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Simmons R, Harris R, Lim AG, Leeman D, Ramsay ME, Hickman M, Mandal S. Estimating Prevalence and Number of People With Chronic Hepatitis B: A Multiplier Method Based on Public Health Surveillance Data in UK (2015-2021). J Viral Hepat 2025; 32:e14019. [PMID: 39412144 PMCID: PMC11899512 DOI: 10.1111/jvh.14019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Revised: 09/10/2024] [Accepted: 09/25/2024] [Indexed: 03/14/2025]
Abstract
Estimates of chronic hepatitis B virus (HBV) prevalence and critically the amount of infection that is undiagnosed or unlinked to care are uncertain-even in countries like UK where vertical transmission and overall prevalence are very low. In the absence of country of birth data, we aim to estimate HBV prevalence through combining public health surveillance data on antenatally screened women by ethnic group and multipliers generated from non-antenatally screened populations by ethnic group with English population denominators. Of 714,287 women aged 16-49 years with ethnic group data tested as part of antenatal care between 2015 and 2021, 4174 (0.6%) were HBsAg-positive; 94% in people of ethnic groups other than White British. Of 1,447,467 people tested for HBsAg with ethnic group data from other testing sources (primary and secondary care excluding occupational health and renal services), 27,628 (1.9%) were HBsAg-positive; 87% in people of ethnic groups other than White British. We estimate that the overall number and prevalence of people with chronic hepatitis B in England is 268,767 (95% CI: 227,896-314,044) and 0.58% (95% CI: 0.50-0.68). Approximately two-thirds were male, one-third female, and 68% were aged under 50. We estimate that over 83% of HBV infections are in people of ethnic groups other than White British, with 23% in people from Black ethnic groups, 21% from other White ethnic groups and 19% in Asian ethnic groups. These estimates are the first step towards establishing whether England can meet World Health Organisation targets to eliminate HBV as a public health problem-using methods that can also be used by other countries.
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Affiliation(s)
- Ruth Simmons
- Blood Safety, Hepatitis, Sexually Transmitted Infections (STIs) and HIV DivisionUK Health Security AgencyLondonUK
- NIHR HPRU in Behavioural Science and EvaluationUniversity of BristolBristolUK
| | - Ross Harris
- Blood Safety, Hepatitis, Sexually Transmitted Infections (STIs) and HIV DivisionUK Health Security AgencyLondonUK
| | - Aaron G. Lim
- NIHR HPRU in Behavioural Science and EvaluationUniversity of BristolBristolUK
- Population Health Sciences, Bristol Medical SchoolUniversity of BristolBristolUK
| | - David Leeman
- Blood Safety, Hepatitis, Sexually Transmitted Infections (STIs) and HIV DivisionUK Health Security AgencyLondonUK
| | - Mary E. Ramsay
- Blood Safety, Hepatitis, Sexually Transmitted Infections (STIs) and HIV DivisionUK Health Security AgencyLondonUK
| | - Matthew Hickman
- NIHR HPRU in Behavioural Science and EvaluationUniversity of BristolBristolUK
- Population Health Sciences, Bristol Medical SchoolUniversity of BristolBristolUK
| | - Sema Mandal
- Blood Safety, Hepatitis, Sexually Transmitted Infections (STIs) and HIV DivisionUK Health Security AgencyLondonUK
- NIHR HPRU in Behavioural Science and EvaluationUniversity of BristolBristolUK
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Duan M, Xiao H, Shi M, Xie Y, Zhao P, Li S, Chi X, Liu X, Zhuang H. Significant liver histological change is common in HBeAg-positive chronic hepatitis B with normal ALT. BMC Infect Dis 2024; 24:723. [PMID: 39044129 PMCID: PMC11264461 DOI: 10.1186/s12879-024-09617-1] [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: 08/31/2023] [Accepted: 07/15/2024] [Indexed: 07/25/2024] Open
Abstract
BACKGROUND AND AIMS Numerous HBeAg-positive chronic hepatitis B (CHB) patients with persistently normal ALT have significant liver histopathology. It is imperative to identify true "immune tolerant" patients. We aimed to evaluate the liver histopathology features of HBeAg-positive CHB patients with normal ALT and the incidence of liver cirrhosis and HCC in CHB patients during follow-up. METHODS 179 HBeAg-positive CHB patients with normal ALT who performed liver biopsy from 2009 to 2018 were retrospectively analyzed. Liver necroinflammation ≥ G2 and/or liver fibrosis ≥ S2 was defined as significant liver histopathological change. RESULTS 57.5% patients were in the indeterminate phase with significant liver histological changes. The proportion of the patients with evident liver necroinflammation was higher in the high-normal ALT group (21-40U/L) when compared with the low-normal ALT group (≤ 20 U/L) (51.3% vs. 30.0%, p < 0.05), and patients aged ≥ 40 years had a higher proportion of significant fibrosis than those aged < 40 years (64.5% vs. 39.9%, p < 0.05). The percentages of patients with ≥ S2 and ≥ G2/S2 in the HBV DNA < 107 IU/mL group were higher than those in the HBV DNA ≥ 107 IU/mL group (72.7% vs. 40.1%, p < 0.01; 81.8% vs. 54.1%, p < 0.05). During follow-up, two of immune tolerant patients and four of indeterminate patients developed into cirrhosis, and one of immune tolerant patients and one of indeterminate patients developed into HCC, respectively. CONCLUSIONS HBeAg-positive CHB patients with high-normal ALT or HBV DNA < 107 IU/mL were tend to be indeterminate. Liver biopsy or noninvasive approaches are recommended to evaluate liver histopathology, and antiviral therapy is recommended for patients with significant liver histopathology.
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Affiliation(s)
- Menghui Duan
- Department of Microbiology and Center of Infectious Diseases, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing, 100191, China
- The Clinical Laboratory of Tianjin Chest Hospital, Tianjin, China
| | - Huanming Xiao
- Hepatology Department, Guangdong Provincial Hospital of Chinese Medicine, 111 Dade Road, Guangzhou, Guangdong Province, 510120, China
| | - Meijie Shi
- Hepatology Department, Guangdong Provincial Hospital of Chinese Medicine, 111 Dade Road, Guangzhou, Guangdong Province, 510120, China
| | - Yubao Xie
- Hepatology Department, Guangdong Provincial Hospital of Chinese Medicine, 111 Dade Road, Guangzhou, Guangdong Province, 510120, China
| | - Pengtao Zhao
- Hepatology Department, Guangdong Provincial Hospital of Chinese Medicine, 111 Dade Road, Guangzhou, Guangdong Province, 510120, China
| | - Sheng Li
- Hepatology Department, Guangdong Provincial Hospital of Chinese Medicine, 111 Dade Road, Guangzhou, Guangdong Province, 510120, China
| | - Xiaoling Chi
- Hepatology Department, Guangdong Provincial Hospital of Chinese Medicine, 111 Dade Road, Guangzhou, Guangdong Province, 510120, China.
| | - Xueen Liu
- Department of Microbiology and Center of Infectious Diseases, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing, 100191, China.
| | - Hui Zhuang
- Department of Microbiology and Center of Infectious Diseases, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing, 100191, China.
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Hou J, Ning Q, Duan Z, Chen Y, Xie Q, Zhang L, Wu S, Tang H, Li J, Lin F, Yang Y, Gong G, Luo Y, Xie S, Wang H, Mateo R, Yazdi T, Abramov F, Yee LJ, Flaherty J, Chen C, Huang Y, Zhang M, Jia J. Five-year Treatment with Tenofovir Alafenamide Achieves High Rates of Viral Suppression, Alanine Aminotransferase Normalization, and Favorable Bone and Renal Safety in Chinese Chronic Hepatitis B Patients. J Clin Transl Hepatol 2024; 12:469-480. [PMID: 38779514 PMCID: PMC11106352 DOI: 10.14218/jcth.2023.00417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Revised: 01/14/2024] [Accepted: 02/02/2024] [Indexed: 05/25/2024] Open
Abstract
BACKGROUND AND AIMS After 3-years (144 week) of double-blind treatment in Chinese chronic hepatitis B patients in two ongoing phase 3 studies, tenofovir alafenamide (TAF) showed similar efficacy to tenofovir disoproxil fumarate (TDF), with improved renal and bone safety. In this study, we aimed to report the 5-year results from 2 years into the open-label TAF treatment phase. METHODS All participants completing the 144-week double-blind treatment were eligible to receive open-label TAF 25 mg once daily up to week 384. Serial analysis of viral suppression (hepatitis B virus DNA <29 IU/mL), alanine aminotransferase normalization, serological responses, and safety outcomes at year 5 (week 240) was performed. RESULTS The open-label phase included 93% (311/334) of the enrolled participants, which included 212 who switched from double-blind TAF to open-label TAF (TAF-TAF) and 99 who switched from double-blind TDF to open-label TAF (TDF-TAF). Baseline characteristics were comparable. Week 240 viral suppression rates were similar between groups [93.4% vs. 93.9%; difference: -1.5%, (95% CI: -6.4 to -3.5), p=0.857]. Alanine aminotransferase normalization and serological response rates were higher in the TAF-TAF group than in the TDF-TAF group. The frequencies of adverse events and laboratory abnormalities were low and similar between groups. Both groups had similar small numerical declines from baseline in estimated glomerular filtration rate at year 5 (week 240, -2.85 mL/min vs. -3.29 mL/min, p=0.910). The greater declines in renal and bone parameters in the TDF-TAF group through week 144 improved after switching to TAF. CONCLUSIONS The 5-year TAF treatment efficacy was high and similar to that of 3-year TDF followed by 2-year TAF in Chinese chronic hepatitis B patients. Favorable effects on bone and renal parameters were sustained with TAF treatment alone and were observed following the switch from TDF to TAF.
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Affiliation(s)
- Jinlin Hou
- Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Qin Ning
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Zhongping Duan
- Beijing YouAn Hospital, Capital Medical University, Beijing, China
| | - Yu Chen
- Beijing YouAn Hospital, Capital Medical University, Beijing, China
| | - Qing Xie
- Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lunli Zhang
- The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Shanming Wu
- Shanghai Public Health Clinical Center, Shanghai, China
| | - Hong Tang
- West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Jun Li
- The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Feng Lin
- Hainan General Hospital, Haikou, Hainan, China
| | - Yongfeng Yang
- The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Guozhong Gong
- The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | | | | | | | | | | | | | | | | | - Chengwei Chen
- The People’s Liberation Army No. 85 Hospital, Shanghai, China
| | - Yan Huang
- Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Mingxiang Zhang
- The Sixth People’s Hospital of Shenyang, Shenyang, Liaoning, China
| | - Jidong Jia
- Beijing Friendship Hospital, Capital Medical University, Beijing, China
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Li J, Yang D, Zhong J, Liao Y. Letter: Determining optimal ALT cut-off values for predicting significant hepatic histological changes in chronic hepatitis B virus infection. Aliment Pharmacol Ther 2024; 59:1156-1157. [PMID: 38591800 DOI: 10.1111/apt.17939] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/10/2024]
Abstract
LINKED CONTENTThis article is linked to Kang et al paper. To view this article, visit https://doi.org/10.1111/apt.17862
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Affiliation(s)
- Jianrong Li
- Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Dalong Yang
- Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Jianhong Zhong
- Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Nanning, China
- Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Nanning, China
| | - Yingyang Liao
- Nutritional Department, Guangxi Medical University Cancer Hospital, Nanning, China
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Gao Y, Wang M, Liu X. Noninvasive serum markers for predicting significant liver histopathology in HBeAg-negative chronic HBV-infected patients with normal alanine aminotransferase. Microbiol Spectr 2024; 12:e0394123. [PMID: 38426768 PMCID: PMC11325860 DOI: 10.1128/spectrum.03941-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Accepted: 12/16/2023] [Indexed: 03/02/2024] Open
Abstract
This study is to explore the proportion of significant liver histopathology in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV)-infected patients with normal alanine aminotransferase (ALT) and investigate noninvasive indicators for predicting significant liver histopathology. A total of 201 HBeAg-negative chronic HBV-infected patients with normal ALT who underwent liver biopsy were involved in this study. Significant liver histological changes were defined as necroinflammation grade ≥2 (G ≥ 2) and/or fibrosis stage ≥2 (S ≥ 2). The results showed that 42.3% (85/201) and 45.8% (92/201) of the HBeAg-negative patients with normal ALT have significant liver necroinflammation (G ≥ 2) and fibrosis (S ≥ 2), respectively. High normal ALT (>22 U/L), high level of serum HBV DNA (>3.42 log IU/mL), and low level of prealbumin (PA) (<170 mg/L) were independent predictors for significant liver necroinflammation, and the predictive value of the combined indicators was 0.750 (P < 0.001), while high normal ALT (>24 U/L) and high level of FIB-4 (>1.53) were independent predictors for significant liver fibrosis, and the predictive value of the combined indicators was 0.740 (P < 0.001). In conclusion, more than 40% of HBeAg-negative patients with normal ALT have significant liver histopathology and require immediate antiviral treatment. ALT, PA, HBV DNA, and FIB-4 can independently predict significant liver inflammation and fibrosis for HBeAg-negative patients with normal ALT. Lowering the treatment threshold of ALT may benefit the HBeAg-negative chronic HBV-infected patients. IMPORTANCE Hepatitis B e antigen (HBeAg)-negative chronic hepatitis B virus (HBV)-infected patients with normal alanine aminotransferase (ALT) were supposed to have a low risk of progression to cirrhosis or hepatocellular carcinoma, and it was recommended to regularly follow up or undergo liver biopsy to assess liver histopathology according to the major international guidelines. However, this study indicates that a considerable number of HBeAg-negative chronic HBV-infected patients with normal ALT have significant liver histopathology and require immediate antiviral treatment. Besides, several clinical commonly used noninvasive indicators were found that can be used to predict significant liver histopathology; thereby liver biopsy might be avoided for HBeAg-negative chronic HBV-infected patients with normal ALT.
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Affiliation(s)
- Yuhua Gao
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Key Clinical Laboratory of Henan Province, Zhengzhou, Henan, China
| | - Mingyang Wang
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Key Clinical Laboratory of Henan Province, Zhengzhou, Henan, China
| | - Xia'nan Liu
- Department of Clinical Laboratory, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
- Key Clinical Laboratory of Henan Province, Zhengzhou, Henan, China
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You H, Wang F, Li T, Xu X, Sun Y, Nan Y, Wang G, Hou J, Duan Z, Wei L, Jia J, Zhuang H. Guidelines for the Prevention and Treatment of Chronic Hepatitis B (version 2022). J Clin Transl Hepatol 2023; 11:1425-1442. [PMID: 37719965 PMCID: PMC10500285 DOI: 10.14218/jcth.2023.00320] [Citation(s) in RCA: 77] [Impact Index Per Article: 38.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Revised: 08/02/2023] [Accepted: 08/03/2023] [Indexed: 09/19/2023] Open
Abstract
To facilitate the achieving of the goal of "eliminating viral hepatitis as a major public health threat by 2030" set by the World Health Organization, the Chinese Society of Hepatology together with the Chinese Society of Infectious Diseases (both are branches of the Chinese Medical Association) organized a panel of experts and updated the guidelines for prevention and treatment of chronic hepatitis B in China (version 2022). With the support of available evidence, this revision of the guidelines focuses on active prevention, large scale testing, and expansion of therapeutic indication of chronic hepatitis B with the aim of reducing the hepatitis B related disease burden.
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Affiliation(s)
- Hong You
- Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Fusheng Wang
- The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Taisheng Li
- Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Xiaoyuan Xu
- Peking University First Hospital, Beijing, China
| | - Yameng Sun
- Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Yuemin Nan
- Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | | | - Jinlin Hou
- Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Zhongping Duan
- Beijing You-An Hospital, Capital Medical University, Beijing, China
| | - Lai Wei
- Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Jidong Jia
- Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Hui Zhuang
- Peking University Health Science Center, Beijing, China
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Xu X, Wang H, Shan S, Sun Y, Xu X, You H, Jia J, Zhuang H, Kong Y, on behalf of the China Registry of Hepatitis B (CR-HepB) Group. The Impact of the Definitions of Clinical Phases on the Profiles of Grey-Zone Patients with Chronic Hepatitis B Virus Infection. Viruses 2023; 15:1212. [PMID: 37243297 PMCID: PMC10222301 DOI: 10.3390/v15051212] [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: 04/06/2023] [Revised: 04/26/2023] [Accepted: 04/30/2023] [Indexed: 05/28/2023] Open
Abstract
We aim to investigate the impact of different clinical phases' definitions of chronic hepatitis B (CHB) infection on the profiles of grey zone, based on HBV guidelines set by the Chinese Society of Hepatology and Chinese Society of Infectious Diseases (CSH/CSID, 2022 version) and guidelines set by the American Association for the Study of Liver Diseases (AASLD, 2018 version). We retrospectively examined untreated CHB patients enrolled in the China Registry of Hepatitis B database. Patients' clinical phases were determined as per CSH/CSID and AASLD. Liver fibrosis was estimated by FIB-4 and/or APRI. Among 3462 CHB patients, 56.9% and 41.7% fell into the grey zone based on AASLD and CSH/CSID. Compared with grey zone patients as per AASLD, those under CSH/CSID guidelines showed lower levels of median ALT (26.0 vs. 37.0 U/L, p < 0.001), AST (25.0 vs. 29.4 U/L, p < 0.001) and APRI (0.3 vs. 0.4, p < 0.001), and lower rates of advanced fibrosis estimated by APRI (7.9% vs. 11.4% p = 0.001), but comparable rates by FIB-4 (13.0% vs. 14.1%, p = 0.389). With the stepwise lowering of ALT upper limits of normal (ULN) values from 50/40 U/L for males/females to 40/40 U/L, 35/25 U/L and 30/19 U/L, the proportions of grey zone patients as per CSH/CSID declined from 46.7% to 41.7%, 34.3% and 28.8%, respectively, whereas they remained stable (55.7%, 56.2%, 56.9% and 57.0%) as per AASLD. Compared with the AASLD guidelines, CSH/CSID guidelines leave fewer and less severe patients in the grey zone. Lowering ALT ULN values reduces the number of grey zone patients as per CSH/CSID, but not under AASLD guidelines.
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Affiliation(s)
- Xiaoqian Xu
- Clinical Epidemiology and EBM Unit, Beijing Friendship Hospital, Capital Medical University, Beijing Clinical Research Institute, Beijing 100050, China
| | - Hao Wang
- Clinical Epidemiology and EBM Unit, Beijing Friendship Hospital, Capital Medical University, Beijing Clinical Research Institute, Beijing 100050, China
| | - Shan Shan
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing 100050, China
| | - Yameng Sun
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing 100050, China
| | - Xiaoyuan Xu
- Department of Infectious Diseases, Peking University First Hospital, Beijing 100034, China
| | - Hong You
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing 100050, China
| | - Jidong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Diseases, Beijing 100050, China
| | - Hui Zhuang
- Department of Microbiology and Infectious Disease Center, Peking University Health Science Center, Beijing 100191, China
| | - Yuanyuan Kong
- Clinical Epidemiology and EBM Unit, Beijing Friendship Hospital, Capital Medical University, Beijing Clinical Research Institute, Beijing 100050, China
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Malik GF, Zakaria N, Majeed MI, Ismail FW. Viral Hepatitis - The Road Traveled and the Journey Remaining. Hepat Med 2022; 14:13-26. [PMID: 35300491 PMCID: PMC8922334 DOI: 10.2147/hmer.s352568] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2021] [Accepted: 02/24/2022] [Indexed: 12/16/2022] Open
Abstract
Hepatitis is defined as inflammation of the liver and is commonly due to infection with The hepatotropic viruses - hepatitis A, B, C, D and E. Hepatitis carries one of the highest disease burdens globally and has caused significant morbidity and mortality among different patient populations. Clinical presentation varies from asymptomatic or acute flu-like illness to acute liver failure or chronic liver disease, characterized by jaundice, hepatomegaly and ascites among many other signs. Eventually, this can lead to fibrosis (cirrhosis) of the liver parenchyma and carries a risk of development into hepatocellular carcinoma. Hepatitis B and C are most notorious for causing liver cirrhosis; in 2019, an estimated 296 million people worldwide had chronic hepatitis B infection and 58 million are currently estimated to have chronic hepatitis C, with 1.5 million new infections of both hepatitis B and C, occurring annually. With the help of latest serological biomarkers and viral nucleic acid amplification tests, it has become rather simple to efficiently screen, diagnose and monitor patients with hepatitis, and to commence with appropriate antiviral treatment. More importantly, the development of vaccinations against some of these viruses has greatly helped to curb the infection rates. Whilst there has been exceptional progress over the years in the management of viral hepatitis, many hurdles still remain which must be addressed in order to proceed towards a hepatitis-free world. This review will shed light on the origin and discovery of the hepatitis viruses, the global epidemiology and clinical symptoms, diagnostic modalities, currently available treatment options, the importance of prevention, and the journey needed to move forward towards the eradication of its global disease burden.
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Affiliation(s)
- Ghulam Fareed Malik
- Section of Gastroenterology, Department of Medicine, The Aga Khan University, Karachi, Pakistan
| | - Noval Zakaria
- Section of Gastroenterology, Department of Medicine, The Aga Khan University, Karachi, Pakistan
| | | | - Faisal Wasim Ismail
- Section of Gastroenterology, Department of Medicine, The Aga Khan University, Karachi, Pakistan
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Liu JF, Chen TY, Zhao YR. Vertical transmission of hepatitis B virus: propositions and future directions. Chin Med J (Engl) 2021; 134:2825-2831. [PMID: 34636774 PMCID: PMC8667965 DOI: 10.1097/cm9.0000000000001800] [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: 06/25/2021] [Indexed: 11/25/2022] Open
Abstract
ABSTRACT Chronic hepatitis B virus (HBV) infection due to vertical transmission remains a critical concern with regards to eliminating HBV infection. Implementation of hepatitis B vaccine, the foundation to prevent perinatal and horizontal transmission, has reduced the prevalence of HBV by >80%. In countries where the hepatitis B immune globulin (HBIG) is available, such as China and the United States, the administration of HBIG and hepatitis B vaccine to the infants of mothers who are positive for hepatitis B surface antigen has become a standard practice and is effective in preventing vertical transmission. Accumulating evidence on the efficacy and safety of antiviral prophylaxis during pregnancy indicates the probability of attaining the goal of the World Health Organization to eliminate hepatitis by 2030. In this review, we discuss the transmission routes, diagnostic criteria, and preventive strategies for vertical transmission. A preventive program that includes screening before pregnancy, antiviral prophylaxis during pregnancy, and postpartum immunoprophylaxis provides "perfect strategies" to eliminate vertical transmission. However, there is still a notable gap between "perfect strategies" and real-world application, including insufficient coverage of timely birth dose vaccine and the efficacy and necessity of HBIG, especially in mothers who are negative for hepatitis B envelope antigen. In particular, there is a clear need for a comprehensive long-term safety profile of antiviral prophylaxis. Therefore, feasible and cost-effective preventive strategies need to be determined across regions. Access also needs to be scaled up to meet the demands for prophylaxis and prevalence targets.
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Affiliation(s)
- Jin-Feng Liu
- Department of Infectious Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China
- Shaanxi Clinical Research Center of Infectious Diseases, Xi’an, Shaanxi 710061, China
| | - Tian-Yan Chen
- Department of Infectious Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China
- Shaanxi Clinical Research Center of Infectious Diseases, Xi’an, Shaanxi 710061, China
| | - Ying-Ren Zhao
- Department of Infectious Diseases, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China
- Shaanxi Clinical Research Center of Infectious Diseases, Xi’an, Shaanxi 710061, China
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Li EM, Xiao LX, Xu Z, Mo ZS, Li JQ, Mei YY, Lin CS. Factors associated with non-compliance with breastfeeding recommendation: a retrospective survey in hepatitis B virus-infected mothers who had taken Nucleos(t)ide analogs during pregnancy. BMC Pregnancy Childbirth 2021; 21:551. [PMID: 34384374 PMCID: PMC8359301 DOI: 10.1186/s12884-021-04020-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Accepted: 07/27/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND We encourage Hepatitis B virus-infected mothers to breastfeed postpartum, even when continuing pregnancy category B nucleos(t)ide analogs (NAs) treatment. However, a large proportion of the Hepatitis B virus-infected mothers were noncompliant with this breastfeeding recommendation. This study aimed to investigate the factors associated with noncompliance with breastfeeding recommendation in Hepatitis B virus-infected mothers who had received NAs treatment during pregnancy. METHODS A total of 155 mothers with chronic hepatitis B receiving NAs treatment for preventing mother-to-child transmission during the late gestation period were included and divided into exclusive breastfeeding (n = 63), mixed feeding (n = 34), and artificial feeding (n = 58) groups according to the postpartum feeding methods. Independent variables associated with feeding methods were analyzed using logistic regression analysis. RESULTS Compared to the breastfeeding and mixed feeding groups, the artificial feeding group had significantly more multiparity, later postpartum timing of stopping NAs treatment, and a lower proportion of having knowledge of NAs medications (all P < 0.05). In addition, multivariable logistic regression analysis confirmed that multiparity, later postpartum timing of stopping NAs treatment, and lacking knowledge of medication were independent factors associated with noncompliance with breastfeeding recommendation. CONCLUSIONS Hepatitis B virus-infected mothers who stopped NAs treatment at late postpartum period or had less knowledge of medication were more likely to be noncompliant with breastfeeding recommendation. Strengthening health education for participants taking NAs may be an important method to improve compliance with breastfeeding recommendation.
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Affiliation(s)
- Er-Mei Li
- Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangdong Province, 510630, Guangzhou, China
| | - Li-Xin Xiao
- Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangdong Province, 510630, Guangzhou, China
| | - Zhen Xu
- Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangdong Province, 510630, Guangzhou, China
| | - Zhi-Shuo Mo
- Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangdong Province, 510630, Guangzhou, China
| | - Jia-Qian Li
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, 510120, Guangzhou, China
| | - Yong-Yu Mei
- Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangdong Province, 510630, Guangzhou, China.
| | - Chao-Shuang Lin
- Department of Infectious Diseases, the Third Affiliated Hospital of Sun Yat-Sen University, 600 Tianhe Road, Guangdong Province, 510630, Guangzhou, China.
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11
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Cornberg M, Sandmann L, Protzer U, Niederau C, Tacke F, Berg T, Glebe D, Jilg W, Wedemeyer H, Wirth S, Höner Zu Siederdissen C, Lynen-Jansen P, van Leeuwen P, Petersen J. S3-Leitlinie der Deutschen Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS) zur Prophylaxe, Diagnostik und Therapie der Hepatitis-B-Virusinfektion – (AWMF-Register-Nr. 021-11). ZEITSCHRIFT FUR GASTROENTEROLOGIE 2021; 59:691-776. [PMID: 34255317 DOI: 10.1055/a-1498-2512] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- Markus Cornberg
- Deutsches Zentrum für Infektionsforschung (DZIF), Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Hannover; Centre for individualised infection Medicine (CiiM), Hannover.,Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Hannover
| | - Lisa Sandmann
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Hannover
| | - Ulrike Protzer
- Institut für Virologie, Technische Universität München/Helmholtz Zentrum München, München
| | | | - Frank Tacke
- Medizinische Klinik m. S. Hepatologie und Gastroenterologie, Charité Universitätsmedizin Berlin, Berlin
| | - Thomas Berg
- Klinik und Poliklinik für Gastroenterologie und Rheumatologie, Universitätsklinikum Leipzig, Leipzig
| | - Dieter Glebe
- Institut für Medizinische Virologie, Nationales Referenzzentrum für Hepatitis-B-Viren und Hepatitis-D-Viren, Justus-Liebig-Universität Gießen, Gießen
| | - Wolfgang Jilg
- Institut für Medizinische Mikrobiologie und Hygiene, Universität Regensberg, Regensburg
| | - Heiner Wedemeyer
- Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Hannover
| | - Stefan Wirth
- Zentrum für Kinder- und Jugendmedizin, Helios Universitätsklinikum Wuppertal, Wuppertal
| | | | - Petra Lynen-Jansen
- Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS), Berlin
| | - Pia van Leeuwen
- Deutsche Gesellschaft für Gastroenterologie, Verdauungs- und Stoffwechselkrankheiten (DGVS), Berlin
| | - Jörg Petersen
- IFI Institut für Interdisziplinäre Medizin an der Asklepios Klinik St. Georg, Hamburg
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12
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Significant histological changes and satisfying antiviral efficacy in chronic hepatitis B virus infection patients with normal alanine aminotransferase. Antiviral therapy decision in chronic HBV patients with normal ALT. Clin Res Hepatol Gastroenterol 2021; 45:101463. [PMID: 32571749 DOI: 10.1016/j.clinre.2020.05.011] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2019] [Accepted: 05/06/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS A proportion of chronic hepatitis B virus (HBV) infection patients with normal alanine aminotransferase (ALT) should start antiviral therapy based on liver biopsy. We aim to evaluate the proportion of such patients, find noninvasive methods for identifying and then evaluate antiviral efficacy. METHODS 253 chronic HBV infection patients with normal ALT were analyzed at baseline and 57 patients with histological indication for antiviral therapy (Histology activity index ≥5 and/or Ishak fibrosis score ≥3) and 140 patients with elevated ALT received entecavir therapy and were followed-up to 78 weeks with a second liver biopsy in this multi-center study. RESULTS 127 (50.2%) of 253 patients with normal ALT fulfilled histological indication for antiviral therapy. Aspartate aminotransferase (P=0.049), anti-hepatitis B virus core antibody (P=0.001) and liver stiffness measurement (P=0.000) were independent variables for identifying histological indication for antiviral therapy. A noninvasive model (AAF) performed best among independent variables and other noninvasive models with area under the operating characteristic curve of 0.887. Antiviral efficacy showed that 38 (66.7%) of 57 patients had undetectable HBV DNA. 12 (41.4%) of 29 patients who were hepatitis B e antigen (HBeAg)-positive at baseline achieved HBeAg loss and 3 (10.3%) achieved HBeAg seroconversion. 25 (43.9%) of 57 patients achieved histological response. Moreover, 57 patients with normal ALT had a similar antiviral therapy efficacy with 140 patients with elevated ALT (P>0.1) except proportion of inflammation improvement and histological response (P=0.005, P=0.049). CONCLUSIONS Half of chronic HBV patients with normal ALT should start antiviral therapy based on liver biopsy. A noninvasive model could be used as a reliable tool for antiviral therapy decision. Patients with normal or elevated ALT had a similar antiviral efficacy.
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13
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Lei T, Tan F, Hou Z, Liu P, Zhao X, Liu H. Hepatitis B Virus Reactivation in Gastrointestinal Stromal Tumor Patients Treated With Imatinib. Front Oncol 2021; 10:596500. [PMID: 33552970 PMCID: PMC7862776 DOI: 10.3389/fonc.2020.596500] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2020] [Accepted: 12/07/2020] [Indexed: 12/12/2022] Open
Abstract
Purpose Hepatitis B virus reactivation (HBVr) in patients with gastrointestinal stromal tumors (GISTs) have not been sufficiently characterized. This study aimed to review the possible mechanism of HBVr induced by imatinib and explore appropriate measures for patient management and monitoring. Methods The clinical data of GIST patients who experienced HBVr due to treatment with imatinib at Xiangya Hospital (Changsha, Hunan, China) were retrospectively analyzed. A literature review was also conducted. Results Five cases were analyzed, including 3 cases in this study. The average age of the patients was 61.8 y, with male preponderance (4 of 5 vs. 1 of 5). These patients received imatinib as adjuvant treatment (n=4) or as neoadjuvant treatment (n=1). Primary tumors were mostly located in the stomach (n=4) or rectum (n=1). High (n=3) or intermediate (n=1) recurrence risk was categorized using the postoperative pathological results (n=4). Imatinib was then started at 400 (n=4) or 200 mg (n=1) daily. Patients first reported abnormal liver function during the 2th (n=1),6th (n=3), or 10th (n=1) month of treatment with imatinib. Some patients (n=4) discontinued imatinib following HBVr; notably, 1 month after discontinuation, 1 patient experienced HBVr. Antivirals (entecavir n=4, tenofovir n=1), artificial extracorporeal liver support (n=1), and liver transplant (n=1) were effective approaches to treating HBVr. Most patients (n=3) showed favorable progress, 1 patient underwent treatment, and 1 patient died due to severe liver failure induced by HBVr. Conclusions Although HBVr is a rare complication (6.12%), HBV screening should be conducted before starting treatment with imatinib in GIST patients. Prophylactic therapy for hepatitis B surface antigen positive patients, prompt antiviral treatment and cessation of imatinib are also necessary.
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Affiliation(s)
- Tianxiang Lei
- Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, China
| | - Fengbo Tan
- Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, China
| | - Zhouhua Hou
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, China
| | - Peng Liu
- Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, China
| | - Xianhui Zhao
- Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, China
| | - Heli Liu
- Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, China
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14
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Xu LM, Liu P. Guidelines for diagnosis and treatment of hepatic fibrosis with integrated traditional Chinese and Western medicine (2019 edition). JOURNAL OF INTEGRATIVE MEDICINE 2020; 18:203-213. [PMID: 32331978 DOI: 10.1016/j.joim.2020.03.001] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/11/2019] [Accepted: 09/25/2019] [Indexed: 12/16/2022]
Abstract
In 2006, the Hepatology Committee of Chinese Association of Integrative Medicine issued the "Guidelines for the Prevention and Treatment of Liver Fibrosis with Integrated Traditional Chinese and Western Medicine." In recent years, the fields of Chinese medicine, Western medicine, and integrative medicine have made rapid advances in basic and clinical research into chronic liver disease, and accumulated new evidence for the prevention and treatment of hepatic fibrosis. Therefore, in order to meet clinical needs, liver disease experts of integrated traditional Chinese and Western medicine were united to revise the previous guidelines in order to help physicians make correct and reasonable decisions in the diagnosis and treatment of hepatic fibrosis.
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Affiliation(s)
- Lie-Ming Xu
- Institute of Liver Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
| | - Ping Liu
- Institute of Liver Diseases, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
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15
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Wu D, Zhang S, Xie Z, Chen E, Rao Q, Liu X, Huang K, Yang J, Xiao L, Ji F, Jiang Z, Zhao Y, Ouyang X, Zhu D, Dai X, Hou Z, Liu B, Deng B, Zhou N, Gao H, Sun Z, Li L. Plasminogen as a prognostic biomarker for HBV-related acute-on-chronic liver failure. J Clin Invest 2020; 130:2069-2080. [PMID: 32175919 PMCID: PMC7108894 DOI: 10.1172/jci130197] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Accepted: 01/14/2020] [Indexed: 12/12/2022] Open
Abstract
BACKGROUNDHBV-related acute-on-chronic liver failure (HBV-ACLF) is hallmarked by high short-term mortality rates, calling for accurate prognostic biomarkers for initial risk stratification.METHODSThree tandem mass tag-labeled (TMT-labeled) quantitative proteomic studies were performed on 10 patients with HBV-related acute hepatic decompensation and on 20 patients with HBV-ACLF. Candidate biomarkers were preliminarily verified in a cross-sectional cohort (n = 144) and further confirmed in 2 prospective cohorts (n = 207 and n = 148).RESULTSPlasminogen, a potential prognostic biomarker for HBV-ACLF, was identified by TMT quantitative proteomics and preliminarily verified in the cross-sectional cohort. Further validation with a prospective cohort (n = 207) showed that plasminogen levels at admission were significantly lower (P < 0.001) in HBV-ACLF nonsurvivors than in survivors. The cumulative survival duration of patients with high plasminogen levels was significantly longer (P < 0.001) than that of patients with low plasminogen levels. During hospitalization, plasminogen levels significantly decreased (P = 0.008) in the deterioration group but significantly increased (P < 0.001) in the improvement group. Additionally, plasminogen levels gradually increased in survivors but gradually decreased in nonsurvivors. The P5 score, a prognostic panel incorporating plasminogen levels, hepatic encephalopathy occurrence, age, international normalized ratio (INR), and total bilirubin, was significantly superior to the Child-Pugh, Model for End-stage Liver Disease (MELD), Chronic Liver Failure Consortium ACLF (CLIF-C ACLF), Chinese Group on the Study of Severe Hepatitis B (COSSH), and HINT (a prognostic score based on hepatic encephalopathy occurrence, INR, neutrophil count, and thyroid-stimulating hormone) scores (all P < 0.05). The performances of the plasminogen level and P5 score were validated in a second multicenter, prospective cohort (n = 148).CONCLUSIONSPlasminogen is a promising prognostic biomarker for HBV-ACLF, and sequential plasminogen measurements could profile the clinical course of HBV-ACLF. P5 is a high-performance prognostic score for HBV-ACLF.FUNDINGThe National Key Research and Development Program (2017YFC1200204); the National Natural Science Foundation of China (81400589, 81600497); the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (81121002); the Chinese High-Tech Research and Development Programs (2012AA020204); the National S&T Major Project (2012ZX10002004); and the Zhejiang Provincial Medicine and Health Science and Technology Project (2016147735).
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Affiliation(s)
- Daxian Wu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases; National Clinical Research Center for Infectious Diseases; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases; The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Department of Infectious Diseases, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Sainan Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases; National Clinical Research Center for Infectious Diseases; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases; The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Zhongyang Xie
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases; National Clinical Research Center for Infectious Diseases; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases; The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Ermei Chen
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases; National Clinical Research Center for Infectious Diseases; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases; The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Qunfang Rao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases; National Clinical Research Center for Infectious Diseases; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases; The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Xiaoli Liu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases; National Clinical Research Center for Infectious Diseases; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases; The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Kaizhou Huang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases; National Clinical Research Center for Infectious Diseases; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases; The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Jing Yang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases; National Clinical Research Center for Infectious Diseases; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases; The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Lanlan Xiao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases; National Clinical Research Center for Infectious Diseases; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases; The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Feiyang Ji
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases; National Clinical Research Center for Infectious Diseases; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases; The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Zhengyi Jiang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases; National Clinical Research Center for Infectious Diseases; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases; The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Yalei Zhao
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases; National Clinical Research Center for Infectious Diseases; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases; The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Xiaoxi Ouyang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases; National Clinical Research Center for Infectious Diseases; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases; The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Danhua Zhu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases; National Clinical Research Center for Infectious Diseases; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases; The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Xiahong Dai
- Department of Infectious Diseases, Shulan Hospital of Hangzhou, Hangzhou, China
| | - Zhouhua Hou
- Department of Infectious Diseases, Xiangya Hospital of Central South University, Changsha, China
| | - Bingjie Liu
- Department of Infectious Diseases, First Affiliated Hospital, College of Medicine, Nanhua University, Hengyang, China
| | - Binbin Deng
- Department of Infectious Diseases, Xiangya Hospital of Central South University, Changsha, China
| | - Ning Zhou
- Department of Infectious Diseases, Second Xiangya Hospital, Central South University, Changsha, China
| | - Hainv Gao
- Department of Infectious Diseases, Shulan Hospital of Hangzhou, Hangzhou, China
| | - Zeyu Sun
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases; National Clinical Research Center for Infectious Diseases; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases; The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases; National Clinical Research Center for Infectious Diseases; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases; The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
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16
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Jia W, Zhu MQ, Qi X, Wang T, Wen X, Chen PD, Fan QQ, Zhang WH, Zhang JM. Serum hepatitis B virus RNA levels as a predictor of HBeAg seroconversion during treatment with peginterferon alfa-2a. Virol J 2019; 16:61. [PMID: 31064399 PMCID: PMC6505123 DOI: 10.1186/s12985-019-1152-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2018] [Accepted: 03/25/2019] [Indexed: 02/08/2023] Open
Abstract
Background Hepatitis B e antigen (HBeAg) seroconversion represents an endpoint of treatment of chronic hepatitis B virus (HBV) infections. Methods We have studied whether levels of serum hepatitis B virus ribonucleic acid (HBV RNA) during pegylated interferon alfa-2a treatment might be helpful for predicting HBeAg seroconversion. 61 HBeAg-positive chronic hepatitis B (CHB) patients treated with pegylated interferon alfa-2a alone or in combination with adefovir (10 mg/day) for 48 weeks were included in this retrospective analysis. Response was defined as HBeAg seroconversion at 24 weeks posttreatment. Receiver operating characteristic analyses were used to identify baseline and on-treatment HBV RNA levels associated with response. Results Twenty-two of 61 (36.1%) patients achieved a response. Baseline HBV RNA levels were lower in responders than in nonresponders (4.55 ± 1.19 and 5.90 ± 1.13 copies/mL, respectively, P = 0.001). Baseline HBV RNA cut off level (200,000 copies/mL) provided a positive predictive value (PPV) of 56.0% and a negative predictive value (NPV) of 77.8%. HBV RNA level (3000 copies/mL) at week 12 provide a PPV of 75.0% and a NPV of 82.8%. Moreover, HBeAg seroconversion rates at 24 weeks posttreatment were significantly higher in patients with HBV RNA ≤ 200,000 copies/mL at baseline and HBV RNA ≤ 3000 copies/mL at week 12 (92.9%) versus others (12.5%) (All P < 0.05). Conclusions In Conclusions, serum HBV RNA levels may serve as a novel tool for prediction of HBeAg seroconversion during therapy with pegylated interferon alfa-2a in HBeAg-positive CHB patients. Electronic supplementary material The online version of this article (10.1186/s12985-019-1152-6) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Wen Jia
- Department of Infectious Diseases, Jing'An District Centre Hospital of Shanghai, Fudan University, Shanghai, China.,Department of Infectious Diseases, Huashan Hospital, Fudan University, Room 510, Building 5, 12 Middle Wulumuqi Road, Shanghai, China
| | - Men Qi Zhu
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Room 510, Building 5, 12 Middle Wulumuqi Road, Shanghai, China
| | - Xun Qi
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Room 510, Building 5, 12 Middle Wulumuqi Road, Shanghai, China
| | - Ting Wang
- Department of Infectious Diseases, Jing'An District Centre Hospital of Shanghai, Fudan University, Shanghai, China.,Department of Infectious Diseases, Huashan Hospital, Fudan University, Room 510, Building 5, 12 Middle Wulumuqi Road, Shanghai, China
| | - Xiao Wen
- Department of Infectious Diseases, Jing'An District Centre Hospital of Shanghai, Fudan University, Shanghai, China.,Department of Infectious Diseases, Huashan Hospital, Fudan University, Room 510, Building 5, 12 Middle Wulumuqi Road, Shanghai, China
| | - Pei Dong Chen
- Department of Infectious Diseases, Jing'An District Centre Hospital of Shanghai, Fudan University, Shanghai, China.,Department of Infectious Diseases, Huashan Hospital, Fudan University, Room 510, Building 5, 12 Middle Wulumuqi Road, Shanghai, China
| | - Qing Qi Fan
- Department of Infectious Diseases, Jing'An District Centre Hospital of Shanghai, Fudan University, Shanghai, China.,Department of Infectious Diseases, Huashan Hospital, Fudan University, Room 510, Building 5, 12 Middle Wulumuqi Road, Shanghai, China
| | - Wen-Hong Zhang
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Room 510, Building 5, 12 Middle Wulumuqi Road, Shanghai, China
| | - Ji Ming Zhang
- Department of Infectious Diseases, Jing'An District Centre Hospital of Shanghai, Fudan University, Shanghai, China. .,Department of Infectious Diseases, Huashan Hospital, Fudan University, Room 510, Building 5, 12 Middle Wulumuqi Road, Shanghai, China.
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17
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Vaginal delivery and HBV mother to child transmission risk after immunoprophylaxis: A systematic review and a meta-analysis. Midwifery 2019; 74:116-125. [PMID: 30953967 DOI: 10.1016/j.midw.2019.03.024] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2018] [Revised: 03/15/2019] [Accepted: 03/29/2019] [Indexed: 01/07/2023]
Abstract
OBJECTIVE HBV mother to child transmission (MTCT) can be prevented by passive and active immunoprophylaxis. In this study, we aim to assess whether vaginal delivery is safe for HBV MTCT after immunoprophylaxis. MATERIAL AND METHODS PubMed and Web of Science were systematically searched. We compared the MTCT incidence of infants at 6 months or older between vaginal delivery and caesarean section. Serological HBV positive incidences for newborns at birth were also compared. RESULTS Eighteen studies with 11,446 mother-child pairs were included in the meta-analysis. The average incidence of serological HBV positive for newborns at birth was 7.2% in the cesarean section group, and 16.6% in the vaginal delivery group. The summary odds ratio (OR) was 0.499 (95% CI 0.364-0.684; Z = 4.33, P < 0.00001) between two groups. However, the average incidences of MTCT were 3.3% and 4.1% for the cesarean section group and the vaginal delivery group, respectively. The summary OR compared between two groups was 0.790 (95% CI 0.614 to 1.016; Z = 1.83, P = 0.067). The funnel plot, Begg's Test (z = -0.55, P = 0.583) and Egger's test (t = -0.29, P = 0.777) suggested there was no publication bias among the included studies. Sensitive analyze showed the ORs were 0.764 (95% CI 0.490 to 1.192; Z = 1.19, P = 0.236), and 0.386 (95% CI 0.132 to 1.125; Z = 1.74, P = 0.0081), respectively. CONCLUSION The vaginal delivery did not increase the HBV MTCT incidence after immunoprophylaxis at 6 months old or more. The existing evidence does not support the conclusion that caesarean section can prevent MTCT in HBsAg-positive mother after immunoprophylaxis. However, this conclusion should be cautious in the HBV mother with high viral load.
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18
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Peng S, Wan Z, Lin X, Li X, Du Y. Maternal hepatitis B surface antigen carrier status increased the incidence of gestational diabetes mellitus. BMC Infect Dis 2019; 19:147. [PMID: 30760217 PMCID: PMC6373004 DOI: 10.1186/s12879-019-3749-1] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2018] [Accepted: 01/28/2019] [Indexed: 12/11/2022] Open
Abstract
Background The relationship between chronic hepatitis B virus (HBV) infection with gestational diabetes mellitus (GDM) remains unclear. This study aimed to identify the association between maternal HBsAg-positive status and GDM. Methods A retrospective cohort study was performed on the pregnant women who delivered from June 2012 to May 2016 at Wuhan Medical Care Center for Women and Children, Wuhan, China. We compared the incidence of GDM between HBsAg-positive pregnant women and HBsAg-negative controls. A multivariate regression model was used to measure the independent association between maternal HBsAg carrier and the risk of developing GDM. Results In total, 964 HBsAg-positive pregnant women and 964 HBsAg-negative women were included into the study. We observed maternal HBsAg carrier (OR 1.47, 95% CI 1.06–2.03), age (OR 1.05, 95% CI 1.00–1.10) and family history of diabetes (OR 3.97, 95% CI 2.05–7.67) had an independent risk for GDM in multivariable logistical regression model. However, no significant association was found between HBeAg carrier status, other HBV markers or viral load in pregnancy and the incidence of GDM. Conclusions Our results indicated that maternal HBsAg carriage is an independent risk factor for GDM, but viral activity indicated by HBeAg status and viral load is not the main reason for this phenomenon. Further studies are warranted to clarify the possible mechanisms behind such association of HBV infection and the additional risk of GDM. Electronic supplementary material The online version of this article (10.1186/s12879-019-3749-1) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Songxu Peng
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13th Hangkong Road, Wuhan, 430030, Hubei, China
| | - Zhihua Wan
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13th Hangkong Road, Wuhan, 430030, Hubei, China
| | - Xiaofang Lin
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13th Hangkong Road, Wuhan, 430030, Hubei, China
| | - Xiu Li
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13th Hangkong Road, Wuhan, 430030, Hubei, China
| | - Yukai Du
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 13th Hangkong Road, Wuhan, 430030, Hubei, China.
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19
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Peng S, Wan Z, Liu T, Zhu H, Du Y. Incidence and Risk Factors of Intrauterine Transmission Among Pregnant Women With Chronic Hepatitis B Virus Infection. J Clin Gastroenterol 2019; 53:51-57. [PMID: 29517711 DOI: 10.1097/mcg.0000000000001001] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
GOALS To identify the potential risk factors of hepatitis B virus (HBV) intrauterine transmission and predict the incidence of HBV intrauterine transmission among hepatitis B surface antigen-positive pregnant women with diverse viral load. BACKGROUND The intrauterine transmission of HBV significantly contributes to the persistence of a high number of patients infected with HBV. However, its risk factors remain unclear. MATERIALS AND METHODS A prospective study was performed on hepatitis B surface antigen-positive pregnant women who delivered from June 2012 to December 2016 at Wuhan Medical Care Center for Women and Children, Wuhan, China. RESULTS In total, 1200 women paired with 1219 infants were enrolled. In total, 11 (0.9%) infants were identified with intrauterine transmission. We observed that all infants with intrauterine transmission were born to hepatitis B e antigen-positive mothers who had serum HBV DNA levels >7 log10 copies/mL. Our study suggested that the HBV DNA levels (for each log10 copies/mL increase, odds ratio=5.43; 95% confidence interval, 1.31-22.43; P=0.019) had independent effects on HBV intrauterine transmission in a multivariate logistic regression model. Moreover, cesarean section (odds ratio=0.18; 95% confidence interval, 0.04-0.74; P=0.018) was associated with a reduced risk of HBV intrauterine transmission. The predictive rates of intrauterine transmission were 0.06%, 0.50%, 2.81%, 8.89% in infants with maternal HBV DNA levels of 10, 10, 10, 10 copies/mL, respectively. CONCLUSIONS Our data confirmed that increasing maternal viral load has the ability to predict intrauterine HBV transmission. Vaginal delivery increased risk of HBV transmission in infants compared with cesarean section. Further studies are warranted to clarify the possible mechanism underlying these associations.
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Affiliation(s)
- Songxu Peng
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - Zhihua Wan
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - Tingting Liu
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
| | - Huiping Zhu
- Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, China
| | - Yukai Du
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan
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Gill US, Kennedy PTF. The impact of currently licensed therapies on viral and immune responses in chronic hepatitis B: Considerations for future novel therapeutics. J Viral Hepat 2019; 26:4-15. [PMID: 30415490 DOI: 10.1111/jvh.13040] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2018] [Accepted: 10/25/2018] [Indexed: 12/14/2022]
Abstract
Despite the availability of a preventative vaccine, chronic hepatitis B (CHB) remains a global healthcare challenge with the risk of disease progression due to cirrhosis and hepatocellular carcinoma. Although current treatment strategies, interferon and nucleos(t)ide analogues have contributed to reducing morbidity and mortality related to CHB, these therapies are limited in providing functional cure. The treatment paradigm in CHB is rapidly evolving with a number of new agents in the developmental pipeline. However, until novel agents with functional cure capability are available in the clinical setting, there is a pressing need to optimize currently licensed therapies. Here, we discuss current agents used alone and/or in combination strategies along with the impact of these therapies on viral and immune responses. Novel treatment strategies are outlined, and the potential role of current therapies in the employment of pipeline agents is discussed.
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Affiliation(s)
- Upkar S Gill
- Barts Liver Centre, Blizard Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, London, UK
| | - Patrick T F Kennedy
- Barts Liver Centre, Blizard Institute, Barts and The London School of Medicine & Dentistry, Queen Mary University of London, London, UK
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21
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Ji SS, Jiang HD, Jiang JC, Li J, Lin ST, Chen B, Xu SH. Applicability of liver stiffness measurement based nomograms to the assessments of hepatitis B related significant fibrosis and cirrhosis. Clin Chim Acta 2018; 489:75-82. [PMID: 30471249 DOI: 10.1016/j.cca.2018.11.029] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2018] [Revised: 11/07/2018] [Accepted: 11/20/2018] [Indexed: 12/23/2022]
Abstract
BACKGROUND We evaluated liver fibrosis in patients with chronic hepatitis B (CHB) and mildly raised alanine transaminase (ALT) activities between 1-2 times the upper limit of normal (ULN) which was near the threshold for initiating treatment. METHODS Nomogram-Fibrosis and Nomogram-Cirrhosis were elaborated with variables independently associated with significant fibrosis and cirrhosis determined by multivariate logistic regression. Calibration, receiver operator characteristic (ROC) and decision curves were applied to comparing nomograms with aspartate aminotransferase (AST) to platelet count (PLT) ratio index (APRI), age-AST-PLT-ALT index (FIB-4) and liver stiffness measurement (LSM). RESULTS The Nomogram-Fibrosis was constructed with LSM, PLT, and gamma-glutamyl transpeptidase (GGT). Nomogram-Cirrhosis contained one more variable of age other than Nomogram-Fibrosis. The calibration demonstrated that the assessments of significant fibrosis or cirrhosis by nomograms were in line with liver biopsy. The AUROC of Nomogram-Fibrosis was 0.788, lager than APRI (0.586), FIB-4 (0.656) and LSM (0.735). The AUROC of Nomogram-Cirrhosis was 0.889, larger than APRI (0.642), FIB-4 (0.725) and LSM (0.837). Furthermore, the decision curve analysis suggested the most net benefits were provided by the nomograms. CONCLUSIONS Nomogram-Fibrosis and Nomogram-Cirrhosis could be promising tools for recognizing significant fibrosis and cirrhosis for CHB patients with mild raised ALT activities.
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Affiliation(s)
- Si-Si Ji
- Department of Ultrasonography, the First Affiliated Hospital of Wenzhou Medical University, China
| | - Hai-Dan Jiang
- Department of Ultrasonography, the First Affiliated Hospital of Wenzhou Medical University, China
| | - Jia-Chun Jiang
- Department of Ultrasonography, the First Affiliated Hospital of Wenzhou Medical University, China
| | - Jia Li
- Department of Ultrasonography, the First Affiliated Hospital of Wenzhou Medical University, China
| | - Shu-Ting Lin
- Department of Ultrasonography, the First Affiliated Hospital of Wenzhou Medical University, China
| | - Bin Chen
- Department of Ultrasonography, the First Affiliated Hospital of Wenzhou Medical University, China.
| | - Shi-Hao Xu
- Department of Ultrasonography, the First Affiliated Hospital of Wenzhou Medical University, China.
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22
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Peng S, Wan Z, Liu T, Li X, Du Y. Cesarean section reduces the risk of early mother-to-child transmission of hepatitis B virus. Dig Liver Dis 2018; 50:1076-1080. [PMID: 29853270 DOI: 10.1016/j.dld.2018.05.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2018] [Revised: 04/10/2018] [Accepted: 05/07/2018] [Indexed: 12/11/2022]
Abstract
AIMS To evaluate the effects of cesarean section (CS) on the prevention of mother-to-child transmission (MTCT) of hepatitis B virus (HBV) among hepatitis B surface antigen (HBsAg) positive pregnant women. METHODS A prospective cohort study was performed on HBsAg-positive pregnant women who delivered from June 2012 to March 2017 at Wuhan Medical Care Center for Women and Children in Wuhan, China. Logistic regression models were used to examine the associations between mode of delivery and the presence of HBV MTCT. RESULTS A total of 1384 women paired with 1407 infants were enrolled. Our study showed that the incidence of HBV MTCT was 1.0% (14/1407) in infants born to HBsAg-positive pregnant women. We observed that the infants born by CS had a smaller percentage of HBV infection than those born by vaginal delivery (VD) (0.5% vs 1.7%, P = 0.043). In the fully adjusted model, CS was significantly associated with a decreased risk of HBV MTCT (OR = 0.26; 95% CI: 0.07-0.95; P = 0.042). CONCLUSION Our data confirmed that CS has a protective effect on early MTCT of HBV. CS for HBeAg-positive mothers with high viral load could reduce risk of MTCT and may become a new preventive measure of HBV MTCT through research on its risk-benefit assessment.
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Affiliation(s)
- Songxu Peng
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Zhihua Wan
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Tingting Liu
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Xiu Li
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yukai Du
- Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
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Chronic lymphocytic leukemia and infection risk in the era of targeted therapies: Linking mechanisms with infections. Blood Rev 2018; 32:387-399. [DOI: 10.1016/j.blre.2018.03.004] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2017] [Revised: 03/09/2018] [Accepted: 03/15/2018] [Indexed: 01/07/2023]
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Koffas A, Dolman GE, Kennedy PT. Hepatitis B virus reactivation in patients treated with immunosuppressive drugs: a practical guide for clinicians. Clin Med (Lond) 2018; 18:212-218. [PMID: 29858430 PMCID: PMC6334086 DOI: 10.7861/clinmedicine.18-3-212] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Hepatitis B virus reactivation (HBVr) is emerging as an important clinical entity, with the advent of highly potent immunosuppression licensed for use as the treatment of a widening range of clinical indications. HBVr can lead to severe acute liver failure and death. Risk can be minimised through appropriate screening, monitoring and antiviral prophylaxis. Screening for serological markers at the -earliest opportunity is recommended. Risk stratification should then be performed on the basis of characteristics of the -underlying disease, markers of viral activity and the potency of proposed immunosuppression. In this review, we summarise the most recent recommendations from the relevant international societies. We also provide suggestions on how a robust multidisciplinary service can be delivered to prevent HBVr in UK clinical practice through optimisation of resources and introduction of checkpoints to prevent the inappropriate administration of immunosuppression to those at significant risk of HBVr.
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Affiliation(s)
- Apostolos Koffas
- Gastroenterology Unit, University Hospital of Larisa, Thessaly, Greece
| | - Grace E Dolman
- Barts Liver Centre, Blizard Institute, Barts and the London School of Medicine and Dentistry, London, UK
| | - Patrick Tf Kennedy
- Barts Liver Centre, Blizard Institute, Barts and the London School of Medicine and Dentistry, London, UK
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25
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Dolman GE, Koffas A, Mason WS, Kennedy PT. Why, who and when to start treatment for chronic hepatitis B infection. Curr Opin Virol 2018; 30:39-47. [PMID: 29655092 DOI: 10.1016/j.coviro.2018.03.006] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2018] [Revised: 03/16/2018] [Accepted: 03/23/2018] [Indexed: 02/07/2023]
Abstract
Chronic hepatitis B remains a major global health challenge due to morbidity and mortality from hepatocellular carcinoma and complications of liver cirrhosis. Current treatment regimens are non-curative and, once initiated, treatment is of indefinite duration for the majority. The decision to initiate treatment decisions is based on risk stratification. Advances in our understanding of the natural history of chronic hepatitis B have led to a paradigm shift in recommendations for treatment. Emerging non-invasive biomarkers of disease activity will further enhance disease stratification. In this review, we summarise the guidance from major international societies on treatment for chronic hepatitis B and explore some of the novel approaches to disease assessment.
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Affiliation(s)
- Grace E Dolman
- Barts Liver Centre, Blizard Institute, Barts and the London School of Medicine and Dentistry, London, UK
| | - Apostolos Koffas
- Gastroenterology Unit, University Hospital of Larisa, Thessaly, Greece
| | | | - Patrick Tf Kennedy
- Barts Liver Centre, Blizard Institute, Barts and the London School of Medicine and Dentistry, London, UK.
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26
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Gill US, Pallett LJ, Kennedy PTF, Maini MK. Liver sampling: a vital window into HBV pathogenesis on the path to functional cure. Gut 2018; 67:767-775. [PMID: 29331944 PMCID: PMC6058064 DOI: 10.1136/gutjnl-2017-314873] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2017] [Revised: 11/29/2017] [Accepted: 12/07/2017] [Indexed: 12/12/2022]
Abstract
In order to optimally refine the multiple emerging drug targets for hepatitis B virus (HBV), it is vital to evaluate virological and immunological changes at the site of infection. Traditionally liver biopsy has been the mainstay of HBV disease assessment, but with the emergence of non-invasive markers of liver fibrosis, there has been a move away from tissue sampling. Here we argue that liver biopsy remains an important tool, not only for the clinical assessment of HBV but also for research progress and evaluation of novel agents. The importance of liver sampling has been underscored by recent findings of specialised subsets of tissue-resident immune subsets capable of efficient pathogen surveillance, compartmentalised in the liver and not sampled in the blood. Importantly, the assessment of virological parameters, such as cccDNA quantitation, also requires access to liver tissue. We discuss strategies to maximise information obtained from the site of infection and disease pathology. Fine needle aspirates of the liver may allow longitudinal sampling of the local virus/host landscape. The careful utilisation of liver tissue and aspirates in conjunction with blood will provide critical information in the assessment of new therapeutics for the functional cure of HBV.
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Affiliation(s)
- Upkar S Gill
- Department of Hepatology, Centre for Immunobiology, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | | | - Patrick T F Kennedy
- Department of Hepatology, Centre for Immunobiology, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Mala K Maini
- Division of Infection and Immunity, UCL, London, UK
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27
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Liu J, Xu L, Chen ZL, Li M, Yi H, Peng FH. Comprehensive analysis of patients with neuromyelitis optica spectrum disorder (NMOSD) combined with chronic hepatitis B (CHB) infection and seropositive for anti-aquaporin-4 antibody. Bosn J Basic Med Sci 2018; 18:35-42. [PMID: 29144890 PMCID: PMC5826672 DOI: 10.17305/bjbms.2017.2255] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2017] [Revised: 08/31/2017] [Accepted: 08/31/2017] [Indexed: 01/03/2023] Open
Abstract
Previous research indicated the association between hepatitis B virus (HBV) infection/vaccination and the onset of demyelinating diseases. However, most of these studies were single case reports, and comprehensive data are still scarce. Here we present a comprehensive analysis of 10 patients with neuromyelitis optica spectrum disorder (NMOSD) combined with chronic hepatitis B (CHB) infection and seropositive for anti-aquaporin-4 antibody (AQP4-Ab). Demographic, clinical, laboratory, neuroimaging, outcome, and follow-up data of the 10 patients were retrospectively analyzed. The median age at the onset of NMOSD was 35 years (range 25-43). Nine patients were female (90%). All patients were positive for HBsAg and had been diagnosed with CHB earlier than with NMOSD. One patient had an autoimmune disease. All patients had normal thyroid function. Paresthesia and visual impairment were the most common clinical symptoms. The cerebrospinal fluid (CSF) parameters (protein and glucose) were normal in 10 cases, whereas slightly higher CSF white blood cell count was detected in 3 patients. The brain and spinal cord magnetic resonance imaging findings were abnormal in 8 patients. All patients were treated with hormone and immunosuppressive therapy, and anti-HBV agents. Patients with detectable serum HBV DNA were more prone to liver damage after receiving high doses of corticosteroids. In 8 patients, the symptoms improved before they were discharged. Two patients with optic neuritis (ON) maintained the symptoms. A month later, 1/8 patient had recurrence of symptoms, and one ON patient progressed to NMO. Overall, the characteristics of NMOSD patients with CHB and seropositive for AQP4-Ab are usually nonspecific. Abnormal liver function test results in NMOSD patients should be a warning of possible CHB infection, and the treatment should be modified accordingly.
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Affiliation(s)
- Jia Liu
- Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.
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Draz MS, Shafiee H. Applications of gold nanoparticles in virus detection. Theranostics 2018; 8:1985-2017. [PMID: 29556369 PMCID: PMC5858513 DOI: 10.7150/thno.23856] [Citation(s) in RCA: 162] [Impact Index Per Article: 23.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2017] [Accepted: 01/09/2018] [Indexed: 12/12/2022] Open
Abstract
Viruses are the smallest known microbes, yet they cause the most significant losses in human health. Most of the time, the best-known cure for viruses is the innate immunological defense system of the host; otherwise, the initial prevention of viral infection is the only alternative. Therefore, diagnosis is the primary strategy toward the overarching goal of virus control and elimination. The introduction of a new class of nanoscale materials with multiple unique properties and functions has sparked a series of breakthrough applications. Gold nanoparticles (AuNPs) are widely reported to guide an impressive resurgence in biomedical and diagnostic applications. Here, we review the applications of AuNPs in virus testing and detection. The developed AuNP-based detection techniques are reported for various groups of clinically relevant viruses with a special focus on the applied types of bio-AuNP hybrid structures, virus detection targets, and assay modalities and formats. We pay particular attention to highlighting the functional role and activity of each core Au nanostructure and the resultant detection improvements in terms of sensitivity, detection range, and time. In addition, we provide a general summary of the contributions of AuNPs to the mainstream methods of virus detection, technical measures, and recommendations required in guidance toward commercial in-field applications.
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Affiliation(s)
- Mohamed Shehata Draz
- Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115
- Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
- Faculty of Science, Tanta University, Tanta 31527, Egypt
| | - Hadi Shafiee
- Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115
- Department of Medicine, Harvard Medical School, Boston, MA 02115, USA
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29
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Hou J, Wang G, Wang F, Cheng J, Ren H, Zhuang H, Sun J, Li L, Li J, Meng Q, Zhao J, Duan Z, Jia J, Tang H, Sheng J, Peng J, Lu F, Xie Q, Wei L, Chinese Society of Hepatology, Chinese Medical Association, Chinese Society of Infectious Diseases, Chinese Medical Association. Guideline of Prevention and Treatment for Chronic Hepatitis B (2015 Update). J Clin Transl Hepatol 2017; 5:297-318. [PMID: 29226097 PMCID: PMC5719188 DOI: 10.14218/jcth.2016.00019] [Citation(s) in RCA: 165] [Impact Index Per Article: 20.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2016] [Revised: 01/14/2017] [Accepted: 01/16/2017] [Indexed: 02/05/2023] Open
Affiliation(s)
- Jinlin Hou
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
- *Correspondence to: Jinlin Hou, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, No. 1838 North Guangzhou avenue, Guangzhou 510515, China. E-mail: ; Lai Wei, Peking University People’s Hospital, Peking University Hepatology Institute, No. 11 Xizhimen South Street, Beijing 100044, China. E-mail:
| | - Guiqiang Wang
- Department of Infectious Diseases, Center for Liver Diseases, Peking University First Hospital, Beijing, China
| | - Fusheng Wang
- The Institute of Translational Hepatology, 302 Hospital of PLA, Peking University, Beijing, China
| | - Jun Cheng
- Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Hong Ren
- Institute for Viral Hepatitis, the Key Laboratory of Molecular Biology for Infectious Diseases, the second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Hui Zhuang
- Department of Microbiology of Peking University Health Science Center, Beijing, China
| | - Jian Sun
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Lanjuan Li
- 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, Zhejiang University, Hangzhou, China
| | - Jie Li
- Department of Microbiology of Peking University Health Science Center, Beijing, China
| | - Qinghua Meng
- Serious Illness Medicine Inpatient Area, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Jingmin Zhao
- Department of Pathology, 302 Hospital of PLA, Peking University, Beijing, China
| | - Zhongping Duan
- Artificial Liver Center, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Jidong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Hong Tang
- Center of Infectious Diseases, West China Hospital of Sichuan University, Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, China
| | - Jifang Sheng
- 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, Zhejiang University, Hangzhou, China
| | - Jie Peng
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Fengmin Lu
- Department of Microbiology of Peking University Health Science Center, Beijing, China
| | - Qing Xie
- Department of Infectious Diseases, Shanghai Jiao Tong University School of Medicine Affiliated Ruijin Hospital, Shanghai, China
| | - Lai Wei
- Hepatology Institute, Peking University People’s Hospital, Beijing, China
- *Correspondence to: Jinlin Hou, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, No. 1838 North Guangzhou avenue, Guangzhou 510515, China. E-mail: ; Lai Wei, Peking University People’s Hospital, Peking University Hepatology Institute, No. 11 Xizhimen South Street, Beijing 100044, China. E-mail:
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Chingle MP, Osagie IA, Adams H, Gwomson D, Emeribe N, Zoakah AI. Risk perception of hepatitis B infection and uptake of hepatitis B vaccine among students of tertiary institution in Jos. Ann Afr Med 2017; 16:59-64. [PMID: 28469118 PMCID: PMC5452710 DOI: 10.4103/aam.aam_49_16] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
Background: Hepatitis B virus (HBV) Infection is endemic in Nigeria. Healthcare students are more vulnerable because of direct contact with patients’ body fluids and blood. Risk perception of HBV and HB vaccine uptake are also poor. The aim of this study was to assess the level of risk perception of hepatitis B infection, and uptake of the HBV vaccine, between medical and other students of the University of Jos. Methods: A comparative cross sectional study was conducted among 1,200 students of the departments of Medicine, Nursing sciences and Public Administration, University of Jos (400 from each arm) using a pretested self-administered questionnaire. A five point Likert scoring system was used to assess risk perception. Data was analyzed using SPSS version 20. A P -value of <0.05 was considered significant. Results: Awareness on HB vaccine prevention was high (88.4%) among University of Jos students. Awareness was similar among medical and nursing students (36.2% and 36.0% respectively) but lower among public administration student (27.8%), P < 0.001. The overall risk perception was 76.8%. This was also similar for medical and nursing students (40.7% and 40.1% respectively), but lower for public administration students (9.1%), P < 0.001. Risk perception is 5x higher among medical students compared to public administration students (OR = 5.22, 95% CI = 2.19 – 12.93; P < 0.001). The uptake of full dose HB vaccine was 60.2%, 20.6% and 15.1% for medical, nursing and public administration students respectively. Medical students are 4x more likely to go for HB vaccination compared with public administration students (OR=3.62; 95% CI=2.39 – 5.48; P < 0.001). Conclusions: Awareness and risk perception on HBV infection are high among University of Jos students, but uptake of HB vaccine is low. Findings are worst for non-health students.
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Affiliation(s)
- M P Chingle
- Department of Community Medicine, Jos University Teaching Hospital, Jos, Plateau State, Nigeria
| | - I A Osagie
- Department of Community Medicine, Jos University Teaching Hospital, Jos, Plateau State, Nigeria
| | - H Adams
- Department of Community Medicine, Jos University Teaching Hospital, Jos, Plateau State, Nigeria
| | - D Gwomson
- Department of Community Medicine, Jos University Teaching Hospital, Jos, Plateau State, Nigeria
| | - N Emeribe
- Department of Community Medicine, Jos University Teaching Hospital, Jos, Plateau State, Nigeria
| | - A I Zoakah
- Department of Community Medicine, Jos University Teaching Hospital, Jos, Plateau State, Nigeria
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Lange B, Roberts T, Cohn J, Greenman J, Camp J, Ishizaki A, Messac L, Tuaillon E, van de Perre P, Pichler C, Denkinger CM, Easterbrook P. Diagnostic accuracy of detection and quantification of HBV-DNA and HCV-RNA using dried blood spot (DBS) samples - a systematic review and meta-analysis. BMC Infect Dis 2017; 17:693. [PMID: 29143616 PMCID: PMC5688458 DOI: 10.1186/s12879-017-2776-z] [Citation(s) in RCA: 68] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND The detection and quantification of hepatitis B (HBV) DNA and hepatitis C (HCV) RNA in whole blood collected on dried blood spots (DBS) may facilitate access to diagnosis and treatment of HBV and HCV infection in resource-poor settings. We evaluated the diagnostic performance of DBS compared to venous blood samples for detection and quantification of HBV-DNA and HCV-RNA in two systematic reviews and meta-analyses on the diagnostic accuracy of HBV DNA and HCV RNA from DBS compared to venous blood samples. METHODS We searched MEDLINE, Embase, Global Health, Web of Science, LILAC and Cochrane library for studies that assessed diagnostic accuracy with DBS. Heterogeneity was assessed and where appropriate pooled estimates of sensitivity and specificity were generated using bivariate analyses with maximum likelihood estimates and 95% confidence intervals. We also conducted a narrative review on the impact of varying storage conditions or different cut-offs for detection from studies that undertook this in a subset of samples. The QUADAS-2 tool was used to assess risk of bias. RESULTS In the quantitative synthesis for diagnostic accuracy of HBV-DNA using DBS, 521 citations were identified, and 12 studies met the inclusion criteria. Overall quality of studies was rated as low. The pooled estimate of sensitivity and specificity for HBV-DNA was 95% (95% CI: 83-99) and 99% (95% CI: 53-100), respectively. In the two studies that reported on cut-offs and limit of detection (LoD) - one reported a sensitivity of 98% for a cut-off of ≥2000 IU/ml and another reported a LoD of 914 IU/ml using a commercial assay. Varying storage conditions for individual samples did not result in a significant variation of results. In the synthesis for diagnostic accuracy of HCV-RNA using DBS, 15 studies met the inclusion criteria, and this included six additional studies to a previously published review. The pooled sensitivity and specificity was 98% (95% CI:95-99) and 98% (95% CI:95-99.0), respectively. Varying storage conditions resulted in a decrease in accuracy for quantification but not for reported positivity. CONCLUSIONS These findings show a high level of diagnostic performance for the use of DBS for HBV-DNA and HCV-RNA detection. However, this was based on a limited number and quality of studies. There is a need for development of standardized protocols by manufacturers on the use of DBS with their assays, as well as for larger studies on use of DBS conducted in different settings and with varying storage conditions.
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Affiliation(s)
- Berit Lange
- Division of Infectious Diseases, Department of Medicine II, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
- Centre for Chronic Immunodeficiency, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
| | | | - Jennifer Cohn
- Department of Infectious Diseases, University of Pennsylvania, Philadelphia, PA, USA
| | - Jamie Greenman
- Department of Infectious Diseases, University of Pennsylvania, Philadelphia, PA, USA
| | - Johannes Camp
- Division of Infectious Diseases, Department of Medicine II, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Azumi Ishizaki
- Global Hepatitis Programme, HIV Department, World Health Organization, Geneva, Switzerland
| | - Luke Messac
- Department of Infectious Diseases, University of Pennsylvania, Philadelphia, PA, USA
| | - Edouard Tuaillon
- Pathogenesis and Control of Chronic Infections UMR 1058, INSERM/Université Montpellier/Etablissement Français du Sang, INSERM, 34394, Cedex 5, Montpellier, France
- Centre Hospitalier Universitaire (CHU) de Montpellier, département de bactériologie-virologie, Montpellier, France
| | - Philippe van de Perre
- Pathogenesis and Control of Chronic Infections UMR 1058, INSERM/Université Montpellier/Etablissement Français du Sang, INSERM, 34394, Cedex 5, Montpellier, France
- Centre Hospitalier Universitaire (CHU) de Montpellier, département de bactériologie-virologie, Montpellier, France
| | - Christine Pichler
- Division of Infectious Diseases, Department of Medicine II, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | | | - Philippa Easterbrook
- Global Hepatitis Programme, HIV Department, World Health Organization, Geneva, Switzerland
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Wu WP, Hoi CI, Chen RC, Lin CP, Chou CT. Comparison of the efficacy of Gd-EOB-DTPA-enhanced magnetic resonance imaging and magnetic resonance elastography in the detection and staging of hepatic fibrosis. Medicine (Baltimore) 2017; 96:e8339. [PMID: 29049250 PMCID: PMC5662416 DOI: 10.1097/md.0000000000008339] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The present study compared the efficacy of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) and magnetic resonance elastography (MRE) in the estimation of hepatic fibrosis stages with histopathologic correlation.This retrospective study included 104 patients (87 men and 17 women; mean age, 60.6 ± 10.6 years) with chronic liver disease who underwent both Gd-EOB-DTPA-enhanced MRI and MRE. The relative enhancement (RE) ratio of the liver parenchyma and the contrast enhancement index (CEI) were calculated as (SIpostliver - SIpreliver)/SIpreliver and SIpost/SIpre, respectively, where SIpost and SIpre were the liver-to-muscle signal intensity ratios on the hepatobiliary phase images and noncontrast-enhanced images, respectively. The liver stiffness values were measured using MRE stiffness maps. The diagnostic performance of MRE, RE ratios, and CEI values for hepatic fibrosis staging were compared.The distribution of fibrosis stages was as follows: F0, n = 3 (2.9%); F1, n = 12 (11.5%); F2, n = 17 (16.3%); F3, n = 26 (25.0%); and F4, n = 46 (44.2%). MRE, RE ratios, and CEI values correlated significantly with hepatic fibrosis (rs = .79, -.35, -.25, respectively, P < .05). MRE showed a significantly higher diagnostic performance than did RE ratios and CEI values for each fibrosis stage, except while distinguishing the F1 fibrosis stage (CEI, P = .15). A cutoff value of RE ratio = 0.89 can be used to identify patients with significant hepatic fibrosis, with positive predictive value, sensitivity, specificity, and negative predictive value of 93.2%, 61.8%, 73.3%, and 24.4%, respectively.Gd-EOB-DTPA-enhanced MRI can potentially predict significant hepatic fibrosis. However, the diagnostic performance of MRE for hepatic fibrosis staging was superior to that of Gd-EOB-DTPA-enhanced MRI.
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Affiliation(s)
- Wen-Pei Wu
- Department of Radiology, Chang-Hua Christian Hospital, Changhua
- Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei
| | - Cheng-In Hoi
- Department of Radiology, Centro Medico Pedder, Macau
| | - Ran-Chou Chen
- Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei
| | - Ching-Po Lin
- Brain Connectivity Laboratory, National Yang-Ming University, Taipei, Taiwan
| | - Chen-Te Chou
- Department of Radiology, Chang-Hua Christian Hospital, Changhua
- Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei
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Wu DX, Fu XY, Gong GZ, Sun KW, Gong HY, Wang L, Wu J, Tan DM. Novel HBV mutations and their value in predicting efficacy of conventional interferon. Hepatobiliary Pancreat Dis Int 2017; 16:189-196. [PMID: 28381384 DOI: 10.1016/s1499-3872(16)60184-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
BACKGROUND Accumulating studies assessing the impacts of hot spot mutations on conventional interferon (IFN) efficacy come to discrepant conclusions; studies regarding the mutations in S and RT regions are also unclear. The present study aimed to evaluate the impacts of HBV mutations on the efficacy of conventional IFN. METHODS A total of 126 patients who received conventional IFN treatment for 48 weeks were enrolled. Biochemical and serological parameters were routinely tested. The sequences of HBV from 78 serum samples were amplified by nested-PCR; mutations were identified with sequence scanner V1.0 after ABI 3730xl direct sequencing, HBV genotypes were determined according to RT gene sequences utilizing NCBI Genotyping Tool which was based on phylogenetic analysis. RESULTS The baseline DNA levels of virological response (VR) group were significantly lower than those of no VR group [7.13+/-0.76 vs 7.69+/-0.56 lg (copies/mL), P=0.001]. The baseline ALT levels were significantly higher in the HBeAg clearance group (204.72+/-88.65 vs 162.80+/-85.81 IU/L, P<0.05) and HBeAg seroconversion group (204.89+/-95.68 vs 166.75+/-84.43 IU/L, P<0.05). Females and lower BMI levels (20.01+/-2.33 vs 21.65+/-3.66 kg/m2, P<0.05) were prone to acquired biochemical response (BR). PC-W28STOP (ntG1896A) was significantly higher in the combined response (CR) group than that in the no CR group (91.7% vs 39.7%, P=0.001). Multivariate logistic regression analysis showed that baseline DNA, PC-P159T (ntC2288A), BCP-N118T (ntA1726C) and BCP-L134L (ntA1775C/G/T) influenced VR independently. PC-G182C (ntG2357T), PC-S64A/T (ntT2003G/A) and BMI were independent influence factors for HBeAg clearance, HBeAg seroconversion and BR, respectively. The new predicting model concluded that baseline DNA and new mutations for VR were established successfully, and ROC analysis showed that AUC was 0.842 (P<0.001) with a sensitivity of 0.652 and a specificity of 0.933. CONCLUSIONS PC-P159T (ntC2288A), BCP-N118T (ntA1726C), BCP-L134L (ntA1775C/G/T), PC-G182C (ntG2357T) and PC-S64A/T (ntT2003G/A) were novel identified mutations that impacted IFN therapeutic efficacy. These novel mutations could serve as important predictors before conventional IFN treatment.
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Affiliation(s)
- Da-Xian Wu
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Key Laboratory of Viral Hepatitis of Hunan Province, Changsha, China.
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Li MH, Zhang L, Qu XJ, Lu Y, Shen G, Wu SL, Chang M, Liu RY, Hu LP, Li ZZ, Hua WH, Song SJ, Xie Y. Kinetics of Hepatitis B Surface Antigen Level in Chronic Hepatitis B Patients who Achieved Hepatitis B Surface Antigen Loss during Pegylated Interferon Alpha-2a Treatment. Chin Med J (Engl) 2017; 130:559-565. [PMID: 28229987 PMCID: PMC5339929 DOI: 10.4103/0366-6999.200554] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2016] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Hepatitis B surface antigen (HBsAg) loss/seroconversion is considered to be the ideal endpoint of antiviral therapy and the ultimate treatment goal in chronic hepatitis B (CHB). This study aimed to assess the patterns of HBsAg kinetics in CHB patients who achieved HBsAg loss during the treatment of pegylated interferon (PEG-IFN) α-2a. METHODS A total of 150 patients were enrolled, composing of 83 hepatitis B envelope antigen (HBeAg)-positive and 67 HBeAg-negative patients. Patients were treated with PEG-IFN α-2a180 μg/week until HBsAg loss/seroconversion was achieved, which occurred within 96 weeks. Serum hepatitis B virus deoxyribonucleic acid and serological indicators (HBsAg, anti-HBs, HBeAg, and anti-HBe) were determined before and every 3 months during PEG-IFN α-2a treatment. Biochemical markers and peripheral blood neutrophil and platelet counts were tested every 1-3 months. RESULTS Baseline HBsAg levels were 2.5 ± 1.3 log IU/ml, and decreased rapidly at 12 and 24 weeks by 48.3% and 88.3%, respectively. The mean time to HBsAg loss was 54.2 ± 30.4 weeks, though most patients needed extended treatment and 30.0% of HBsAg loss occurred during 72-96 weeks. Baseline HBsAg levels were significantly higher in HBeAg-positive patients (2.9 ± 1.1 log IU/ml) compared with HBeAg-negative patients (2.0 ± 1.3 log IU/ml; t = 4.733, P < 0.001), but the HBsAg kinetics were similar. Patients who achieved HBsAg loss within 48 weeks had significantly lower baseline HBsAg levels and had more rapid decline of HBsAg at 12 weeks compared to patients who needed extended treatment to achieve HBsAg loss. CONCLUSIONS Patients with lower baseline HBsAg levels and more rapid decline during early treatment with PEG-IFN are more likely to achieve HBsAg loss during 96 weeks of treatment, and extended therapy longer than 48 weeks may be required to achieve HBsAg loss.
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Affiliation(s)
- Ming-Hui Li
- Liver Diseases Center, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Lu Zhang
- Liver Diseases Center, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Xiao-Jing Qu
- Liver Diseases Center, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Yao Lu
- Liver Diseases Center, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Ge Shen
- Liver Diseases Center, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Shu-Ling Wu
- Liver Diseases Center, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Min Chang
- Liver Diseases Center, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Ru-Yu Liu
- Liver Diseases Center, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Lei-Ping Hu
- Liver Diseases Center, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Zhen-Zhen Li
- Liver Diseases Center, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Wen-Hao Hua
- Clinical Test Center, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Shu-Jing Song
- Clinical Test Center, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
| | - Yao Xie
- Liver Diseases Center, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
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Gill US, Peppa D, Micco L, Singh HD, Carey I, Foster GR, Maini MK, Kennedy PTF. Interferon Alpha Induces Sustained Changes in NK Cell Responsiveness to Hepatitis B Viral Load Suppression In Vivo. PLoS Pathog 2016; 12:e1005788. [PMID: 27487232 PMCID: PMC4972354 DOI: 10.1371/journal.ppat.1005788] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2016] [Accepted: 07/05/2016] [Indexed: 12/16/2022] Open
Abstract
NK cells are important antiviral effectors, highly enriched in the liver, with the potential to regulate immunopathogenesis in persistent viral infections. Here we examined whether changes in the NK pool are induced when patients with eAg-positive CHB are 'primed' with PegIFNα and importantly, whether these changes are sustained or further modulated long-term after switching to nucleos(t)ides (sequential NUC therapy), an approach currently tested in the clinic. Longitudinal sampling of a prospectively recruited cohort of patients with eAg+CHB showed that the cumulative expansion of CD56bright NK cells driven by 48-weeks of PegIFNα was maintained at higher than baseline levels throughout the subsequent 9 months of sequential NUCs. Unexpectedly, PegIFNα-expanded NK cells showed further augmentation in their expression of the activating NK cell receptors NKp30 and NKp46 during sequential NUCs. The expansion in proliferating, functional NK cells was more pronounced following sequential NUCs than in comparison cohorts of patients treated with de novo NUCs or PegIFNα only. Reduction in circulating HBsAg concentrations, a key goal in the path towards functional cure of CHB, was only achieved in those patients with enhancement of NK cell IFNγ and cytotoxicity but decrease in their expression of the death ligand TRAIL. In summary, we conclude that PegIFNα priming can expand a population of functional NK cells with an altered responsiveness to subsequent antiviral suppression by NUCs. Patients on sequential NUCs with a distinct NK cell profile show a decline in HBsAg, providing mechanistic insights for the further optimisation of treatment strategies to achieve sustained responses in CHB.
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Affiliation(s)
- Upkar S. Gill
- Hepatology, Centre for Immunobiology, Blizard Institute, Barts and The London School of Medicine & Dentistry, QMUL, London, United Kingdom
- Department of Hepatology, The Royal London Hospital, Barts Health NHS Trust, London, United Kingdom
| | - Dimitra Peppa
- Division of Infection & Immunity, UCL, London, United Kingdom
| | - Lorenzo Micco
- Division of Infection & Immunity, UCL, London, United Kingdom
| | | | - Ivana Carey
- Institute of Liver Studies, Kings College Hospital, London, United Kingdom
| | - Graham R. Foster
- Hepatology, Centre for Immunobiology, Blizard Institute, Barts and The London School of Medicine & Dentistry, QMUL, London, United Kingdom
- Department of Hepatology, The Royal London Hospital, Barts Health NHS Trust, London, United Kingdom
| | - Mala K. Maini
- Division of Infection & Immunity, UCL, London, United Kingdom
- * E-mail: (MKM); (PTFK)
| | - Patrick T. F. Kennedy
- Hepatology, Centre for Immunobiology, Blizard Institute, Barts and The London School of Medicine & Dentistry, QMUL, London, United Kingdom
- Department of Hepatology, The Royal London Hospital, Barts Health NHS Trust, London, United Kingdom
- * E-mail: (MKM); (PTFK)
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Persistent risk of HBV reactivation despite extensive lamivudine prophylaxis in haematopoietic stem cell transplant recipients who are anti-HBc-positive or HBV-negative recipients with an anti-HBc-positive donor. Clin Microbiol Infect 2016; 22:946.e1-946.e8. [PMID: 27475741 DOI: 10.1016/j.cmi.2016.07.021] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2016] [Revised: 07/08/2016] [Accepted: 07/16/2016] [Indexed: 02/08/2023]
Abstract
The overall rate of hepatitis B virus (HBV) reactivation was evaluated in a population of 373 haematological stem cell transplant (HSCT) patients treated with lamivudine (LMV) if they were anti-HBc-positive/HBV-DNA-negative recipients or if they were HBV-negative recipients with an anti-HBc-positive donor. The incidence of HBV reactivation was calculated in two groups of autologous (auto) or allogeneic (allo) HSCT patients who were stratified according to their HBV serostatus. The former group included 57 cases: 10 auto-HSCT and 27 allo-HSCT anti-HBc-positive recipients, two auto-HSCT and three allo-HSCT inactive carriers, and 15 allo-HSCT recipients with an anti-HBc-positive donor. Forty-seven (82.4%) patients in this group received LMV prophylaxis (the median (interquartile range, IQR) of LMV treatment was 30 (20-38) months). The second group consisted of 320 anti-HBc-negative auto-HSCT and allo-HSCT recipients with anti-HBc-negative donors. None of these patients received any prophylaxis. Two patients in the first group and two in the second group experienced reactivation of HBV infection, with an incidence of 3.5% (95% CI 0.4-12.1%) and 0.6% (95% CI 0.1-2.2%), respectively. Only one out of four reactivated patients was LMV-treated. The cumulative probability of HBV reactivation at 6 years from HSCT was 15.8% (95% CI 15.2-16.4%). Three of four viral isolates obtained from the HBV-reactivated patients harboured mutations in the immune-active HBsAg-region. In a HSCT population carefully evaluated for HBV prophylaxis, a risk of HBV reactivation persisted in the group of patients who were not LMV-treated. Only one LMV-treated patient experienced reactivation of HBV with a resistant HBV isolate.
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Barr RG, Ferraioli G, Palmeri ML, Goodman ZD, Garcia-Tsao G, Rubin J, Garra B, Myers RP, Wilson SR, Rubens D, Levine D. Elastography Assessment of Liver Fibrosis: Society of Radiologists in Ultrasound Consensus Conference Statement. Ultrasound Q 2016; 32:94-107. [PMID: 27233069 DOI: 10.1097/ruq.0000000000000209] [Citation(s) in RCA: 94] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Richard G Barr
- *Department of Radiology, Northeastern Ohio Medical University, Rootstown, OH; †Southwoods Imaging, Boardman, OH; ‡Ultrasound Unit, Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy; §Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC; ∥Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA; ¶Section of Digestive Diseases, Department of Medicine, Yale University, New Haven, CO; #VA Connecticut Healthcare System, West Haven, CT; **Department of Radiology, University of Michigan Medical Center, Ann Arbor, MI; ††Department of Radiology, Washington DC VA Medical Center, Washington, DC; ‡‡Division of Imaging, Diagnostics and Software Reliability, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, MD; §§Departments of Hepatology and ∥∥Radiology, University of Calgary, Calgary, Alberta, Canada; ¶¶Departments of Imaging Science, Oncology, and Biomedical Engineering, University of Rochester Medical Center, Rochester, NY; and ##Department of Radiology, Beth Israel Deaconess Medical Center, Boston, MA
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Wang W, Wang J, Dang S, Zhuang G. Cost-effectiveness of antiviral therapy during late pregnancy to prevent perinatal transmission of hepatitis B virus. PeerJ 2016; 4:e1709. [PMID: 27042389 PMCID: PMC4811175 DOI: 10.7717/peerj.1709] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2015] [Accepted: 01/28/2016] [Indexed: 12/18/2022] Open
Abstract
Background. Hepatitis B virus (HBV) infections are perinatally transmitted from chronically infected mothers. Supplemental antiviral therapy during late pregnancy with lamivudine (LAM), telbivudine (LdT), or tenofovir (TDF) can substantially reduce perinatal HBV transmission compared to postnatal immunoprophylaxis (IP) alone. However, the cost-effectiveness of these measures is not clear. Aim. This study evaluated the cost-effectiveness from a societal perspective of supplemental antiviral agents for preventing perinatal HBV transmission in mothers with high viral load (>6 log10 copies/mL). Methods. A systematic review and network meta-analysis were performed for the risk of perinatal HBV transmission with antiviral therapies. A decision analysis was conducted to evaluate the clinical and economic outcomes in China of four competing strategies: postnatal IP alone (strategy IP), or in combination with perinatal LAM (strategy LAM + IP), LdT (strategy LdT + IP), or TDF (strategy TDF + IP). Antiviral treatments were administered from week 28 of gestation to 4 weeks after birth. Outcomes included treatment-related costs, number of infections, and quality-adjusted life years (QALYs). One- and two-way sensitivity analyses were performed to identify influential clinical and cost-related variables. Probabilistic sensitivity analyses were used to estimate the probabilities of being cost-effective for each strategy. Results. LdT + IP and TDF + IP averted the most infections and HBV-related deaths, and gained the most QALYs. IP and TDF + IP were dominated as they resulted in less or equal QALYs with higher associated costs. LdT + IP had an incremental $2,891 per QALY gained (95% CI [$932-$20,372]) compared to LAM + IP (GDP per capita for China in 2013 was $6,800). One-way sensitivity analyses showed that the cost-effectiveness of LdT + IP was only sensitive to the relative risk of HBV transmission comparing LdT + IP with LAM + IP. Probabilistic sensitivity analyses demonstrated that LdT + IP was cost-effective in most cases across willingness-to-pay range of $6,800 ∼ $20,400 per QALY gained. Conclusions. For pregnant HBV-infected women with high levels of viremia, supplemental use of LdT during late pregnancy combined with postnatal IP for infants is cost-effective in China.
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Affiliation(s)
- Wenjun Wang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Department of Epidemiology and Biostatistics, Medical School of Xi’an Jiaotong University, Xi’an, China
| | - Jingjing Wang
- Department of Pediatrics, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Shuangsuo Dang
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Department of Epidemiology and Biostatistics, Medical School of Xi’an Jiaotong University, Xi’an, China
| | - Guihua Zhuang
- Department of Epidemiology and Biostatistics, Medical School of Xi’an Jiaotong University, Xi’an, China
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van de Klundert MAA, Zaaijer HL, Kootstra NA. Identification of FDA-approved drugs that target hepatitis B virus transcription. J Viral Hepat 2016; 23:191-201. [PMID: 26456011 DOI: 10.1111/jvh.12479] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2015] [Accepted: 09/12/2015] [Indexed: 12/23/2022]
Abstract
In the treatment of chronic hepatitis B virus (HBV) infection, polymerase inhibitors successfully suppress HBV DNA production. However, the production of viral proteins continues unhindered, which hampers viral clearance. Here, we screen for compounds that suppress HBV transcription, which would prevent viral protein production. A total of 640 FDA-approved drugs were evaluated for their ability to inhibit HBV transcription in a transfection-based HBV reporter assay. The assay was performed in the presence and absence of the HBV accessory protein X (HBx), which is essential for in vivo HBV RNA transcription. We observed that in the absence of HBx 47, and in the presence of HBx 24 compounds suppressed transcription by more than 20%. We selected the 24 most potent compounds in each condition for further analysis. On average, the selected compounds reduced transcription by 33.9% (range: 24.1-65.8%) in the absence of HBx expression, and 30.6% (range: 20.4-48.9%) in the presence of HBx. The two selections of 24 compounds had 12 compounds in common, resulting in a final selection of 36 compounds, which were evaluated for their capacity to suppress HBV replication in constitutively HBV-replicating HepG2.2.15 cells. Twenty-three of these compounds reduced HBV replication by interfering with RNA transcription. Further analysis revealed that one of the compounds, terbinafine, potently and specifically suppressed HBx-mediated HBV RNA transcription in HepG2 cells. Inhibition of HBV protein production is a promising step towards HBV clearance. In combination with an HBV polymerase inhibitor, the added suppression of HBV RNA transcription may markedly improve antiviral treatment outcome.
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Affiliation(s)
- M A A van de Klundert
- Department of Blood-borne Infections, Sanquin Research, Amsterdam, The Netherlands.,Department of Experimental Immunology, Landsteiner Laboratory, and Center for Infectious Diseases and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands
| | - H L Zaaijer
- Department of Blood-borne Infections, Sanquin Research, Amsterdam, The Netherlands
| | - N A Kootstra
- Department of Experimental Immunology, Landsteiner Laboratory, and Center for Infectious Diseases and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands
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Chen J, Zhang DH, Xu CR, Zhu MY, Yang ZT, Gong QM, Yu DM, Zhang XX. Quantitative hepatitis B surface antigen combined with hepatitis B e antigen as sustained virological response predictors during extended therapy with Peginterferon alfa-2a for hepatitis B e antigen-positive chronic hepatitis B. J Clin Virol 2015; 72:88-94. [PMID: 26476325 DOI: 10.1016/j.jcv.2015.09.012] [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: 02/26/2015] [Revised: 09/24/2015] [Accepted: 09/30/2015] [Indexed: 10/22/2022]
Abstract
BACKGROUND The best strategy for chronic hepatitis B patients with poor response to 48 weeks of Peginterferon-based therapy has been controversial and the predictive value of hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and hepatitis B virus (HBV) DNA levels for determining the sustained virological response (SVR) of these patients is uncertain. OBJECTIVES To optimize management of these patients and evaluate the use of these serobiomarkers to predict SVR. STUDY DESIGN Eighty-one patients with an unsatisfactory response after 48 weeks of Peginterferon-based therapy were treated with extended Peginterferon therapy with or without nucleo(s) tide analogues (NAs), for a total of 96 weeks of Peginterferon treatment. HBsAg, HBeAg and HBV DNA levels were measured serially during the treatment and follow-up. RESULTS AND CONCLUSIONS Twenty-six of 81 patients (32.1%) attained SVR during the 72-week follow-up. The SVR rate was not statistically different between groups receiving 1-year prolongation of Peginterferon with or without NAs. The serum HBsAg cut-off of 1800IU/mL at week 48 had area under curve (AUC) of 0.727, and the serum HBsAg cut-off of 1500IU/mL, combined with HBeAg loss at week 72, had AUC of 0.753 to predict SVR during the follow-up. In conclusion, extended treatment with Peginterferon with or without NAs for patients with unsatisfactory response after 48 weeks of Peginterferon-based therapy is a promising strategy to achieve SVR, and quantitative serum HBsAg at week 48 and HBsAg level combined with HBeAg loss at week 72 of therapy can predict SVR to prolongation therapy with Peginterferon.
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Affiliation(s)
- Jie Chen
- Research Unit of Clinical Virology, Institute of Infectious and Respiratory Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China
| | - Dong-Hua Zhang
- Research Unit of Clinical Virology, Institute of Infectious and Respiratory Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China
| | - Cheng-Run Xu
- Department of Infection Diseases, Southeast Hospital, Xiamen University, Zhangzhou 363000, People's Republic of China
| | - Ming-Yu Zhu
- Research Unit of Clinical Virology, Institute of Infectious and Respiratory Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China
| | - Zhi-Tao Yang
- Research Unit of Clinical Virology, Institute of Infectious and Respiratory Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China
| | - Qi-Ming Gong
- Research Unit of Clinical Virology, Institute of Infectious and Respiratory Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China
| | - De-Min Yu
- Research Unit of Clinical Virology, Institute of Infectious and Respiratory Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China.
| | - Xin-Xin Zhang
- Research Unit of Clinical Virology, Institute of Infectious and Respiratory Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People's Republic of China; Translational Medicine Research Center, Ruijin Hospital North, Shanghai Jiaotong University School of Medicine, Shanghai 200025, People's Republic of China.
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Abstract
INTRODUCTION The hepatitis B virus (HBV) causes chronic hepatitis B (CHB) in ∼350 million people worldwide who have an increased risk of end-stage liver disease and/or hepatocellular carcinoma. SOURCES OF DATA Several peer-reviewed papers featuring new approaches to anti-HBV management. Additionally, we also reviewed recent abstract presentations at international congresses. AREAS OF AGREEMENT There has been great progress in CHB therapy with the development of standard and pegylated interferon (i.e. PEG-IFN) as well as nucleos/tide analogs (NAs). IFN has both antiviral and immunomodulatory effects and through immune-mediated destruction of infected hepatocytes offers the possibility of finite therapy. However, this 'killing for a cure' antiviral strategy may not be tolerated in many, especially in cirrhotic patients. NAs inhibit viral reverse transcriptase, have few side effects and prevent liver disease progression, but cannot offer a cure as they have little effect on the resilient HBV covalently closed circular DNA (cccDNA) intermediate. Moreover, NAs such as tenofovir and entecavir offer a high genetic barrier to resistance, but are expensive and not readily available in many global regions. GROWING POINTS Despite significant treatment advances, there is increased recognition of the need for improved anti-HBV treatments, and new virologic tests for monitoring treatment response. AREAS OF CONTROVERSY The role of quantitative hepatitis B surface antigen, intrahepatic cccDNA levels and viral genotype in selecting treatment candidates and refining NA stopping rules. AREAS TIMELY FOR DEVELOPING NEW RESEARCH Potential new therapies include viral entry inhibitors, RNA interference technologies (i.e. RNAi) and small molecules that modulate cccDNA transcription, as well as novel immunomodulatory therapies to boost HBV-specific T cell responses. The ultimate goal of new tests and anti-HBV therapies is to reduce the burden and expense of life-long CHB treatment, as 'only diamonds are forever'.
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Affiliation(s)
- Carla S Coffin
- Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, University of Calgary, Calgary, AB, Canada
| | - Samuel S Lee
- Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, University of Calgary, Calgary, AB, Canada
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Barr RG, Ferraioli G, Palmeri ML, Goodman ZD, Garcia-Tsao G, Rubin J, Garra B, Myers RP, Wilson SR, Rubens D, Levine D. Elastography Assessment of Liver Fibrosis: Society of Radiologists in Ultrasound Consensus Conference Statement. Radiology 2015; 276:845-861. [PMID: 26079489 DOI: 10.1148/radiol.2015150619] [Citation(s) in RCA: 431] [Impact Index Per Article: 43.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The Society of Radiologists in Ultrasound convened a panel of specialists from radiology, hepatology, pathology, and basic science and physics to arrive at a consensus regarding the use of elastography in the assessment of liver fibrosis in chronic liver disease. The panel met in Denver, Colo, on October 21-22, 2014, and drafted this consensus statement. The recommendations in this statement are based on analysis of current literature and common practice strategies and are thought to represent a reasonable approach to the noninvasive assessment of diffuse liver fibrosis.
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Affiliation(s)
- Richard G Barr
- From the Department of Radiology, Northeastern Ohio Medical University, Rootstown, Ohio (R.G.B.); Southwoods Imaging, 7623 Market St, Boardman, OH 44512 (R.G.B.); Ultrasound Unit, Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy (G.F.); Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC (M.L.P.); Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, Va (Z.D.G.); Section of Digestive Diseases, Department of Medicine, Yale University, New Haven, Conn (G.G.T.); VA Connecticut Healthcare System, West Haven, Conn (G.G.T.); Department of Radiology, University of Michigan Medical Center, Ann Arbor, Mich (J.R.); Department of Radiology, Washington DC VA Medical Center, Washington, DC (B.G.); Division of Imaging, Diagnostics and Software Reliability, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, Md (B.G.); Departments of Hepatology (R.P.M.) and Radiology (S.R.W.), University of Calgary, Calgary, Alberta, Canada; Departments of Imaging Science, Oncology, and Biomedical Engineering, University of Rochester Medical Center, Rochester, NY (D.R.); and Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Mass (D.L.)
| | - Giovanna Ferraioli
- From the Department of Radiology, Northeastern Ohio Medical University, Rootstown, Ohio (R.G.B.); Southwoods Imaging, 7623 Market St, Boardman, OH 44512 (R.G.B.); Ultrasound Unit, Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy (G.F.); Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC (M.L.P.); Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, Va (Z.D.G.); Section of Digestive Diseases, Department of Medicine, Yale University, New Haven, Conn (G.G.T.); VA Connecticut Healthcare System, West Haven, Conn (G.G.T.); Department of Radiology, University of Michigan Medical Center, Ann Arbor, Mich (J.R.); Department of Radiology, Washington DC VA Medical Center, Washington, DC (B.G.); Division of Imaging, Diagnostics and Software Reliability, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, Md (B.G.); Departments of Hepatology (R.P.M.) and Radiology (S.R.W.), University of Calgary, Calgary, Alberta, Canada; Departments of Imaging Science, Oncology, and Biomedical Engineering, University of Rochester Medical Center, Rochester, NY (D.R.); and Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Mass (D.L.)
| | - Mark L Palmeri
- From the Department of Radiology, Northeastern Ohio Medical University, Rootstown, Ohio (R.G.B.); Southwoods Imaging, 7623 Market St, Boardman, OH 44512 (R.G.B.); Ultrasound Unit, Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy (G.F.); Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC (M.L.P.); Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, Va (Z.D.G.); Section of Digestive Diseases, Department of Medicine, Yale University, New Haven, Conn (G.G.T.); VA Connecticut Healthcare System, West Haven, Conn (G.G.T.); Department of Radiology, University of Michigan Medical Center, Ann Arbor, Mich (J.R.); Department of Radiology, Washington DC VA Medical Center, Washington, DC (B.G.); Division of Imaging, Diagnostics and Software Reliability, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, Md (B.G.); Departments of Hepatology (R.P.M.) and Radiology (S.R.W.), University of Calgary, Calgary, Alberta, Canada; Departments of Imaging Science, Oncology, and Biomedical Engineering, University of Rochester Medical Center, Rochester, NY (D.R.); and Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Mass (D.L.)
| | - Zachary D Goodman
- From the Department of Radiology, Northeastern Ohio Medical University, Rootstown, Ohio (R.G.B.); Southwoods Imaging, 7623 Market St, Boardman, OH 44512 (R.G.B.); Ultrasound Unit, Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy (G.F.); Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC (M.L.P.); Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, Va (Z.D.G.); Section of Digestive Diseases, Department of Medicine, Yale University, New Haven, Conn (G.G.T.); VA Connecticut Healthcare System, West Haven, Conn (G.G.T.); Department of Radiology, University of Michigan Medical Center, Ann Arbor, Mich (J.R.); Department of Radiology, Washington DC VA Medical Center, Washington, DC (B.G.); Division of Imaging, Diagnostics and Software Reliability, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, Md (B.G.); Departments of Hepatology (R.P.M.) and Radiology (S.R.W.), University of Calgary, Calgary, Alberta, Canada; Departments of Imaging Science, Oncology, and Biomedical Engineering, University of Rochester Medical Center, Rochester, NY (D.R.); and Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Mass (D.L.)
| | - Guadalupe Garcia-Tsao
- From the Department of Radiology, Northeastern Ohio Medical University, Rootstown, Ohio (R.G.B.); Southwoods Imaging, 7623 Market St, Boardman, OH 44512 (R.G.B.); Ultrasound Unit, Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy (G.F.); Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC (M.L.P.); Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, Va (Z.D.G.); Section of Digestive Diseases, Department of Medicine, Yale University, New Haven, Conn (G.G.T.); VA Connecticut Healthcare System, West Haven, Conn (G.G.T.); Department of Radiology, University of Michigan Medical Center, Ann Arbor, Mich (J.R.); Department of Radiology, Washington DC VA Medical Center, Washington, DC (B.G.); Division of Imaging, Diagnostics and Software Reliability, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, Md (B.G.); Departments of Hepatology (R.P.M.) and Radiology (S.R.W.), University of Calgary, Calgary, Alberta, Canada; Departments of Imaging Science, Oncology, and Biomedical Engineering, University of Rochester Medical Center, Rochester, NY (D.R.); and Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Mass (D.L.)
| | - Jonathan Rubin
- From the Department of Radiology, Northeastern Ohio Medical University, Rootstown, Ohio (R.G.B.); Southwoods Imaging, 7623 Market St, Boardman, OH 44512 (R.G.B.); Ultrasound Unit, Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy (G.F.); Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC (M.L.P.); Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, Va (Z.D.G.); Section of Digestive Diseases, Department of Medicine, Yale University, New Haven, Conn (G.G.T.); VA Connecticut Healthcare System, West Haven, Conn (G.G.T.); Department of Radiology, University of Michigan Medical Center, Ann Arbor, Mich (J.R.); Department of Radiology, Washington DC VA Medical Center, Washington, DC (B.G.); Division of Imaging, Diagnostics and Software Reliability, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, Md (B.G.); Departments of Hepatology (R.P.M.) and Radiology (S.R.W.), University of Calgary, Calgary, Alberta, Canada; Departments of Imaging Science, Oncology, and Biomedical Engineering, University of Rochester Medical Center, Rochester, NY (D.R.); and Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Mass (D.L.)
| | - Brian Garra
- From the Department of Radiology, Northeastern Ohio Medical University, Rootstown, Ohio (R.G.B.); Southwoods Imaging, 7623 Market St, Boardman, OH 44512 (R.G.B.); Ultrasound Unit, Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy (G.F.); Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC (M.L.P.); Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, Va (Z.D.G.); Section of Digestive Diseases, Department of Medicine, Yale University, New Haven, Conn (G.G.T.); VA Connecticut Healthcare System, West Haven, Conn (G.G.T.); Department of Radiology, University of Michigan Medical Center, Ann Arbor, Mich (J.R.); Department of Radiology, Washington DC VA Medical Center, Washington, DC (B.G.); Division of Imaging, Diagnostics and Software Reliability, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, Md (B.G.); Departments of Hepatology (R.P.M.) and Radiology (S.R.W.), University of Calgary, Calgary, Alberta, Canada; Departments of Imaging Science, Oncology, and Biomedical Engineering, University of Rochester Medical Center, Rochester, NY (D.R.); and Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Mass (D.L.)
| | - Robert P Myers
- From the Department of Radiology, Northeastern Ohio Medical University, Rootstown, Ohio (R.G.B.); Southwoods Imaging, 7623 Market St, Boardman, OH 44512 (R.G.B.); Ultrasound Unit, Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy (G.F.); Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC (M.L.P.); Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, Va (Z.D.G.); Section of Digestive Diseases, Department of Medicine, Yale University, New Haven, Conn (G.G.T.); VA Connecticut Healthcare System, West Haven, Conn (G.G.T.); Department of Radiology, University of Michigan Medical Center, Ann Arbor, Mich (J.R.); Department of Radiology, Washington DC VA Medical Center, Washington, DC (B.G.); Division of Imaging, Diagnostics and Software Reliability, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, Md (B.G.); Departments of Hepatology (R.P.M.) and Radiology (S.R.W.), University of Calgary, Calgary, Alberta, Canada; Departments of Imaging Science, Oncology, and Biomedical Engineering, University of Rochester Medical Center, Rochester, NY (D.R.); and Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Mass (D.L.)
| | - Stephanie R Wilson
- From the Department of Radiology, Northeastern Ohio Medical University, Rootstown, Ohio (R.G.B.); Southwoods Imaging, 7623 Market St, Boardman, OH 44512 (R.G.B.); Ultrasound Unit, Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy (G.F.); Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC (M.L.P.); Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, Va (Z.D.G.); Section of Digestive Diseases, Department of Medicine, Yale University, New Haven, Conn (G.G.T.); VA Connecticut Healthcare System, West Haven, Conn (G.G.T.); Department of Radiology, University of Michigan Medical Center, Ann Arbor, Mich (J.R.); Department of Radiology, Washington DC VA Medical Center, Washington, DC (B.G.); Division of Imaging, Diagnostics and Software Reliability, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, Md (B.G.); Departments of Hepatology (R.P.M.) and Radiology (S.R.W.), University of Calgary, Calgary, Alberta, Canada; Departments of Imaging Science, Oncology, and Biomedical Engineering, University of Rochester Medical Center, Rochester, NY (D.R.); and Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Mass (D.L.)
| | - Deborah Rubens
- From the Department of Radiology, Northeastern Ohio Medical University, Rootstown, Ohio (R.G.B.); Southwoods Imaging, 7623 Market St, Boardman, OH 44512 (R.G.B.); Ultrasound Unit, Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy (G.F.); Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC (M.L.P.); Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, Va (Z.D.G.); Section of Digestive Diseases, Department of Medicine, Yale University, New Haven, Conn (G.G.T.); VA Connecticut Healthcare System, West Haven, Conn (G.G.T.); Department of Radiology, University of Michigan Medical Center, Ann Arbor, Mich (J.R.); Department of Radiology, Washington DC VA Medical Center, Washington, DC (B.G.); Division of Imaging, Diagnostics and Software Reliability, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, Md (B.G.); Departments of Hepatology (R.P.M.) and Radiology (S.R.W.), University of Calgary, Calgary, Alberta, Canada; Departments of Imaging Science, Oncology, and Biomedical Engineering, University of Rochester Medical Center, Rochester, NY (D.R.); and Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Mass (D.L.)
| | - Deborah Levine
- From the Department of Radiology, Northeastern Ohio Medical University, Rootstown, Ohio (R.G.B.); Southwoods Imaging, 7623 Market St, Boardman, OH 44512 (R.G.B.); Ultrasound Unit, Department of Infectious Diseases, Fondazione IRCCS Policlinico San Matteo, University of Pavia, Pavia, Italy (G.F.); Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC (M.L.P.); Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, Va (Z.D.G.); Section of Digestive Diseases, Department of Medicine, Yale University, New Haven, Conn (G.G.T.); VA Connecticut Healthcare System, West Haven, Conn (G.G.T.); Department of Radiology, University of Michigan Medical Center, Ann Arbor, Mich (J.R.); Department of Radiology, Washington DC VA Medical Center, Washington, DC (B.G.); Division of Imaging, Diagnostics and Software Reliability, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, Md (B.G.); Departments of Hepatology (R.P.M.) and Radiology (S.R.W.), University of Calgary, Calgary, Alberta, Canada; Departments of Imaging Science, Oncology, and Biomedical Engineering, University of Rochester Medical Center, Rochester, NY (D.R.); and Department of Radiology, Beth Israel Deaconess Medical Center, Boston, Mass (D.L.)
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Zhao S, Chen T, Peng C, Zhou H, Li H, Huang D, Xu Q, Wei S. The putative acceleration of optic neuritis when combined with chronic hepatitis B. J Neurol Sci 2015; 358:207-12. [PMID: 26363926 DOI: 10.1016/j.jns.2015.08.1538] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2015] [Revised: 08/26/2015] [Accepted: 08/26/2015] [Indexed: 01/07/2023]
Abstract
PURPOSE To review the clinical features of optic neuritis (ON) combined with chronic hepatitis B (CHB) retrospectively. METHOD Clinical data were reviewed for hospitalized patients diagnosed with isolated ON combined with chronic hepatitis B (CHB-ON) in the Chinese People's Liberation Army General Hospital. The ON diagnosis was confirmed following the criteria of the Optic Neuritis Treatment Trial (ONTT) group. The diagnostic criteria for CHB was serological positivity for hepatitis B surface antigen (HBsAg) for more than 6 months. Other infectious conditions that might lead to bias were excluded. RESULTS A total of 13 patients (6 female and 7 male, 23 involved eyes) diagnosed with CHB-ON were selected. A total of 12/13 patients presented as atypical ON: 10/13 of the patients exhibited simultaneous or early sequential bilateral eye involvement; 11/13 involved eyes in the acute phase presented with pronounced optic disc edema; and 11/13 patients exhibited corticosteroid resistant. A total of 12/23 affected eyes suffered severe vision loss (<20/200) at the end of the follow-up period, which averaged 13.7 (4-31) months. None of the patients progressed to multiple sclerosis (MS) or neuromyelitis optica (NMO). All blood samples were negative for serological aquaporin 4-antibody using the cell-based assay. CONCLUSIONS CHB-ON usually presented as the atypical form. Chronic hepatitis B virus infection may lead to the tendency for ON exacerbation.
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Affiliation(s)
- Shuo Zhao
- Department of Neuro-Ophthalmology, The Chinese People's Liberation Army General Hospital, Beijing, China; Medical School of Nankai University, Tianjin, China
| | - Tingjun Chen
- Department of Neuro-Ophthalmology, The Chinese People's Liberation Army General Hospital, Beijing, China
| | - Chunxia Peng
- Department of Neuro-Ophthalmology, The Chinese People's Liberation Army General Hospital, Beijing, China
| | - Huanfen Zhou
- Department of Neuro-Ophthalmology, The Chinese People's Liberation Army General Hospital, Beijing, China
| | - Hongyang Li
- Department of Neuro-Ophthalmology, The Chinese People's Liberation Army General Hospital, Beijing, China
| | - Dehui Huang
- Department of Neurology, The Chinese People's Liberation Army General Hospital, Beijing, China
| | - Quangang Xu
- Department of Neuro-Ophthalmology, The Chinese People's Liberation Army General Hospital, Beijing, China.
| | - Shihui Wei
- Department of Neuro-Ophthalmology, The Chinese People's Liberation Army General Hospital, Beijing, China.
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Locarnini S, Hatzakis A, Chen DS, Lok A. Strategies to control hepatitis B: Public policy, epidemiology, vaccine and drugs. J Hepatol 2015; 62:S76-86. [PMID: 25920093 DOI: 10.1016/j.jhep.2015.01.018] [Citation(s) in RCA: 184] [Impact Index Per Article: 18.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2014] [Revised: 01/07/2015] [Accepted: 01/13/2015] [Indexed: 12/04/2022]
Abstract
The last 50 years of hepatitis B research has resulted in the development of effective screening assays for surveillance, vaccines for prevention and antiviral drugs that significantly improve patient clinical outcomes. Not surprisingly then, the global epidemiology of hepatitis B virus (HBV) is set to change dramatically over the next decade. For example, the success and the high coverage of universal HBV vaccination and the ageing cohorts of patients with chronic hepatitis B (CHB) will result in reductions of incidence and prevalence of chronic hepatitis, cirrhosis and probably hepatocellular carcinoma. This will be further accelerated by the impressive progress in the treatment outcomes for patients with CHB. In spite of this success, challenges remain, such as planning for the impact of migration from countries with high prevalence rates to those countries with low rates of HBV infection. The recent establishment of the World Health Organisation Global Hepatitis Program with the provision of a framework for global action has become the cornerstone for all countries to now frame their own particular national responses to control hepatitis B. An effective policy framework can prevent new infections, ensure people can access clinical care, and in doing so reduce the burden of infection at an individual, country and regional level. These developments present a real opportunity to reduce the significant, social and economic burden of global hepatitis B, ultimately the critical next steps to render the world hepatitis B free.
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Affiliation(s)
- Stephen Locarnini
- Research & Molecular Development, Victorian Infectious Diseases Reference Laboratory, Melbourne, Australia.
| | - Angelos Hatzakis
- Department of Hygiene & Epidemiology & Medical Statistics, Athens University Medical School, Athens, Greece
| | - Ding-Shinn Chen
- Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Anna Lok
- Division of Gastroenterology, University of Michigan Medical Centre, Ann Arbor, MI, USA
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Kemp W, Levy M, Weltman M, Lubel J. Australian Liver Association (ALA) expert consensus recommendations for the use of transient elastography in chronic viral hepatitis. J Gastroenterol Hepatol 2015; 30:453-62. [PMID: 25532416 DOI: 10.1111/jgh.12865] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/09/2014] [Indexed: 12/16/2022]
Abstract
Since the introduction of Transient Elastography (TE) into Australia in 2008, non-invasive liver fibrosis assessments have integrated themselves into clinical hepatology. The Australian Liver Association (ALA) recognizes these technologies perform an important role in the assessment of chronic viral hepatitis B and C. However, in the setting of viral hepatitis and many other chronic liver diseases, there remains no consensus or guidelines regarding the performance, utility or reporting of TE. Accordingly, the ALA sought to produce an expert consensus statement for the use of TE in chronic viral hepatitis. The recommendations incorporated in this document are based upon a thorough literature review and draw on extensive clinical experience using TE. The initial draft was presented at Australian Gastroenterology Week (AGW) 2013. Through a collaborative process and expert external review a finalized document was presented at AGW 2014.
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Affiliation(s)
- William Kemp
- Department of Gastroenterology, Alfred Hospital, Melbourne, Victoria, Australia
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Williams R, Aspinall R, Bellis M, Camps-Walsh G, Cramp M, Dhawan A, Ferguson J, Forton D, Foster G, Gilmore I, Hickman M, Hudson M, Kelly D, Langford A, Lombard M, Longworth L, Martin N, Moriarty K, Newsome P, O'Grady J, Pryke R, Rutter H, Ryder S, Sheron N, Smith T. Addressing liver disease in the UK: a blueprint for attaining excellence in health care and reducing premature mortality from lifestyle issues of excess consumption of alcohol, obesity, and viral hepatitis. Lancet 2014; 384:1953-97. [PMID: 25433429 DOI: 10.1016/s0140-6736(14)61838-9] [Citation(s) in RCA: 444] [Impact Index Per Article: 40.4] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Dyson JK, Hudson M, McPherson S. Lesson of the month 2: Severe reactivation of hepatitis B after immunosuppressive chemotherapy. Clin Med (Lond) 2014; 14:551-5. [PMID: 25301924 PMCID: PMC4951972 DOI: 10.7861/clinmedicine.14-5-551] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Patients with current or past hepatitis B virus (HBV) infection are at risk of viral reactivation if they receive immune-modulating treatment or chemotherapy. This can range from subclinical elevation in HBV DNA levels, to abnormal liver function tests, to severe hepatitis with liver failure and risk of death. All patients should be screened for hepatitis B with surface antigen and core antibody before receiving immunosuppression. Patients with positive hepatitis B serology should be referred for specialist advice. Prophylactic antiviral treatment is recommended for patients with current/past hepatitis B who receive immunosuppressive chemotherapy.
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Affiliation(s)
- Jessica Katharine Dyson
- Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Mark Hudson
- Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust and Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
| | - Stuart McPherson
- Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust and Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
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Tang CM, Yau TO, Yu J. Management of chronic hepatitis B infection: current treatment guidelines, challenges, and new developments. World J Gastroenterol 2014; 20:6262-6278. [PMID: 24876747 PMCID: PMC4033464 DOI: 10.3748/wjg.v20.i20.6262] [Citation(s) in RCA: 98] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2013] [Revised: 11/24/2013] [Accepted: 01/19/2014] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis B (CHB) virus infection is a global public health problem, affecting more than 400 million people worldwide. The clinical spectrum is wide, ranging from a subclinical inactive carrier state, to progressive chronic hepatitis, cirrhosis, decompensation, and hepatocellular carcinoma. However, complications of hepatitis B virus (HBV)-related chronic liver disease may be reduced by viral suppression. Current international guidelines recommend first-line treatment of CHB infection with pegylated interferon, entecavir, or tenofovir, but the optimal treatment for an individual patient is controversial. The indications for treatment are contentious, and increasing evidence suggests that HBV genotyping, as well as serial on-treatment measurements of hepatitis B surface antigen and HBV DNA kinetics should be used to predict antiviral treatment response. The likelihood of achieving a sustained virological response is also increased by extending treatment duration, and using combination therapy. Hence the paradigm for treatment of CHB is constantly evolving. This article summarizes the different indications for treatment, and systematically reviews the evidence for the efficacy of various antiviral agents. It further discusses the shortcomings of current guidelines, use of rescue therapy in drug-resistant strains of HBV, and highlights the promising clinical trials for emerging therapies in the pipeline. This concise overview presents an updated practical approach to guide the clinical management of CHB.
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Dyson JK, Waller J, Turley A, Michael E, Moses S, Valappil M, Hudson M, Bassendine M, McPherson S. Hepatitis B in pregnancy. Frontline Gastroenterol 2014; 5:111-117. [PMID: 24683447 PMCID: PMC3963528 DOI: 10.1136/flgastro-2013-100361] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2013] [Revised: 09/21/2013] [Accepted: 09/25/2013] [Indexed: 02/04/2023] Open
Abstract
OBJECTIVE Vertical transmission of the hepatitis B virus (HBV) is the commonest mode of infection and can be prevented with immunoprophylaxis of the infant and antiviral therapy in the mother. Our aim was to review a cohort of subjects with HBV in pregnancy to determine the prevalence of active disease or high HBV-DNA levels that required treatment to prevent transmission, and to review the management of mothers and infants. METHODS A retrospective case-note review was conducted of all the HBV-infected pregnant women and their infants who attended the Newcastle obstetric services from 2007 to 2011. RESULTS There were 113 pregnancies in 81 women (median age 28 years; 15% hepatitis B e antigen (HBeAg) positive) during 2007-11. 71% of mothers were first diagnosed with HBV during pregnancy. The mothers were born in 28 different countries. 69% of mothers had an HBV-DNA level less than 2000 IU/mL and 13% had HBV-DNA levels greater than 1.0×107 IU/mL so would be eligible for antiviral therapy to prevent transmission to the infant. 9% had active eAg-positive HBV and 3% had active eAg-negative HBV requiring treatment. All infants born to HBeAg-positive mothers received hepatitis B immunoglobulin (HBIG) appropriately and 76% of infants received a full HBV vaccination course. One infant born to an HBeAg-negative mother was hepatitis B surface antigen positive 1 year post-delivery. CONCLUSIONS One in six women had active HBV requiring treatment or high HBV-DNA levels that would benefit from antiviral treatment to reduce the transmission risk. HBIG was administered appropriately but completion of the vaccination course was suboptimal.
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Affiliation(s)
- Jessica Katharine Dyson
- Liver Unit, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Julia Waller
- Health Protection Agency, Newcastle upon Tyne, UK
| | - Andrena Turley
- Department of Obstetrics, Royal Victoria Infirmary, Newcastle Upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, UK
| | - Enid Michael
- Department of Obstetrics, Royal Victoria Infirmary, Newcastle Upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, UK
| | - Samuel Moses
- Health Protection Agency, Newcastle upon Tyne, UK,Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
| | - Manoj Valappil
- Health Protection Agency, Newcastle upon Tyne, UK,Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
| | - Mark Hudson
- Liver Unit, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK,Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
| | - Margaret Bassendine
- Liver Unit, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK,Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
| | - Stuart McPherson
- Liver Unit, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK,Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
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Boglione L, Cusato J, Cariti G, Di Perri G, D'Avolio A. The E genotype of hepatitis B: clinical and virological characteristics, and response to interferon. J Infect 2014; 69:81-7. [PMID: 24631900 DOI: 10.1016/j.jinf.2014.02.018] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2013] [Revised: 01/24/2014] [Accepted: 02/24/2014] [Indexed: 02/06/2023]
Abstract
OBJECTIVES 10 hepatitis B virus (HBV) genotypes are known with different geographic distribution and response to interferon (IFN) therapy. The E genotype is the more prevalent genotype in West and Central Africa, but few data about response to IFN are available. We describe the epidemiological and clinical characteristics in a cohort of patients immigrants from Africa in our country with HBV E genotype chronic hepatitis infection (CHB). METHODS 63 patients with CHB and E genotype were included; 41 with CHB and low viral load were treated with PEG-IFN monotherapy; 10 with CHB and high viral load with sequential approach (entecavir and PEG-IFN). 12 patients with inactive CHB were followed with blood sample and abdomen ultrasonography every six months. RESULTS The virological response in the monotherapy group was 17.9%. Hepatitis B surface antigen (HBsAg) loss was observed in 1 patient (2.5%); 56 patients (88%) showed at the time of diagnosis of CHB another infectious diseases that required specific treatment before PEG-IFN; this treatment was also affected by an higher incidence of side-effects (>50%). All patients with high viremia showed a primary non-response to PEG-IFN. CONCLUSIONS The HBV E genotype evidences the worse response to PEG-IFN and maybe requires novel treatment options.
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Affiliation(s)
- Lucio Boglione
- Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, C.so Svizzera 164, Turin, Italy.
| | - Jessica Cusato
- Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, C.so Svizzera 164, Turin, Italy
| | - Giuseppe Cariti
- Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, C.so Svizzera 164, Turin, Italy
| | - Giovanni Di Perri
- Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, C.so Svizzera 164, Turin, Italy
| | - Antonio D'Avolio
- Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, C.so Svizzera 164, Turin, Italy.
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