| | - Rajesh Sharma
- Department of Gastroenterology, Indira Gandhi Medical College, Shimla, India
| | - Amit Sachdeva
- Department of Community Medicine, Indira Gandhi Medical College, Shimla, India
| | - Anmol Gupta
- Department of Community Medicine, Indira Gandhi Medical College, Shimla, India
| | - Anil Kanga
- Department of Microbiology, Indira Gandhi Medical College, Shimla, India
| | - Dikshant Sharma
- Pandit Jawahar Lal Nehru Government Medical College, Chamba, India
| | - Ashish Chauhan
- Department of Gastroenterology, Indira Gandhi Medical College, Shimla, India
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Varghese N, Majeed A, Nyalakonda S, Boortalary T, Halegoua-DeMarzio D, Hann HW. Review of Related Factors for Persistent Risk of Hepatitis B Virus-Associated Hepatocellular Carcinoma. Cancers (Basel) 2024; 16:777. [PMID: 38398168 PMCID: PMC10887172 DOI: 10.3390/cancers16040777] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2023] [Revised: 01/30/2024] [Accepted: 02/05/2024] [Indexed: 02/25/2024] Open
Abstract
Chronic hepatitis B virus (HBV) infection is the largest global cause of hepatocellular carcinoma (HCC). Current HBV treatment options include pegylated interferon-alpha and nucleos(t)ide analogues (NAs), which have been shown to be effective in reducing HBV DNA levels to become undetectable. However, the literature has shown that some patients have persistent risk of developing HCC. The mechanism in which this occurs has not been fully elucidated. However, it has been discovered that HBV's covalently closed circular DNA (cccDNA) integrates into the critical HCC driver genes in hepatocytes upon initial infection; additionally, these are not targets of current NA therapies. Some studies suggest that HBV undergoes compartmentalization in peripheral blood mononuclear cells that serve as a sanctuary for replication during antiviral therapy. The aim of this review is to expand on how patients with HBV may develop HCC despite years of HBV viral suppression and carry worse prognosis than treatment-naive HBV patients who develop HCC. Furthermore, HCC recurrence after initial surgical or locoregional treatment in this setting may cause carcinogenic cells to behave more aggressively during treatment. Curative novel therapies which target the life cycle of HBV, modulate host immune response, and inhibit HBV RNA translation are being investigated.
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Affiliation(s)
- Nevin Varghese
- Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA; (N.V.); (A.M.); (S.N.); (T.B.); (D.H.-D.)
| | - Amry Majeed
- Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA; (N.V.); (A.M.); (S.N.); (T.B.); (D.H.-D.)
| | - Suraj Nyalakonda
- Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA; (N.V.); (A.M.); (S.N.); (T.B.); (D.H.-D.)
| | - Tina Boortalary
- Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA; (N.V.); (A.M.); (S.N.); (T.B.); (D.H.-D.)
- Division of Gastroenterology and Hepatology, Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Dina Halegoua-DeMarzio
- Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA; (N.V.); (A.M.); (S.N.); (T.B.); (D.H.-D.)
- Division of Gastroenterology and Hepatology, Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
| | - Hie-Won Hann
- Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA; (N.V.); (A.M.); (S.N.); (T.B.); (D.H.-D.)
- Division of Gastroenterology and Hepatology, Department of Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA
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Stroffolini T, Stroffolini G. Vaccination Campaign against Hepatitis B Virus in Italy: A History of Successful Achievements. Vaccines (Basel) 2023; 11:1531. [PMID: 37896935 PMCID: PMC10610604 DOI: 10.3390/vaccines11101531] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Revised: 09/25/2023] [Accepted: 09/26/2023] [Indexed: 10/29/2023] Open
Abstract
In Italy, the vaccination campaign against hepatitis B virus has been characterized by two phases. In the first phase (1984-1991), vaccination with plasma-derived vaccines was first recommended for the high-risk group. In the second phase (1991-nowadays), recombinant vaccine targeted, by law, infants 2 months old and teenagers 12 years old (limited to the first 12 years of campaign); screening for HBsAg became compulsory for all pregnant women during the third trimester of pregnancy. Successful achievements have been attained: No acute HBV case has been observed in the age group targeted by vaccination, the pool of chronic HBsAg carriers is strongly reduced, perinatal HBV transmission is under control, and acute delta virus hepatitis cases are nearly eliminated. The key point of this success has been the peculiar vaccination policy adopted. The combined vaccination of teenagers has generated an early immune cohort of youths, who are no longer at risk of acquiring HBV infection by sources of exposure (i.e., drug use and unsafe sex practices) typical of the young adults. Vaccination of household contacts with HBsAg-positive subjects represents an area of improvement; providing migrants and refugees access to healthcare services is also a focal point. In 2020, Italy became the first country in Europe to achieve the WHO's regional hepatitis targets.
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Affiliation(s)
- Tommaso Stroffolini
- Department of Tropical and Infectious Diseases, Policlinico Umberto I, 00161 Rome, Italy;
| | - Giacomo Stroffolini
- Department of Infectious-Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Via Don A. Sempreboni, 5, Negrar, 37024 Verona, Italy
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Stroffolini T, Stroffolini G. Five Decades of HBV Infection in Italy: A Continuous Challenge. BIOLOGY 2023; 12:1075. [PMID: 37626961 PMCID: PMC10451692 DOI: 10.3390/biology12081075] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Revised: 07/28/2023] [Accepted: 07/31/2023] [Indexed: 08/27/2023]
Abstract
In Italy, Hepatitis B virus (HBV) infection has been characterized by several changes over the last five decades. In 2019, the incidence of acute HBV among subjects targeted by the vaccination campaign was 0 cases in the age group 0-14 years and 0.1/100,000 in the age group 15-24. Nowadays, the burden of different stages of HBV-related chronic liver diseases is minimal. Intravenous drug use is no longer a risk factor (O.R. 0.7; 95% C.I. 0.5-1.02) for acquiring acute HBV; the proportion of cases reporting this exposure fell from 29.8% to 3.3% over the last two decades. The key public health intervention has been the compulsory vaccination campaign started in 1991 for infants 3 months old and 1-2 years old (the latter group for the first 12 years of the campaign). Moreover, non-immunogenic factors and the availability of effective oral antiviral drugs have played and continue to play a prominent role. The potential availability of new oral antiviral drugs with the inherent ability to eliminate the genomic HBV reservoirs may represent a further crucial step in the elimination of the virus in people that are already infected.
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Affiliation(s)
- Tommaso Stroffolini
- Department of Tropical and Infectious Diseases, Policlinico Umberto I, 00186 Rome, Italy;
| | - Giacomo Stroffolini
- Department of Infectious-Tropical Diseases and Microbiology, IRCCS Sacro Cuore Don Calabria Hospital, Via Don A. Sempreboni, 5, Negrar, 37024 Verona, Italy
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Hsu YC, Huang DQ, Nguyen MH. Global burden of hepatitis B virus: current status, missed opportunities and a call for action. Nat Rev Gastroenterol Hepatol 2023:10.1038/s41575-023-00760-9. [PMID: 37024566 DOI: 10.1038/s41575-023-00760-9] [Citation(s) in RCA: 225] [Impact Index Per Article: 112.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/24/2023] [Indexed: 04/08/2023]
Abstract
Chronic hepatitis B virus (HBV) infection affects about 296 million people worldwide and is the leading aetiology of cirrhosis and liver cancer globally. Major medical complications also include acute flares and extrahepatic manifestations. In addition, people living with HBV infection also experience stigma. HBV-related cirrhosis resulted in an estimated 331,000 deaths in 2019, and it is estimated that the number of deaths from HBV-related liver cancer in 2019 was 192,000, an increase from 156,000 in 2010. Meanwhile, HBV remains severely underdiagnosed and effective measures that can prevent infection and disease progression are underutilized. Birth dose coverage for HBV vaccines remains low, particularly in low-income countries or regions where HBV burden is high. Patients with HBV infection are inadequately evaluated and linked to care and are undertreated worldwide, even in high-income countries or regions. Despite the goal of the World Health Organization to eliminate viral hepatitis as a public health problem by 2030, the annual global deaths from HBV are projected to increase by 39% from 2015 to 2030 if the status quo remains. In this Review, we discuss the current status and future projections of the global burden of HBV infection. We also discuss gaps in the current care cascade and propose future directions.
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Affiliation(s)
- Yao-Chun Hsu
- Center for Liver Diseases, E-Da Hospital, Kaohsiung, Taiwan.
- School of Medicine, I-Shou University, Kaohsiung, Taiwan.
- Division of Gastroenterology, Fu-Jen Catholic University Hospital, New Taipei, Taiwan.
- Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, New Taipei, Taiwan.
| | - Daniel Q Huang
- Division of Gastroenterology and Hepatology, National University Health System, Singapore, Singapore
- Department of Medicine, National University of Singapore, Singapore, Singapore
| | - Mindie H Nguyen
- Department of Medicine, Stanford University Medical Centre, Palo Alto, CA, USA.
- Department of Epidemiology and Population Health, Stanford University Medical Centre, Palo Alto, CA, USA.
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Harris AM, Schillie S. Hepatitis B and Hepatitis D Viruses. PRINCIPLES AND PRACTICE OF PEDIATRIC INFECTIOUS DISEASES 2023:1125-1133.e4. [DOI: 10.1016/b978-0-323-75608-2.00213-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Choi WM, Choi J, Lim YS. Hepatitis B: epidemiology, natural history, and diagnosis. COMPREHENSIVE GUIDE TO HEPATITIS ADVANCES 2023:183-203. [DOI: 10.1016/b978-0-323-98368-6.00007-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Screening of Occult Hepatitis B and C Virus Infection in Working Children, Tehran, Iran. ARCHIVES OF PEDIATRIC INFECTIOUS DISEASES 2022. [DOI: 10.5812/pedinfect-118763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Background: Working children are susceptible to infection with various infectious microorganisms. Unfortunately, the difficulties of working children are growing at a remarkable speed worldwide. Objectives: The aim of this research was to determine the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, as well as to evaluate the level of anemia, calcium, and phosphorus in working children. Methods: This cross-sectional research was performed on 370 Iranian and Afghan working children from February 2018 to May 2019. Hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis B core antibody (HBcAb), and anti-HCV Ab were evaluated using an enzyme-linked immunosorbent assay (ELISA). Furthermore, HCV-RNA and genomic HBV-DNA in the plasma and peripheral blood mononuclear cell (PBMC) specimens of the participants were investigated. The restriction fragment length polymorphism (RFLP) method was used to determine the genotype of HCV, and sequencing was performed to confirm. Results: The mean age of the participants was 10.1 ± 2.1 years (range, 6 - 15 years), and 229 (61.9%) were male. None of the studied children had any detectable HBV-DNA in the plasma and PBMC. The HCV genome was not detected in the plasma of the children, but HCV-RNA was assessed in the PBMC sample of 1 child (0.3%). Therefore, one of the children had occult HCV infection (OCI). The genotype of HCV in this child was subtype 1a. Furthermore, HBsAb was detected in Iranian (41.5%) and Afghan children (40.0%), and 2 (0.54%) of the working children were HBsAg positive. In 3 participants (0.8%), a positive HBcAb test result was noted. Conclusions: The prevalence of HCV and HBV infection in working children in Iran is extremely rare. However, there is a possibility of the presence of OCI in these children.
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Nagra N, Kozarek RA, Burman BE. Therapeutic Advances in Viral Hepatitis A-E. Adv Ther 2022; 39:1524-1552. [PMID: 35220557 DOI: 10.1007/s12325-022-02070-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 01/31/2022] [Indexed: 11/25/2022]
Abstract
Viral hepatitis remains a significant global health problem. All forms of viral hepatitis A through E (A-E) can lead to acute symptomatic infection, while hepatitis B and C can lead to chronic infection associated with significant morbidity and mortality related to progression to cirrhosis, end-stage-liver disease, and liver cancer. Viral hepatitis occurs worldwide, though certain regions are disproportionately affected. We now, remarkably, have highly effective curative regimens for hepatitis C, and safe and tolerable medications to suppress hepatitis B activity, and to prevent liver damage and slow disease progression. We have effective vaccines for hepatitis A and B which provide long-lasting immunity, while improved sanitation and awareness can curb outbreaks of hepatitis A and E. However, more effective and available preventive and curative strategies are needed to achieve global eradication of viral hepatitis. This review provides an overview of the epidemiology, transmission, diagnosis, and clinical features of each viral hepatitis with a primary focus on current and future therapeutic and curative options.
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Affiliation(s)
- Navroop Nagra
- Department of Gastroenterology, University of Louisville, Louisville, KY, 40202, USA
| | - Richard A Kozarek
- Center for Digestive Health, Virginia Mason Franciscan Health, 1100 9th Ave., Seattle, WA, 98101, USA
| | - Blaire E Burman
- Center for Digestive Health, Virginia Mason Franciscan Health, 1100 9th Ave., Seattle, WA, 98101, USA.
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Heck JE, Wu CK, Huang X, Chew KW, Tong M, Federman N, Ritz B, Arah OA, Li CY, Yu F, Olsen J, Hansen J, Lee PC. Cohort study of familial viral hepatitis and risks of paediatric cancers. Int J Epidemiol 2021; 51:448-457. [PMID: 34966942 PMCID: PMC9308392 DOI: 10.1093/ije/dyab262] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Accepted: 12/07/2021] [Indexed: 02/03/2023] Open
Abstract
BACKGROUND Although viral hepatitis causes paediatric hepatocellular carcinoma and hepatic and extrahepatic cancers in adults, there are few epidemiologic studies on paediatric-cancer risks from parental viral hepatitis. In a nationwide study in a viral hepatitis endemic region and with confirmation in another population-based sample, we examined associations between parental hepatitis B (HBV) and C (HCV) infections and risks of cancers in offspring. METHODS We included all children born in Taiwan in 2004-2014 (N = 2 079 037) with 2160 cancer cases ascertained from the Cancer Registry. We estimated risks for paediatric cancers using Cox proportional-hazard regressions. We checked these associations in a nationwide case-control study in Denmark (6422 cases, 160 522 controls). RESULTS In Taiwan, paternal HBV was related to child's hepatoblastoma [hazard ratio (HR) = 1.77, 95% confidence interval (CI) = 1.05, 2.97] when identified at any time in the medical record, and when analyses were limited to hepatitis diagnoses occurring before the child's birth, risks increased (HR = 2.08, 95% CI = 1.13-3.80). Paternal HCV was related to child's non-Hodgkin lymphoma (HR = 2.06, 95% CI = 1.13-3.74). Maternal HCV was weakly related to increased risks of all childhood cancers [all types combined; HR = 1.45, 95% CI = 0.95-2.22]. The population-attributable fraction of hepatoblastoma for maternal, paternal and child HBV was 2.6%, 6.8% and 2.8%, respectively. CONCLUSIONS Parental HBV and HCV may be risk factors for hepatic and non-hepatic cancers in children. If associations are causal, then parental screening and treatment with antivirals may prevent some paediatric cancers.
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Affiliation(s)
- Julia E Heck
- Department of Rehabilitation and Health Services, College of Health and Public Service, University of North Texas, Denton, TX, USA,Center for Racial and Ethnic Equity in Health and Society, University of North Texas, Denton, TX, USA,Corresponding author. College of Health and Public Service, University of North Texas, 1155 Union Circle #311340, Denton, TX 76203-5017, USA. E-mail:
| | - Chia-Kai Wu
- Department of Health Care Management, National Taipei University of Nursing and Health Sciences, Beitou Dist, Taipei, Taiwan
| | - Xiwen Huang
- Center for Racial and Ethnic Equity in Health and Society, University of North Texas, Denton, TX, USA
| | - Kara W Chew
- Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Myron Tong
- Asian Liver Center, Geffen School of Medicine and Ronald Reagan Medical Center, UCLA, Los Angeles, CA, USA
| | - Noah Federman
- Department of Pediatrics, Geffen School of Medicine, UCLA, Los Angeles, CA, USA
| | - Beate Ritz
- Department of Epidemiology, Fielding School of Public Health, University of California (UCLA), Los Angeles, CA, USA
| | - Onyebuchi A Arah
- Department of Epidemiology, Fielding School of Public Health, University of California (UCLA), Los Angeles, CA, USA,Department of Statistics, UCLA College of Letters and Science, Los Angeles, CA, USA,Department of Public Health, Faculty of Health, Aarhus University, Aarhus, Denmark
| | - Chung-Yi Li
- Department of Public Health, National Cheng Kung University, Tainan, Taiwan,Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan
| | - Fei Yu
- Department of Biostatistics, Fielding School of Public Health UCLA, Los Angeles, CA, USA
| | - Jorn Olsen
- Department of Clinical Epidemiology, Aarhus University, Aarhus N, Denmark
| | - Johnni Hansen
- Danish Cancer Society Research Center, Copenhagen, Denmark
| | - Pei-Chen Lee
- Department of Health Care Management, National Taipei University of Nursing and Health Sciences, Beitou Dist, Taipei, Taiwan,Department of Psychiatry, Taipei City Hospital, Taipei, Taiwan,Inserm U1018, Team ‘Exposome, Heredity, Cancer and Health’, CESP, Villejuif, France
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Hu H, Shen Y, Hu M, Zheng Y, Xu K, Li L. Incidence and Influencing Factors of New Hepatitis B Infections and Spontaneous Clearance: A Large-Scale, Community-Based Study in China. Front Med (Lausanne) 2021; 8:717667. [PMID: 34869415 PMCID: PMC8637118 DOI: 10.3389/fmed.2021.717667] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Accepted: 08/23/2021] [Indexed: 01/05/2023] Open
Abstract
Background: Hepatitis B surface antigen (HBsAg) is widely used in hepatitis B screening, and HBsAg seroclearance indicates hepatitis B eradication. Few studies have explored the incidence of and determinants for spontaneous seroclearance using a long-term follow-up cohort study. Our research aimed to examine the incidence of and influencing factors for hepatitis B virus infection and spontaneous clearance of HBsAg from a large-scale cohort in China. Methods: A total of 151,926 resident individuals in Tongxiang underwent HBsAg screening at least thrice in a 7-year period. Serum samples collected at baseline and follow-up examinations were tested for HBsAg. Cox proportional hazard models were used to analyze determinants of HBsAg seroclearance and persistent HBsAg presence. Results: Among the 151,926 participants, new hepatitis B infections occurred in 4,497 participants, yielding an incidence rate of 571.38 per 100,000 person-years. The incidence rate for males was higher than that for females. In the multivariate Cox regression analysis, female gender, alcohol drinking history, hepatitis family history and middle-age group were predictors for persistent positive HBsAg status. Conclusions: The incidence rate of new hepatitis B infections was 571.38 per 100,000 person-years. Male and aged people in this community cohort have a higher infection rate. Alcohol drinking and hepatitis family history were risk factor leading to chronic infection. Female and middle-aged people were prone to persistent positive HBsAg status.
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Affiliation(s)
- Haiyang Hu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
| | - Yangfan Shen
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
| | - Ming Hu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
| | - Yang Zheng
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
| | - Kaijin Xu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
| | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, School of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
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Li C, He WQ. The impact of universal hepatitis B vaccine on the trend of liver cancer from the Global Burden of Disease Study 2017. Liver Int 2021; 41:1762-1774. [PMID: 33590659 DOI: 10.1111/liv.14821] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Revised: 01/13/2021] [Accepted: 02/11/2021] [Indexed: 12/14/2022]
Abstract
AIMS This study aims to assess the trend of hepatitis B virus (HBV)-attributable liver cancer as well as the impact of HBV vaccine on it. METHODS We retrieved data from Global Burden Disease study to estimate trends of HBV-attributable liver cancer by region and age from 1990 to 2017 and HBV vaccine data from World Health Organization to assess its impact on these trends for children (0-14 years), adolescents and young adults (15-29 years). Change of cancer cases, age-standardized incidence rate (ASR) and estimated annual percentage change (EAPC) were used to quantify the trends of HBV-attributable liver cancer. RESULTS In this study, reduction in HBV-attributable cancer incident cases was found among children (from 2080 to 1430), adolescents and young adults (from 10 890 to 9090). In terms of ASR, overall reduction was observed globally by an average of -0.45% (95% CI: -0.62 to -0.29) per year in the same period. The highest reduction in ASR was found in adolescents and young adults with EAPC of -3.02 (95% CI: -3.57 to -2.46). Although the ASR has decreased from all the five regions with universal HBV immunization programme, it has increased in the region without universal vaccination and the highest increase was found among children with EAPC of 1.97 (95% CI: 1.71-2.23). CONCLUSION Significant reduction in HBV-attributable liver cancer among children was mainly because of the universal HBV vaccination. However, the increasing trend of HBV-attributable liver cancer in region without universal HBV vaccination suggested the necessity of introducing universal immunization.
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Affiliation(s)
- Chenxi Li
- School of Population Health, UNSW Sydney, Sydney, Australia
| | - Wen-Qiang He
- School of Population Health, UNSW Sydney, Sydney, Australia
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Campos-Valdez M, Monroy-Ramírez HC, Armendáriz-Borunda J, Sánchez-Orozco LV. Molecular Mechanisms during Hepatitis B Infection and the Effects of the Virus Variability. Viruses 2021; 13:v13061167. [PMID: 34207116 PMCID: PMC8235420 DOI: 10.3390/v13061167] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2021] [Revised: 06/10/2021] [Accepted: 06/11/2021] [Indexed: 12/16/2022] Open
Abstract
The immunopathogenesis and molecular mechanisms involved during a hepatitis B virus (HBV) infection have made the approaches for research complex, especially concerning the patients’ responses in the course of the early acute stage. The study of molecular bases involved in the viral clearance or persistence of the infection is complicated due to the difficulty to detect patients at the most adequate points of the disease, especially in the time lapse between the onset of the infection and the viral emergence. Despite this, there is valuable data obtained from animal and in vitro models, which have helped to clarify some aspects of the early immune response against HBV infection. The diversity of the HBV (genotypes and variants) has been proven to be associated not only with the development and outcome of the disease but also with the response to treatments. That is why factors involved in the virus evolution need to be considered while studying hepatitis B infection. This review brings together some of the published data to try to explain the immunological and molecular mechanisms involved in the different stages of the infection, clinical outcomes, viral persistence, and the impact of the variants of HBV in these processes.
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Affiliation(s)
- Marina Campos-Valdez
- Centro Universitario de Ciencias de la Salud, Departamento de Biología Molecular y Genómica, Instituto de Biología Molecular en Medicina, Universidad de Guadalajara, Guadalajara 44340, Jalisco, México; (M.C.-V.); (H.C.M.-R.); (J.A.-B.)
| | - Hugo C. Monroy-Ramírez
- Centro Universitario de Ciencias de la Salud, Departamento de Biología Molecular y Genómica, Instituto de Biología Molecular en Medicina, Universidad de Guadalajara, Guadalajara 44340, Jalisco, México; (M.C.-V.); (H.C.M.-R.); (J.A.-B.)
| | - Juan Armendáriz-Borunda
- Centro Universitario de Ciencias de la Salud, Departamento de Biología Molecular y Genómica, Instituto de Biología Molecular en Medicina, Universidad de Guadalajara, Guadalajara 44340, Jalisco, México; (M.C.-V.); (H.C.M.-R.); (J.A.-B.)
- Escuela de Medicina y Ciencias de la Salud, Tecnológico de Monterrey, Campus Guadalajara, Zapopan 45201, Jalisco, México
| | - Laura V. Sánchez-Orozco
- Centro Universitario de Ciencias de la Salud, Departamento de Biología Molecular y Genómica, Instituto de Biología Molecular en Medicina, Universidad de Guadalajara, Guadalajara 44340, Jalisco, México; (M.C.-V.); (H.C.M.-R.); (J.A.-B.)
- Correspondence: ; Tel.: +52-33-3954-5677
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Duarte G, Pezzuto P, Barros TD, Mosimann G, Martinez-Espinosa FE. Brazilian Protocol for Sexually Transmitted Infections 2020: viral hepatitis. Rev Soc Bras Med Trop 2021; 54:e2020834. [PMID: 33729415 PMCID: PMC8210490 DOI: 10.1590/0037-8682-834-2020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Accepted: 03/10/2021] [Indexed: 12/09/2022] Open
Abstract
This article discusses viral hepatitis, a theme addressed by the Clinical Protocol and Therapeutic Guidelines to Comprehensive Care for People with Sexually Transmitted Infections and, more precisely, by the Clinical Protocols and Therapeutic Guidelines for Hepatitis B and Hepatitis C and Coinfections, published by the Brazilian Ministry of Health. Besides the broad spectrum of health impairment, hepatitis A, B, and C viruses also present different transmission forms, whether parenteral, sexual, vertical, or fecal-oral. Among the strategies suggested for the control of viral hepatitis, in addition to behavioral measures, are expanded diagnosis, early vaccination against hepatitis A and hepatitis B viruses, and access to available therapeutic resources. Considering vertical transmission of the hepatitis B and hepatitis C viruses, screening for pregnant women with chronic hepatitis B and C is an essential perinatal health strategy, indicating with precision those who can benefit from the prophylactic interventions. Viral hepatitis A, B, and C are responsible for more than 1.34 million deaths worldwide every year, from which 66% are the result of hepatitis B, 30% of hepatitis C, and 4% of hepatitis A.
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Affiliation(s)
- Geraldo Duarte
- Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Ribeirão Preto, SP, Brasil
| | - Paula Pezzuto
- Ministério da Saúde, Secretaria de Vigilância em Saúde, Brasília, DF, Brasil
| | - Tiago Dahrug Barros
- Ministério da Saúde, Secretaria de Vigilância em Saúde, Brasília, DF, Brasil
| | - Gláucio Mosimann
- Ministério da Saúde, Secretaria de Vigilância em Saúde, Brasília, DF, Brasil
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Duarte G, Pezzuto P, Barros TD, Mosimann Junior G, Martínez-Espinosa FE. [Brazilian Protocol for Sexually Transmitted Infections 2020: viral hepatitis]. ACTA ACUST UNITED AC 2021; 30:e2020834. [PMID: 33729415 DOI: 10.1590/s1679-4974202100016.esp1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Accepted: 10/03/2020] [Indexed: 01/01/2023]
Abstract
This article discusses viral hepatitis, a theme addressed by the Clinical Protocol and Therapeutic Guidelines to Comprehensive Care for People with Sexually Transmitted Infections and, more precisely, by the Clinical Protocols and Therapeutic Guidelines for Hepatitis B and Hepatitis C and Coinfections, published by the Brazilian Ministry of Health. Besides the broad spectrum of health impairment, hepatitis A, B and C viruses also present different forms of transmission, whether parenteral, sexual, vertical or oral. Among the strategies suggested for the control of viral hepatitis, in addition to behavioral measures, are expanded diagnosis, early vaccination against hepatitis A and hepatitis B viruses, and access to available therapeutic resources. Considering vertical transmission of the hepatitis B and hepatitis C viruses, screening for pregnant women with chronic hepatitis B and C is an important perinatal health strategy, indicating with precision those who can benefit from the prophylactic interventions.
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Affiliation(s)
- Geraldo Duarte
- Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Ribeirão Preto, SP, Brasil
| | - Paula Pezzuto
- Ministério da Saúde, Secretaria de Vigilância em Saúde, Brasília, DF, Brasil
| | - Tiago Dahrug Barros
- Ministério da Saúde, Secretaria de Vigilância em Saúde, Brasília, DF, Brasil
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Wu J, Tseng T, Liu C, Su T, Liu C, Chen P, Chen D, Kao J. Both hepatitis A and hepatitis D infections may be associated with more advanced liver disease in patients with chronic hepatitis B. ADVANCES IN DIGESTIVE MEDICINE 2020. [DOI: 10.1002/aid2.13222] [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: 11/12/2022]
Affiliation(s)
- Jer‐Wei Wu
- Division of Gastroenterology, Department of Internal Medicine National Taiwan University Hospital Taipei Taiwan
| | - Tai‐Chung Tseng
- Division of Gastroenterology, Department of Internal Medicine National Taiwan University Hospital Taipei Taiwan
- Hepatitis Research Center National Taiwan University Hospital Taipei Taiwan
| | - Chun‐Jen Liu
- Division of Gastroenterology, Department of Internal Medicine National Taiwan University Hospital Taipei Taiwan
- Hepatitis Research Center National Taiwan University Hospital Taipei Taiwan
- Graduate Institute of Clinical Medicine National Taiwan University College of Medicine Taipei Taiwan
| | - Tung‐Hung Su
- Division of Gastroenterology, Department of Internal Medicine National Taiwan University Hospital Taipei Taiwan
- Hepatitis Research Center National Taiwan University Hospital Taipei Taiwan
| | - Chen‐Hua Liu
- Division of Gastroenterology, Department of Internal Medicine National Taiwan University Hospital Taipei Taiwan
- Hepatitis Research Center National Taiwan University Hospital Taipei Taiwan
| | - Pei‐Jer Chen
- Division of Gastroenterology, Department of Internal Medicine National Taiwan University Hospital Taipei Taiwan
- Hepatitis Research Center National Taiwan University Hospital Taipei Taiwan
- Graduate Institute of Clinical Medicine National Taiwan University College of Medicine Taipei Taiwan
| | - Ding‐Shinn Chen
- Division of Gastroenterology, Department of Internal Medicine National Taiwan University Hospital Taipei Taiwan
- Hepatitis Research Center National Taiwan University Hospital Taipei Taiwan
- Graduate Institute of Clinical Medicine National Taiwan University College of Medicine Taipei Taiwan
- Genomics Research Center, Academia Sinica Taipei Taiwan
| | - Jia‐Horng Kao
- Division of Gastroenterology, Department of Internal Medicine National Taiwan University Hospital Taipei Taiwan
- Hepatitis Research Center National Taiwan University Hospital Taipei Taiwan
- Graduate Institute of Clinical Medicine National Taiwan University College of Medicine Taipei Taiwan
- Department of Medical Research National Taiwan University Hospital Taipei Taiwan
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El-Khayat H, Kamal EM, Mahmoud H, Gomaa A, Ebeid B, Sameh Y, Hasseb A, El Raziky M, El Serafy M, Doss W, Esmat G, Fouad Y, Attia D. Retreatment of chronic hepatitis C virus genotype-4 patients after non-structural protein 5A inhibitors' failure: efficacy and safety of different regimens. Eur J Gastroenterol Hepatol 2020; 32:440-446. [PMID: 31688311 DOI: 10.1097/meg.0000000000001581] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Nonstructural protein 5A (NS5A) is an important regimen for the treatment of chronic hepatitis C virus (HCV) genotype-4 infected patients. Retreatments for NS5A virologic failure are limited. The aim of this study is to provide real-life data regarding the effectiveness and safety of retreatment with different regimens after NS5A regimen virologic failure in GT4 patients. PATIENTS AND METHODS A total of 524 HCV patients (mean age 48 ± 11 years, 71% males), with virologic failure to sofosbuvir+daclatasvir, n = 450 and sofosbuvir/ledipasvir, n = 74 were included in this study. Patients were retreated with sofosbuvir + ombitasvir/paritaprevir/ritonavir + ribavirin, n = 278 and sofosbuvir + simeprevir + daclatasvir + ribavirin, n = 246. Response was evaluated 12 weeks after the end of treatment (SVR12). RESULTS Overall, SVR12 was 95.2% [95% confidence interval (CI) 93.3%-97.1%]. In sofosbuvir + ombitasvir/paritaprevir/ritonavir + ribavirin and sofosbuvir + simeprevir + daclatasvir + ribavirin, SVR12s were 94.9% (95% CI 92.5%-97.4%) and 95.5% (95% CI 92.8%-98%), respectively. In liver cirrhosis patients, SVR12s were 96.4% (95% CI 90.7%-100%) and 98% (95% CI 94.9%-100%), respectively. Relapse in the sofosbuvir + ombitasvir/paritaprevir/ritonavir + ribavirin was n = 14 patients, and n = 11 patients in sofosbuvir + simeprevir + daclatasvir + ribavirin. Three patients developed hepatic encephalopathy, haematemesis, lower limb oedema, and one patient died in the SOF + OBV/PTV/RTV + RIB. In the sofosbuvir + simeprevir + daclatasvir + ribavirin, three patients developed hepatocellular carcinoma and one patient died. No treatment discontinuation due to anaemia. CONCLUSION Salvage treatment for NS5A-treatment failure is effective and well tolerated in genotype-4 patients, in both noncirrhotic and compensated cirrhotic groups.
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Affiliation(s)
- Hisham El-Khayat
- Department of Gastroenterology, Hepatology and Endemic Medicine, Theodor Bilharz Institute
| | - Enas M Kamal
- Department of Gastroenterology, Hepatology and Endemic Medicine, Faculty of Medicine, Minia University Hospitals, Minya
| | - Hani Mahmoud
- Department of Gastroenterology, Hepatology and Endemic Medicine, Faculty of Medicine, Beni-Suef University, Beni-Suef
| | - Ahmed Gomaa
- Department of Gastroenterology, Hepatology and Endemic Medicine, Faculty of Medicine, Fayoum University, Faiyum
| | - Bassel Ebeid
- Department of Gastroenterology, Hepatology and Endemic Medicine, Faculty of Medicine, Fayoum University, Faiyum
| | - Yehia Sameh
- Department of Gastroenterology, Hepatology and Endemic Medicine, Faculty of Medicine, Beni-Suef University, Beni-Suef
| | - Alaa Hasseb
- Department of Gastroenterology, Hepatology and Endemic Medicine, Faculty of Medicine, Beni-Suef University, Beni-Suef
| | - Maissa El Raziky
- Department of Gastroenterology, Hepatology and Endemic Medicine, Faculty of Medicine, Cairo University
| | - Magdy El Serafy
- National Committee of Viral Hepatitis MOH, Cairo University, Cairo, Egypt
| | - Wahid Doss
- National Committee of Viral Hepatitis MOH, Cairo University, Cairo, Egypt
| | - Gamal Esmat
- National Committee of Viral Hepatitis MOH, Cairo University, Cairo, Egypt
| | - Yasser Fouad
- Department of Gastroenterology, Hepatology and Endemic Medicine, Faculty of Medicine, Minia University Hospitals, Minya
| | - Dina Attia
- Department of Gastroenterology, Hepatology and Endemic Medicine, Faculty of Medicine, Beni-Suef University, Beni-Suef
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Abstract
Currently, despite the use of a preventive vaccine for several decades as well as the use of effective and well-tolerated viral suppressive medications since 1998, approximately 250 million people remain infected with the virus that causes hepatitis B worldwide. Hepatitis C virus (HCV) and hepatitis B virus (HBV) are the leading causes of liver cancer and overall mortality globally, surpassing malaria and tuberculosis. Linkage to care is estimated to be very poor both in developing countries and in high-income countries, such as the United States, countries in Western Europe, and Japan. In the United States, by CDC estimates, only one-third of HBV-infected patients or less are aware of their infection. Some reasons for these low rates of surveillance, diagnosis, and treatment include the asymptomatic nature of chronic hepatitis B until the very late stages, a lack of curative therapy with a finite treatment duration, a complex natural history, and a lack of knowledge about the disease by both care providers and patients. In the last 5 years, more attention has been focused on the important topics of HBV screening, diagnosis of HBV infection, and appropriate linkage to care. There have also been rapid clinical developments toward a functional cure of HBV infection, with novel compounds currently being in various phases of progress. Despite this knowledge, many of the professional organizations provide guidelines focused only on specific questions related to the treatment of HBV infection. This focus leaves a gap for care providers on the other HBV-related issues, which include HBV's epidemiological profile, its natural history, how it interacts with other viral hepatitis diseases, treatments, and the areas that still need to be addressed in order to achieve HBV elimination by 2030. Thus, to fill these gaps and provide a more comprehensive and relevant document to regions worldwide, we have taken a global approach by using the findings of global experts on HBV as well as citing major guidelines and their various approaches to addressing HBV and its disease burden.
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Lee LY, Lee GH, Mattar C, Saw S, Aw M. Maternal HBeAg positivity and viremia associated with umbilical cord blood hepatitis B viremia. Pediatr Neonatol 2019; 60:517-522. [PMID: 30683599 DOI: 10.1016/j.pedneo.2019.01.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/26/2018] [Revised: 10/29/2018] [Accepted: 01/02/2019] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND Hepatitis B (HBV) transmission may result from in utero transmission. We aimed to determine the correlation between maternal serum and umbilical cord blood HBV DNA levels in infants delivered by chronic HBV-infected mothers and to describe the effect of cord blood viremia on vertical transmission. METHODS A prospective cohort of 92 chronic HBV-infected mother-and-child pairs recruited over three years was analyzed. Maternal and cord blood were tested for HBV DNA by real-time PCR. Standard immunoprophylaxis with both active and passive immunization was administered to all infants. Serological testing was performed on all infants at 9 months of age. RESULTS Moderate positive correlation of the maternal HBV DNA with cord blood HBV DNA was demonstrated (r2 = 0.521, p = <0.001). HBeAg +ve mothers were younger with higher HBV and cord viremia. At 9 months of age, one infant was infected. Infants delivered by HBeAg positive mothers and mothers with high HBV DNA of more than 6 LOG IU/mL (1 x 106 IU/mL) have increased relative risk of cord blood viremia. CONCLUSIONS Maternal HBV DNA and presence of HBeAg were positively correlated to cord blood HBV DNA in infants delivered by chronic HBV-infected mothers. Our data suggest that reducing maternal viremia during the antenatal period may help to reduce cord blood viremia.
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Affiliation(s)
- Le Ye Lee
- Department of Neonatology, National University Hospital, Singapore; Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
| | - Guan Huei Lee
- Department of Medicine, National University Hospital, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Citra Mattar
- Department of Obstetrics and Gynaecology, National University Hospital, Singapore; Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Sharon Saw
- Department of Laboratory Medicine, National University Hospital, Singapore
| | - Marion Aw
- Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore
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Han LF, Zheng JM, Zheng LQ, Gao HB, Chen LX, Xu QL, Chai YH, Zhang X, Pan C, Yao LF. Telbivudine can safely reduce mother-to-child transmission in chronic hepatitis B women after 12 weeks of gestation. BMC Infect Dis 2019; 19:614. [PMID: 31299917 PMCID: PMC6626355 DOI: 10.1186/s12879-019-4250-6] [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: 03/29/2018] [Accepted: 07/03/2019] [Indexed: 12/12/2022] Open
Abstract
Background To evaluate the efficacy and safety of telbivudine in chronic hepatitis B women during the second and third trimesters of pregnancy. Methods The week 12–34 of pregnant women were screened in this prospective non-intervention study, with HBV DNA > 106 IU/mL and alanine aminotransferase > 50 IU/L. The patients were received telbivudine treatment as a treatment group or without antiviral treatment as a control group. All infants were received recombinant hepatitis B vaccine 10 μg within 12 h of birth, at week 4 and week 24, immunoglobulin G within 12 h of birth and were detected HBV markers at the range from 7 to 12 months after delivery. Results A total of 241 patients were finally enrolled, 139 patients in telbivudine group and 102 patients in control group. HBsAg negative rate of infants was 99.3% (135/136) in telbivudine group and was 91.9% (91/99) in control group after 7 months (P = 0.005), respectively. The incidence of undetectable HBV DNA levels (47.5%) was significantly lower in telbivudine-treated mothers than that in the controls (0%), and 75.5% patients alanine aminotransferase returned to normal in telbivudine group, and 51% in control group at delivery (P < 0.001), respectively. Conclusions Telbivudine can safely reduce mother-to-child transmission in chronic hepatitis B women after 12 weeks of gestation.
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Affiliation(s)
- Li-Fen Han
- Department of Liver Diseases, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
| | - Jian-Ming Zheng
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, 200040, China
| | - Li-Qing Zheng
- Department of Liver Diseases, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
| | - Hai-Bing Gao
- Department of Liver Diseases, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
| | - Li-Xia Chen
- Department of Liver Diseases, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
| | - Qing-Ling Xu
- Department of Liver Diseases, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
| | - Yi-Hong Chai
- Department of Liver Diseases, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
| | - Xin Zhang
- Department of Liver Diseases, The Second Hospital of Longyan, Fuzhou, 350025, China
| | - Chen Pan
- Department of Liver Diseases, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
| | - Lv-Feng Yao
- Department of Liver Diseases, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China.
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Hsu HY, Chang MH. Hepatitis B Virus Infection and the Progress toward its Elimination. J Pediatr 2019; 205:12-20. [PMID: 30244984 DOI: 10.1016/j.jpeds.2018.08.017] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2018] [Revised: 07/20/2018] [Accepted: 08/09/2018] [Indexed: 02/07/2023]
Affiliation(s)
- Hong-Yuan Hsu
- Department of Pediatrics, National Taiwan University Children's Hospital and College of Medicine, National Taiwan University, Taipei; Graduate Institute of Medical Education and Bioethics, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Mei-Hwei Chang
- Department of Pediatrics, National Taiwan University Children's Hospital and College of Medicine, National Taiwan University, Taipei.
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Koc ÖM, Robaeys G, Yildirim B, Posthouwer D, Hens N, Koek GH. The influence of ethnicity on disease outcome in patients with chronic hepatitis B infection. J Med Virol 2018; 91:623-629. [PMID: 30381836 PMCID: PMC6587848 DOI: 10.1002/jmv.25353] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2018] [Accepted: 10/29/2018] [Indexed: 12/18/2022]
Abstract
Since the cultural diversity in Western Europe is growing, this study assessed whether foreign‐born chronic hepatitis B (CHB) patients have more cirrhosis than Dutch‐ or Belgian‐born patients, with a main focus on the Turkish population. Baseline characteristics (eg, socioeconomic status [SES]), biological characteristics, and disease outcome (eg, cirrhosis) were collected for all patients. Between December 2009 and January 2015, 269 CHB patients participated from the outpatient departments of three hospitals in the Netherlands, Belgium, and Turkey. Out of the 269 CHB patients, 210 were foreign‐born and 59 were Dutch‐ or Belgian‐born. Compared with Dutch‐ or Belgian‐born patients, foreign‐born patients had a higher prevalence of low SES (58% vs 31%; P = 0.001) and cirrhosis (27% vs 10%; P = 0.007). Among the Turkish population, there were no significant differences regarding the prevalence of low SES (73% vs 61%; P = 0.170), alcohol abuse (1% vs 5%; P = 0.120), anti‐hepatitis C virus positivity (4% vs 0%; P = 0.344), anti‐hepatitis D virus positivity (1% vs 6%; P = 0.297), and cirrhosis (37% vs 27%; P = 0.262) between patients (n = 102) living in Turkey (local) and Turkish CHB (n = 38) patients living in the Netherlands or Belgium (immigrant). In multivariate analysis, low SES (odds ratio, 5.7; 95% confidence interval, 2.3‐14.5; P < 0.001) was associated with cirrhosis. In this study, foreign‐born CHB patients were associated with more advanced HBV‐related liver disease with 27% having cirrhosis. However, ethnicity was not associated with cirrhosis when SES was included in the multivariate analysis. The similar prevalence of cirrhosis in local Turkish compared to immigrant Turkish CHB patients is novel and warrants further investigation.
Foreign‐born individuals have a higher prevalence of cirrhosis than Dutch‐ or Belgian‐ born individuals There was a lower socioeconomic status in the foreign‐born individuals No difference in the prevalence of cirrhosis was seen between the local and immigrant Turkish population Socioeconomic status and not ethnicity was an independent predictor of cirrhosis
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Affiliation(s)
- Özgür M Koc
- Department of Internal Medicine, Infectious Diseases and Medical Microbiology, Maastricht University Medical Centre, Maastricht, The Netherlands.,School of Nutrition and Translational Research in Metabolism, University Maastricht, Maastricht, The Netherlands.,Department of Gastroenterology and Hepatology, Ziekenhuis Oost-Limburg, Genk, Belgium.,Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium
| | - Geert Robaeys
- Department of Gastroenterology and Hepatology, Ziekenhuis Oost-Limburg, Genk, Belgium.,Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium.,Department of Hepatology, UZ Leuven, Leuven, Belgium
| | - Beytullah Yildirim
- Department of Gastroenterology, Ondokuz Mayis University, School of Medicine, Samsun, Turkey
| | - Dirk Posthouwer
- Department of Internal Medicine, Infectious Diseases and Medical Microbiology, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Niel Hens
- Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Hasselt University, Hasselt, Belgium.,Centre for Health Economic Research and Modelling Infectious Diseases, Vaccine and Infectious Disease Institute, University of Antwerp, Antwerp, Belgium
| | - Ger H Koek
- School of Nutrition and Translational Research in Metabolism, University Maastricht, Maastricht, The Netherlands.,Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre, Maastricht, The Netherlands.,Department of Surgery, University Hospital of the RWTH, Aachen, Germany
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25
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Tziomalos K, Neokosmidis G, Mavromatidis G, Dinas K. Novel insights in the prevention of perinatal transmission of hepatitis B. World J Hepatol 2018; 10:795-798. [PMID: 30533180 PMCID: PMC6280156 DOI: 10.4254/wjh.v10.i11.795] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2018] [Revised: 08/14/2018] [Accepted: 08/26/2018] [Indexed: 02/06/2023] Open
Abstract
Perinatal transmission of hepatitis B virus (HBV) infection is major contributor to the growing burden of chronic hepatitis B worldwide. Administration of HBV immunoglobulin and HBV vaccination as soon after pregnancy as possible are the mainstay of prevention of perinatal transmission of HBV infection. In women with high viral loads, antiviral prophylaxis also appears to be useful. Lamivudine, telbivudine and tenofovir have been shown to be both safe and effective in this setting but tenofovir is the first-line option due to its low potential for resistance and more favorable safety profile.
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Affiliation(s)
- Konstantinos Tziomalos
- First Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki 54636, Greece.
| | - Georgios Neokosmidis
- First Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki 54636, Greece
| | - Georgios Mavromatidis
- Third Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki 54642, Greece
| | - Konstantinos Dinas
- Second Department of Obstetrics and Gynecology, Medical School, Aristotle University of Thessaloniki, Hippokration Hospital, Thessaloniki 54642, Greece
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26
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Mani SKK, Andrisani O. Interferon signaling during Hepatitis B Virus (HBV) infection and HBV-associated hepatocellular carcinoma. Cytokine 2018; 124:154518. [PMID: 30126685 DOI: 10.1016/j.cyto.2018.08.012] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2018] [Revised: 08/09/2018] [Accepted: 08/11/2018] [Indexed: 02/06/2023]
Abstract
Chronic Hepatitis B Virus (HBV) infection is linked to hepatocellular carcinoma (HCC) pathogenesis. The World Health Organization estimates that globally 257 million people are chronic HBV carriers at risk of developing liver cancer. Current therapies for prevention and treatment of HCC are inadequate. Although interferon-based treatment strategies hold great promise for combating chronic infection and HCC, many patients do not respond to the IFN-based drugs for reasons not completely understood. Interferon signaling plays key roles in activation of innate and adaptive immunity. However, HBV has evolved various mechanisms to suppress IFN signaling. In this review, we present the basics about HBV infection and interferon signaling. Next, we discuss mechanisms through which HBV downregulates the function -activity and transcription- of the transcription factor STAT1 during acute and chronic infection. STAT1 is activated in response to all types (I/II/III) of interferon signaling and is essential in mediating all types (I/II/III) of interferon responses. Lastly, we discuss emerging evidence from different human cancers linking loss of interferon signaling to aggressive cancer and cancer stem cells. Whether the same occurs during HBV-associated hepatocarcinogenesis is discussed and currently under investigation.
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Affiliation(s)
- Saravana Kumar Kailasam Mani
- Department of Basic Medical Sciences and Purdue Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA.
| | - Ourania Andrisani
- Department of Basic Medical Sciences and Purdue Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA.
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27
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Hsu YC, Hsu CW. Septic acute kidney injury patients in emergency department: The risk factors and its correlation to serum lactate. Am J Emerg Med 2018; 37:204-208. [PMID: 29776828 DOI: 10.1016/j.ajem.2018.05.012] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2018] [Revised: 04/24/2018] [Accepted: 05/09/2018] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Acute kidney injury (AKI) is a common complication in septic patients, imposing a heavy burden of illness in terms of morbidity and mortality. Serum lactate is a widely used marker predicting the severity of sepsis. A paucity of research has investigated septic AKI in emergency departments (EDs) and its correlation with initial serum lactate level. This study aimed at identifying risk factors for septic AKI and clarifying the link between initial serum lactate level and septic AKI in ED patients. METHODS A retrospective cohort study was conducted at a single tertiary referral medical center. The medical records of all adult ED patients with measurement of serum lactate and creatinine between January 2012 and December 2016 were reviewed. A total of 696 septic patients were stratified into AKI and non-AKI groups according to Acute Kidney Injury Network (AKIN) criteria for further statistical analysis. RESULTS Ninety-nine septic patients (14.2%) had AKI, with AKIN-I, AKIN-II, and AKIN-III in 71.7%, 11.1%, and 17.2% of patients, respectively. Compared with the non-AKI group, the AKI group had a significantly higher mortality rate (71.7% vs. 21.3%, p < 0.001). Independent risk factors for septic AKI included liver disease (adjusted odds ratio [AOR] = 2.02, 95% confidence interval [CI] = 1.16-3.52), diabetes mellitus (AOR = 1.73, 95% CI = 1.11-2.69), chronic kidney disease (AOR = 1.68, 95% CI = 1.06-2.66), and initial serum lactate (AOR = 1.08, 95% CI = 1.02-1.14). CONCLUSIONS Patients with septic AKI had an overwhelmingly higher mortality rate. The comorbidities of liver disease, diabetes mellitus, and chronic kidney disease were correlated with septic AKI and in combination with an elevated initial serum lactate level had predictive regarding AKI and further mortality in ED septic patients.
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Affiliation(s)
- Yin-Chou Hsu
- Department of Emergency Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
| | - Chih-Wei Hsu
- Department of Emergency Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan.
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28
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Terrault NA, Lok ASF, McMahon BJ, Chang KM, Hwang JP, Jonas MM, Brown RS, Bzowej NH, Wong JB. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology 2018; 67:1560-1599. [PMID: 29405329 PMCID: PMC5975958 DOI: 10.1002/hep.29800] [Citation(s) in RCA: 2787] [Impact Index Per Article: 398.1] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Accepted: 01/11/2018] [Indexed: 12/11/2022]
Affiliation(s)
- Norah A Terrault
- Division of Gastroenterology/Hepatology, University of California San Francisco, San Francisco, CA
| | - Anna S F Lok
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI
| | - Brian J McMahon
- Liver Diseases and Hepatitis Program, Alaska NativeTribal Health Consortium, Anchorage, AK
| | - Kyong-Mi Chang
- Division of Gastroenterology, Corporal Michael J. Crescenz VA Medical Center & University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Jessica P Hwang
- Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Maureen M Jonas
- Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA
| | - Robert S Brown
- Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, NY
| | | | - John B Wong
- Division of Clinical Decision Making, Tufts Medical Center, Tufts University School of Medicine, Boston, MA
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29
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Dusheiko G. Current and future directions of management of hepatitis B: steps toward a cure. Future Virol 2018. [DOI: 10.2217/fvl-2017-0103] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Universal hepatitis B virus vaccination has been effective in reducing incident chronic hepatitis B but will not have the requisite effect on the prevalence of end-stage liver disease in chronically infected persons. The natural history and immunological stages of hepatitis B virus infection are still being defined. Over three decades, current therapies have reduced morbidity from chronic hepatitis B. The majority require nucleoside analog maintenance therapy. The preferential preservation of covalently closed circular DNA (cccDNA), and capsid reverse transcriptase–cccDNA interactions currently precludes cure in most. A functional cure in the host may require several synergistic antiviral and immunological intercessions. The correct sequencing and combinations of treatment with either host or viral targeting agents have yet to be determined. Proven surrogates for cccDNA for clinical trials are required. Different strategies may become apparent for patients at different stages of the disease. Curative therapies will require affordability. This review focuses on steps toward a cure.
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Affiliation(s)
- Geoffrey Dusheiko
- Kings College Hospital & University College London Medical School, Denmark Hill, London SE5 9RS, UK
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30
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Sarpel D, Kushner T, Carter D, Huisman T, Chiu S, Dieterich D. Mother-to-child transmission of hepatitis B and C virus: review of the epidemiology and current treatment options. Future Virol 2018. [DOI: 10.2217/fvl-2017-0069] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Hepatitis B and C viruses are the leading causes of liver-related morbidity and mortality throughout the world. Hepatitis B virus is predominantly transmitted perinatally, particularly in endemic areas. The rate of mother-to-child transmission of hepatitis C virus is on the rise, largely due to the increasing opioid epidemic. While there are guidelines established for the screening and treatment of pregnant females at risk for chronic hepatitis B infection, there no such guidelines or treatment options available in pregnant females with chronic hepatitis C infection. This review examines the epidemiology of mother-to-child transmission of chronic hepatitis B and C as well as the current treatment options during pregnancy and breastfeeding for both.
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Affiliation(s)
- Dost Sarpel
- Division of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai West/St Luke's Campus, 1000 10th Avenue, Clinic 2T, New York, NY 10019, USA
| | - Tatyana Kushner
- Department of Medicine, Institute of Liver Medicine, Icahn School of Medicine at Mount Sinai, Annenberg 5–04, 1468 Madison Ave Box 1123, New York, NY 10029, USA
| | - Danielle Carter
- Department of Medicine, Institute of Liver Medicine, Icahn School of Medicine at Mount Sinai, Annenberg 5–04, 1468 Madison Ave Box 1123, New York, NY 10029, USA
| | - Tsipora Huisman
- Department of Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave L Levy Place, New York, NY 10029, USA
| | - Sophia Chiu
- Department of Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave L Levy Place, New York, NY 10029, USA
| | - Douglas Dieterich
- Department of Medicine, Institute of Liver Medicine, Icahn School of Medicine at Mount Sinai, Annenberg 5–04, 1468 Madison Ave Box 1123, New York, NY 10029, USA
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31
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Collier MG, Schillie S. Hepatitis B and Hepatitis D Viruses. PRINCIPLES AND PRACTICE OF PEDIATRIC INFECTIOUS DISEASES 2018:1107-1114.e4. [DOI: 10.1016/b978-0-323-40181-4.00213-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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32
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Heath RD, Tahan V. Natural History of Hepatitis B Virus. VIRAL HEPATITIS: CHRONIC HEPATITIS B 2018:1-10. [DOI: 10.1007/978-3-319-93449-5_1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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33
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Hsu CW, Chen YC, Chang ML, Lin CC, Lin SM, Chen WT, Chu YD, Yeh CT. Durability of Telbivudine-Associated Improvement of Renal Function Following Withdrawal or Switching of Antivirals in Chronic Hepatitis B Patients. Open Forum Infect Dis 2017; 5:ofx271. [PMID: 29362723 PMCID: PMC5772403 DOI: 10.1093/ofid/ofx271] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2017] [Accepted: 12/13/2017] [Indexed: 12/22/2022] Open
Abstract
Background Besides antiviral activities against hepatitis B virus (HBV), telbivudine has an extrahepatic pharmaceutical effect: to improve renal function assessed by estimated glomerular filtration rate (eGFR). However, the durability of this effect after withdrawal of telbivudine or switching to other antivirals has never been investigated. Methods We conducted a postmarketing, real-world observation study for telbivudine treatment. The durability of telbivudine-associated renal function improvement was examined following withdrawal/switching of antivirals. Results Of 160 telbivudine-treated, chronic hepatitis B patients, 21, 6, and 2 patients were loss to follow-up, dead, and pregnant during the study, respectively. Of the remaining 131 patients, 26, 47, 28, and 30 patients experienced telbivudine withdrawal, continuous use of telbivudine, switching to entecavir, or switching to tenofovir, respectively. During the first 2 years, eGFR in telbivudine-treated patients significantly improved before withdrawal/switching of antivirals (P = .009). Thereafter, eGFR remained unchanged for >1 year in the withdrawal (P = .100) and continuous use (P = .517) subgroups, but decreased significantly in the switching to entecavir (P = .002) and switching to tenofovir (P < .001) subgroups. Multivariate logistic regression analysis revealed that switching to tenofovir and poor liver functional reserve were predictors for eGFR deterioration. Conclusions Telbivudine-associated renal function improvement was durable after withdrawal or continuous use of telbivudine. However, renal function deteriorated if patients were switched to entecavir or tenofovir.
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Affiliation(s)
- Chao-Wei Hsu
- Liver Research Center, Chang Gung Memorial Hospital-Lin Kou, Chang Gung University College of Medicine, Taipei, Taiwan
| | - Yi-Cheng Chen
- Liver Research Center, Chang Gung Memorial Hospital-Lin Kou, Chang Gung University College of Medicine, Taipei, Taiwan
| | - Ming-Ling Chang
- Liver Research Center, Chang Gung Memorial Hospital-Lin Kou, Chang Gung University College of Medicine, Taipei, Taiwan
| | - Chen-Chun Lin
- Liver Research Center, Chang Gung Memorial Hospital-Lin Kou, Chang Gung University College of Medicine, Taipei, Taiwan
| | - Shi-Ming Lin
- Liver Research Center, Chang Gung Memorial Hospital-Lin Kou, Chang Gung University College of Medicine, Taipei, Taiwan
| | - Wei-Ting Chen
- Liver Research Center, Chang Gung Memorial Hospital-Lin Kou, Chang Gung University College of Medicine, Taipei, Taiwan
| | - Yu-De Chu
- Liver Research Center, Chang Gung Memorial Hospital-Lin Kou, Chang Gung University College of Medicine, Taipei, Taiwan
| | - Chau-Ting Yeh
- Liver Research Center, Chang Gung Memorial Hospital-Lin Kou, Chang Gung University College of Medicine, Taipei, Taiwan
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34
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Stevens CE, Toy P, Kamili S, Taylor PE, Tong MJ, Xia GL, Vyas GN. Eradicating hepatitis B virus: The critical role of preventing perinatal transmission. Biologicals 2017; 50:3-19. [DOI: 10.1016/j.biologicals.2017.08.008] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2017] [Revised: 08/12/2017] [Accepted: 08/14/2017] [Indexed: 12/19/2022] Open
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35
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Hsieh AR, Fann CSJ, Yeh CT, Lin HC, Wan SY, Chen YC, Hsu CL, Tai J, Lin SM, Tai DI. Effects of sex and generation on hepatitis B viral load in families with hepatocellular carcinoma. World J Gastroenterol 2017; 23:876-884. [PMID: 28223732 PMCID: PMC5296204 DOI: 10.3748/wjg.v23.i5.876] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/12/2016] [Revised: 12/14/2016] [Accepted: 01/04/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To explore factors associated with persistent hepatitis B virus (HBV) infection in a cohort of hepatocellular carcinoma (HCC)-affected families and then investigate factors that correlate with individual viral load among hepatitis B surface antigen (HBsAg)-positive relatives. METHODS We evaluated non-genetic factors associated with HBV replication in relatives of patients with HCC. Relatives of 355 HCC cases were interviewed using a structured questionnaire. Demographics, relationship to index case, HBsAg status of mothers and index cases were evaluated for association with the HBV persistent infection or viral load by generalized estimating equation analysis. RESULTS Among 729 relatives enrolled, parent generation (P = 0.0076), index generation (P = 0.0044), mothers positive for HBsAg (P = 0.0007), and HBsAg-positive index cases (P = 5.98 × 10-8) were associated with persistent HBV infection. Factors associated with HBV viral load were evaluated among 303 HBsAg-positive relatives. Parent generation (P = 0.0359) and sex (P = 0.0007) were independent factors associated with HBV viral load. The intra-family HBV viral load was evaluated in families clustered with HBsAg-positive siblings. An intra-family trend of similar HBV viral load was found for 27 of 46 (58.7%) families. Male offspring of HBsAg-positive mothers (P = 0.024) and older siblings were associated with high viral load. CONCLUSION Sex and generation play important roles on HBV viral load. Maternal birth age and nutritional changes could be the reasons of viral load difference between generations.
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36
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Wen WH, Lai MW, Chang MH. A review of strategies to prevent mother-to-infant transmission of hepatitis B virus infection. Expert Rev Gastroenterol Hepatol 2016; 10:317-30. [PMID: 26566769 DOI: 10.1586/17474124.2016.1120667] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Hepatitis B virus (HBV) infection causes long-term, life-threatening liver diseases worldwide. HBV is transmitted through either the horizontal or mother-to-infant route, which is the major route of transmission in endemic areas. Administration of hepatitis B immunoglobulin and hepatitis B vaccine to newborns of infected mothers prevents mother-to-infant transmission. Implementation of a universal hepatitis B vaccination program has proven successful in eliminating the infection and related complications. Nevertheless, efforts are still needed to improve global coverage of the hepatitis B vaccine. Infants born to highly viremic mothers are still at risk of infection despite current immunoprophylaxis. An increasing number of reports have shown promising efficacy and safety profiles with the use of nucleoside/nucleotide analogues in highly viremic pregnant women to prevent mother-to-infant transmission.
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Affiliation(s)
- Wan-Hsin Wen
- a Department of Pediatrics , Cardinal Tien Hospital , New Taipei City , Taiwan.,b School of Medicine, College of Medicine , Fu-Jen Catholic University , New Taipei City , Taiwan
| | - Ming-Wei Lai
- c Division of Pediatric Gastroenterology, Department of Pediatrics , Chang Gung Memorial Hospital , Linkou , Taiwan.,d College of Medicine , Chang Gung University , Taoyuan , Taiwan
| | - Mei-Hwei Chang
- e Department of Pediatrics , National Taiwan University Hospital, College of Medicine, National Taiwan University , Taipei , Taiwan
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37
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Nelson NP, Easterbrook PJ, McMahon BJ. Epidemiology of Hepatitis B Virus Infection and Impact of Vaccination on Disease. Clin Liver Dis 2016; 20:607-628. [PMID: 27742003 PMCID: PMC5582972 DOI: 10.1016/j.cld.2016.06.006] [Citation(s) in RCA: 213] [Impact Index Per Article: 23.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Integration of hepatitis B vaccination into national immunization programs has resulted in substantial reductions of hepatitis B virus (HBV) transmission in previously high endemic countries. The key strategy for control of the HBV epidemic is birth dose and infant vaccination. Additional measures include use of hepatitis B immunoglobulin (HBIG) and diagnosis of mothers at high risk of transmitting HBV and use of antiviral agents during pregnancy to decrease maternal DNA concentrations to undetectable concentrations. Despite the substantial decrease in HBV cases since vaccination introduction, implementation of birth dose vaccination in low-income and middle-income countries and vaccination of high-risk adults remain challenging.
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Affiliation(s)
- Noele P. Nelson
- Clinical Interventions Team, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, 1600 Clifton Road, MS-G37, Atlanta, GA 30329-4018, USA,Corresponding author.
| | - Philippa J. Easterbrook
- Global Hepatitis Programme, HIV Department, World Health Organization, 20 Via Appia, Geneva 1211, Switzerland
| | - Brian J. McMahon
- Liver Disease and Hepatitis Program, Alaska Native Medical Center, Alaska Native Tribal Health Consortium, 4315 Diplomacy Drive, Anchorage, AK 99508, USA
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38
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Abstract
Hepatitis B virus is a worldwide leading cause of acute and chronic liver disease including cirrhosis and hepatocellular carcinoma. Effective vaccines have been available since the early '80s. Vaccination against hepatitis B virus infection has proved highly successful in reducing the disease burden, the development of the carrier state and the hepatitis B-related morbidity and mortality in the countries where vaccination has been implemented. Despite success and efficacy of preventive vaccines, a huge number of chronically infected patients still remain. Therapeutic vaccination may prove to be useful coupled with current antivirals and other immunomodulatory approaches to treat these patients. This review summarizes current unresolved issues and future perspectives on vaccination required for global cure of hepatitis B virus infection.
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Affiliation(s)
- Marie-Louise Michel
- Laboratoire PVHB, Bâtiment Lwoff, Inserm U994, Institut Pasteur, 28, rue du Docteur Roux, 75015 Paris, France
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39
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Gish RG, Sollano JD, Lapasaran A, Ong JP. Chronic hepatitis B virus in the Philippines. J Gastroenterol Hepatol 2016; 31:945-952. [PMID: 26643262 DOI: 10.1111/jgh.13258] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/24/2015] [Indexed: 12/21/2022]
Abstract
Multiple studies have shown a high prevalence of chronic hepatitis B (CHB) infection in the Philippines, not only in high-risk populations but also in the general population. The most recent national study estimated HBsAg seroprevalence to be 16.7%, corresponding to an estimated 7.3 million CHB adults. The factors underlying the high prevalence of CHB and its sequelae include the inadequate use of vaccination for prevention and the lack of treatment for many Filipinos. Because without medical monitoring and treatment of CHB the risk of progression to liver failure and death is 25-30%, the ultimate medical and societal costs will be very high if the Philippines fails to properly address hepatitis B infection. It will be very important to move forward with programs that can help to ensure universal vaccination of newborns, screening and vaccination nationwide, and monitoring and treatment for CHB persons. It will also be crucial to address transmission of HBV in the health-care setting (via contaminated needles and syringes and inadequately sterilized hospital equipment) and via injection drug use and tattooing. Because of the relatively low average per capita income and the lack of coverage by PhilHealth of outpatient visits and medications, there is an urgent need to move forward with a nationally supported program that includes education for both the general public and health-care workers on liver disease and screening for hepatitis viruses, followed by, as appropriate, vaccination or treatment, with expanded government coverage for these for all those who could not otherwise afford it.
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Affiliation(s)
- Robert G Gish
- Department of Medicine, Division of Gastroenterology and Hepatology, Stanford University, Stanford, California, USA
- National Viral Hepatitis Roundtable, San Francisco, California, USA
- FAIR Foundation, Palm Desert, California, USA
- Hepatitis B Foundation, Doylestown, Pennsylvania, USA
| | - Jose D Sollano
- Section of Gastroenterology, University of Santo Tomas, Manila, Philippines
| | - Alex Lapasaran
- Schools of Nursing and Medicine, University of NevadaߚReno, Nevada, Reno, USA
| | - Janus P Ong
- Section of Gastroenterology, Department of Medicine, University of the Philippines-Philippine General Hospital, Manila, Philippines
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40
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Demma S, Dusheiko G. The current treatment situation and definitions of a cure for chronic HBV infection. Future Virol 2016. [DOI: 10.2217/fvl.15.93] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
HBV vaccination, while effective in reducing incident chronic disease in endemic regions, will not have the desired impact on the rates of end-stage liver disease in chronically infected persons. Over three decades, IFN-α and nucleoside analogs have reduced the morbidity from the disease. A large reservoir of chronic infection remains. The natural history of HBV infection is still being defined. Understanding the interactions between HBV and the host will be fundamental to achieving higher rates of cure. Curing hepatitis B will require several steps for either eradication, or a functional cure in the host. It is unclear whether covently closed circular DNA chromatin would need to be cleared to cure hepatitis B, or whether low threshold levels would slow the disease.
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Affiliation(s)
- Shirin Demma
- UCL institute of Liver & Digestive Health & Royal Free NHS Foundation Trust, London, UK
- Hepatology Unit, Department of Medical & Pediatric Sciences, University of Catania, Policlinic, Via S. Sofia No 78, 95123 Catania, Italy
| | - Geoffrey Dusheiko
- UCL institute of Liver & Digestive Health & Royal Free NHS Foundation Trust, London, UK
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Brown RS, McMahon BJ, Lok ASF, Wong JB, Ahmed AT, Mouchli MA, Wang Z, Prokop LJ, Murad MH, Mohammed K. Antiviral therapy in chronic hepatitis B viral infection during pregnancy: A systematic review and meta-analysis. Hepatology 2016; 63:319-33. [PMID: 26565396 DOI: 10.1002/hep.28302] [Citation(s) in RCA: 231] [Impact Index Per Article: 25.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2015] [Accepted: 10/15/2015] [Indexed: 12/11/2022]
Abstract
UNLABELLED Perinatal or mother-to-child transmission (MTCT) of hepatitis B virus (HBV) remains the major risk factor for chronic HBV infection worldwide. In addition to hepatitis B immune globulin and vaccination, oral antiviral therapies in highly viremic mothers can further decrease MTCT of HBV. We conducted a systematic review and meta-analysis to synthesize the evidence on the efficacy and maternal and fetal safety of antiviral therapy during pregnancy. A protocol was developed by the American Association for the Study of Liver Diseases guideline writing committee. We searched multiple databases for controlled studies that enrolled pregnant women with chronic HBV infection treated with antiviral therapy. Outcomes of interest were reduction of MTCT and adverse outcomes to mothers and newborns. Study selection and data extraction were done by pairs of independent reviewers. We included 26 studies that enrolled 3622 pregnant women. Antiviral therapy reduced MTCT, as defined by infant hepatitis B surface antigen seropositivity (risk ratio = 0.3, 95% confidence interval 0.2-0.4) or infant HBV DNA seropositivity (risk ratio = 0.3, 95% confidence interval 0.2-0.5) at 6-12 months. No significant differences were found in the congenital malformation rate, prematurity rate, and Apgar scores. Compared to control, lamivudine or telbivudine improved maternal HBV DNA suppression at delivery and during 4-8 weeks' postpartum follow-up. Tenofovir showed improvement in HBV DNA suppression at delivery. No significant differences were found in postpartum hemorrhage, cesarean section, and elevated creatinine kinase rates. CONCLUSIONS Antiviral therapy improves HBV suppression and reduces MTCT in women with chronic HBV infection with high viral load compared to the use of hepatitis B immunoglobulin and vaccination alone; the use of telbivudine, lamivudine, and tenofovir appears to be safe in pregnancy with no increased adverse maternal or fetal outcome.
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Affiliation(s)
- Robert S Brown
- Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, NY
| | - Brian J McMahon
- Liver Diseases and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, AK
| | - Anna S F Lok
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI
| | - John B Wong
- Division of Clinical Decision Making, Tufts Medical Center, Boston, MA
| | - Ahmed T Ahmed
- Evidence-Based Practice Research Program.,Center for the Science of Health Care Delivery
| | | | - Zhen Wang
- Evidence-Based Practice Research Program.,Center for the Science of Health Care Delivery
| | | | - Mohammad Hassan Murad
- Evidence-Based Practice Research Program.,Center for the Science of Health Care Delivery.,Division of Preventive, Occupational and Aerospace Medicine, Mayo Clinic, Rochester, MN
| | - Khaled Mohammed
- Evidence-Based Practice Research Program.,Center for the Science of Health Care Delivery.,Division of Preventive, Occupational and Aerospace Medicine, Mayo Clinic, Rochester, MN
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Lok ASF. Hepatitis B: 50 years after the discovery of Australia antigen. J Viral Hepat 2016; 23:5-14. [PMID: 26280668 DOI: 10.1111/jvh.12444] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2015] [Accepted: 07/16/2015] [Indexed: 12/13/2022]
Abstract
It is an honour to be invited to recount the progress in our understanding and management of hepatitis B 50 years after the discovery of Australia antigen (Au Ag). During this half century, we have gone from identifying the causative agent--hepatitis B virus (HBV), understanding its biology and the disease it causes, to having vaccines that can prevent HBV infection and antiviral therapy that can suppress HBV replication and prevent progression of HBV-related liver disease. As a result of the progress, prevalence of HBV infection and morbidity and mortality from chronic HBV infection has declined.
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Affiliation(s)
- A Suk-Fong Lok
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA
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McMahon BJ. Two Key Components to Address Chronic Hepatitis B in Children: Detection and Prevention. J Pediatr 2015; 167:1186-7. [PMID: 26409308 DOI: 10.1016/j.jpeds.2015.09.015] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2015] [Accepted: 09/03/2015] [Indexed: 01/11/2023]
Affiliation(s)
- Brian J McMahon
- Liver Disease and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, Alaska.
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Total lesion glycolysis determined per RECIST 1.1 criteria predicts survival in EGFR mutation-negative patients with advanced lung adenocarcinoma. Clin Nucl Med 2015; 40:e295-9. [PMID: 25783515 DOI: 10.1097/rlu.0000000000000774] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
OBJECTIVE The aim of this retrospective study was to investigate the clinical impact of F-FDG PET in patients with advanced lung adenocarcinoma stratified according to the epidermal growth factor receptor (EGFR) mutation status. PATIENTS AND METHODS A total of 56 patients with advanced lung adenocarcinoma were included in the study. Thirty-one patients (55%) were EGFR mutation-positive, whereas the remaining 25 (45%) participants tested negative for EGFR mutations. All of the patients underwent F-FDG PET/CT for pretreatment planning. The main outcome measure was overall survival (OS) at 24 months. The following F-FDG PET/CT-derived variables were tested for their associations with OS: main tumor SUVmax, main tumor total lesion glycolysis, and target lesions TLG determined per RECIST (Response Evaluation Criteria In Solid Tumors) 1.1 criteria (TLGRECIST). We also investigated the clinical characteristics in relation to OS and EGFR mutation status. RESULTS In EGFR mutation-positive patients, neither the clinical characteristics nor F-FDG PET/CT-derived parameters were significantly associated with OS. In contrast, univariate analysis identified male sex, a positive history of smoking, and TLGRECIST greater than or equal to 412 g as adverse prognostic factors for OS in EGFR mutation-negative patients. After adjustment for potential confounders in multivariate analysis, TLGRECIST was the sole independent predictor of OS in this subgroup. CONCLUSIONS TLG determined per RECIST 1.1 criteria is an independent predictor of OS in EGFR mutation-negative patients with advanced lung adenocarcinoma. Further studies are needed to investigate whether this parameter may be a promising tool for stratifying such patients for risk-adapted therapies.
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Yin J, Ji Z, Liang P, Wu Q, Cui F, Wang F, Liang X, Zhuang G. The doses of 10 μg should replace the doses of 5 μg in newborn hepatitis B vaccination in China: A cost-effectiveness analysis. Vaccine 2015; 33:3731-8. [PMID: 26057138 DOI: 10.1016/j.vaccine.2015.05.082] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2015] [Revised: 05/11/2015] [Accepted: 05/27/2015] [Indexed: 12/20/2022]
Abstract
OBJECTIVE To identify whether Chinese current series of three 5 μg doses for newborn hepatitis B vaccination should be replaced by the series of three 10 μg doses. METHODS A cost-effectiveness analysis was conducted from the societal perspective based on the constructed decision tree-Markov model. Model parameters were estimated from published literatures, government documents and our surveys. The expected cost and effectiveness were compared between the 3-dose 5 μg series (the 5 μg strategy) and the 3-dose 10 μg series (the 10 μg strategy), and the incremental cost-effectiveness ratio (ICER, additional cost per quality-adjusted life-years gained) was calculated. Threshold values of the efficacy difference of the two series for the ICER=0, 1 and 3 times per capita gross domestic product were analyzed under different scenarios to understand whether the 10 μg strategy should replace the 5 μg strategy according to the recommendation of World Health Organization. RESULTS The 10 μg strategy would be cost-saving compared with the 5 μg strategy under the base-case scenario. Under keeping all the other parameters at the base-case values or further adjusting any one of them to the value most unfavorable to the 10 μg strategy, as long as the efficacy of 3-dose 10 μg series was slightly higher than that of 3-dose 5 μg series, the 10 μg strategy would be cost-effective, highly cost-effective, or even cost-saving. Even under the most pessimistic scenario, i.e. all the other parameters, but the discount rate, at the values most unfavorable to the 10 μg strategy, the 10 μg strategy would be cost-effective if the efficacy difference reached higher than 1.23 percentage point. CONCLUSION For newborn hepatitis B vaccination in China, the 10 μg strategy should be cost-effective, even more possibly highly cost-effective or cost-saving compared with the current 5 μg strategy. The doses of 10 μg should be considered to replace the doses of 5 μg in newborn hepatitis B vaccination in China.
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Affiliation(s)
- Juan Yin
- Department of Epidemiology and Biostatistics, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China
| | - Zhenhao Ji
- Department of Epidemiology and Biostatistics, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China
| | - Peifeng Liang
- Department of Epidemiology and Biostatistics, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China
| | - Qian Wu
- Department of Epidemiology and Biostatistics, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China
| | - Fuqiang Cui
- Chinese Center for Disease Control and Prevention, Beijing 100050, China
| | - Fuzhen Wang
- Chinese Center for Disease Control and Prevention, Beijing 100050, China
| | - Xiaofeng Liang
- Chinese Center for Disease Control and Prevention, Beijing 100050, China
| | - Guihua Zhuang
- Department of Epidemiology and Biostatistics, School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China.
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Li Z, Hou X, Cao G. Is mother-to-infant transmission the most important factor for persistent HBV infection? Emerg Microbes Infect 2015; 4:e30. [PMID: 26060603 PMCID: PMC4451268 DOI: 10.1038/emi.2015.30] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2015] [Revised: 03/24/2015] [Accepted: 04/06/2015] [Indexed: 02/06/2023]
Abstract
Of the infants born to hepatitis B surface antigen (HBsAg)-positive mothers globally, 42.1% who did not receive hepatitis B virus (HBV) passive-active immunoprophylaxis and 2.9% of infants who received the immunoprophylaxis acquired HBV infection perinatally. Moreover, perinatal infection occurred in 84.2% (18.8%-100%) and 8.7% (0.0-21.0%) of infants born to hepatitis B e-antigen (HBeAg)-positive mothers who did not and did receive immunoprophylaxis, respectively; by contrast, the infection rates were 6.7% (0.0-15.4%) and 0.4% (0.0-2.5%) for infants born to HBeAg-negative-carrier mothers, respectively. The chronicity rates of HBV infection acquired perinatally were 28.2% (17.4%-33.9%) in infants born to HBeAg-negative mothers and 64.5% (53.5%-100%) in infants born to HBeAg-positive mothers. HBV mother-to-child transmission was more frequent in East Asia relative to other areas. In addition to differences in the endemic HBV genotype, the interchange of allelic dominance in genetic polymorphisms in HLA class II and NF-κB between the Chinese and European populations may explain why chronic HBV infection frequently affects the Chinese. The risk of progressing into chronic infection was inversely related to the age of children at the time of horizontal transmission. To further diminish HBV chronic infection, it is necessary to enforce antiviral treatment after the 28th week of gestation for HBeAg-positive mothers and to improve the health habits of carrier mothers and household sanitary conditions.
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Affiliation(s)
- Zixiong Li
- Department of Epidemiology, Second Military Medical University , Shanghai 200433, China
| | - Xiaomei Hou
- Department of Epidemiology, Second Military Medical University , Shanghai 200433, China
| | - Guangwen Cao
- Department of Epidemiology, Second Military Medical University , Shanghai 200433, China
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Abstract
Hepatitis B virus (HBV) causes life-threatening liver disease. It is transmitted through a horizontal route or a mother-to-infant route, and the latter is the major route in endemic areas. Prevention of HBV infection by immunization is the best way to eliminate HBV-related diseases. The HBV vaccine is the first human vaccine using a viral antigen from infected persons, which is safe and effective. Either passive immunization by hepatitis B immunoglobulin (HBIG) or active immunization by HBV vaccine is effective, and a combination of both yields the best efficacy in preventing HBV infection. The impact of universal HBV immunization is huge, with 90%-95% effectiveness in preventing chronic HBV infection. It is the first cancer preventive vaccine with a protective efficacy against hepatocellular carcinoma (HCC) of ∼ 70%. Nevertheless, further effort is still needed to avoid vaccine failure and to increase the global coverage rate.
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Affiliation(s)
- Mei-Hwei Chang
- Department of Pediatrics, National Taiwan University Hospital, Taipei 10016, Taiwan Hepatitis Research Center, National Taiwan University Hospital, Taipei 10016, Taiwan
| | - Ding-Shinn Chen
- Hepatitis Research Center, National Taiwan University Hospital, Taipei 10016, Taiwan Internal Medicine, National Taiwan University Hospital, Taipei 10016, Taiwan Genomics Research Center, Academia Sinica, Nankang 11529, Taiwan
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Tseng YR, Wu JF, Kong MS, Hu FC, Yang YJ, Yeung CY, Huang FC, Huang IF, Ni YH, Hsu HY, Chang MH, Chen HL. Infantile hepatitis B in immunized children: risk for fulminant hepatitis and long-term outcomes. PLoS One 2014; 9:e111825. [PMID: 25380075 PMCID: PMC4224399 DOI: 10.1371/journal.pone.0111825] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2014] [Accepted: 10/01/2014] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Infantile hepatitis B after neonatal immunoprophylaxis is a rare yet distinct disease. This study aimed to analyze the long-term outcomes and risk factors in immunized infants with hepatitis B. METHODS The clinical parameters and outcomes of 41 infants born after universal immunization, and admitted for HBV-positive hepatitis were studied. All patients were followed for at least 6 months (median = 4.4 years, range 0.6-18.1 years). Patient survival, changes of HBsAg and HBeAg status, and complications were analyzed. RESULTS Among the 41 cases (32 males, 9 females), 21 presented with fulminant hepatitis (FH), and 20 with non-fulminant hepatitis (NFH). Ninety-five percent (36/38) of the mothers were positive for hepatitis B surface antigen (HBsAg). Multivariate analyses revealed younger age of onset (age <7 months) and negative maternal hepatitis B e antigen (HBeAg) were associated with FH (p = 0.03 and p = 0.01, respectively). An infantile fulminant hepatitis B risk score using maternal/infant HBeAg positivity and onset age was proposed. Among the FH cases, the rate of mortality, HBsAg clearance, and chronic HBV infection were 47.6%, 38.1%, and 14.3%, respectively. Among the NFH cases, 35% developed chronic infection. Of the 9 chronically infected children received long-term follow-up, 8 had HBeAg seroconversion before 4 years of age. One case of FH developed hepatocellular carcinoma 14 years later. CONCLUSIONS Maternal HBsAg + /HBeAg- and early onset age were risk factors for FH in immunized infants. A significant portion of patients with FH or NFH evolve to chronic HBV infection, with HBeAg seroconversion in young childhood. Close surveillance for hepatocellular carcinoma is warranted in patients surviving infantile hepatitis B.
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Affiliation(s)
- Yu-Ru Tseng
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
| | - Jia-Feng Wu
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
| | - Man-Shan Kong
- Department of Pediatrics, Chang-Gung Memorial Hospital, Taoyuan, Taiwan
| | - Fu-Chang Hu
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Yao-Jong Yang
- Department of Pediatrics, Institute of Clinical Medicine, College of Medicine, National Cheng-Kung University and Hospital, Tainan, Taiwan
| | - Chun-Yan Yeung
- Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan
| | - Fu-Chen Huang
- Department of Pediatrics, Chang-Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - I-Fei Huang
- Department of Pediatrics, Veterans General Hospital, Kaohsiung, Taiwan
| | - Yen-Hsuan Ni
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
| | - Hong-Yuan Hsu
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
- Department of Medical Education and Bioethics, National Taiwan University, College of Medicine, Taipei, Taiwan
| | - Mei-Hwei Chang
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Huey-Ling Chen
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
- Department of Medical Education and Bioethics, National Taiwan University, College of Medicine, Taipei, Taiwan
- Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
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Efficacy and safety of tenofovir disoproxil fumarate in pregnancy to prevent perinatal transmission of hepatitis B virus. J Hepatol 2014; 61:502-7. [PMID: 24801414 DOI: 10.1016/j.jhep.2014.04.038] [Citation(s) in RCA: 130] [Impact Index Per Article: 11.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2014] [Revised: 04/02/2014] [Accepted: 04/24/2014] [Indexed: 12/21/2022]
Abstract
BACKGROUND & AIMS Perinatal transmission of hepatitis B virus still occurs despite immunoprophylaxis in approximately 9% of children from highly viraemic mothers. Antiviral therapy in this setting has been suggested, however with limited evidence to direct agent choice. METHODS We conducted a multi-centre, prospective, opt-in observational study of antiviral safety and efficacy in pregnant women with high viral load (>7 log IU/ml); lamivudine was used from 2007 to 2010 and tenofovir disoproxil fumarate (TDF) from late 2010. Outcomes of treated and untreated cohorts were compared. RESULTS 120 women with 130 pregnancies used TDF (58), lamivudine (52 including four who switched due to TDF intolerance) and no therapy (20). 96% were HBeAg positive, with baseline viral load mean 7.8 log IU/ml (±0.72) and ALT median 25 U/L (18.75-33). Duration of antiviral theraphy before birth was mean 58 days (±19) TDF and 53 (±14) lamivudine. Viral load declined by 3.64 log IU/ml (±0.9) TDF and 2.81 log IU/ml (±1.33) lamivudine. Virologic failure (birth viral load >7 IU/ml) occurred in 3% and 18% respectively. Congenital abnormality rate and neonatal growth centiles were similar across cohorts. Perinatal transmission reduced significantly to 2% and 0% in TDF and lamivudine cohorts, compared with 20% in untreated. CONCLUSIONS TDF in this setting is safe, effective and more potent than lamivudine. Antiviral therapy did not adversely impact obstetric or infant parameters. More TDF intolerance occurred than expected. Perinatal transmission was significantly reduced in antiviral therapy cohorts.
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