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Hwang H, Kim JH, Ko E, Kim JY, Ko HK, Gwon DI, Shin JH, Kim GH, Chu HH. Chemoembolization as first-line treatment for hepatocellular carcinoma invading segmental portal vein with tumour burden limited to a monosegmental level. Br J Radiol 2024; 97:1038-1043. [PMID: 38445658 PMCID: PMC11075972 DOI: 10.1093/bjr/tqae052] [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: 10/16/2023] [Revised: 01/18/2024] [Accepted: 02/29/2024] [Indexed: 03/07/2024] Open
Abstract
OBJECTIVES To evaluate the safety and effectiveness of chemoembolization for hepatocellular carcinoma (HCC) with portal vein tumour thrombosis (PVTT) confined to a monosegment of the liver. METHODS A total of 192 treatment-naive patients who received chemoembolization between March 2008 and January 2023 as a first-line treatment for locally advanced HCC with PVTT limited to a monosegment were retrospectively analysed. Overall survival (OS) and the identification of pretreatment risk factors related to OS were investigated using Cox regression analysis. Complications, radiologic tumour response, and progression-free survival (PFS) following chemoembolization were investigated. RESULTS After chemoembolization, the 1-, 3-, and 5-year OS rates were 86%, 48%, and 39%, respectively, and the median OS was 33 months. Multivariable analyses revealed four significant pretreatment risk factors: infiltrative HCC (P = .02; HR, 1.60), beyond the up-to-11 criteria (P = .002; HR, 2.26), Child-Pugh class B (P = .01; HR, 2.35), and serum AFP ≥400 ng/mL (P = .01; HR, 1.69). The major complication rate was 5%. Of the 192 patients, 1 month after chemoembolization, 35% achieved a complete response, 47% achieved a partial response, 11% had stable disease, and 7% showed progressive disease. The median PFS after chemoembolization was 12 months. CONCLUSIONS Chemoembolization shows high safety and efficiency, and contributes to improved survival in patients with HCC with PVTT confined to a monosegment. Four risk factors were found to be significantly associated with improved survival rates after chemoembolization in patients with HCC with PVTT confined to a monosegment. ADVANCES IN KNOWLEDGE (1) Although systemic therapy with a combination of atezolizumab and bevacizumab (Atezo-Bev) is recommended as the first-line treatment when HCC invades the portal vein, chemoembolization is not infrequently performed in HCC cases in which tumour burden is limited. (2) Our study cohort (n=192) had a median OS of 33 months and a 5% major complication rate following chemoembolization, findings in the range of candidates typically accepted as ideal for chemoembolization. Thus, patients with HCC with PVTT confined to a monosegment may be good candidates for first-line chemoembolization.
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Affiliation(s)
- Hyeonseung Hwang
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Korea
| | - Jin Hyoung Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Korea
| | - Eunbyeol Ko
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Korea
| | - Jeong-Yeon Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Korea
| | - Heung-Kyu Ko
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Korea
| | - Dong Il Gwon
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Korea
| | - Ji Hoon Shin
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Korea
| | - Gun Ha Kim
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Korea
| | - Hee Ho Chu
- Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736, Korea
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Luo T, Lin Z, Wu Z, Cen P, Nong A, Huang R, Che J, Liang F, Yang Y, Liu J, Huang L, Cai J, Ou Y, Ye L, Bao L, Liang B, Liang H. Trends and associated factors of HIV, HCV and syphilis infection among different drug users in the China-Vietnam border area: an 11-year cross-sectional study (2010-2020). BMC Infect Dis 2023; 23:575. [PMID: 37667212 PMCID: PMC10478360 DOI: 10.1186/s12879-023-08239-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Accepted: 04/10/2023] [Indexed: 09/06/2023] Open
Abstract
BACKGROUND Data on recent human immunodeficiency virus (HIV), hepatitis C virus (HCV) and syphilis prevalence among drug users in the Southwest China are sparse despite the high burden of drug use. This study aims at assessing the prevalence trends and related factors of HIV, HCV and syphilis infection among different drug users in the China-Vietnam border area. METHODS A continuous cross-sectional survey was conducted among drug users from 2010 to 2020 in the China-Vietnam border area. Chi-square trend tests were used to assess the trend of HIV, HCV and syphilis prevalence and the proportion for drug type used by drug users. Multivariate logistic regression was used to identify associated factors of HIV, HCV and syphilis infection in different drug users. RESULTS In this study, a total of 28,951 drug users were included, of which 27,893 (96.45%) male, 15,660 (54.09%) aged 13-34 years, 24,543 (84.77%) heroin-only users, 2062 (7.12%) synthetic drug-only (SD-only) users and 2346 (8.10%) poly-drug users. From 2010 to 2020, the proportion of heroin-only users decreased from 87.79% to 75.46%, whereas SD-only users and poly-drug users increased from 5.16% to 16.03%, and from 7.05% to 8.52%, respectively. The prevalence of HIV, HCV, and syphilis during the study period declined from 12.76%, 60.37% and 5.72% to 4.35%, 53.29% and 4.53%, respectively, among heroin-only users and declined from 18.30%, 66.67% and 15.69% to 6.95%, 27.81% and 5.35%, respectively, among poly-drug users; however, the prevalence of HIV and HCV among SD-only users increased from 0.89% and 8.93% to 2.84% and 18.75%, respectively. Having ever injected drugs and needle sharing were common associated factors for both HIV and HCV infection among poly-drug users and heroin-only users. Aged ≥ 35 years old was an associated factor for HIV, HCV and syphilis infection among the SD-only users. Female drug users were at high risk of contracting syphilis among three different drug users. CONCLUSIONS The prevalence of HIV, HCV and syphilis among heroin-only users and poly-drug users decreased during the study period. However, the prevalence of HIV and HCV among SD-only users increased. Comprehensive intervention strategies, particularly focusing on the SD-only users are needed in order to bring down the disease burden in this population in the China-Vietnam border areas.
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Affiliation(s)
- Tong Luo
- Guangxi Key Laboratory of AIDS Prevention and Treatment, School of Public Health, Guangxi Medical University, Nanning, 530021, Guangxi, China
- Collaborative Innovation Centre of Regenerative Medicine and Medical Bioresource Development and Application Co-constructed by the Province and Ministry, Life Science Institute, Guangxi Medical University, Nanning, 530021, Guangxi, China
| | - Zhaosen Lin
- Qinzhou Center for Disease Control and Prevention, Qinzhou, 535000, Guangxi, China
| | - Zhenxian Wu
- Chongzuo Center for Disease Control and Prevention, Chongzuo, 532200, Guangxi, China
| | - Ping Cen
- Guangxi Key Laboratory of AIDS Prevention and Treatment, School of Public Health, Guangxi Medical University, Nanning, 530021, Guangxi, China
| | - Aidan Nong
- Chongzuo Center for Disease Control and Prevention, Chongzuo, 532200, Guangxi, China
| | - Rongye Huang
- Qinzhou Center for Disease Control and Prevention, Qinzhou, 535000, Guangxi, China
| | - Jianhua Che
- Chongzuo Center for Disease Control and Prevention, Chongzuo, 532200, Guangxi, China
| | - Fengfeng Liang
- Qinzhou Center for Disease Control and Prevention, Qinzhou, 535000, Guangxi, China
| | - Yuan Yang
- Collaborative Innovation Centre of Regenerative Medicine and Medical Bioresource Development and Application Co-constructed by the Province and Ministry, Life Science Institute, Guangxi Medical University, Nanning, 530021, Guangxi, China
| | - Jie Liu
- Guangxi Key Laboratory of AIDS Prevention and Treatment, School of Public Health, Guangxi Medical University, Nanning, 530021, Guangxi, China
- Collaborative Innovation Centre of Regenerative Medicine and Medical Bioresource Development and Application Co-constructed by the Province and Ministry, Life Science Institute, Guangxi Medical University, Nanning, 530021, Guangxi, China
| | - Li Huang
- Chongzuo Center for Disease Control and Prevention, Chongzuo, 532200, Guangxi, China
| | - Jie Cai
- Chongzuo Center for Disease Control and Prevention, Chongzuo, 532200, Guangxi, China
| | - Yanyun Ou
- Chongzuo Center for Disease Control and Prevention, Chongzuo, 532200, Guangxi, China
| | - Li Ye
- Guangxi Key Laboratory of AIDS Prevention and Treatment, School of Public Health, Guangxi Medical University, Nanning, 530021, Guangxi, China
- Collaborative Innovation Centre of Regenerative Medicine and Medical Bioresource Development and Application Co-constructed by the Province and Ministry, Life Science Institute, Guangxi Medical University, Nanning, 530021, Guangxi, China
| | - Lijuan Bao
- Chongzuo Center for Disease Control and Prevention, Chongzuo, 532200, Guangxi, China.
| | - Bingyu Liang
- Guangxi Key Laboratory of AIDS Prevention and Treatment, School of Public Health, Guangxi Medical University, Nanning, 530021, Guangxi, China.
- Collaborative Innovation Centre of Regenerative Medicine and Medical Bioresource Development and Application Co-constructed by the Province and Ministry, Life Science Institute, Guangxi Medical University, Nanning, 530021, Guangxi, China.
| | - Hao Liang
- Guangxi Key Laboratory of AIDS Prevention and Treatment, School of Public Health, Guangxi Medical University, Nanning, 530021, Guangxi, China.
- Collaborative Innovation Centre of Regenerative Medicine and Medical Bioresource Development and Application Co-constructed by the Province and Ministry, Life Science Institute, Guangxi Medical University, Nanning, 530021, Guangxi, China.
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Liver Transplantation from a Human Leukocyte Antigen-Matched Sibling Donor: Effectiveness of Direct-Acting Antiviral Therapy against Hepatitis C Virus Infection. REPORTS 2022. [DOI: 10.3390/reports5040049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/09/2022] Open
Abstract
Through living-donor liver transplantation (LDLT) from a human leukocyte antigen (HLA)-matched sibling donor, it may be possible to stop the use of immunosuppressants. It is possible that acute antibody-mediated rejection and chronic active antibody-mediated rejection through the positivity of donor-specific anti-HLA antibodies and/or T cell-mediated rejection may affect the prognosis of liver transplantation. The etiologies of liver diseases of the recipient may also affect the post-transplantation course. Herein, we report on the successful re-treatment with direct-acting antiviral (DAA) therapy against hepatitis C virus (HCV) infection in a patient who underwent a LDLT from HLA-matched sibling donor. After liver transplantation for HCV-related liver diseases, it is easy for HCV to re-infect the graft liver under a lack of immunosuppressants. DAA therapy against HCV re-infection immediately after transplantation should be commenced, and it is important to eradicate HCV for better prognosis of the recipients in LDLT for HCV-related liver diseases.
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Huang YC, Huang CF, Liu SF, Liu HY, Yeh ML, Huang CI, Hsieh MH, Dai CY, Chen SC, Yu ML, Chuang WL, Huang JF. The performance of HCV GT plus RUO reagent in determining Hepatitis C virus genotypes in Taiwan. PLoS One 2021; 16:e0246376. [PMID: 33513184 PMCID: PMC7845948 DOI: 10.1371/journal.pone.0246376] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2020] [Accepted: 01/15/2021] [Indexed: 11/18/2022] Open
Abstract
Background and aims Hepatitis C virus (HCV) genotyping is a pivotal tool for epidemiological investigation, guiding management and antiviral treatment. Challenge existed in identifying subtypes of genotype-1 (G-1) and genotype (GT) of indeterminate. Recently, the Abbott HCV RealTime Genotype Plus RUO assay (HCV GT Plus) has been developed aiming to overcome the limitations. We aimed to evaluate the performance of the assay compared with 5’ UTR sequencing in clinical samples. Materials and methods Eligible individuals were treatment chronic hepatitis C patients that were enrolled consecutively in a medical center and two core regional hospitals in southern Taiwan from Oct 2017 through Aug 2018. The patient with genotype 1 without subtype and indeterminate previously genotyped by Abbott RealTime HCV GT II will further determinate by Abbott HCV RealTime HCV GT Plus. All of the genotype results were validated by 5' UTR sequencing as a reference standard. Results A total of 100 viremic CHC patients were recruited, including 63 G-1 patients (male: 28), and 37 patients (male: 15) of indeterminate genotyped by Abbott RealTime HCV GT II assay (HCV GT II), respectively. The detection rate of 63 GT1 samples without subtype were 93.7% (59/63), 37 indeterminate samples without genotype were 62.2 (23/37) by HCV GT Plus. 5' UTR sequencing confirmed HCV GT Plus characterized results for 84.7% (50/59) of type1, with 100% (4/4), 82.8 (24/29) and 84.6% (22/26) for 1a, 1b and type6; 65.2% (15/23) of indeterminate with 100% (3/3) and 60% (12/20) for 1b and type 6 samples, respectively. Conclusions The Abbott RealTime HCV GT Plus RUO assay provides additional performance in GT detection.
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Affiliation(s)
- Ying-Chou Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatitis Centre, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Shu-Fen Liu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Hung-Yin Liu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatitis Centre, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ching-I Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatitis Centre, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Meng-Hsuan Hsieh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatitis Centre, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatitis Centre, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Shinn-Chern Chen
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatitis Centre, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatitis Centre, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatitis Centre, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatitis Centre, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- * E-mail:
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Sood AK, Manrai M, Thareja S, Shukla R, Patel A. Epidemiology of hepatitis C virus infection in a tertiary care hospital. Med J Armed Forces India 2020; 76:443-450. [PMID: 33162654 PMCID: PMC7606104 DOI: 10.1016/j.mjafi.2019.08.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2018] [Accepted: 08/25/2019] [Indexed: 01/04/2023] Open
Abstract
BACKGROUND There are epidemiological lacunae in literature of hepatitis C virus (HCV) infection. We report a prospective observational study of asymptomatic HCV infected patients from a tertiary care Government Hospital. METHODS All consecutive asymptomatic antibodies to hepatitis C virus (anti-HCV) positive patients were studied from July 2011 to April 2016. Patients were reviewed for demographic factors including symptom profile, risk factors, family screening, and point prevalence in relation to various districts of Punjab and Haryana. RESULTS One thousand twelve patients were studied with median age of 52 years (range:13-85) with a male to female ratio of 0.87. Eight hundred (79.25%) patients were from Punjab and 110 (10.67%) from Haryana. Forty percent patients were in 40-60 age group. Six hundred seventy patients (66.21%) did not have any apparent risk factor, 274 (27.08%) had one risk factor, and 68 patients (6.72%) had > 2 risk factors. Commonest risk factor was h/o surgery in 243 patients (24.01%), 32 patients had h/o IV drug abuse and 29 among them were < 30 years. Three hundred and sixty-seven families and children were screened, and 27 spouses and 16 children were found to be anti-HCV positive. The risk factor of IV drug abuse was more common in the younger adults with age ≤ 30 years as compared with age > 30 years (p = 0.001). CONCLUSION HCV infection was common in certain districts of Punjab and common in adults of 40-60 years. This finding needs to be confirmed in larger population-based study. The IV drug abuse is the risk factor of concern among young adults.
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Affiliation(s)
| | - Manish Manrai
- Associate Professor, Department of Internal Medicine, Armed Forces Medical College, Pune 411040, India
| | | | - Rajat Shukla
- Commandant, Military Hospital Namkum, Ranchi, Jharkhand, India
| | - Amol Patel
- Classified Specialist (Medicine) & Medical Oncologist, Army Hospital (R&R), New Delhi-110010, India
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Chistyakova MV, Govorin AV, Parkhomenko YV. Remodeling of the Pulmonary Circulation in Patients with Viral Liver Cirrhosis. RATIONAL PHARMACOTHERAPY IN CARDIOLOGY 2019. [DOI: 10.20996/1819-6446-2019-15-2-204-208] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
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Response to: Comment on "48-Week Outcome after Cessation of Nucleos(t)ide Analogue Treatment in Chronic Hepatitis B Patient and the Associated Factors with Relapse". Can J Gastroenterol Hepatol 2019; 2019:2970510. [PMID: 31187027 PMCID: PMC6521547 DOI: 10.1155/2019/2970510] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Accepted: 04/09/2019] [Indexed: 11/21/2022] Open
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Impact of direct-acting antivirals on leukocytic DNA telomere length in hepatitis C virus-related hepatic cirrhosis. Eur J Gastroenterol Hepatol 2019; 31:494-498. [PMID: 30444746 DOI: 10.1097/meg.0000000000001306] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
BACKGROUND Direct-acting antiviral (DAAs) represent advancement in the management of hepatitis C virus (HCV)-related hepatic cirrhosis. A high proportion of patients achieve a sustained virologic response; eradication of HCV is coupled with a decreased risk of hepatocellular carcinoma. Recent evidence suggests that shortening of the DNA telomere may be linked to cellular senescence as well as predisposition to malignant transformation. OBJECTIVE This study aimed to assess pretreatment leukocytic DNA telomere length in HCV-related cirrhosis and post viral eradication using DAAs. PATIENTS AND METHODS This study included 24 patients with HCV-related cirrhosis, Child-Pugh A. Whole-blood samples were obtained from patients before treatment and 12 weeks after the end of treatment, as well as from 24 healthy controls. Terminal restriction fragment, corresponding to telomere length, was measured using a nonradioactive Southern blot technique, detected by chemiluminescence. RESULTS DNA telomere length was significantly shorter before treatment compared with 12 weeks after end of treatment in HCV-related cirrhotic patients. Also, it was significantly shorter in patients before treatment compared with healthy individuals. CONCLUSION Telomere elongation in blood leukocytes can be considered a marker of recovery of inflammation after DAAs-induced HCV eradication. Still, the possibility of activation by cancer initiation cannot be excluded.
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Goutzamanis S, Doyle J, Higgs P, Hellard M. Improving hepatitis C direct-acting antiviral access and uptake: A role for patient-reported outcomes and lived experience. J Viral Hepat 2019; 26:218-223. [PMID: 30315689 DOI: 10.1111/jvh.13020] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2018] [Revised: 09/05/2018] [Accepted: 09/10/2018] [Indexed: 12/12/2022]
Abstract
Hepatitis C virus contributes to substantial and growing mortality and morbidity. Fortunately, the advent of highly effective interferon-free direct-acting antiviral (DAA) medications and new diagnostic tests has the potential to dramatically alter the epidemiologic trajectory of hepatitis C, particularly for "hard-to-reach" populations. Treatment advances and cure will also likely alter the individual experience of living with hepatitis C. However, it is not yet known in what capacity. This paper provides an overview of the population-level impact of DAA treatment, highlighting the need to further our understanding of the impact of treatment on behaviour, health and wellbeing through lived experience and more sensitive patient-reported outcome measures.
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Affiliation(s)
- Stelliana Goutzamanis
- Disease Elimination Program, Burnet Institute, Melbourne, Victoria, Australia
- School of Population Health and Preventive Medicine, Monash University, Melbourne, Australia
| | - Joseph Doyle
- Disease Elimination Program, Burnet Institute, Melbourne, Victoria, Australia
- Department of Infectious Diseases, Alfred Health, Melbourne, Australia
| | - Peter Higgs
- Disease Elimination Program, Burnet Institute, Melbourne, Victoria, Australia
- Department of Public Health, La Trobe University, Bundoora, Victoria, Australia
| | - Margaret Hellard
- Disease Elimination Program, Burnet Institute, Melbourne, Victoria, Australia
- School of Population Health and Preventive Medicine, Monash University, Melbourne, Australia
- Department of Infectious Diseases, Alfred Health, Melbourne, Australia
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Su S, Zhang L, Cheng F, Li S, Li S, Jing J, Fairley CK, Chen L, Zhao J, Mao L. Association between recreational drug use and sexual practices among people who inject drugs in Southwest China: a cross-sectional study. BMJ Open 2018; 8:e019730. [PMID: 29961003 PMCID: PMC6042564 DOI: 10.1136/bmjopen-2017-019730] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
OBJECTIVE To describe the differences in sexual practices among individuals with various drug administration patterns. SETTING A detoxification centre in Southwest China, a part of the Chinese national sentential surveillance network for hepatitis C virus (HCV), HIV and syphilis infections, was recruited. PARTICIPANTS A total of 610 newly enrolled injection drug users (IDUs) from detoxification centre were included during 2015. PRIMARY AND SECONDARY OUTCOME MEASURES Self-reported sexual activities, drug-related practices and laboratory-confirmed HCV, HIV and syphilis infection status were collected. RESULTS Of the 610 IDU, 295 (48.4%) used heroin only, 277 (45.4%) poly-drug users reported the mixed use of synthetic drugs (SDs) with heroin and 38 (6.2%) used SDs only. The average daily drug injection frequency for poly-drug users (3.3±1.2 times) was the highest, followed by heroin-only (2.2±0.8 times) and SD-only users (1.2±0.4 time). SD-only drug users reported the highest proportion (86.8%) of engaging in sexual activities in the previous month, with more than half (54.5%) reporting any condomless sex. A higher frequency of daily injecting in heroin-only users was significantly correlated with the less likelihood of sex, condomless sex in the past month, having sex with fixed partners, condomless commercial sex in the previous 12 months (all p<0.01). In poly-drug users, who injected drugs two times per day was associated with the highest proportion of people who engaged in sex and commercial sex (p<0.05). For SD-only users, increased drug use was not associated with reducing sexual risk (p>0.05). Different patterns of HCV, HIV and syphilis infections prevalence rates were shown among the IDU depending on the roles and length of exposure. CONCLUSIONS The daily drug injecting frequency of heroin-only and poly-drug users was negatively associated with sexual activities, but SD-only users kept a high frequent engagement in sex. The interventions for relevant diseases should adapt to characteristics of IDU.
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Affiliation(s)
- Shu Su
- School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia
| | - Lei Zhang
- School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia
- Research Center for Public Health, Tsinghua University, Beijing, China
- Melbourne Sexual Health Centre, Alfred Health, Melbourne, Victoria, Australia
- Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia
| | - Feng Cheng
- Research Center for Public Health, Tsinghua University, Beijing, China
| | - Shunxiang Li
- Division of HIV/AIDS and STI Control, Centers for Disease Control and Prevention, Yuxi Prefecture, Yunnan, China
| | - Shifu Li
- Division of HIV/AIDS and STI Control, Centers for Disease Control and Prevention, Yuxi Prefecture, Yunnan, China
| | - Jun Jing
- Research Center for Public Health, Tsinghua University, Beijing, China
- Division of HIV/AIDS and STI Control, Centers for Disease Control and Prevention, Yuxi Prefecture, Yunnan, China
| | - Christopher Kincaid Fairley
- Melbourne Sexual Health Centre, Alfred Health, Melbourne, Victoria, Australia
- Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Victoria, Australia
| | - Liang Chen
- Division of HIV/AIDS and STI Control, Centers for Disease Control and Prevention, Yuxi Prefecture, Yunnan, China
| | - Jinxian Zhao
- Division of HIV/AIDS and STI Control, Centers for Disease Control and Prevention, Yuxi Prefecture, Yunnan, China
| | - Limin Mao
- Center for Social Research in Health, Faculty of Arts and Social Science, University of New South Wales, Sydney, New South Wales, Australia
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Su S, Mao L, Zhao J, Chen L, Jing J, Cheng F, Zhang L. Epidemics of HIV, HCV and syphilis infection among synthetic drugs only users, heroin-only users and poly-drug users in Southwest China. Sci Rep 2018; 8:6615. [PMID: 29700352 PMCID: PMC5919913 DOI: 10.1038/s41598-018-25038-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Accepted: 03/28/2018] [Indexed: 11/18/2022] Open
Abstract
The number of poly-drug users who mix use heroin and synthetic drugs (SD) is increasing worldwide. The objective of this study is to measure the risk factors for being infected with hepatitis C (HCV), human immunodeficiency virus (HIV) and syphilis among SD-only users, heroin-only users and poly-drug users. A cross-sectional study was conducted in 2015 from a national HIV surveillance site in Southwest China, 447 poly-drug, 526 SD-only and 318 heroin-only users were recruited. Poly-drug users have higher drug-use frequency, higher rates of drug-sharing and unsafe sexual acts than other users (p < 0.05). About a third (36.7%) of poly-drug users experienced sexual arousal due to drug effects, which is higher than the rate among other drug users. Poly-drug users had the highest prevalence of HIV (10.5%) and syphilis (3.6%), but heroin-only users had the highest prevalence of HCV (66.0%) (all p < 0.05) among three groups. Logistic regression shows among poly-drug users, having sex following drug consumption and using drugs ≥1/day were the major risk factors for both HIV (Adjusted odds ratio (AOR) = 2.4, 95% CI [1.8–3.4]; 2.3, [1.6–3.1]) and syphilis infection (AOR = 4.1, [2.1–6.9]; 3.9, [1.8–5.4]). Elevated risk of both HIV and syphilis infection have been established among poly-drug users.
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Affiliation(s)
- Shu Su
- School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia
| | - Limin Mao
- Center for Social Research in Health, Arts and Social Sciences, UNSW Australia, Sydney, NSW, Australia
| | - Jinxian Zhao
- Division of HIV/AIDS and STI Control, Centers for Disease Control and Prevention, Yuxi Prefecture, Yunnan, China
| | - Liang Chen
- Division of HIV/AIDS and STI Control, Centers for Disease Control and Prevention, Yuxi Prefecture, Yunnan, China
| | - Jun Jing
- Research Center for Public Health, School of Medicine, Tsinghua University, Beijing, China
| | - Feng Cheng
- Research Center for Public Health, School of Medicine, Tsinghua University, Beijing, China.
| | - Lei Zhang
- School of Public Health and Preventive Medicine, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, VIC, Australia. .,Research Center for Public Health, School of Medicine, Tsinghua University, Beijing, China. .,Melbourne Sexual Health Centre, Alfred Health, Melbourne, Victoria, Australia.
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12
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Elevated body mass index is a risk factor associated with possible liver cirrhosis across different etiologies of chronic liver disease. J Formos Med Assoc 2018; 117:268-275. [DOI: 10.1016/j.jfma.2017.09.002] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2017] [Revised: 08/22/2017] [Accepted: 09/04/2017] [Indexed: 12/16/2022] Open
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13
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Lu MY, Huang CI, Hsieh MY, Hsieh TJ, Hsi E, Tsai PC, Tsai YS, Lin CC, Hsieh MH, Liang PC, Lin YH, Hou NJ, Yeh ML, Huang CF, Lin ZY, Chen SC, Huang JF, Chuang WL, Dai CY, Yu ML. Dynamics of PBMC gene expression in hepatitis C virus genotype 1-infected patients during combined peginterferon/ribavirin therapy. Oncotarget 2018; 7:61325-61335. [PMID: 27542257 PMCID: PMC5308654 DOI: 10.18632/oncotarget.11348] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2016] [Accepted: 08/10/2016] [Indexed: 12/29/2022] Open
Abstract
Hepatitis C virus (HCV) can replicate in peripheral blood mononuclear cells (PBMCs), which can produce interferon to defend against virus infection. We hypothesized that dynamic gene expression in PBMCs might impact the treatment efficacy of peginterferon/ribavirin in HCV patients. PBMCs were collected at baseline, 1st week and 4th week of treatment from 27 chronic HCV-1 patients with 48-week peginterferon/ribavirin therapy (screening dataset n = 7; validation dataset n = 20). A sustained virologic response (SVR) was defined as undetectable HCV RNA throughout the 24 weeks after end-of-treatment. A complete early virologic response (cEVR) was defined as negative HCV RNA at treatment week 12. Forty-three differentially expressed genes identified by Affymetrix microarray were validated by quantitative polymerase chain reaction. Thirteen genes at week 1 and 24 genes at week 4 were upregulated in the SVR group compared with the non-SVR group. We selected 8 target genes (RSAD2, LOC26010, HERC5, HERC6, IFI44, SERPING1, IFITM3, and DDX60) at week 1 as the major components of the predictive model. This predictive model reliably stratified the responders and non-responders at week 1 (AUC = 0.89, p = 0.007 for SVR; AUC = 0.95, p = 0.003 for cEVR), especially among patients carrying the IL28B rs8099917 TT genotype (AUC = 0.89, p = 0.02 for SVR; AUC = 1.0, p = 0.008 for cEVR). The performance of this predictive model was superior to traditional predictors, including the rapid virologic response, viral load and IL28B genotype.
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Affiliation(s)
- Ming-Ying Lu
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ching-I Huang
- Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Yen Hsieh
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Tusty-Juan Hsieh
- Department of Genome Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Edward Hsi
- Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Pei-Chien Tsai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Yi-Shan Tsai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ching-Chih Lin
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Meng-Hsuan Hsieh
- Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan.,Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Po-Cheng Liang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Yi-Hung Lin
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Nai-Jen Hou
- Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan.,Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan.,Department of Occupational Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Zu-Yau Lin
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shinn-Cherng Chen
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan.,Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.,Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan.,Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.,Liver Center, Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
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14
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Annual Change in FIB-4, but not in APRI, was a Strong Predictor for Liver Disease Progression in Chinese Patients with Chronic Hepatitis C. HEPATITIS MONTHLY 2017. [DOI: 10.5812/hepatmon.57250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
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15
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Moosavy SH, Davoodian P, Nazarnezhad MA, Nejatizaheh A, Eftekhar E, Mahboobi H. Epidemiology, transmission, diagnosis, and outcome of Hepatitis C virus infection. Electron Physician 2017; 9:5646-5656. [PMID: 29238510 PMCID: PMC5718874 DOI: 10.19082/5646] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2016] [Accepted: 08/24/2016] [Indexed: 12/11/2022] Open
Abstract
Hepatitis C infection is one of the main causes of chronic liver disorders worldwide. Nearly three percent (3%) of the world population has an HCV infection. Prevalence of HCV infection was higher in some groups such as injected drug users (IDUs) and HIV positive populations. Acute hepatitis has proven asymptomatic in most cases, and delay of diagnosis might lead to late onset of hepatocellular carcinoma and cirrhosis. Some host characteristics such as age, gender, body mass index, and viral properties are associated with HCV outcome hepatitis. Although disease progression is typically slow, some risk factors such as alcohol abuse and coinfection of patients with HBV and HIV can worsen the disease. On the other hand, viral overload is one of the main causes of prediction of HCV infection outcome. Prevalence of HCV infection will increase if we do not consider means of transmission, virus behaviors, and immunologic responses. Rapid diagnostic tests can help us to create preventive strategies among undeveloped villages and prisoners. Screening and training of the high-risk population such as IV drug users, dialysis patients, and hemophiliacs must be one of main HCV preventive programs. The present review is intended to help health policymakers to design suitable preventive and management programs.
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Affiliation(s)
- Seyed Hamid Moosavy
- M.D., Gastroenterologist and Hepatologist, Associate Professor, Department of Internal Medicine, Infectious and Tropical Disease Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Hormozgan, Iran
| | - Parivash Davoodian
- M.D., Infectionist, Associate Professor, Infectious and Tropical Disease Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Hormozgan, Iran
| | - Mirza Ali Nazarnezhad
- M.D., Ph.D. Candidate of Infectious and Tropical Disease, Infectious and Tropical Disease Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Hormozgan, Iran
| | - Abdolazim Nejatizaheh
- Ph.D. of Genetics, Associate Professor, Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Hormozgan, Iran
| | - Ebrahim Eftekhar
- Ph.D. of Clinical Biochemistry, Assistant Professor, Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Hormozgan, Iran
| | - Hamidreza Mahboobi
- M.D., Resident of Internal Medicine, Infectious and Tropical Disease Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Hormozgan, Iran
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16
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Mogahed EA, Abdelaziz H, Helmy H, Ghita H, Abdel Mawla MA, Hassanin F, Fadel FI, El-Karaksy H. Safety and Efficacy of Pegylated Interferon Alpha-2b Monotherapy in Hepatitis C Virus-Infected Children with End-Stage Renal Disease on Hemodialysis. J Interferon Cytokine Res 2016; 36:681-688. [PMID: 27656950 DOI: 10.1089/jir.2016.0019] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Treatment of hepatitis C virus (HCV) in end-stage renal disease (ESRD) patients is an important issue before kidney transplantation (KT). The aim of the study is to assess the efficacy and tolerability of HCV treatment with pegylated interferon (PEG IFN)-α 2b in children with ESRD. The study included 17 children, aged 3-18 years with ESRD on hemodialysis (HD), with chronic HCV. They received 40 μg/m2 of PEG IFN-α 2b once-weekly subcutaneous injections for 48 weeks. Early virological response (EVR) was achieved in 76.5%. At week 24, 8 patients had negative HCV RNA. Six patients received KT during therapy. Treatment was discontinued in 2 patients: one for anemia and another for retinopathy. Two patients completed 48 weeks of therapy and both achieved end-of-treatment response and sustained virological response (SVR). Constitutional symptoms were the most frequently reported side effects. Neutropenia occurred in 10 patients (58.8%), drop in hemoglobin in 10, and thrombocytopenia in 9. HCV-infected children with ESRD on HD have high EVR (76.5%) on IFN monotherapy. SVR could not be assessed due to the high dropout rate related mainly to early transplantation. Constitutional symptoms and hematological side effects were the most frequently reported side effects.
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Affiliation(s)
- Engy A Mogahed
- 1 Department of Pediatrics, Kasr Alainy Medical School, Cairo University , Cairo, Egypt
| | - Hanan Abdelaziz
- 1 Department of Pediatrics, Kasr Alainy Medical School, Cairo University , Cairo, Egypt
| | - Heba Helmy
- 1 Department of Pediatrics, Kasr Alainy Medical School, Cairo University , Cairo, Egypt
| | - Haytham Ghita
- 1 Department of Pediatrics, Kasr Alainy Medical School, Cairo University , Cairo, Egypt
| | | | - Fetouh Hassanin
- 3 Faculty of Pharmacy, Misr International University , Cairo, Egypt
| | - Fatina I Fadel
- 1 Department of Pediatrics, Kasr Alainy Medical School, Cairo University , Cairo, Egypt
| | - Hanaa El-Karaksy
- 1 Department of Pediatrics, Kasr Alainy Medical School, Cairo University , Cairo, Egypt
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17
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Omata M, Kanda T, Wei L, Yu ML, Chuang WL, Ibrahim A, Lesmana CRA, Sollano J, Kumar M, Jindal A, Sharma BC, Hamid SS, Dokmeci AK, Al-Mahtab M, McCaughan GW, Wasim J, Crawford DHG, Kao JH, Yokosuka O, Lau GKK, Sarin SK. APASL consensus statements and recommendations for hepatitis C prevention, epidemiology, and laboratory testing. Hepatol Int 2016; 10:681-701. [PMID: 27229718 PMCID: PMC5003900 DOI: 10.1007/s12072-016-9736-3] [Citation(s) in RCA: 66] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2016] [Accepted: 04/20/2016] [Indexed: 02/06/2023]
Abstract
The Asian Pacific Association for the Study of the Liver (APASL) convened an international working party on "APASL consensus statements and recommendations for management of hepatitis C" in March 2015 to revise the "APASL consensus statements and management algorithms for hepatitis C virus infection" (Hepatol Int 6:409-435, 2012). The working party consisted of expert hepatologists from the Asian-Pacific region gathered at the Istanbul Congress Center, Istanbul, Turkey on 13 March 2015. New data were presented, discussed, and debated during the course of drafting a revision. Participants of the consensus meeting assessed the quality of the cited studies. The finalized recommendations for hepatitis C prevention, epidemiology, and laboratory testing are presented in this review.
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Affiliation(s)
- Masao Omata
- Yamanashi Prefectural Central Hospital, 1-1-1 Fujimi, Kofu-shi, Yamanashi, 400-8506, Japan.
- The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
| | - Tatsuo Kanda
- Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Lai Wei
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing, China
| | - Ming-Lung Yu
- Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
| | - Wang-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Alaaeldin Ibrahim
- GI/Liver Division, Department of Internal Medicine, University of Benha, Banha, Egypt
| | | | - Jose Sollano
- University Santo Tomas Hospital, Manila, Philippines
| | - Manoj Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Ankur Jindal
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | | | - Saeed S Hamid
- Department of Medicine, Aga Khan University and Hospital, Stadium Road, Karachi, 74800, Pakistan
| | - A Kadir Dokmeci
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
| | - Mamun Al-Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, 1000, Bangladesh
| | - Geofferey W McCaughan
- Royal Prince Alfred Hospital, Centenary Institute, University of Sydney, Sydney, Australia
| | - Jafri Wasim
- Department of Medicine, Aga Khan University and Hospital, Stadium Road, Karachi, 74800, Pakistan
| | - Darrell H G Crawford
- University of Queensland, School of Medicine, Woolloongabba, QLD, 4102, Australia
| | - Jia-Horng Kao
- National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan
| | - Osamu Yokosuka
- Graduate School of Medicine, Chiba University, Chiba, Japan
| | - George K K Lau
- The Institute of Translational Hepatology, Beijing 302 Hospital, Beijing, China
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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18
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Omata M, Kanda T, Wei L, Yu ML, Chuang WL, Ibrahim A, Lesmana CRA, Sollano J, Kumar M, Jindal A, Sharma BC, Hamid SS, Dokmeci AK, Mamun-Al-Mahtab, McCaughan GW, Wasim J, Crawford DHG, Kao JH, Yokosuka O, Lau GKK, Sarin SK. APASL consensus statements and recommendation on treatment of hepatitis C. Hepatol Int 2016; 10:702-26. [PMID: 27130427 PMCID: PMC5003907 DOI: 10.1007/s12072-016-9717-6] [Citation(s) in RCA: 153] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2015] [Accepted: 02/18/2016] [Indexed: 12/18/2022]
Abstract
The Asian-Pacific Association for the Study of the Liver (APASL) convened an international working party on the "APASL consensus statements and recommendation on management of hepatitis C" in March, 2015, in order to revise "APASL consensus statements and management algorithms for hepatitis C virus infection (Hepatol Int 6:409-435, 2012)". The working party consisted of expert hepatologists from the Asian-Pacific region gathered at Istanbul Congress Center, Istanbul, Turkey on 13 March 2015. New data were presented, discussed and debated to draft a revision. Participants of the consensus meeting assessed the quality of cited studies. Finalized recommendations on treatment of hepatitis C are presented in this review.
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Affiliation(s)
- Masao Omata
- Yamanashi Prefectural Central Hospital, 1-1-1 Fujimi, Kofu-Shi, Yamanashi, 400-8506, Japan.
- The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
| | - Tatsuo Kanda
- Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Lai Wei
- Peking University Hepatology Institute, Peking University People's Hospital, Beijing, China
| | - Ming-Lung Yu
- Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan
| | - Wang-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Alaaeldin Ibrahim
- GI/Liver Division, Department of Internal Medicine, University of Benha, Benha, Egypt
| | | | - Jose Sollano
- University Santo Tomas Hospital, Manila, Philippines
| | - Manoj Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Ankur Jindal
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | | | - Saeed S Hamid
- Department of Medicine, Aga Khan University and Hospital, Stadium Road, Karachi, 74800, Pakistan
| | - A Kadir Dokmeci
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
| | - Mamun-Al-Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, 1000, Bangladesh
| | - Geofferey W McCaughan
- Centenary Institute, Royal Prince Alfred Hospital, University of Sydney, Sydney, Australia
| | - Jafri Wasim
- Department of Medicine, Aga Khan University and Hospital, Stadium Road, Karachi, 74800, Pakistan
| | - Darrell H G Crawford
- School of Medicine, University of Queensland, Woolloongabba, QLD, 4102, Australia
| | - Jia-Horng Kao
- National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan
| | - Osamu Yokosuka
- Graduate School of Medicine, Chiba University, Chiba, Japan
| | - George K K Lau
- The Institute of Translational Hepatology, Beijing 302 Hospital, Beijing, China
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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19
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Xu Y, Li N, Lu M, Myers RP, Dixon E, Walker R, Sun L, Zhao X, Quan H. Development and validation of method for defining conditions using Chinese electronic medical record. BMC Med Inform Decis Mak 2016; 16:110. [PMID: 27542973 PMCID: PMC4992264 DOI: 10.1186/s12911-016-0348-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2016] [Accepted: 08/05/2016] [Indexed: 01/10/2023] Open
Abstract
Background The adoption of the electronic medical record (EMR) is rapidly growing in China. Constantly evolving, Chinese EMRs contain vast amounts of clinical and financial data, providing tremendous potential for research and policy use; however, they are only partially standardized and contain free text or unstructured data. To utilize the information contained in Chinese EMRs, the development of data extraction methodology is urgently needed. The purpose of this study is to develop and validate methods to extract clinical information from the Chinese EMR for research use. Methods Using 2010 to 2014 EMR data from YouAn Hospital, a large teaching hospital affiliated with Capital Medical University in Beijing, China, we developed extraction methods including 40 EMR definitions for defining 6 liver disease, 5 disease severity conditions, and 29 comorbidities and treatments. We conducted a chart review of 450 randomly selected EMRs. Using physician chart review results as a reference, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated to validate each EMR definition. Results The sensitivity of the 6 EMR definitions for liver diseases ranged from 78.9 to 100.0 %, and PPV ranged from 82.1 to 100.0 %. The sensitivity of the 5 definitions on disease severity conditions ranged from 91.0 to 100.0 %, and PPV ranged from 79.2 to 100.0 %. Among the 29 EMR definitions for comorbidities and treatments, 23 had sensitivity over 90.0 % and 25 had PPV over 80.0 %. The specificity and NPV for all 40 EMR definitions were over 90.0 %. Conclusion The extraction method developed is a valid way of extracting information on liver diseases, comorbidities and related treatments from YouAn hospital EMRs. Our method should be modified for application to other Chinese EMR systems, following our framework for extracting conditions. Electronic supplementary material The online version of this article (doi:10.1186/s12911-016-0348-6) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Yuan Xu
- Beijing YouAn Hospital, Capital Medical University, 8 Xitoutiao Fengtai, Beijing, 100069, China.,Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Ning Li
- Beijing YouAn Hospital, Capital Medical University, 8 Xitoutiao Fengtai, Beijing, 100069, China.
| | - Mingshan Lu
- Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.,Department of Economics, University of Calgary, Calgary, Alberta, Canada
| | - Robert P Myers
- Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.,Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Elijah Dixon
- Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada.,Division of General Surgery, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Robin Walker
- Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Libo Sun
- Beijing YouAn Hospital, Capital Medical University, 8 Xitoutiao Fengtai, Beijing, 100069, China
| | - Xiaofei Zhao
- Beijing YouAn Hospital, Capital Medical University, 8 Xitoutiao Fengtai, Beijing, 100069, China
| | - Hude Quan
- Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
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20
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Zhang R, Shao C, Huo N, Li M, Xu X. Association of IL28B Genotypes and Baseline Serum Interferon-γ-Inducible- Protein-10 Levels with Treatment Response in Hepatitis C Virus Patients in China. Gut Liver 2016; 10:446-55. [PMID: 26470765 PMCID: PMC4849699 DOI: 10.5009/gnl15162] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2015] [Revised: 05/19/2015] [Accepted: 05/28/2015] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND/AIMS Several studies have demonstrated that serum interferon-γ-inducible-protein-10 (IP-10) levels at baseline and single nucleotide polymorphisms (SNPs) near the IL28B gene were associated with viral response and treatment outcomes. Our purpose was to assess the combination of pretreatment IP-10 levels with IL28B SNPs as predictors of treatment response to pegylated interferon α-2a plus ribavirin in patients infected with genotype 1 hepatitis C virus in China. METHODS Seventy-two patients with chronic hepatitis C without fibrosis/cirrhosis were enrolled in the study. The virologic parameters and baseline serum IP-10 levels were determined. IL-28B genotypes were determined by sequencing. RESULTS In this cohort, serum baseline IP-10 levels lower than 426.7 pg/mL could predict rapid virological response/ sustained virological response (SVR). Patients carrying favorable IL28B SNP genotypes had higher SVRs than did those carrying unfavorable variants (IL28B rs12979860, p=0.002; IL28B rs8099917, p=0.020). Combining both baseline IP- 10 and IL28B SNPs could improve the prediction of SVR in favorable allele carriers of IL28B, rs12979860 CC and rs8099917 TT. Serum baseline IP-10 levels and IL28B genotypes were independent predictors of SVR. CONCLUSIONS Our study shows that the combination of baseline serum IP-10 levels and the determination of IL28B SNPs increase the predictability of SVR rates in this cohort. (Gut Liver 2016;10446-455).
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Affiliation(s)
- Renwen Zhang
- Department of Infectious Diseases, Peking University First Hospital, Beijing,
China
| | - Cuiping Shao
- Department of Infectious Diseases, Peking University First Hospital, Beijing,
China
| | - Na Huo
- Department of Infectious Diseases, Peking University First Hospital, Beijing,
China
| | - Minran Li
- Department of Infectious Diseases, Peking University First Hospital, Beijing,
China
| | - Xiaoyuan Xu
- Department of Infectious Diseases, Peking University First Hospital, Beijing,
China
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Jha V, Prasad N. CKD and Infectious Diseases in Asia Pacific: Challenges and Opportunities. Am J Kidney Dis 2016; 68:148-60. [PMID: 26943982 DOI: 10.1053/j.ajkd.2016.01.017] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2015] [Accepted: 01/15/2016] [Indexed: 02/06/2023]
Abstract
The exact number of patients with chronic kidney disease (CKD) in Asia Pacific is uncertain. In numeric terms, the region is home to the largest population of patients with untreated chronic kidney failure. The climatic, geographic, social, cultural, economic, and environmental diversity within this region is higher than in any other part of the world. Large parts of the region face a climate-related burden of infectious diseases. Infections contribute to the development and progression of CKD and complicate the course of patients with pre-existing CKD (especially those on dialysis therapy or who are immunosuppressed), increase the cost of CKD care, and contribute to mortality and morbidity. Kidney involvement is a feature of several infectious diseases prevalent in Asia Pacific. Examples include malaria, leptospirosis, scrub typhus, tuberculosis, hepatitis B and C virus, dengue hemorrhagic fever, and Hantaan virus infections. The contribution of infection-associated acute kidney injury to the overall burden of CKD has not been evaluated systematically. Research is needed to quantify the impact of infections on kidney health by undertaking prospective studies. Nephrologists need to work with infectious disease research groups and government infection surveillance and control programs.
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Affiliation(s)
- Vivekanand Jha
- Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India; Department of Nephrology, George Institute for Global Health, New Delhi, India; Department of Nephrology, University of Oxford, Oxford, United Kingdom.
| | - Narayan Prasad
- Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
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Response to Pegylated Interferon Plus Ribavirin in Patients with Hepatitis C Virus Genotype 6a Infection from Guangdong and Guangxi Province of China. Gastroenterol Res Pract 2016; 2016:5397407. [PMID: 27034655 PMCID: PMC4789432 DOI: 10.1155/2016/5397407] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2015] [Revised: 10/31/2015] [Accepted: 11/04/2015] [Indexed: 11/18/2022] Open
Abstract
Aim. Our aim is to survey the treatment effect of PEG-IFN plus ribavirin in patients infected with HCV genotype 6a in Guangdong and Guangxi province of China and investigate best course of antiviral treatment for patients with HCV-6a infection. Methods. 515 eligible patients received subcutaneous 180 μg PEG-IFNα-2a or 1.5 μg/kg PEG-IFNα-2b once weekly plus oral ribavirin. Primary outcome was SVR by intention-to-treat analysis. Secondary outcome was RVR, cEVR, ETR, and relapse rate. Results. SVR in patients with HCV-6a infection treated for 48 weeks was comparable to that in patients with HCV-2/3 infection (80.9% versus 82.5%, p = 0.812) and higher than that in patients with HCV-1b infection (80.9% versus 67.2%, p = 0.014). ETR (98.9% versus 90.6%, p = 0.016), virological response at month 3 of end-of- treatment (88.8% versus 76.6%, p = 0.044), SVR (80.9% versus 65.6%, p = 0.032), and virological response at month 12 of end-of-treatment (76.4% versus 60.9%, p = 0.04) in patients with HCV-6a infection treated for 48 weeks were higher than those in patients with HCV-6a infection treated for 24 weeks. Conclusion. SVR in patients with HCV-6a treated for 48 weeks was comparable to that in patients with HCV-2/3 infection and higher than that in patients with HCV-1b infection; patients with HCV-6a infection treated for 48 weeks had a superior treatment response than patients treated for 24 weeks.
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Song PP, Xia JF, Inagaki Y, Hasegawa K, Sakamoto Y, Kokudo N, Tang W. Controversies regarding and perspectives on clinical utility of biomarkers in hepatocellular carcinoma. World J Gastroenterol 2016; 22:262-274. [PMID: 26755875 PMCID: PMC4698491 DOI: 10.3748/wjg.v22.i1.262] [Citation(s) in RCA: 90] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2015] [Revised: 07/27/2015] [Accepted: 10/13/2015] [Indexed: 02/06/2023] Open
Abstract
The prevalence of hepatocellular carcinoma (HCC) worldwide parallels that of persistent infection with the hepatitis B virus (HBV) and/or hepatitis C virus (HCV). According to recommendations by the World Health Organization guidelines for HBV/HCV, alpha-fetoprotein (AFP) testing and abdominal ultrasound should be performed in routine surveillance of HCC every 6 mo for high-risk patients. These examinations have also been recommended worldwide by many other HCC guidelines over the past few decades. In recent years, however, the role of AFP in HCC surveillance and diagnosis has diminished due to advances in imaging modalities. AFP was excluded from the surveillance and/or diagnostic criteria in the HCC guidelines published by the American Association for the Study of Liver Diseases in 2010, the European Association for the Study of the Liver in 2012, and the National Comprehensive Cancer Network in 2014. Other biomarkers, including the Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), des-γ-carboxyprothrombin, Dickkopf-1, midkine, and microRNA, are being studied in this regard. Furthermore, increasing attention has focused on the clinical utility of biomarkers as pre-treatment predictors for tumor recurrence and as post-treatment monitors. Serum and tissue-based biomarkers and genomics may aid in the diagnosis of HCC, determination of patient prognosis, and selection of appropriate treatment. However, further studies are needed to better characterize the accuracy and potential role of these approaches in clinical practice.
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Abstract
OBJECTIVE The purpose of this article is to familiarize radiologists with uncommon presentations of hepatocellular carcinoma (HCC) with an emphasis on the CT spectrum of atypical appearances. CONCLUSION HCC is the fifth most common neoplasm worldwide and the second most common cause of cancer-related death. In many cases, HCC can be confidently diagnosed with noninvasive imaging. However, there are numerous unusual appearances of HCC with which the radiologist must be familiar.
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Abstract
The hepatitis C virus (HCV) has a significant medical and economic impact on societies around the world, and it has been estimated that 130-180 million people are infected with HCV. Therapies for HCV are currently undergoing a revolution. In recent years, several new treatments have been approved by the United States Food and Drug Administration, and many other treatments are in phase II or III clinical trials, including direct antiviral agents (DAAs). Due to recent major advances in the field of HCV therapy, a summary of findings on new HCV therapies are provided in this review article, including reports on new DAAs.
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Affiliation(s)
- Bandar Al-Judaibi
- Department of Medicine, Multi-Organ Transplant Unit, Western University, London, Ontario, Canada
- Department of Medicine, Division of Gastroenterology, King Saud University, Riyadh, Saudi Arabia
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Deng L, Wang XH. Progress in antiviral treatment of chronic hepatitis C virus genotype 1 infection. Shijie Huaren Xiaohua Zazhi 2015; 23:4368-4375. [DOI: 10.11569/wcjd.v23.i27.4368] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Hepatitis C virus (HCV) genotype 1 infection is difficult to treat, and the efficacy of peginterferon-α (PEG-IFN-α) and ribavirin (RBV) combination therapy is not very satisfactory. In recent years, direct-acting antiviral drugs (DAAs) have been developed and licensed for the treatment of HCV infection. The first-generation DAAs are NS3/4 polymerase inhibitors, which are often used in combination with PEG-IFN-α and RBV. Subsequently, some IFN-free regimens of NS5A inhibitors and NS5B polymerase inhibitors have shown promising results. Harvoni and VIEKIRA PAK have been approved by the United States Food and Drug Administration. These regimens have excellent response rates, short-duration and minimal toxicities and will bring hope to patients who are difficult to cure or with contraindications to the use of RBV or PEG-IFN-α.
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Zhang RW, Shao CP, Huo N, Li MR, Xi HL, Yu M, Xu XY. Thyroid dysfunction in Chinese hepatitis C patients: Prevalence and correlation with TPOAb and CXCL10. World J Gastroenterol 2015; 21:9765-9773. [PMID: 26361424 PMCID: PMC4562961 DOI: 10.3748/wjg.v21.i33.9765] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2015] [Revised: 06/02/2015] [Accepted: 07/08/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the relationship among pretreatment serum CXC chemokine ligand 10 (CXCL10), thyroid peroxidase antibody (TPOAb) levels and thyroid dysfunction (TD) in Chinese hepatitis C patients.
METHODS: One hundred and thirty-nine treatment-naive genotype 1 chronic hepatitis C patients with no history of TD or treatment with thyroid hormones were enrolled in this study. Patients underwent peginterferon alfa-2a/ribavirin (PegIFNα-2a/RBV) treatment for 48 wk, followed by detection of clinical factors at each follow-up point. Hepatitis C virus (HCV) antibodies were analyzed using microsomal chemiluminescence, and serum HCV RNA was measured by real-time PCR assay at 0, 4, 12, 24 and 48 wk after the initiation of therapy and 24 wk after the end of therapy. To assess thyroid function, serum thyroid stimulating hormone (TSH), free thyroxine (FT4), free triodothyronine (FT3) and TPOAb/thyroglobulin antibody (TGAb) levels were determined using chemiluminescent immunoassays every 3 mo. Serum CXCL10 levels were determined at baseline.
RESULTS: The prevalence of TD was 18.0%. Twenty-one (84.0%) out of twenty-five patients exhibited normal thyroid function at week 24 after therapy. The rate of sustained virological response to PegIFNα-2a/RBV in our study was 59.0% (82/139), independent of thyroid function. Pretreatment serum CXCL10 levels were significantly increased in patients with euthyroid status compared with patients with TD (495.2 ± 244.2 pg/mL vs 310.0 ± 163.4 pg/mL, P = 0.012). Patients with TD were more frequently TPOAb-positive than non-TD (NTD) patients (24.2% vs 12.3%, P = 0.047) at baseline. Three of the one hundred and fifteen patients without TPOAb at baseline developed TD at the end of treatment (37.5% vs 2.6%, P = 0.000). Female patients exhibited an increased risk for developing TD compared with male patients (P = 0.014).
CONCLUSION: Lower pretreatment serum CXCL10 levels are associated with TD, and TD prevalence increases in female patients and patients who are positive for TPOAb at baseline.
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Ashtari S, Pourhoseingholi MA, Sharifian A, Zali MR. Hepatocellular carcinoma in Asia: Prevention strategy and planning. World J Hepatol 2015; 7:1708-1717. [PMID: 26140091 PMCID: PMC4483553 DOI: 10.4254/wjh.v7.i12.1708] [Citation(s) in RCA: 84] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2014] [Revised: 12/31/2014] [Accepted: 05/27/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To review all of epidemiological and etiological aspects of hepatocellular carcinoma (HCC) and examined the prevention of this disease in Asia.
METHODS: We conducted a systematic review according to the PRISMA guidelines. We were chosen articles that published previously, from PubMed (MEDLINE), the Cochrane database and Scopus. The key words used in this research were as follows: HCC in Asia and the way of prevention of this disease, with no language limitations. We selected those papers published before 2014 that we considered to be most important and appropriate. All relevant articles were accessed in full text and all relevant materials was evaluated and reviewed.
RESULTS: More than 70% of all new cases of liver cancer were diagnosed in Asia, a region that 75% of all those chronically infected with hepatitis B virus (HBV) in the world. Chronic HBV infection is the main cause of HCC in Asia, where the virus is endemic and vertical transmission is common. Japan, Saudi Arabia, Egypt and Pakistan are exception because of high prevalence of HCV infection in these regions. The prevalence of this cancer is high in Eastern and South-Eastern Asia, But Middle Eastern countries are characterized as moderate prevalence rate of HCC region and Central Asia and some part of Middle Eastern countries are known as low prevalence rate of HCC. In addition of HBV and HCV the other factors such as aflatoxin, alcohol, obesity, diabetes and non-alcoholic fatty liver disease (NAFLD) might be responsible for a low prevalence of HCC in Asian countries. Currently available HCC therapies, chemotherapy, surgical are inefficient, mainly due to usually late diagnosis and high recurrence rates after surgical resection, and usually end with treatment failure. Liver transplantation also remains as a difficult strategy in patients with HCC. Thus prevention of HCC by treating and prevention HBV and HCV infection, the major causative agents of HCC, and the other risk factors such as aflatoxin, alcohol, obesity, diabetes and NAFLD is of a great medical importance.
CONCLUSION: The main challenge which still present in Asia, is the high prevalence of chronic hepatitis. So, prevention of HBV and HCV is the key strategy to reduce the incidence of HCC in Asia.
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Kuo YH, Chen PF, Wang JH, Chang KC, Kee KM, Tsai MC, Lin CY, Lin SC, Tsai LS, Chen SC, Lu SN. Comparison Stratagems of Post-Screening Management of Anti-HCV-Positive Community Residents: Simple Notification, Active Referral, or Accessible Medical Care. PLoS One 2015; 10:e0126031. [PMID: 25970487 PMCID: PMC4430481 DOI: 10.1371/journal.pone.0126031] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2014] [Accepted: 03/27/2015] [Indexed: 12/24/2022] Open
Abstract
To elucidate the results of post-screening care stratagems for anti-hepatitis C virus (HCV)-positive subjects in the community. Part I methods: The intervention program: A total of 151,790 subjects underwent a large-scale healthcare screening. Subjects aged less than 65 years, with anti-HCV-positive and alanine aminotransferase (ALT) level more than 80 IU/L were followed-up to answer a structured questionnaire. Those responders who met the reimbursement criteria of Taiwan’s National Health Insurance for anti-HCV treatment were referred for treatment. Part II: The accessible medical care program: In Yujing township, 271 HCV residents who have been screened before were invited to a bi-weekly hepatitis clinic in Yujing health center. Part-I results: A total of 907 anti-HCV-positive subjects responded and 197(21.7%) were advised the treatment, but only 83(9.2%) did. Finally, 47 patients achieved a sustained virological response (SVR). After this intervention program, 96(10.6%) additional patients were encouraged to be referred, 33(3.6%) received treatment and 20 obtained a SVR. Part II: A total of 140(51.7%) subjects responded and 112 were anti-HCV-positive including 31(27.7%) HCV RNA-negative, 49(43.8%) HCV RNA-positive plus ALT less than 40 IU/L and 32(28.5%) HCV RNA-positive plus ALT more than 40 IU/L. During the follow-up, 14 of 49 patients had ALT more than 40 IU/L. Among 46 eligible HCV patients, 15(32.6%) received treatment and 10 achieved a SVR. Simple notification only made 9.2% of the screened HCV patients treat. Active referral could encourage additional 3.6% to be treated. Additionally, accessible medical care program could result in treatment of 32.6% elderly eligible patients.
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Affiliation(s)
- Yuan-Hung Kuo
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Pao-Fei Chen
- Health Center of Yanpu Township, Pingtung, Taiwan
| | - Jing-Houng Wang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Kuo-Chin Chang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Kwong-Ming Kee
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Ming-Chao Tsai
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chun-Yin Lin
- Health Center of Yujing district, Tainan, Taiwan
| | - Sheng-Che Lin
- Department of Health, Tainan City Government, Tainan, Taiwan
| | - Lin-San Tsai
- Department of Health, Tainan City Government, Tainan, Taiwan
| | - Shu-Chuan Chen
- Department of Health, Tainan City Government, Tainan, Taiwan
| | - Sheng-Nan Lu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
- * E-mail:
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Imran M, Manzoor S, Azam S, Resham S. Genetic variant of IL28B rs12979860, as predictive marker of interferon-based therapy in Pakistani population. APMIS 2015; 123:342-9. [PMID: 25703417 DOI: 10.1111/apm.12365] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2014] [Accepted: 12/17/2014] [Indexed: 12/12/2022]
Abstract
Hepatitis C virus (HCV) genotypes and genetic variants of interleukin 28B (IL28B) are significantly associated with interferon plus ribavirin treatment of HCV infection. We investigated the distribution of HCV genotypes and single-nucleotide polymorphisms (SNPs) of IL28B (rs12979860 and rs8099917) in Pakistani population. IL28B genotyping was performed by allele-specific PCR and restriction fragment length polymorphism PCR in 140 chronic hepatitis C patients (CHC) and 120 healthy controls. HCV genotype 3 (HCVG3) was the most prevalent genotype, 71.4% (n = 100/140) and with the highest treatment response of 90% (n = 90/100). The overall treatment response of all the HCV genotypes was 82% (n = 115/140). The distribution of IL28B rs12979860CC genotype in treatment responder and non-responder groups was 40.8% (n = 47/115) and 16% (n = 4/25) respectively. IL28B rs12979860CC genotype demonstrated a significant correlation (p = 0.019) with interferon-based therapy of HCV infection. However, there was no observed association of IL28B rs8099917 polymorphism with treatment response in CHC patients (p = 0.264). In conclusion, HCV genotypes and IL28B rs12979860 are predictive markers for the efficiency of interferon plus ribavirin combinational therapy of HCV infection. We recommend the inclusion of testing for these markers in the clinical criteria for decision making for HCV therapy in Pakistani population.
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Affiliation(s)
- Muhammad Imran
- Atta-ur-Rahman School of Applied Bio-Sciences, Department of Healthcare Biotechnology, National University of Sciences and Technology (NUST), Islamabad, Pakistan
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Yoo SJ, Wang LL, Ning HC, Tao CM, Hirankarn N, Kuakarn S, Yang R, Han TH, Chan RC, Hussain BM, Hussin H, Muliaty D, Shen L, Liu H, Wei L. Evaluation of the Elecsys(®) Anti-HCV II assay for routine hepatitis C virus screening of different Asian Pacific populations and detection of early infection. J Clin Virol 2014; 64:20-7. [PMID: 25728074 DOI: 10.1016/j.jcv.2014.12.015] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2014] [Revised: 12/12/2014] [Accepted: 12/23/2014] [Indexed: 02/05/2023]
Abstract
BACKGROUND Early diagnosis of hepatitis C virus (HCV) infection is essential to allow appropriate treatment and prevent transmission. OBJECTIVES To evaluate the Elecsys(®) Anti-HCV II assay as a routine screening assay in Asia using a large number of samples from different Asian Pacific populations and compare its performance with other HCV assays routinely used in the region. STUDY DESIGN The sensitivity and specificity of the Elecsys(®) Anti-HCV II assay were determined using routine hospital samples and compared with at least one of the following comparator assays at nine independent centers: ARCHITECT™ Anti-HCV; Serodia(®)-HCV Particle Agglutination; Vitros(®) ECi Anti-HCV; Elecsys(®) Anti-HCV; ADVIA Centaur(®) HCV; InTec(®) HCV EIA; or Livzon(®) Anti-HCV. Commercially available seroconversion panels were used to assess sensitivity for early detection of infection. RESULTS The Elecsys(®) Anti-HCV II assay was more sensitive in recognizing early infection and detected acute HCV infection earlier on average than the comparator assays for all six panels tested. 7,726 routine samples were tested and 322 identified as HCV positive. Elecsys(®) Anti-HCV II had a sensitivity of 100% and a specificity of 99.66%, both of which were comparable or superior to the results obtained for competitor assays, which ranged from 87.5-100% and 98.98-100%, respectively. CONCLUSIONS The Elecsys(®) Anti-HCV II assay has the sensitivity and specificity to support its use as a routine screening method in the Asia Pacific region. Furthermore, this assay shortens the diagnostic window between infection and the detection of antibodies compared with established methods.
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Affiliation(s)
- Soo Jin Yoo
- Inje University Sanggye Paik Hospital, 1342, Dongilro, Nowon-gu, Seoul 139-707, South Korea.
| | - Lan Lan Wang
- West China Hospital, Sichuan University, 37 GuoXue Xiang, Chengdu, Sichuan Province 610041, China.
| | - Hsiao-Chen Ning
- Chang Gung Memorial Hospital, 5 Fusing Street, Gueishan Township, Taoyuan County 333, Taiwan ROC.
| | - Chuan Min Tao
- West China Hospital, Sichuan University, 37 GuoXue Xiang, Chengdu, Sichuan Province 610041, China.
| | - Nattiya Hirankarn
- Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, 1873 Rama Road, Pathumwan, Bangkok 10330, Thailand.
| | - Sunida Kuakarn
- Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, 1873 Rama Road, Pathumwan, Bangkok 10330, Thailand.
| | - Ruifeng Yang
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Xizhimen South Street No 11, Xicheng District, Beijing 100044, China.
| | - Tae Hee Han
- Inje University Sanggye Paik Hospital, 1342, Dongilro, Nowon-gu, Seoul 139-707, South Korea.
| | - Raymond C Chan
- Royal Prince Alfred Hospital, Camperdown, Sydney, NSW 2050, Australia.
| | - Baizurah Mohd Hussain
- Hospital Ampang, Jalan Mewah Utara, Pandan Mewah, 68000 Ampang, Selangor DE, Malaysia.
| | - Hazilawati Hussin
- Hospital Ampang, Jalan Mewah Utara, Pandan Mewah, 68000 Ampang, Selangor DE, Malaysia.
| | - Dewi Muliaty
- Prodia Clinical Laboratory, Kramat Raya Street No. 150, Jakarta 10430, Indonesia.
| | - Lisong Shen
- Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 Kong Jiang Road, Shanghai 200092, China.
| | - Hongjing Liu
- Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, 1665 Kong Jiang Road, Shanghai 200092, China.
| | - Lai Wei
- Peking University People's Hospital, Peking University Hepatology Institute, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Xizhimen South Street No 11, Xicheng District, Beijing 100044, China.
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Lin SY, Chen TC, Lu PL, Lin CY, Lin WR, Yang YH, Chen YH. Incidence rates of tuberculosis in chronic hepatitis C infected patients with or without interferon based therapy: a population-based cohort study in Taiwan. BMC Infect Dis 2014; 14:705. [PMID: 25523602 PMCID: PMC4307221 DOI: 10.1186/s12879-014-0705-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2014] [Accepted: 12/11/2014] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND It is debated whether interferon-based therapy (IBT) would affect the incidence of active tuberculosis (TB) among hepatitis C virus (HCV) infected patients. Although some case reports have demonstrated a possible association, the results are currently inconclusive. Therefore, we conducted a nation-wide population study to investigate the incidence of active TB in HCV infected patients receiving IBT in Taiwan. METHODS This 9-year cohort study was based on the Longitudinal Health Insurance Database 2000 (LHID 2000) consisting of 1,000,000 beneficiaries randomly selected from all Taiwan National Health Insurance enrollees in 2000 ( >23.7 million). This insurance program covers all citizens in Taiwan. We conducted a retrospective cohort study that identified subjects with HCV infection. IBTs were defined as regimens that included interferon α, peginterferon α2a and peginterferon α2b for at least 2 months. Among them, 621 subjects received IBT, and 2,460 age- and gender-matched subjects were enrolled for analysis. The Cox proportional hazards models were used to estimate the hazard ratio (HR) for active TB, and associated confidence intervals (CIs), comparing IBT cohort and untreated cohort. The endpoint in this study was whether an enrolled subject had a new diagnosis of active TB. RESULTS During the 9-year enrollment period, the treated and untreated cohorts were followed for a mean (± SD) duration of 6.97 ± 0.02 years and 8.21 ± 0.01 years, respectively. The cumulative incidence rate of active TB during this study period was 0.150 and 0.151 per 100 person-years in the IBT treated and untreated cohorts, respectively. There was no significant difference in the incidence of active TB in either cohort during a 1-year follow-up (Adjusted Hazard Ratio (AHR): 2.81, 95% Confidence Interval (95% CI): 0.61-12.98) or the long-term follow-up (AHR: 1.02, 95% CI: 0.28-3.78). The Cox proportional hazards model demonstrated that IBT was not a risk factor for active TB . The only risk factor for active TB was the occurrence of hepatic encephalopathy. CONCLUSION Our results showed that IBT is associated with increased hazard of active TB in HCV infected patients in 1-year follow-up; however, the effect sizes were not statistically significant.
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Affiliation(s)
- Shang-Yi Lin
- Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
- School of Medicine, Graduate Institute of Medicine, Sepsis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - Tun-Chieh Chen
- Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
- Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, 100 Tzyou 1st Road, Kaohsiung City, Taiwan.
| | - Po-Liang Lu
- School of Medicine, Graduate Institute of Medicine, Sepsis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
- Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, 100 Tzyou 1st Road, Kaohsiung City, Taiwan.
- Department of Biological Science and Technology, College of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan.
- Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
| | - Chun-Yu Lin
- School of Medicine, Graduate Institute of Medicine, Sepsis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
- Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, 100 Tzyou 1st Road, Kaohsiung City, Taiwan.
| | - Wei-Ru Lin
- Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, 100 Tzyou 1st Road, Kaohsiung City, Taiwan.
| | - Yi-Hsin Yang
- School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan.
- Division of Statistical Analysis, Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
| | - Yen-Hsu Chen
- School of Medicine, Graduate Institute of Medicine, Sepsis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
- Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, 100 Tzyou 1st Road, Kaohsiung City, Taiwan.
- Department of Biological Science and Technology, College of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan.
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Faisal N, Mumtaz K, Marquez M, Renner EL, Lilly LB. High sustained virological response to pegylated interferon and ribavirin for recurrent genotype 3 hepatitis C infection post-liver transplantation. Hepatol Int 2014; 9:76-83. [PMID: 25788382 DOI: 10.1007/s12072-014-9589-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2014] [Accepted: 10/20/2014] [Indexed: 12/17/2022]
Abstract
INTRODUCTION Treatment outcomes of recurrent HCV genotype 3 (GT-3) after liver transplantation (LT) are ill-defined. AIMS To determine efficacy, predictors, and long-term survival after treatment of recurrent HCV GT-3 infection, post-LT, with a combination of pegylated interferon (PEG) and ribavirin (RBV). METHODS We studied all LT recipients (LTR) in our program treated with PEG and RBV for recurrent HCV GT-3 between Jan 1st 2002 and Dec 31st 2013. Antiviral therapy (AVT) was started if histology showed recurrent HCV with ≥ stage 2 fibrosis. Treatment was intended for 24 or 36 weeks, depending on early virologic response, and/or 24 weeks consolidation. Primary endpoint was sustained virological response (SVR). We also studied predictors of SVR and long-term patient survival. RESULTS Among 492 LT for HCV-related cirrhosis and/or hepatocellular carcinoma performed during the study period, 110 (22%) had HCV GT-3 infection. Fifty-two (10.5%) HCV GT-3 patients had indications for AVT. Six were unable to complete the AVT, three because of clinical decompensation and one each because of metastatic disease involving the brain, lung cancer, and ductopenic rejection. Forty-seven (90%) patients achieved early virological response (EVR) and 37 (71%) achieved SVR. Predictors of SVR were EVR (p < 0.001), stage ≤ 3 fibrosis (p = 0.008), and 36 weeks treatment duration (p < 0.001). Less advanced fibrosis ≤ 3 was independent predictor of SVR (OR 0.18, 95% CI 0.05-0.67). SVR patients had actuarial (Kaplan-Meier) 1, 3, and 10 year post-treatment survival of 100, 100, and 95%, compared with 87, 78, and 20% for non-SVR patients (p < 0.001, log rank test). CONCLUSION Efficacy of AVT for recurrent HCV GT-3 post-LT is high, and comparable with that for non-transplant patients. Less advanced fibrosis is an independent predictor of SVR. SVR improves long-term survival.
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Affiliation(s)
- Nabiha Faisal
- Liver Transplant Program/Multi-Organ Transplant Program, University Health, Network/Toronto General Hospital, University of Toronto, Toronto, ON, Canada
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Naveira M, Barbosa J, Sereno L, Domanico A, Mesquita F, de Souza LA. 12 years of universal access to hepatitis C treatment: Brazil's comprehensive response. J Int Assoc Provid AIDS Care 2014; 13:560-7. [PMID: 25158974 DOI: 10.1177/2325957414547739] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Hepatitis C is considered one of the most neglected diseases in world. Worldwide about 150 million people are chronically infected by hepatitis C virus (HCV), and 60% to 70% of them will develop severe liver disease. This article describes Brazil's response to hepatitis C, from the first steps in 1993 to a national program in 2002. We reviewed the available literature, most of it in Brazilian Portuguese, and compiled them in order to share this experience with those seeking some pragmatic solutions. After 12 years, the national program has achieved universal coverage of treatment, resulting in saved lives and resources for the health system. There is abundant evidence that the HCV epidemic deserves attention. The overall consequence of long-term HCV infection is a negative impact on the health care economy. The Brazilian experience can be adapted to many countries in the world, in compliance with the 2010 World Health Organization World Health Assembly Resolution.
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Affiliation(s)
- Marcelo Naveira
- Seção Centro de Referência em AIDS (SECRAIDS), Santos, São Paulo, Brazil
| | - Jarbas Barbosa
- Ministry of Health, Secretariat of Health Surveillance, Brasília, Brazil
| | - Leandro Sereno
- Instituto de Infectologia Emílio Ribas, Guarujá, São Paulo, Brazil
| | - Andrea Domanico
- Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil
| | - Fábio Mesquita
- Ministry of Health, National Department of STD, HIV/AIDS and Viral Hepatitis, Brasília, Brazil
| | - Laura Alves de Souza
- Ministry of Health, National Department of STD, HIV/AIDS and Viral Hepatitis, Brasília, Brazil
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Zhang B, Hu M, Huang L, Pu Y, Pei H, Hua Z, Yao S. Effect of Fuzheng Huayu capsule combined with Pegasys on genotype 1 hepatitis C fibrosis and cell apoptosis. Exp Ther Med 2014; 8:1123-1126. [PMID: 25187808 PMCID: PMC4151630 DOI: 10.3892/etm.2014.1891] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2014] [Accepted: 07/28/2014] [Indexed: 12/19/2022] Open
Abstract
The aim of the present study was to observe the effects of Fuzheng Huayu capsule combined with Pegasys (peginterferon α-2a) on hepatic fibrosis in rats and in the treatment of patients with genotype 1 hepatitis C and hepatic cirrhosis. A dimethylnitrosamine (DMN)-induced rat model of liver injury was established. Fuzheng Huayu capsule combined with Pegasys was administered to the rats and the DMN-induced hepatocyte apoptosis was observed. In addition, a total of 100 patients with genotype 1 hepatitis C and hepatic cirrhosis were treated by oral administration of Fuzheng Huayu capsule combined with Pegasys or with Pegasys alone. The therapeutic effect of Fuzheng Huayu capsule combined with Pegasys was analyzed. Following the oral administration of Fuzheng Huayu capsule combined with Pegasys to the DMN model rats, the expression of α-smooth muscle actin was found to be significantly reduced, hemopoietic stem cell apoptosis was increased and liver cell apoptosis was reduced. These indices were significantly different compared with those in the model group (P<0.05). Liver function and liver fibrosis were markedly recovered in hepatitis C patients with hepatic cirrhosis following treatment with the combination treatment compared with those in the patients treated with Pegasys alone (P<0.05). In conclusion, the combination of Fuzheng Huayu capsule with Pegasys inhibited liver fibrosis and cell apoptosis, and may be a novel therapeutic strategy for the treatment of patients with compensated cirrhosis due to hepatitis C. This study provides a method for the optimization of existing treatment strategies and for the establishment of potentially effective combination therapies.
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Affiliation(s)
- Bo Zhang
- Department of Infectious Diseases, The Fifth People's Hospital of Wuxi, Wuxi, Jiangsu 214005, P.R. China
| | - Mintao Hu
- Department of Infectious Diseases, The Fifth People's Hospital of Wuxi, Wuxi, Jiangsu 214005, P.R. China
| | - Lihua Huang
- Department of Infectious Diseases, The Fifth People's Hospital of Wuxi, Wuxi, Jiangsu 214005, P.R. China
| | - Yunchuan Pu
- Department of Infectious Diseases, The Fifth People's Hospital of Wuxi, Wuxi, Jiangsu 214005, P.R. China
| | - Hao Pei
- Department of Infectious Diseases, The Fifth People's Hospital of Wuxi, Wuxi, Jiangsu 214005, P.R. China
| | - Zhong Hua
- Department of Infectious Diseases, The Fifth People's Hospital of Wuxi, Wuxi, Jiangsu 214005, P.R. China
| | - Shangzhi Yao
- Department of Infectious Diseases, The Fifth People's Hospital of Wuxi, Wuxi, Jiangsu 214005, P.R. China
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Mangia A, Bányai T, De Bartolomeo G, Gervain J, Habersetzer F, Mulkay JP, Ouzan D, Parruti G, Passariello N, Remy AJ, Rizzetto M, Shiffman ML, Tice AD, Schmitz M, Tatsch F, Rodriguez-Torres M. In routine clinical practice, few physicians use early viral kinetics to guide HCV dual therapy treatment decisions. Liver Int 2014; 34:e217-28. [PMID: 24251988 DOI: 10.1111/liv.12352] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2013] [Accepted: 09/25/2013] [Indexed: 12/17/2022]
Abstract
BACKGROUND & AIMS PROPHESYS is a large, multinational, non-interventional prospective cohort study of chronic hepatitis C patients treated with peginterferon alfa/ribavirin. This subanalysis assesses rates of premature treatment discontinuation stratified by on-treatment virological response (VR). METHODS This PROPHESYS subanalysis is restricted to treatment-naive, hepatitis C virus (HCV) genotype (G)1/2/3 mono-infected patients who received peginterferon alfa-2a (40KD)/ribavirin with intended treatment duration of 48 (G1) or 24 weeks (G2/3). Early virological responses were classified into four mutually exclusive categories [rapid VR (RVR), complete early VR (cEVR), partial EVR (pEVR), no RVR/EVR], using standard criteria. RESULTS The likelihood for shortening treatment owing to good efficacy was highest among patients with an RVR and HCV RNA≤400 000 IU/ml (G1 10.0%; G2/3 5.8%) whereas for poor efficacy, it was highest in G1 non-RVR/EVR patients with HCV RNA>400 000 IU/ml (56.6%). Factors significantly associated with early treatment discontinuation as a result of good efficacy in G1 patients included RVR vs. no RVR/EVR and, at baseline, lower HCV RNA, lower FIB-4 score, HCV infection via injection drug use. For G2/3 patients, factors included lower baseline HCV RNA and G2 vs. G3 infection. Most patients started with the recommended peginterferon alfa-2a dose, but a high proportion received a higher-than-recommended ribavirin dose. CONCLUSIONS Despite international guidelines, few physicians used early viral kinetics to abbreviate treatment. Therefore, relatively few patients with an RVR and low baseline HCV RNA abbreviated treatment. In addition, there were deviations in ribavirin starting doses, suggesting that physicians tailor treatment according to local guidelines or previous experience.
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Affiliation(s)
- Alessandra Mangia
- Liver Unit, IRCCS Hospital 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, Italy
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KASL clinical practice guidelines: management of hepatitis C. Clin Mol Hepatol 2014; 20:89-136. [PMID: 25032178 PMCID: PMC4099340 DOI: 10.3350/cmh.2014.20.2.89] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2014] [Accepted: 05/20/2014] [Indexed: 12/16/2022] Open
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Xu CJ, Zhang CP, Wang XH, Liu LJ, Zhou SS, Wang JH, He QJ, Wang YZ, Guo WS, Zhu WB, Jiang Y. An individualized strategy for treatment of hepatitis C virus carriers with normal aminotransferase levels: Analysis of 73 cases. Shijie Huaren Xiaohua Zazhi 2014; 22:2317-2322. [DOI: 10.11569/wcjd.v22.i16.2317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the efficacy and safety of peginterferon alpha-2a (PEG-IFN α-2a) combined with ribavirin (RBV) in the treatment of chronic hepatitis C (CHC) patients with normal aminotransferase levels.
METHODS: Patients with CHC and at least three normal aminotransferase values over an 18-month period or increased aminotransferase were offered a treatment with PEG-IFN α-2a 180 μg/wk and ribavirin (800 mg/d for weight ≤ 65 kg; 1000 mg/d for weight > 65 and < 75 kg; 1200 mg/d for weight ≥ 75 kg). All patients were followed for 24 wk post treatment. Curative effects were evaluated at 4 and 12 wk during the treatment and 24 wk post treatment. The adverse effects were also recorded.
RESULTS: A total of 161 patients completed the therapy. The 73 patients with normal transaminase and the 88 patients with increased transaminase had similar baseline characteristics. Overall, the two groups showed similar rapid virologic response (RVR) rate (78.1% vs 75.0%, P > 0.05), complete early virologic response (cEVR) rate (93.2% vs 92.0%, P > 0.05) and sustained virologic response (SVR) rate (92.7% vs 91.9%, P > 0.05).
CONCLUSION: Combination therapy with PEG-IFN α-2a and RBV is safe and effective in CHC patients with persistently normal aminotransferase levels.
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Wang KL, Xing HQ, Zhao H, Liu JW, Gao DL, Zhang XH, Yao HY, Yan L, Zhao J. Efficacy and tolerability of low-dose interferon-α in hemodialysis patients with chronic hepatitis C virus infection. World J Gastroenterol 2014; 20:4071-4075. [PMID: 24744598 PMCID: PMC3983465 DOI: 10.3748/wjg.v20.i14.4071] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2013] [Revised: 11/21/2013] [Accepted: 01/05/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the efficacy and tolerability of low-dose standard or pegylated interferon (PEG-IFN) in hepatitis C virus (HCV)-positive hemodialysis patients.
METHODS: In total, 19 patients were enrolled in this study, of which 12 received PEG-IFNα-2a 67.5 μg 1 time/wk (Group 1) and 7 received standard interferon α-2b subcutaneously 1.5 × 106 U 3 times/wk (Group 2). The treatment durations were 48 wk for patients infected with HCV genotype 1 and 24 wk for patients infected with HCV genotype 2/3. All patients were prospectively followed after the completion of therapy. The efficacy and tolerability of the treatment were evaluated based on the sustained virological response (SVR) and treatment-related drop-out rate.
RESULTS: In Group 1, 11 of the 12 patients completed the treatment. Early virological response (EVR) and sustained virological response (SVR) rates were 83.3% and 91.7%, respectively. One patient withdrew from treatment due to an adverse event (leukopenia). The drop-out rate was 8.3% in this group. In Group 2, 5 of the 7 patients completed the treatment with an EVR and SVR of 85.7% and 71.4%, respectively. Two patients withdrew due to treatment-related adverse events (nausea and depression). In this group, the drop-out rate was 28.6%. In total, 16 of the patients attained EVR, and 15 of them completed the treatment. The SVR rate for the patients who attained EVR was 93.7%. Anemia was the most frequent side effect and was observed in 10/19 patients (55.5%), but could be effectively managed with erythropoietin.
CONCLUSION: Low-dose interferon monotherapy, either with PEG-IFNα-2a or standard interferon α-2b, is an effective treatment option for hemodialysis patients with chronic hepatitis C.
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Thong VD, Akkarathamrongsin S, Poovorawan K, Tangkijvanich P, Poovorawan Y. Hepatitis C virus genotype 6: virology, epidemiology, genetic variation and clinical implication. World J Gastroenterol 2014; 20:2927-40. [PMID: 24659883 PMCID: PMC3961978 DOI: 10.3748/wjg.v20.i11.2927] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2013] [Revised: 01/06/2014] [Accepted: 01/19/2014] [Indexed: 02/07/2023] Open
Abstract
Hepatitis C virus (HCV) is a serious public health problem affecting 170 million carriers worldwide. It is a leading cause of chronic hepatitis, cirrhosis, and liver cancer and is the primary cause for liver transplantation worldwide. HCV genotype 6 (HCV-6) is restricted to South China, South-East Asia, and it is also occasionally found in migrant patients from endemic countries. HCV-6 has considerable genetic diversity with 23 subtypes (a to w). Although direct sequencing followed by phylogenetic analysis is the gold standard for HCV-6 genotyping and subtyping, there are also now rapid genotyping tests available such as the reverse hybridization line probe assay (INNO-LiPA II; Innogenetics, Zwijnaarde, Belgium). HCV-6 patients present with similar clinical manifestations as patients infected with other genotypes. Based on current evidence, the optimal treatment duration of HCV-6 with pegylated interferon/ribavirin should be 48 wk, although a shortened treatment duration of 24 wk could be sufficient in patients with low pretreatment viral load who achieve rapid virological response. In addition, the development of direct-acting antiviral agents is ongoing, and they give high response rate when combined with standard therapy. Herein, we review the epidemiology, classification, diagnosis and treatment as it pertain to HCV-6.
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Esmat G, El Kassas M, Hassany M, Gamil M, El Raziky M. Optimizing treatment for HCV genotype 4: PEG-IFN alfa 2a vs. PEG-IFN alfa 2b; the debate continues. Liver Int 2014; 34 Suppl 1:24-8. [PMID: 24373075 DOI: 10.1111/liv.12397] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Hepatitis C virus (HCV) remains one of the leading causes of morbidity and mortality worldwide. Combined therapy with pegylated interferon (PEG-IFN) and ribavirin is the current standard of care treatment for HCV genotype 4. Two types of PEG-IFN are commercially available. The limited number of trials that were conducted for HCV genotype 4 and the few head to head comparisons make it impossible to know which is the best option? In this article we review all available PEG-IFN trials performed worldwide for HCV genotype 4 since 2004. Unless another molecule is developed as a standalone for the treatment of HCV, PEG-IFN will continue to be a source of debate.
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Affiliation(s)
- Gamal Esmat
- Endemic Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt; Tropical Medicine Department, National Hepatology & Tropical Medicine Research Institute, Cairo, Egypt
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Wada Y, Tamai H, Uno A, Kawashima A, Shingaki N, Mori Y, Moribata K, Miyata K, Higashi K, Deguchi H, Ueda K, Inoue I, Maekita T, Iguchi M, Kato J, Ichinose M. Prediction of efficacy to pegylated interferon-α-2b plus ribavirin in patients with genotype 2 hepatitis C virus using viral response within 2 weeks. Hepatol Res 2014; 44:179-86. [PMID: 23531032 DOI: 10.1111/hepr.12101] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2012] [Revised: 12/28/2012] [Accepted: 02/18/2013] [Indexed: 12/26/2022]
Abstract
AIM Rapid virological response (RVR), defined as serum hepatitis C virus (HCV) RNA negativity at 4 weeks, is the most useful predictor of sustained virological response (SVR) to standard pegylated interferon (PEG IFN) plus ribavirin therapy for patients infected with genotype 2 HCV. The aim of the present study was to predict SVR using viral response within 2 weeks of therapy initiation. METHODS Of 64 HCV genotype 2 patients with a high viral load treated with standard PEG IFN-α-2b plus weight-based ribavirin for 24 weeks, 58 patients whose adherence was more than 67% were analyzed. RNA and core antigen levels were measured at four time points: the day of therapy initiation, the following day, and at 1 and 2 weeks. RESULTS SVR was achieved in 73% (47/64) of patients. Univariate analysis of SVR contributing factors showed significant differences with age, bodyweight, white blood cell count, platelet count, fibrosis marker levels, baseline core antigen level and viral response. The area under the receiver-operator curve (AUC) of the core antigen level at 1 week (AUC, 0.940) was the highest among the significant SVR predicting factors. Setting 100 fmol/L as the cut-off value for core antigen level at 1 week, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy for predicting SVR were 100%, 86%, 96%, 100% and 97%, respectively, and for predicting RVR were 66%, 93%, 97%, 46% and 72%, respectively. CONCLUSION The HCV core antigen level at 1 week after therapy initiation is the most useful predictor for SVR.
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Affiliation(s)
- Yuki Wada
- Second Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan
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Borgna-Pignatti C, Gamberini MR. Complications of thalassemia major and their treatment. Expert Rev Hematol 2014; 4:353-66. [DOI: 10.1586/ehm.11.29] [Citation(s) in RCA: 85] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
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Crawford B, Yeung CK, Tanaka E, Kraemer M, Leteneux C. Hepatitis C virus in Asia: utility values based on the Short Form-36 questionnaire. Expert Rev Pharmacoecon Outcomes Res 2014; 12:765-73. [DOI: 10.1586/erp.12.61] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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Chen MY, Liu CH, Chen TC, Su TH, Chen PJ, Chen DS, Kao JH, Liu CJ. Value of interleukin-28B genetic polymorphism on retreatment outcomes of chronic hepatitis C genotype 1 relapsers by peginterferon alfa plus ribavirin. J Gastroenterol Hepatol 2014; 29:102-9. [PMID: 23829453 DOI: 10.1111/jgh.12329] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/22/2013] [Indexed: 01/18/2023]
Abstract
BACKGROUND AND AIM Chronic hepatitis C (CHC) infection is a leading cause of cirrhosis and hepatocellular carcinoma worldwide. Pegylated interferon (PEG-IFN) plus ribavirin (RBV) combination therapy remains the standard of care for CHC genotype 1 in many Asian countries, and single nucleotide polymorphism or genotype of the interleukin-28B (IL28B) gene is associated with the development of sustained virologic response (SVR). The predictive value of IL28B genotype for retreatment outcomes of patients with CHC was only partly clarified and deserves further investigation. METHODS A total of 75 CHC genotype 1 Taiwanese patients who relapsed after 24-week PEG-IFN/RBV combination therapy and received retreatment with a 48-week PEG-IFN/RBV therapy were consecutively enrolled since November 2009. The associations among IL28B rs8099917 genotype, virologic kinetics, and treatment outcomes were evaluated. RESULTS Rapid virologic response (RVR) at week 4, end-of-treatment virologic response (EOT-VR) and SVR was 37%, 73%, and 52%, respectively. Relapse rate was 29%. None of patients had rs8099917 GG genotype. Patients with TT genotype (n = 54, 72%) had higher rates of RVR (50% vs 5%, P = 0.0002), end-of-treatment virologic response (85% vs 43%, P = 0.0001), and SVR (67% vs 14%, P = 0.0001) than those with GT genotype (n = 21, 28%). Combination of IL28B TT genotype and achieving RVR had 85% positive and 90% negative predictive values of SVR. CONCLUSIONS About half of the Taiwanese CHC relapsers to a previous 24-week combination therapy achieve SVR after retreatment for 48 weeks. IL28B genotype influences on-treatment viral kinetics and SVR rate in these retreated patients. Baseline IL28B genotype and RVR can serve as early predictors for treatment success.
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Affiliation(s)
- Ming-Yao Chen
- Department of Internal Medicine, Shuang-Ho Hospital, Taipei Medical University, Taipei, Taiwan
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Kin KC, Lin B, Chaung KT, Ha NB, Trinh HN, Garcia RT, Nguyen HA, Nguyen KK, Levitt BS, da Silveira EB, Nguyen MH. Less-established risk factors are common in Asian Americans with hepatitis C virus: a case-controlled study. Dig Dis Sci 2013; 58:3342-7. [PMID: 24081641 DOI: 10.1007/s10620-013-2884-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2013] [Accepted: 09/10/2013] [Indexed: 12/29/2022]
Abstract
BACKGROUND AND AIMS The Centers for Disease Control and Prevention recommend screening for hepatitis C virus (HCV) in patients with injection drug use, blood transfusion before 1992, stigmata of liver disease, or born between 1945 and 1965. The purpose of this study was to examine risk factors for HCV acquisition in Asian Americans. METHODS This was a case-controlled study, with 471 consecutive patients testing positive for anti-HCV between January 2001 and December 2008. Controls included 471 patients with negative HCV matched at a one-to-one ratio for sex, age (±5 years), and ethnicity. RESULTS For Asian patients, the most common risk factors were blood transfusion and acupuncture or exposure to dirty needles (27 and 20 %, respectively). On multiple logistic regression, potential predictors for a positive anti-HCV test in Asians were acupuncture or exposure to dirty needles (OR = 12.9, P < 0.0001), body tattoo (OR = 12.0, P = 0.001), and history of blood transfusion (OR = 5.7, P < 0.0001). DISCUSSION Acupuncture and exposure to dirty needles are independent risk factors of HCV infection. Asians coming from endemic areas should be screened for HCV even when commonly-known risk factors for Western patients are not present.
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Affiliation(s)
- Kevin C Kin
- Pacific Health Foundation, San Jose, CA, USA,
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Chen DS, Locarnini S, Wait S, Bae SH, Chen PJ, Fung JYY, Kim HS, Lu SN, Sung J, Tanaka J, Wakita T, Ward J, Wallace J. Report from a Viral Hepatitis Policy Forum on implementing the WHO Framework for Global Action on viral hepatitis in North Asia. J Hepatol 2013; 59:1073-80. [PMID: 23850942 DOI: 10.1016/j.jhep.2013.06.029] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2013] [Accepted: 06/29/2013] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS The World Health Organisation (WHO) Prevention & Control of Viral Hepatitis Infection: Framework for Global Action offers a global vision for the prevention and control of viral hepatitis. In October 2012, the Coalition to Eradicate Viral Hepatitis in Asia Pacific (CEVHAP) organised the North Asia Workshop on Viral Hepatitis in Taipei to discuss how to implement the WHO Framework in the North Asia region. This paper presents outcomes from this workshop. METHODS Twenty-eight representatives from local liver associations, patient organisations, and centres of excellence in Hong Kong, Japan, Korea, and Taiwan participated in the workshop. FINDINGS Priority areas for action were described along the four axes of the WHO Framework: (1) awareness, advocacy and resources; (2) evidence and data; (3) prevention of transmission; and (4) screening and treatment. Priorities included: axis 1: greater public and professional awareness, particularly among primary care physicians and local advocacy networks. Axis 2: better economic data and identifying barriers to screening and treatment uptake. Axis 3: monitoring of vaccination outcomes and targeted harm reduction strategies. Axis 4: strengthening links between hospitals and primary care providers, and secure funding of screening and treatment, including for hepatocellular carcinoma. CONCLUSIONS The WHO Framework provides an opportunity to develop comprehensive and cohesive policies in North Asia and the broader region. A partnership between clinical specialists, primary care physicians, policy makers, and people with or at risk of viral hepatitis is essential in shaping future policies.
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Affiliation(s)
- Ding-Shinn Chen
- National Taiwan University College of Medicine, Taipei, Taiwan
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