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Lai JCT, Wong GLH, Tse YK, Hui VWK, Lai MSM, Chan HLY, Wong VWS, Yip TCF. Histological severity, clinical outcomes and impact of antiviral treatment in indeterminate phase of chronic hepatitis B: A systematic review and meta-analysis. J Hepatol 2025; 82:992-1003. [PMID: 39577468 DOI: 10.1016/j.jhep.2024.11.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Revised: 11/10/2024] [Accepted: 11/13/2024] [Indexed: 11/24/2024]
Abstract
BACKGROUND & AIMS Current international guidelines recommend close monitoring and evaluation of patients with chronic hepatitis B (CHB) in the indeterminate phase, and treatment of patients at high risk of adverse outcomes. Clinical outcomes and the effect of antiviral therapy on the indeterminate phase remain unclear. We performed a systematic review and meta-analysis to study the incidence of adverse clinical outcomes including hepatocellular carcinoma (HCC), cirrhosis, and hepatic decompensation, and the effect of antiviral therapy, in the indeterminate phase. METHODS Two investigators independently searched Embase, MEDLINE, Web of Science and China National Knowledge Infrastructure from 1/1/2007 to 31/12/2023. Three investigators independently assessed study eligibility and quality. We included cohort studies and a randomised-controlled trial, allowing for calculation of the incidence rate of adverse clinical outcomes, and cross-sectional studies that reported the prevalence of moderate-to-severe inflammation and different degrees of fibrosis. Incidence rates and prevalence were pooled using generalised linear mixed-effects models and random-effects models, respectively. RESULTS One hundred and three studies (70 case-control studies [18,739 patients], 32 cohort studies [15,118 patients], and one RCT [160 patients]) were included. The annual incidence rate of HCC in patients in the indeterminate phase was 0.32% (95% CI 0.21-0.48%, I2 = 85.7%), and those of cirrhosis and hepatic decompensation were 0.67% (95% CI 0.30-1.49%, I2 = 94.3%) and 0.34% (95% CI 0.17-0.69%, I2 = 51.8%), respectively. The pooled prevalence of moderate-to-severe liver inflammation, significant fibrosis, advanced fibrosis, and cirrhosis was 40.7%, 39.7%, 17.9%, and 7.2%, respectively. Use of antiviral therapy was associated with a lower risk of HCC in patients in the indeterminate phase (adjusted incidence rate ratio 0.38, 95% CI 0.18-0.79, p = 0.009). CONCLUSIONS Patients in the indeterminate phase are at risk of developing advanced liver disease and HCC. Although inherent heterogeneity across studies limited the evidence to support expanding treatment to all patients in the indeterminate phase, antiviral therapy may reduce the risk of HCC development in high-risk subgroups. IMPACT AND IMPLICATIONS Current international guidelines recommend close monitoring and evaluation of patients with chronic hepatitis B (CHB) in the indeterminate phase, in whom antiviral treatment is not always indicated. Based on the systematic review and meta-analysis with significant heterogeneity across studies, patients in the indeterminate phase are at risk of developing hepatocellular carcinoma, cirrhosis, and hepatic decompensation. Meta-regression findings on platelet count, positive HBeAg, and age highlighted the importance of liver fibrosis assessment, accurate phase classification, and timely detection of phase transition to identify antiviral treatment indications, supporting current guideline recommendations. Antiviral treatment may reduce the risk of hepatocellular carcinoma in the high-risk subgroups of patients in the indeterminate phase. PROSPERO REGISTRATION NUMBER CRD42024537095.
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Affiliation(s)
- Jimmy Che-To Lai
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Grace Lai-Hung Wong
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Yee-Kit Tse
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Vicki Wing-Ki Hui
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Mandy Sze-Man Lai
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Henry Lik-Yuen Chan
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Department of Internal Medicine, Union Hospital, Hong Kong Special Administrative Region of China
| | - Vincent Wai-Sun Wong
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China
| | - Terry Cheuk-Fung Yip
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region of China.
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Potter BI, Thijssen M, Trovão NS, Pineda-Peña A, Reynders M, Mina T, Alvarez C, Amini-Bavil-Olyaee S, Nevens F, Maes P, Lemey P, Van Ranst M, Baele G, Pourkarim MR. Contemporary and historical human migration patterns shape hepatitis B virus diversity. Virus Evol 2024; 10:veae009. [PMID: 38361827 PMCID: PMC10868554 DOI: 10.1093/ve/veae009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Revised: 10/16/2023] [Accepted: 01/26/2024] [Indexed: 02/17/2024] Open
Abstract
Infection by hepatitis B virus (HBV) is responsible for approximately 296 million chronic cases of hepatitis B, and roughly 880,000 deaths annually. The global burden of HBV is distributed unevenly, largely owing to the heterogeneous geographic distribution of its subtypes, each of which demonstrates different severity and responsiveness to antiviral therapy. It is therefore crucial to the global public health response to HBV that the spatiotemporal spread of each genotype is well characterized. In this study, we describe a collection of 133 newly sequenced HBV strains from recent African immigrants upon their arrival in Belgium. We incorporate these sequences-all of which we determine to come from genotypes A, D, and E-into a large-scale phylogeographic study with genomes sampled across the globe. We focus on investigating the spatio-temporal processes shaping the evolutionary history of the three genotypes we observe. We incorporate several recently published ancient HBV genomes for genotypes A and D to aid our analysis. We show that different spatio-temporal processes underlie the A, D, and E genotypes with the former two having originated in southeastern Asia, after which they spread across the world. The HBV E genotype is estimated to have originated in Africa, after which it spread to Europe and the Americas. Our results highlight the use of phylogeographic reconstruction as a tool to understand the recent spatiotemporal dynamics of HBV, and highlight the importance of supporting vulnerable populations in accordance with the needs presented by specific HBV genotypes.
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Affiliation(s)
- Barney I Potter
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Rega Institute, Laboratory for Clinical and Epidemiological Virology, Herestraat 49, Leuven BE-3000, Belgium
| | - Marijn Thijssen
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Rega Institute, Laboratory for Clinical and Epidemiological Virology, Herestraat 49, Leuven BE-3000, Belgium
| | - Nídia Sequeira Trovão
- Division of International Epidemiology and Population Studies, Fogarty International Center, National Institutes of Health, Bethesda, MD 20892, United States
| | - Andrea Pineda-Peña
- Global Health and Tropical Medicine, GHTM, Instituto de Higiene e Medicina Tropical, IHMT; Universidade Nova de Lisboa, UNL, Portugal Rua da Junqueira No 100, Lisbon 1349-008, Portugal
- Molecular Biology and Immunology Department, Fundacion Instituto de Inmunología de Colombia (FIDIC); Faculty of Animal Science, Universidad de Ciencias Aplicadas y Ambientales (U.D.C.A.), Avenida 50 No. 26-20, Bogota 0609, Colombia
| | - Marijke Reynders
- Department of Laboratory Medicine, Medical Microbiology, AZ Sint-Jan Brugge-Oostende AV, Ruddershove 10, Bruges B-8000, Belgium
| | - Thomas Mina
- Nonis Lab Microbiology—Virology Unit, Gregori Afxentiou 5, Limassol 4003, Cyprus
| | - Carolina Alvarez
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Rega Institute, Laboratory for Clinical and Epidemiological Virology, Herestraat 49, Leuven BE-3000, Belgium
| | - Samad Amini-Bavil-Olyaee
- Cellular Sciences Department, Process Virology, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA
| | - Frederik Nevens
- Department of Gastroenterology and Hepatology, University Hospital Leuven, KU Leuven, Herestraat 49, Leuven 3000, Belgium
| | - Piet Maes
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Rega Institute, Laboratory for Clinical and Epidemiological Virology, Herestraat 49, Leuven BE-3000, Belgium
| | - Philippe Lemey
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Rega Institute, Laboratory for Clinical and Epidemiological Virology, Herestraat 49, Leuven BE-3000, Belgium
| | - Marc Van Ranst
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Rega Institute, Laboratory for Clinical and Epidemiological Virology, Herestraat 49, Leuven BE-3000, Belgium
| | - Guy Baele
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Rega Institute, Laboratory for Clinical and Epidemiological Virology, Herestraat 49, Leuven BE-3000, Belgium
| | - Mahmoud Reza Pourkarim
- Department of Microbiology, Immunology and Transplantation, KU Leuven, Rega Institute, Laboratory for Clinical and Epidemiological Virology, Herestraat 49, Leuven BE-3000, Belgium
- Health Policy Research Centre, Institute of Health, Shiraz University of Medical Sciences, Shiraz 71348-14336, Iran
- Blood Transfusion Research Centre, High Institute for Research and Education in Transfusion, Hemmat Exp.Way, Tehran 14665-1157, Iran
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Huang R, Liu J, Wang J, Qiu Y, Zhu L, Li Y, Liu Y, Zhan J, Xue R, Jiang S, Geng Y, Wan Y, Li M, Mao M, Gao D, Gu Y, Zhang Y, Yin S, Tong X, Xia J, Yan X, Ding W, Chen Y, Li J, Zhu C, Wu C. Histological features of chronic hepatitis B patients with normal alanine aminotransferase according to different criteria. Hepatol Commun 2024; 8:e0357. [PMID: 38206209 PMCID: PMC10786593 DOI: 10.1097/hc9.0000000000000357] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Accepted: 10/28/2023] [Indexed: 01/12/2024] Open
Abstract
BACKGROUND The upper limits of normal (ULNs) for alanine aminotransferase (ALT) are different among international guidelines for chronic hepatitis B (CHB). We aimed to investigate the proportion of significant histological disease in Asian patients with CHB with detectable hepatitis B virus (HBV) DNA under diverse ALT ULNs. METHODS Consecutive patients with CHB and detectable HBV DNA who underwent liver biopsy were retrospectively included from four tertiary hospitals. Above grade 2 inflammation and stage 2 fibrosis were defined as significant inflammation and significant fibrosis, respectively. Significant histological disease was defined as above grade 2 inflammation or stage 2 fibrosis. RESULTS Among the 414 patients with detectable HBV DNA and normal ALT, the proportion of those with significant histological disease was lower (59.7%) according to the ULN for ALT at 30/19 U/L (male/female), while the corresponding proportions were 66.7% and 62.3% according to the ULNs of 40 U/L and 35/25 U/L (male/female), respectively. In patients with detectable HBV DNA and normal ALT levels without significant fibrosis, the proportions of significant inflammation were comparable among different ULNs of ALT at 40 U/L (30.7%), 35/25 U/L (27.3%) and 30/19 U/L (25.0%). The proportion of significant histological disease was significantly lower in patients with normal ALT for 2 determinations at least 6 months apart compared to patients with normal ALT once. CONCLUSIONS Although a more stringent ALT ULN may reduce the risk of the presence of significant histological disease in patients with detectable HBV DNA, the rates of significant histological disease remain high. Persistently normal ALT levels are more important for excluding patients with CHB with a high probability of significant histological disease.
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Affiliation(s)
- Rui Huang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Jiacheng Liu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Jian Wang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
| | - Yuanwang Qiu
- Department of Infectious Diseases, The Fifth People’s Hospital of Wuxi, Wuxi, Jiangsu, China
| | - Li Zhu
- Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Yiguang Li
- Department of Infectious Diseases, The Fifth People’s Hospital of Wuxi, Wuxi, Jiangsu, China
| | - Yilin Liu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Jie Zhan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Ruifei Xue
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Suling Jiang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Yu Geng
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Yawen Wan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Xuzhou Medical University, Nanjing, Jiangsu, China
| | - Ming Li
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Minxin Mao
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Dongmei Gao
- Department of Hepatology, Huai’an No. 4 People’s Hospital, Huai’an, Jiangsu, China
| | - Yan Gu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Yao Zhang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Shengxia Yin
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
| | - Xin Tong
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
| | - Juan Xia
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Xiaomin Yan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Weimao Ding
- Department of Hepatology, Huai’an No. 4 People’s Hospital, Huai’an, Jiangsu, China
| | - Yuxin Chen
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
- Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Jie Li
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Chuanwu Zhu
- Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Chao Wu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
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Kuwano A, Miyazaki M, Yada M, Tanaka K, Koga Y, Masumoto A, Motomura K. FIB‑4 index and serum α‑fetoprotein are useful predictors of hepatocellular carcinoma occurrence in hepatitis B patients with nucleos(t)ide analogs therapy. Exp Ther Med 2023; 26:441. [PMID: 37614433 PMCID: PMC10443030 DOI: 10.3892/etm.2023.12140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2023] [Accepted: 07/18/2023] [Indexed: 08/25/2023] Open
Abstract
Current antiviral therapies cannot achieve eradication of hepatitis B virus (HBV) and can reduce but not eliminate the risk of hepatocellular carcinoma (HCC) in patients with chronic HBV infection. The present study aimed to identify the risk factors for HCC development by analyzing nucleoside analogue (NA)-treated patients as a retrospective cohort using fibrosis-4 index (FIB-4 index) as a non-invasive fibrosis marker. A total of 260 patients with HBV receiving NAs without a history of HCC between January 2001 and January 2021 were included in the present study. The incidence of HCC in patients with HBV during NA therapy and the factors contributing to HCC occurrence were identified using clinical characteristics and blood test results. Among the 260 patients, 40 patients (15.4%) developed HCC. Univariate and multivariate analysis showed that age [hazard ratio (HR), 1.03; P=0.045], male sex (HR, 3.14; P<0.01) and FIB-4 index at 6 months after NA treatment <1.95 (HR, 4.35; P<0.01) correlated with the incidence of HCC. The cumulative incidence of HCC in patients with FIB-4 index at 6 months after NA treatment >1.95 was significantly higher compared with that in patients with FIB-4 index ≤1.95 (P<0.01). Multivariate analysis in patients in which serum α-fetoprotein (AFP) level at 6 months after NA treatment was measured showed that FIB-4 index >1.95 (HR, 8.27; P=0.014) and serum AFP level >4 ng/ml (HR, 4.26; P=0.033) contributed to HCC occurrence. FIB-4 index at 6 months after NA treatment and serum AFP levels at 6 months after NA treatment were predictors for the development of HCC in patients with HBV during NA treatment. Further study of hepatocarcinogenesis during NA with a longer follow-up period and larger numbers of participants is required.
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Affiliation(s)
- Akifumi Kuwano
- Department of Hepatology, Aso Iizuka Hospital, Iizuka, Fukuoka 820-8505, Japan
| | - Masayuki Miyazaki
- Department of Hepatology, Aso Iizuka Hospital, Iizuka, Fukuoka 820-8505, Japan
- Department of Hepatology and Pancreatology, Saiseikai Fukuoka General Hospital, Fukuoka, Fukuoka 810-0001, Japan
| | - Masayoshi Yada
- Department of Hepatology, Aso Iizuka Hospital, Iizuka, Fukuoka 820-8505, Japan
| | - Kosuke Tanaka
- Department of Hepatology, Aso Iizuka Hospital, Iizuka, Fukuoka 820-8505, Japan
| | - Yuta Koga
- Department of Hepatology, Aso Iizuka Hospital, Iizuka, Fukuoka 820-8505, Japan
| | - Akihide Masumoto
- Department of Hepatology, Aso Iizuka Hospital, Iizuka, Fukuoka 820-8505, Japan
| | - Kenta Motomura
- Department of Hepatology, Aso Iizuka Hospital, Iizuka, Fukuoka 820-8505, Japan
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Dezan MGF, Cavalcante LN, Cotrim HP, Lyra AC. Hepatobiliary disease after bone marrow transplant. Expert Rev Gastroenterol Hepatol 2023; 17:129-143. [PMID: 36655915 DOI: 10.1080/17474124.2023.2169671] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Accepted: 01/13/2023] [Indexed: 01/20/2023]
Abstract
INTRODUCTION Bone marrow transplantation (BMT) is the standard treatment for several hematologic pathologies. Post-BMT patients may develop hepatobiliary complications that impact morbidity and mortality. The differential diagnosis may include drug-induced liver injury (DILI), sepsis-associated liver injury (SALI), sinusoidal obstruction syndrome (SOS), graft-versus-host disease (GVHD), viral hepatitis, ischemic and fulminant hepatitis, among others. AREA COVERED Defining the etiology of hepatobiliary injury is challenging due to the overlapping symptoms. Thus, it is necessary to be aware of and understand the clinical characteristics of these hepatobiliary complications and provide adequate management with possible better outcomes. We reviewed the scientific literature focused on early hepatobiliary complications associated with BMT. We searched the PubMed database using the following descriptors: hepatic complications, drug-induced liver disease, graft-versus-host disease, cholestasis, sepsis, sinusoidal obstruction syndrome, cytomegalovirus, viral hepatitis, bone marrow transplantation, and hematopoietic stem cell transplantation. EXPERT OPINION Post-BMT hepatobiliary complications comprise several differential diagnoses and are challenges for the hepatologist's clinical practice. When evaluating these patients, it is necessary to consider the temporality between the use of certain medications, the increase in liver enzymes, and the presence of infection, in addition to applying diagnostic criteria and complementary tests for a specific diagnosis.
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Affiliation(s)
- Maria Gabriela Fernandes Dezan
- Instituto D'Or de Pesquisa e Ensino (IDOR) and Hospital São Rafael Gastro-Hepatology Service, Hospital São Rafael, Salvador, Bahia, Brazil
- Gastro-Hepatology Service - University Hospital Professor Edgard Santos (HUPES), PPGMS - Federal University of Bahia, Salvador, Bahia, Brazil
| | - Lourianne Nascimento Cavalcante
- Instituto D'Or de Pesquisa e Ensino (IDOR) and Hospital São Rafael Gastro-Hepatology Service, Hospital São Rafael, Salvador, Bahia, Brazil
- Gastro-Hepatology Service - University Hospital Professor Edgard Santos (HUPES), PPGMS - Federal University of Bahia, Salvador, Bahia, Brazil
| | - Helma Pinchemel Cotrim
- Gastro-Hepatology Service - University Hospital Professor Edgard Santos (HUPES), PPGMS - Federal University of Bahia, Salvador, Bahia, Brazil
| | - Andre Castro Lyra
- Instituto D'Or de Pesquisa e Ensino (IDOR) and Hospital São Rafael Gastro-Hepatology Service, Hospital São Rafael, Salvador, Bahia, Brazil
- Gastro-Hepatology Service - University Hospital Professor Edgard Santos (HUPES), PPGMS - Federal University of Bahia, Salvador, Bahia, Brazil
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Comparable Mortality Between Asian Patients with Chronic Hepatitis B Under Long-Term Antiviral Therapy vs Matched Control: A Population-Based Study. Am J Gastroenterol 2022:00000434-990000000-00555. [PMID: 36288330 DOI: 10.14309/ajg.0000000000002074] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Accepted: 10/06/2022] [Indexed: 12/05/2022]
Abstract
INTRODUCTION Antiviral therapy (AVT) substantially improved the prognosis for patients with chronic hepatitis B (CHB). Head-to-head comparisons of prognosis between treated patients with CHB and the general population are scarce. We directly compared the prognosis between Asian patients with CHB receiving AVT and the general population. METHODS From the South Korean National Health Insurance Service database, patients with CHB receiving AVT ≥3 years, aged 40-64 years, who underwent health examinations between 2011 and 2012 (AVT-CHB group) were recruited. As a control, propensity score-matched general population was chosen among patients without CHB. The primary outcome was all-cause mortality; secondary outcomes were cardiovascular disease (CVD), hepatocellular carcinoma (HCC), and all types of non-HCC malignancies. RESULTS During follow-up (median 7.2 years), 26,467 and 75,469 individuals in the AVT-CHB group and matched general population were analyzed. The 5- and 7-year cumulative all-cause mortality rates were 0.40% and 1.0% for the AVT-CHB group vs 0.50% and 1.0% for the matched general population (adjusted hazard ratio [aHR] 0.96, 95% confidence interval [CI] 0.83-1.10; P = 0.51). The AVT-CHB group had a lower risk of CVD than the matched general population (aHR 0.70, 95% CI: 0.62-0.79; P < 0.001). Although the AVT-CHB group was more likely to develop HCC than the matched general population (aHR 13.16, 95% CI: 10.90-15.89; P < 0.001), the non-HCC malignancy risks in the AVT-CHB group were comparable to the matched general population (aHR 1.05, 95% CI 0.98-1.13; P = 0.137). DISCUSSION The AVT-CHB group had a similar risk of all-cause mortality and non-HCC malignancies and a lower risk of CVD than the matched general population.
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Papatheodoridi M, Papatheodoridis GV. State-of-the-art and emerging antivirals for chronic hepatitis B infection. Expert Opin Pharmacother 2022; 23:1999-2012. [DOI: 10.1080/14656566.2022.2144219] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Margarita Papatheodoridi
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens “Laiko”, Athens, Greece
| | - George V. Papatheodoridis
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, General Hospital of Athens “Laiko”, Athens, Greece
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Abstract
This article reviews the incidence of acute hepatitis B virus (HBV) infection, its clinical course, strategies to prevent acute HBV infection in susceptible individuals, and the management of patients with acute HBV.
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Affiliation(s)
- Simone E Dekker
- Department of Medicine, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239, USA
| | - Ellen W Green
- Department of Medicine, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239, USA
| | - Joseph Ahn
- Division of Gastroenterology and Hepatology, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, MNP 4112, Portland, OR 97239, USA.
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Buti M, Riveiro-Barciela M, Esteban R. Treatment of Chronic Hepatitis B Virus with Oral Anti-Viral Therapy. Clin Liver Dis 2021; 25:725-740. [PMID: 34593150 DOI: 10.1016/j.cld.2021.06.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Nucleoside analogues are the drugs most commonly used in the treatment of chronic hepatitis B. They act by inhibiting viral replication and have minimal impact on HBsAg loss. Nucleoside analogues are indicated in patients with chronic hepatitis, cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, and in those with extrahepatic manifestations. Real-world experience has been ongoing for more than 10 years, and the efficacy and safety results obtained are similar to those reported in clinical trials. Prolonged use is needed to maintain suppression of viral replication, prevent the development of liver cirrhosis and decompensated cirrhosis, and to decrease the risk of hepatocellular carcinoma.
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Affiliation(s)
- Maria Buti
- Liver Unit, Internal Medicine Department, Hospital Universitari Vall d'Hebron, Passeig Vall d'Hebron 119-129, General Hospital, 5th floor, Barcelona 08035, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
| | - Mar Riveiro-Barciela
- Liver Unit, Internal Medicine Department, Hospital Universitari Vall d'Hebron, Passeig Vall d'Hebron 119-129, General Hospital, 5th floor, Barcelona 08035, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
| | - Rafael Esteban
- Liver Unit, Internal Medicine Department, Hospital Universitari Vall d'Hebron, Passeig Vall d'Hebron 119-129, General Hospital, 5th floor, Barcelona 08035, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain
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10
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García-Cortés M, Ortega-Alonso A, Andrade RJ. Safety of treating acute liver injury and failure. Expert Opin Drug Saf 2021; 21:191-203. [PMID: 34254839 DOI: 10.1080/14740338.2021.1955854] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Acute liver injury and progression to acute liver failure can be life-threatening conditions that require prompt careful clinical assessment and therapeutic management. AREAS COVERED The aim of this article is to review the safety and side effect profile of pharmacological therapies used in the treatment of acute liver injury with specific focus on hepatic toxicity. We performed an extensive literature search with the terms 'acute liver injury,' 'acute liver failure,' 'therapy,' 'safety,' 'adverse reactions' and 'drug induced liver injury.' A thorough discussion of the main drugs and devices used in patients with acute liver injury and acute liver failure, its safety profile and the management of complications associated to therapy of these conditions is presented. EXPERT OPINION Several pharmacological approaches are used in acute liver injury and acute liver failure in an empirical basis. Whilst steroids are frequently tried in serious drug-induced liver injury there is concern on a potential harmful effect of these agents because of the higher mortality in patients receiving the drug; hence, statistical approaches such as propensity score matching might help resolve this clinical dilemma. Likewise, properly designed clinical trials using old and new drugs for subjects with serious drug-induced liver injury are clearly needed.
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Affiliation(s)
- Miren García-Cortés
- Servicio De Aparato Digestivo, Instituto De Investigación Biomédica De Málaga-IBIMA. Hospital Universitario Virgen De La Victoria, Universidad De Málaga, Centro De Investigación Biomédica En Red De Enfermedades Hepáticas Y Digestivas CIBERehd, Málaga, Spain
| | - Aida Ortega-Alonso
- Servicio De Aparato Digestivo, Instituto De Investigación Biomédica De Málaga-IBIMA. Hospital Universitario Virgen De La Victoria, Universidad De Málaga, Centro De Investigación Biomédica En Red De Enfermedades Hepáticas Y Digestivas CIBERehd, Málaga, Spain
| | - Raúl J Andrade
- Servicio De Aparato Digestivo, Instituto De Investigación Biomédica De Málaga-IBIMA. Hospital Universitario Virgen De La Victoria, Universidad De Málaga, Centro De Investigación Biomédica En Red De Enfermedades Hepáticas Y Digestivas CIBERehd, Málaga, Spain
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11
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Hornuss D, Rudi A, Koerner L, Mohr I, Merle U, Wehling C, Rupp C, Dill MT, Golriz M, Schnitzler P, Brenner T, Mehrabi A, Weiss KH, Mieth M. HBV-infection rate and long-term outcome after liver-transplantation of anti-HBc-positive liver-grafts to HBV-naïve recipients: A retrospective study. Clin Res Hepatol Gastroenterol 2021; 45:101496. [PMID: 33740476 DOI: 10.1016/j.clinre.2020.07.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Revised: 07/04/2020] [Accepted: 07/06/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND Anti-HBc only positive liver grafts may be suitable for HBV-naive recipients insofar as an appropriate infection prophylaxis is performed. Therefore, we investigated the effect of prophylactic regimens on HBV infection prevention and long-term outcome of anti-HBc-positive graft recipients. PATIENTS AND METHODS This retrospective monocenter study consisted of a cohort of 1912 patients who underwent deceased donor liver transplantation at our transplant center between June 1987 and July 2019. 81 HBV-naïve patients after reception of an anti-HBc-positive liver-graft and consecutive HBV prophylaxis were selected for further examination. HBV infection rate and host- and graft-survival rates were compared to a matched control group consisting of 162 HBV-naïve patients after reception of anti-HBc-negative grafts. Pharmaceutical HBV prophylaxis included: only HBIG, only NUCs, or combined HBIG and NUCs. RESULTS Compared to control cases of HBV-naïve anti-HBc-negative graft recipients, no differences in host- and graft-survival rate were determined.13 of 81 anti-HBc-positive graft recipients (16%) developed HBV-infection after liver transplantation. No patient suffered from HBV infection after receiving modern NUCs. Survival analysis showed no statistical differences between patients with and without infection concerning host- and graft-survival. CONCLUSION Especially in times of organ shortage, anti-HBc-positive liver grafts may be useful for liver transplantation in HBV-naïve recipients. Efficient prophylactic regimens can prevent HBV-infection.
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Affiliation(s)
- Daniel Hornuss
- Department of Gastroenterology and Hepatology, University Hospital Heidelberg, INF 410, 69120 Heidelberg, Germany
| | - Anna Rudi
- Department of Gastroenterology and Hepatology, University Hospital Heidelberg, INF 410, 69120 Heidelberg, Germany
| | - Lucas Koerner
- Department of Gastroenterology and Hepatology, University Hospital Heidelberg, INF 410, 69120 Heidelberg, Germany
| | - Isabelle Mohr
- Department of Gastroenterology and Hepatology, University Hospital Heidelberg, INF 410, 69120 Heidelberg, Germany
| | - Uta Merle
- Department of Gastroenterology and Hepatology, University Hospital Heidelberg, INF 410, 69120 Heidelberg, Germany
| | - Cyrill Wehling
- Department of Gastroenterology and Hepatology, University Hospital Heidelberg, INF 410, 69120 Heidelberg, Germany
| | - Christian Rupp
- Department of Gastroenterology and Hepatology, University Hospital Heidelberg, INF 410, 69120 Heidelberg, Germany
| | - Michael T Dill
- Department of Gastroenterology and Hepatology, University Hospital Heidelberg, INF 410, 69120 Heidelberg, Germany
| | - Mohammad Golriz
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, INF 110, 69120 Heidelberg, Germany
| | - Paul Schnitzler
- Center for Infectious Diseases, Virology, University Hospital Heidelberg, INF 324, 69120 Heidelberg, Germany
| | - Thorsten Brenner
- Department of Anesthesiology, Heidelberg University Hospital, INF 110, 69120 Heidelberg, Germany
| | - Arianeb Mehrabi
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, INF 110, 69120 Heidelberg, Germany
| | - Karl Heinz Weiss
- Department of Gastroenterology and Hepatology, University Hospital Heidelberg, INF 410, 69120 Heidelberg, Germany
| | - Markus Mieth
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, INF 110, 69120 Heidelberg, Germany.
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12
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Lee SK, Kwon JH, Lee SW, Jang JW, Nam H, Baik KW, Yoo SH, Nam SW, Sung PS, Bae SH, Choi JY, Yoon SK. Sustained off therapy response after peglyated interferon favours functional cure and no disease progression in chronic hepatitis B. Liver Int 2021; 41:288-294. [PMID: 33043567 DOI: 10.1111/liv.14701] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 08/31/2020] [Accepted: 10/06/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND & AIMS Nucleos(t)ide analogue (NA) therapy in chronic hepatitis B (CHB) patients reduces liver-related mortality. However, long-term outcomes after pegylated interferon (PEG-IFN) therapy remain to be elucidated. Therefore, we aimed to investigate the long-term effectiveness and clinical outcomes of PEG-IFN therapy. METHODS A total of 190 patients treated with PEG-IFN for CHB or compensated cirrhosis were consecutively enrolled between 2005 and 2014, and 122 patients who completed the treatment were analysed. The initial response was assessed at 6 months post-treatment and defined as achieving both <2000 IU/mL HBV DNA and HBeAg loss or seroconversion in the HBeAg-positive group, and <2000 IU/mL HBV DNA in the HBeAg-negative group. The rates of HBsAg loss, disease progression to cirrhosis or HCC, and sustained off-therapy response, defined as not requiring further NAs because of low viremia and liver enzymes, were analysed. RESULTS The median follow-up period was 7.2 years. Forty-three (35.2%) patients achieved an initial response and 53 patients (43.4%) achieved a sustained response. Initial responders displayed higher rates of sustained response than noninitial responders (69.6% vs 32.5%, P < .001). A higher rate of HBsAg loss was observed in patients who achieved a sustained response than in non-sustained responders (16.2% vs 2.5%, P = .01). Disease progression to cirrhosis or HCC was observed in eight patients (6.6%) who were nonsustained responders. CONCLUSIONS During long-term follow-up after PEG-IFN treatment, nearly half of patients achieved sustained response without the need of further NA and these patients displayed favourable outcomes, including HBsAg loss and no disease progression.
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Affiliation(s)
- Soon Kyu Lee
- Division of Hepatology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea
- The Catholic University Liver Research Center, The Catholic University of Korea, Seoul, Korea
| | - Jung Hyun Kwon
- The Catholic University Liver Research Center, The Catholic University of Korea, Seoul, Korea
- Division of Hepatology, Department of Internal Medicine, Incheon St. Mary's Hospital, The Catholic University of Korea, Incheon, Korea
| | - Sung Won Lee
- The Catholic University Liver Research Center, The Catholic University of Korea, Seoul, Korea
- Division of Hepatology, Department of Internal Medicine, Bucheon St. Mary's Hospital, The Catholic University of Korea, Bucheon, Korea
| | - Jeong Won Jang
- Division of Hepatology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea
- The Catholic University Liver Research Center, The Catholic University of Korea, Seoul, Korea
| | - Heechul Nam
- Division of Hepatology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea
- The Catholic University Liver Research Center, The Catholic University of Korea, Seoul, Korea
| | - Kyoung Won Baik
- The Catholic University Liver Research Center, The Catholic University of Korea, Seoul, Korea
- Division of Hepatology, Department of Internal Medicine, Incheon St. Mary's Hospital, The Catholic University of Korea, Incheon, Korea
| | - Sun Hong Yoo
- The Catholic University Liver Research Center, The Catholic University of Korea, Seoul, Korea
- Division of Hepatology, Department of Internal Medicine, Incheon St. Mary's Hospital, The Catholic University of Korea, Incheon, Korea
| | - Soon Woo Nam
- The Catholic University Liver Research Center, The Catholic University of Korea, Seoul, Korea
- Division of Hepatology, Department of Internal Medicine, Incheon St. Mary's Hospital, The Catholic University of Korea, Incheon, Korea
| | - Pil Soo Sung
- Division of Hepatology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea
- The Catholic University Liver Research Center, The Catholic University of Korea, Seoul, Korea
| | - Si Hyun Bae
- The Catholic University Liver Research Center, The Catholic University of Korea, Seoul, Korea
- Division of Hepatology, Department of Internal Medicine, Eunpyeong St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea
| | - Jong Young Choi
- Division of Hepatology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea
- The Catholic University Liver Research Center, The Catholic University of Korea, Seoul, Korea
| | - Seung Kew Yoon
- Division of Hepatology, Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea
- The Catholic University Liver Research Center, The Catholic University of Korea, Seoul, Korea
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13
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Canzoni M, Marignani M, Sorgi ML, Begini P, Biondo MI, Caporuscio S, Colonna V, Casa FD, Conigliaro P, Marrese C, Celletti E, Modesto I, Peragallo MS, Laganà B, Picchianti-Diamanti A, Rosa RD, Ferlito C, Salemi S, D’Amelio R, Stroffolini T. Prevalence of Hepatitis B Virus Markers in Patients with Autoimmune Inflammatory Rheumatic Diseases in Italy. Microorganisms 2020; 8:microorganisms8111792. [PMID: 33207663 PMCID: PMC7696870 DOI: 10.3390/microorganisms8111792] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Revised: 11/11/2020] [Accepted: 11/13/2020] [Indexed: 12/15/2022] Open
Abstract
Chronic hepatitis B virus (HBV) infection may be reactivated by immunosuppressive drugs in patients with autoimmune inflammatory rheumatic diseases. This study evaluates HBV serum markers' prevalence in rheumatic outpatients belonging to Spondyloarthritis, Chronic Arthritis and Connective Tissue Disease diagnostic groups in Italy. The study enrolled 302 subjects, sex ratio (M/F) 0.6, mean age ± standard deviation 57 ± 15 years, 167 (55%) of whom were candidates for immunosuppressive therapy. The Spondyloarthritis group included 146 subjects, Chronic Arthritis 75 and Connective Tissue Disease 83 (two patients had two rheumatic diseases; thus, the sum is 304 instead of 302). Ten subjects (3%) reported previous anti-HBV vaccination and tested positive for anti-HBs alone with a titer still protective (>10 IU/mL). Among the remaining 292 subjects, the prevalence of positivity for HBsAg, isolated anti-HBc, anti-HBc/anti-HBs, and any HBV marker was 2%, 4%, 18%, and 24%, respectively. A total of 26/302 (9%) patients with γ-globulin levels ≤0.7 g/dL were more frequently (p = 0.03455) prescribed immunosuppressive therapy, suggesting a more severe rheumatic disease. A not negligible percentage of rheumatic patients in Italy are at potential risk of HBV reactivation related to immunosuppressive therapy. Before starting treatment, subjects should be tested for HBV markers. Those resulting positive should receive treatment or prophylaxis with Nucleos (t) ides analogue (NUCs) at high barrier of resistance, or pre-emptive therapy, according to the pattern of positive markers. HB vaccination is recommended for those who were never exposed to the virus.
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Affiliation(s)
- Marco Canzoni
- UOC di Immunologia Clinica e Reumatologia, Sapienza Università di Roma, AOU S. Andrea, 00189 Roma, Italy; (M.L.S.); (M.I.B.); (S.C.); (V.C.); (F.D.C.); (B.L.); (A.P.-D.); (R.D.R.); (C.F.); (S.S.); (R.D.)
- Correspondence: (M.C.); (M.M.); Tel.: +39-333-4460720 (M.C.)
| | - Massimo Marignani
- UOC Malattie Apparato Digerente e Fegato, Sapienza Università di Roma, AOU S. Andrea, 00189 Roma, Italy;
- Correspondence: (M.C.); (M.M.); Tel.: +39-333-4460720 (M.C.)
| | - Maria Laura Sorgi
- UOC di Immunologia Clinica e Reumatologia, Sapienza Università di Roma, AOU S. Andrea, 00189 Roma, Italy; (M.L.S.); (M.I.B.); (S.C.); (V.C.); (F.D.C.); (B.L.); (A.P.-D.); (R.D.R.); (C.F.); (S.S.); (R.D.)
| | - Paola Begini
- UOC Malattie Apparato Digerente e Fegato, Sapienza Università di Roma, AOU S. Andrea, 00189 Roma, Italy;
| | - Michela Ileen Biondo
- UOC di Immunologia Clinica e Reumatologia, Sapienza Università di Roma, AOU S. Andrea, 00189 Roma, Italy; (M.L.S.); (M.I.B.); (S.C.); (V.C.); (F.D.C.); (B.L.); (A.P.-D.); (R.D.R.); (C.F.); (S.S.); (R.D.)
| | - Sara Caporuscio
- UOC di Immunologia Clinica e Reumatologia, Sapienza Università di Roma, AOU S. Andrea, 00189 Roma, Italy; (M.L.S.); (M.I.B.); (S.C.); (V.C.); (F.D.C.); (B.L.); (A.P.-D.); (R.D.R.); (C.F.); (S.S.); (R.D.)
| | - Vincenzo Colonna
- UOC di Immunologia Clinica e Reumatologia, Sapienza Università di Roma, AOU S. Andrea, 00189 Roma, Italy; (M.L.S.); (M.I.B.); (S.C.); (V.C.); (F.D.C.); (B.L.); (A.P.-D.); (R.D.R.); (C.F.); (S.S.); (R.D.)
| | - Francesca Della Casa
- UOC di Immunologia Clinica e Reumatologia, Sapienza Università di Roma, AOU S. Andrea, 00189 Roma, Italy; (M.L.S.); (M.I.B.); (S.C.); (V.C.); (F.D.C.); (B.L.); (A.P.-D.); (R.D.R.); (C.F.); (S.S.); (R.D.)
| | - Paola Conigliaro
- UOC di Reumatologia, Dipartimento di “Medicina dei Sistemi”, Università di Tor Vergata, 00133 Roma, Italy;
| | - Cinzia Marrese
- Ambulatorio di Reumatologia, ASL Roma 1, Presidio Nuovo Regina Margherita, 00153 Roma, Italy;
| | - Eleonora Celletti
- Istituto di Clinica Medica, ASL Lanciano-Vasto-Chieti, 66100 Chieti, Italy;
| | - Irene Modesto
- Unità Operativa di Medicina Interna, Università degli Studi di Palermo, AO Ospedali Riuniti Villa Sofia-Cervello, PO Vincenzo Cervello, 90146 Palermo, Italy;
| | | | - Bruno Laganà
- UOC di Immunologia Clinica e Reumatologia, Sapienza Università di Roma, AOU S. Andrea, 00189 Roma, Italy; (M.L.S.); (M.I.B.); (S.C.); (V.C.); (F.D.C.); (B.L.); (A.P.-D.); (R.D.R.); (C.F.); (S.S.); (R.D.)
| | - Andrea Picchianti-Diamanti
- UOC di Immunologia Clinica e Reumatologia, Sapienza Università di Roma, AOU S. Andrea, 00189 Roma, Italy; (M.L.S.); (M.I.B.); (S.C.); (V.C.); (F.D.C.); (B.L.); (A.P.-D.); (R.D.R.); (C.F.); (S.S.); (R.D.)
| | - Roberta Di Rosa
- UOC di Immunologia Clinica e Reumatologia, Sapienza Università di Roma, AOU S. Andrea, 00189 Roma, Italy; (M.L.S.); (M.I.B.); (S.C.); (V.C.); (F.D.C.); (B.L.); (A.P.-D.); (R.D.R.); (C.F.); (S.S.); (R.D.)
| | - Claudia Ferlito
- UOC di Immunologia Clinica e Reumatologia, Sapienza Università di Roma, AOU S. Andrea, 00189 Roma, Italy; (M.L.S.); (M.I.B.); (S.C.); (V.C.); (F.D.C.); (B.L.); (A.P.-D.); (R.D.R.); (C.F.); (S.S.); (R.D.)
| | - Simonetta Salemi
- UOC di Immunologia Clinica e Reumatologia, Sapienza Università di Roma, AOU S. Andrea, 00189 Roma, Italy; (M.L.S.); (M.I.B.); (S.C.); (V.C.); (F.D.C.); (B.L.); (A.P.-D.); (R.D.R.); (C.F.); (S.S.); (R.D.)
| | - Raffaele D’Amelio
- UOC di Immunologia Clinica e Reumatologia, Sapienza Università di Roma, AOU S. Andrea, 00189 Roma, Italy; (M.L.S.); (M.I.B.); (S.C.); (V.C.); (F.D.C.); (B.L.); (A.P.-D.); (R.D.R.); (C.F.); (S.S.); (R.D.)
| | - Tommaso Stroffolini
- Dipartimento di Malattie Infettive e Tropicali, Policlinico Umberto I, 00161 Roma, Italy;
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14
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Combination of hepatocyte fraction and diffusion-weighted imaging as a predictor in quantitative hepatic fibrosis evaluation. Abdom Radiol (NY) 2020; 45:3681-3689. [PMID: 32266505 DOI: 10.1007/s00261-020-02520-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OBJECTIVE To investigate the performance of the combined hepatocyte fraction (HepF) and apparent diffusion coefficient (ADC) values to stage hepatic fibrosis (HF) in patients with hepatitis B/C. MATERIALS AND METHODS A total of 281 patients with hepatitis B/C prospectively underwent gadoxetate disodium-based T1 mapping and diffusion-weighted imaging. HepF was determined from pre and postcontrast T1 mapping with pharmacokinetics. The independent predictors of the HF stage (S0-4) were identified from HepF, ADC, conventional T1-based parameters, and age using a logistic regression analysis. The performances of independent and combined predictors in diagnosing various HF stages were compared by analyzing receiver operating characteristic curves. The intraclass correlation coefficient (ICC) was used to assess the interobserver reproducibility of each predictor. RESULTS In total, 167 patients with various stages of HF were included. All measurements had excellent interobserver agreement (ICC ≥ 0.75). The hepatic relative enhancement, HepF ,and ADC values were significantly different among various HF stages (p < 0.05). The HepF and ADC were independent predictors of > S0, > S1, > S2 , and > S3 disease (p < 0.05). T1Liver, T1Spleen, and T1Liver/Spleen were independent predictors of S > 2 disease (p < 0.05). The performance of HepF combined with the ADC (area under the curve (AUC) = 0.84-0.95) was higher than HepF (AUC = 0.79-0.92) or ADC (AUC = 0.82-0.89) alone in diagnosing > S0, > S1, > S2 , and > S3 disease. CONCLUSION The combined predictor of HepF and ADC shows acceptable performance for staging HF.
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15
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Husseini AA, Islam Saeed KM, Yurdcu E, Bozdayı AM. Molecular epidemiology of Hepatitis B virus, Hepatitis C virus, and Hepatitis D virus in general population of Afghanistan. TURKISH JOURNAL OF GASTROENTEROLOGY 2020; 31:658-666. [PMID: 33090103 DOI: 10.5152/tjg.2020.19169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
BACKGROUND/AIMS This study gives a clue about genotypes, subgenotypes and subtypes of HBV, HCV and HDV viruses in general population of Afghanistan. MATERIALS AND METHODS A total of 234 HBsAg, 44 anti-HCV and 5 Anti-Delta positive patients belong to 25-70 age group were obtained through a rapid screening test among 5898 residents of Afghanistan. After quantifying viral load, genotyping of 61 HBV, 29 HCV and 1 HDV samples were accomplished by sequencing of a segment of the HBV Pre S, HCV NS5B, and HDV Delta antigen regions respectively. Clinically important variants of the HBV polymerase gene, the "a" determinant of HBsAg, HCV NS5B and NS3 regions were assessed. RESULTS All HBV isolates were dispersed throughout the genotype D branch and ayw2 was the only subtypes found. The anti-HDV prevalence among HBsAg positive individuals was 2.2% and the single HDV sample, belonged to HDV genotype I. Analysis of HCV isolates revealed subtype HCV-1b in 75.86%, HCV-3a in 20.69% and HCV-3b in 3.44% patients. The observed mutant variants in the MHR of HBsAg were Y100 15%, Q101 5%, G102 15%, T115 45%, P120 5%, T131 5%. Likewise, S213T 10%, Q215P 5% and N248H 100% mutations were detected in the HBV polymerase region. C316N mutation was prevalent in 72.7% of HCV 1b participants. CONCLUSION Genotypic variation in Afghan patients is in line with the ones existing in neighboring countries and regions. HBV genotypes D1, subtype ayw2, HDV RNA type I, and HCV RNA genotype 1b are likely to be dominant in Afghan patients.
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Affiliation(s)
- Abbas Ali Husseini
- Institute of Hepatology, Ankara University School of Medicine, Ankara, Turkey
| | - Khwaja Mir Islam Saeed
- Grant and Service Contract Management Unit (GCMU), Ministry of Public Health, Kabul, Afghanistan
| | - Esra Yurdcu
- Institute of Hepatology, Ankara University School of Medicine, Ankara, Turkey
| | - A Mithat Bozdayı
- Institute of Hepatology, Ankara University Faculty of Medicine, Ankara, Turkey
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16
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Lazarevic I, Banko A, Miljanovic D, Cupic M. Biological features of hepatitis B virus strains associated with fulminant hepatitis. Future Virol 2020. [DOI: 10.2217/fvl-2020-0011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Accumulating evidence suggests that hepatitis B virus (HBV) biological features may influence the course and clinical manifestations of infection and possibly the development of fulminant hepatitis (FH). Since HBV is not a cytocidal virus, virus-induced liver damage results from an interplay between the virus replication and the host's defense. Therefore, viral factors contributing to enhanced replication, induction of a stronger immune attack or apoptosis of hepatocytes could be crucial in development of FH. Numerous mutations in basal core promoter, pre-C, C and S regions of the HBV genome contribute to development of FH by different mechanisms, including enhanced viral replication, the loss of a decoy for immune response, unbalanced expression of viral proteins and retention of unprocessed cytotoxic proteins in hepatocytes.
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Affiliation(s)
- Ivana Lazarevic
- Institute of Microbiology & Immunology, Faculty of Medicine, University of Belgrade, Dr Subotica 1, 11000 Belgrade, Serbia
| | - Ana Banko
- Institute of Microbiology & Immunology, Faculty of Medicine, University of Belgrade, Dr Subotica 1, 11000 Belgrade, Serbia
| | - Danijela Miljanovic
- Institute of Microbiology & Immunology, Faculty of Medicine, University of Belgrade, Dr Subotica 1, 11000 Belgrade, Serbia
| | - Maja Cupic
- Institute of Microbiology & Immunology, Faculty of Medicine, University of Belgrade, Dr Subotica 1, 11000 Belgrade, Serbia
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17
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Hepatocellular carcinoma prediction beyond year 5 of oral therapy in a large cohort of Caucasian patients with chronic hepatitis B. J Hepatol 2020; 72:1088-1096. [PMID: 31981727 DOI: 10.1016/j.jhep.2020.01.007] [Citation(s) in RCA: 79] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2019] [Revised: 11/27/2019] [Accepted: 01/04/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS Hepatocellular carcinoma (HCC) may develop in patients with chronic hepatitis (CHB) even after 5 years of oral therapy and cannot be easily predicted. We assessed predictors of HCC development and the need for HCC surveillance in this setting. METHODS Of 1,951 adult Caucasians with CHB included in the PAGE-B cohort, 1,427 (73%) had completed >5 years of follow-up under therapy without developing HCC by year 5. Median follow-up was 8.4 years from treatment onset. Points-based risk scores were developed to predict HCC risk after year 5. RESULTS In years 5-12, HCC was diagnosed in 33/1,427 (2.3%) patients with cumulative incidences of 2.4%, 3.2% and 3.8% at 8, 10 and 12 years, respectively. Older age or age >50 years, baseline cirrhosis and liver stiffness (LSM) ≥12 kPa at year 5 were independently associated with increased HCC risk. The HCC incidence was lower in non-cirrhotics than cirrhotics at baseline with year-5 LSM <12; among cirrhotics at baseline, it was lower in those with year-5 LSM <12 than ≥12 kPa. CAGE-B score was based on age at year 5 and baseline cirrhosis in relation to LSM at year 5 and SAGE-B score was based only on age and LSM at year 5 (c-index = 0.809-0.814, 0.805-0.806 after bootstrap validation). Both scores offered 100% negative predictive values for HCC development in their low risk groups. CONCLUSIONS In Caucasians with CHB, the HCC risk after the first 5 years of antiviral therapy depends on age, baseline cirrhosis status and LSM at year 5. CAGE-B and particularly SAGE-B represent simple and reliable risk scores for HCC prediction and surveillance beyond year 5 of therapy. LAY SUMMARY In Caucasians with chronic hepatitis B, the risk of hepatocellular carcinoma after the first 5 years of entecavir or tenofovir therapy depends on age, baseline cirrhosis status and liver stiffness at year 5, which can provide simple and reliable risk scores for hepatocellular carcinoma prediction and surveillance beyond year 5. In patients with cirrhosis at baseline, liver stiffness <12 kPa at year 5 is associated with lower HCC risk, but surveillance may be still required.
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Thijssen M, Lemey P, Amini-Bavil-Olyaee S, Dellicour S, Alavian SM, Tacke F, Verslype C, Nevens F, Pourkarim MR. Mass migration to Europe: an opportunity for elimination of hepatitis B virus? Lancet Gastroenterol Hepatol 2020; 4:315-323. [PMID: 30860067 DOI: 10.1016/s2468-1253(19)30014-7] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2018] [Revised: 01/08/2019] [Accepted: 01/10/2019] [Indexed: 02/07/2023]
Abstract
People from low-to-middle income countries have been migrating to western Europe on a large scale in recent years. Data indicate that the number of first-time asylum applications by non-EU members increased from 290 000 in 2011 to more than 1·3 million in 2015. During the peak period of migration, The Global Health Sector Strategy on Viral Hepatitis was adopted by WHO. Viral hepatitis, and particularly hepatitis B virus (HBV), is an important disease because of its high prevalence and associated mortality. In some cases, HBV can be carried by refugees arriving from regions of high and intermediate prevalence. Refugees with HBV might not show clinical symptoms and not be diagnosed in destination countries with a low prevalence, where screening is not regularly done. Although transmission to the host population is low, dedicated surveillance and tailored public health policies are required. It is important to note that some of the countries that receive many migrants do not have a universal HBV vaccination programme. In this Viewpoint, we argue that the current large-scale movement from regions with high or intermediate HBV prevalence should be taken as an opportunity to achieve viral hepatitis elimination targets, by establishing a well prepared infrastructure for HBV screening, vaccination, and treatment.
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Affiliation(s)
- Marijn Thijssen
- Department of Microbiology and Immunology, Rega Institute, Laboratory of Clinical and Epidemiological Virology, KU Leuven, Leuven, Belgium
| | - Philippe Lemey
- Laboratory of Evolutionary and Computational Virology, KU Leuven, Leuven, Belgium
| | | | - Simon Dellicour
- Laboratory of Evolutionary and Computational Virology, KU Leuven, Leuven, Belgium; Spatial Epidemiology Lab, Université Libre de Bruxelles, Brussels, Belgium
| | - Seyed Moayed Alavian
- Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Frank Tacke
- Department of Medicine III, Rheinisch-Westfälische Technische Hochschule-University Hospital Aachen, Aachen, Germany
| | - Chris Verslype
- Department of Gastroenterology and Hepatology, University Hospitals KU Leuven, Leuven Belgium
| | - Frederik Nevens
- Department of Gastroenterology and Hepatology, University Hospitals KU Leuven, Leuven Belgium
| | - Mahmoud Reza Pourkarim
- Department of Microbiology and Immunology, Rega Institute, Laboratory of Clinical and Epidemiological Virology, KU Leuven, Leuven, Belgium; Health Policy Research Center, Institute of Health, Shiraz University of Medical Sciences, Shiraz, Iran.
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19
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Kim SU, Seo YS, Lee HA, Kim MN, Lee EJ, Shin HJ, Lee YR, Lee HW, Park JY, Kim DY, Ahn SH, Han KH, Um SH, Tak WY, Kweon YO, Kim BK, Park SY. Hepatocellular Carcinoma Risk Steadily Persists over Time Despite Long-Term Antiviral Therapy for Hepatitis B: A Multicenter Study. Cancer Epidemiol Biomarkers Prev 2020; 29:832-837. [PMID: 31988073 DOI: 10.1158/1055-9965.epi-19-0614] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2019] [Revised: 10/16/2019] [Accepted: 01/16/2020] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Long-term antiviral therapy (AVT) for chronic hepatitis B (CHB) reduces the risk of hepatocellular carcinoma (HCC). We assessed the temporal trends in the incidence of HCC over time during long-term AVT among Asian patients with CHB. METHODS Patients with CHB receiving entecavir/tenofovir (ETV/TDF) as a first-line antiviral were recruited from four academic hospitals in the Republic of Korea. We compared the incidence of HCC during and after the first 5 years of ETV/TDF treatment. RESULTS Among 3,156 patients, the median age was 49.6 years and males predominated (62.4%). During the follow-up, 9.0% developed HCC. The annual incidence of HCC per 100 person-years during the first 5 years (n = 1,671) and after the first 5 years (n = 1,485) was statistically similar (1.93% vs. 2.27%, P = 0.347). When the study population was stratified according to HCC prediction model, that is, modified PAGE-B score, the annual incidence of HCC was 0.11% versus 0.39% in the low-risk group (<8 points), 1.26% versus 1.82% in the intermediate-risk group (9-12 points), and 4.63% versus 5.24% in the high-risk group (≥13 points; all P > 0.05). A Poisson regression analysis indicated that the duration of AVT did not significantly affect the overall trend of the incidence of HCC (adjusted annual incidence rate ratio = 0.85; 95% confidence interval, 0.66-1.11; P = 0.232). CONCLUSIONS Despite long-term AVT, the risk of HCC steadily persists over time among patients with CHB in the Republic of Korea, in whom HBV genotype C2 predominates. IMPACT Careful HCC surveillance is still essential.
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MESH Headings
- Adult
- Antiviral Agents/therapeutic use
- Carcinoma, Hepatocellular/epidemiology
- Carcinoma, Hepatocellular/pathology
- Carcinoma, Hepatocellular/prevention & control
- Carcinoma, Hepatocellular/virology
- DNA, Viral/genetics
- DNA, Viral/isolation & purification
- Drug Therapy, Combination/methods
- Female
- Follow-Up Studies
- Genotype
- Guanine/analogs & derivatives
- Guanine/therapeutic use
- Hepatitis B virus/genetics
- Hepatitis B virus/isolation & purification
- Hepatitis B, Chronic/drug therapy
- Hepatitis B, Chronic/pathology
- Hepatitis B, Chronic/virology
- Humans
- Incidence
- Liver/diagnostic imaging
- Liver/pathology
- Liver Neoplasms/epidemiology
- Liver Neoplasms/pathology
- Liver Neoplasms/prevention & control
- Liver Neoplasms/virology
- Male
- Middle Aged
- Molecular Typing
- Republic of Korea/epidemiology
- Risk Adjustment/statistics & numerical data
- Risk Factors
- Tenofovir/therapeutic use
- Time Factors
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Affiliation(s)
- Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Yeon Seok Seo
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Han Ah Lee
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Mi Na Kim
- Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea
| | - Eun Ju Lee
- Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hye Jung Shin
- Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yu Rim Lee
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Kwang-Hyub Han
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Soon Ho Um
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Republic of Korea
| | - Won Young Tak
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Young Oh Kweon
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea
| | - Soo Young Park
- Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, Republic of Korea.
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20
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Park SK, Choi CH, Chun J, Lee H, Kim ES, Park JJ, Park CH, Lee BI, Jung Y, Park DI, Kim DY, Park H, Jeen YT. Prevention and management of viral hepatitis in inflammatory bowel disease: a clinical practice guideline by the Korean Association for the Study of Intestinal Diseases. Intest Res 2020; 18:18-33. [PMID: 32013312 PMCID: PMC7000641 DOI: 10.5217/ir.2019.09155] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2019] [Accepted: 12/27/2019] [Indexed: 02/06/2023] Open
Abstract
The treatment of inflammatory bowel disease (IBD) has been revolutionized for the last 10 years by the increasing use of immunomodulators and biologics. With immunosuppression of this kind, opportunistic infection is an important safety concern for patients with IBD. In particular, viral hepatitis is determined by the interaction between the virus and the host's immunity, and the risk of reactivation increases if immunity is compromised by immunosuppression therapy. Parts of Asia, including Korea, still show intermediate endemicity for the hepatitis A virus and hepatitis B virus compared with the United States and Western Europe. Thus, members of IBD research group of the Korean Association for the Study of Intestinal Diseases have produced a guideline on the prevention and management of viral hepatitis in IBD.
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Affiliation(s)
- Soo-Kyung Park
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Chang Hwan Choi
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Jaeyoung Chun
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Heeyoung Lee
- Center for Preventive Medicine and Public Health, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Eun Sun Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Jae Jun Park
- Department of Internal Medicine, Institute of Gastroenterology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Chan Hyuk Park
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
| | - Bo-In Lee
- Division of Gastroenterology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Yunho Jung
- Division of Gastroenterology, Department of Medicine, Soonchunhyang University College of Medicine, Cheonan, Korea
| | - Dong-Il Park
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Do Young Kim
- Department of Internal Medicine, Institute of Gastroenterology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Hana Park
- Health Screening and Promotion Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Yoon Tae Jeen
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
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- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
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21
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Tan Z, Cao L, He X, Dong H, Liu Q, Zhao P, Li Y, Zhang D, Ma W. A label-free immunosensor for the sensitive detection of hepatitis B e antigen based on PdCu tripod functionalized porous graphene nanoenzymes. Bioelectrochemistry 2020; 133:107461. [PMID: 32018170 DOI: 10.1016/j.bioelechem.2020.107461] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2019] [Revised: 01/13/2020] [Accepted: 01/14/2020] [Indexed: 01/19/2023]
Abstract
Nanomaterials with enzyme properties possess excellent catalytic activity and stability. We prepared new nanoenzymes to construct a label-free electrochemical immunosensor for the detection of hepatitis B e antigen (HBe Ag). In this study, PdCu tripod (PdCu TP) functionalized porous graphene (PG) nanoenzymes (PdCu TPs/PG) were prepared through the in situ reduction of PdCu tripods onto porous graphene. The catalytic Michaelis-Menten kinetic parameters of PdCu TPs/PG are better than horseradish peroxidase (HRP) and show enhanced peroxidase-like activity. Therefore, we used PdCu TPs/PG to catalyse the electrochemically active matrix of H2O2 and generate the synergistically amplified current signal for the subsequent sensitive detection of HBe Ag. Due to the good conductivity, large specific surface area and synergistic amplification of PdCu TPs/PG, the quantitative detection of HBe Ag shows a detection limit of 20 fg·mL-1 and linear range from 60 fg·mL-1 to 100 ng·mL-1. During the detection of human serum samples, PdCu TPs/PG shows good accuracy based on the standard addition method and a comparison with an ELISA. The prepared immunosensors exhibiting good selectivity, stability and reproducibility provide an important basis for determining the prognosis of hepatitis B and show potential applications in medical applications.
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Affiliation(s)
- Zhaoling Tan
- School of Chemistry and Chemical Engineering, Shandong University of Technology, Zibo 255049, PR China
| | - Linlin Cao
- Department of Laboratory Medicine, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China; Department of Clinical Laboratory, Zibo Central Hospital, Zibo 255036, PR China
| | - Xiuxian He
- School of Chemistry and Chemical Engineering, Shandong University of Technology, Zibo 255049, PR China
| | - Hui Dong
- School of Chemistry and Chemical Engineering, Shandong University of Technology, Zibo 255049, PR China
| | - Qing Liu
- School of Chemistry and Chemical Engineering, Shandong University of Technology, Zibo 255049, PR China.
| | - Pingping Zhao
- College of Chemical and Environmental Engineering, Shandong University of Science and Technology Qingdao 266590, PR China
| | - Yueyun Li
- School of Chemistry and Chemical Engineering, Shandong University of Technology, Zibo 255049, PR China
| | - Daopeng Zhang
- School of Chemistry and Chemical Engineering, Shandong University of Technology, Zibo 255049, PR China
| | - Wanshan Ma
- Department of Laboratory Medicine, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan 250014, PR China
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22
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Rossotti R, Puoti M. Sexually Transmitted Hepatitis. Sex Transm Infect 2020. [DOI: 10.1007/978-3-030-02200-6_13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
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23
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Papatheodoridis GV, Rigopoulou EI, Papatheodoridi M, Zachou K, Xourafas V, Gatselis N, Hadziyannis E, Vlachogiannakos J, Manolakopoulos S, Dalekos GN. DARING-B: discontinuation of effective entecavir or tenofovir disoproxil fumarate long-term therapy before HBsAg loss in non-cirrhotic HBeAg-negative chronic hepatitis B. Antivir Ther 2019; 23:677-685. [PMID: 30044765 DOI: 10.3851/imp3256] [Citation(s) in RCA: 68] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/17/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND The remission rates after stopping antivirals in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) vary among studies, while reliable predictors of relapse have not been identified. This prospective study assessed rates and predictors of relapse and retreatment in 57 non-cirrhotic hepatitis B surface antigen (HBsAg)-positive patients with HBeAg-negative CHB who discontinued effective ≥4-year entecavir or tenofovir disoproxil fumarate (TDF) therapy. METHODS A total of 57 patients discontinued therapy after median virological remission of 5.3 years and remained under close follow-up. They were retreated with entecavir/TDF if they fulfilled predetermined criteria. RESULTS During median follow-up of 18 months, no patient died, developed jaundice or liver decompensation. The cumulative relapse rates varied according to HBV DNA and alanine aminotransferase cutoffs; for HBV DNA >2,000 IU/ml, they were 56%, 70% and 72% at 3, 12 and 18 months after stopping entecavir/TDF. The cumulative probability of retreatment was 18% and 26% at 3 and 12 months being significantly affected only by pretreatment fibrosis severity (adjusted relative hazard: 3.43; P=0.015). Cumulative rates of HBsAg loss were 5%, 16% and 25% at 6, 12 and 18 months being higher in patients with lower HBsAg levels at treatment discontinuation. CONCLUSIONS Our prospective study shows that effective ≥4-year entecavir/TDF therapy can be safely discontinued in non-cirrhotic HBeAg-negative CHB patients. The probability of relapse decreased after month 6. Despite common virological relapses, most patients, particularly those with mild-moderate pretreatment fibrosis, remain without retreatment, at least in the first 18 months, as a substantial proportion of them clear HBsAg and the majority eventually enters into an inactive carrier state.
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Affiliation(s)
- George V Papatheodoridis
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece
| | - Eirini I Rigopoulou
- Department of Medicine and Research Laboratory of Internal Medicine, Thessaly University Medical School, Larissa, Greece
| | - Margarita Papatheodoridi
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece
| | - Kalliopi Zachou
- Department of Medicine and Research Laboratory of Internal Medicine, Thessaly University Medical School, Larissa, Greece
| | - Vassilios Xourafas
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece
| | - Nikolaos Gatselis
- Department of Medicine and Research Laboratory of Internal Medicine, Thessaly University Medical School, Larissa, Greece
| | - Emilia Hadziyannis
- 2nd Department of Internal Medicine, Medical School of National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece
| | - John Vlachogiannakos
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece
| | - Spilios Manolakopoulos
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece.,2nd Department of Internal Medicine, Medical School of National and Kapodistrian University of Athens, Hippokration General Hospital, Athens, Greece
| | - George N Dalekos
- Department of Medicine and Research Laboratory of Internal Medicine, Thessaly University Medical School, Larissa, Greece
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24
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Aghemo A, Piroth L, Bhagani S. What do clinicians need to watch for with direct-acting antiviral therapy? J Int AIDS Soc 2019; 21 Suppl 2:e25076. [PMID: 29633552 PMCID: PMC5978638 DOI: 10.1002/jia2.25076] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2017] [Accepted: 01/18/2018] [Indexed: 12/15/2022] Open
Abstract
Introduction The introduction of drugs targeting the virus replication cycle has revolutionized treatment of chronic hepatitis C virus. These drugs, called direct‐acting antivirals, have brought about extremely high rates of virological cure and have increased the number of patients who can receive treatment due to the lack of absolute contraindications. A combination of different classes of direct‐acting antivirals is the current standard of care. Although treatment administration and monitoring has been simplified in recent years, it is still relatively complex and mostly in the hands of specialists. Several factors must be assessed before starting treatment to maximize efficacy and minimize side effects of treatment. In this review, we describe the factors that impact on the efficacy and safety of antiviral treatment for hepatitis C and provide clear recommendations for clinicians prescribing direct‐acting antivirals. Methods We reviewed literature to define best practice, based on factors associated with treatment efficacy and safety data to recommend treatment options, baseline and on‐treatment assessments. The review included searches in PubMed, and the abstracts presented at the International Liver Congress TM and The Liver Meeting TM between January 2013 and September 2017. Results Clinical features that must be assessed before starting treatment include virological factors, such as hepatitis C virus genotype, HIV and hepatitis B coinfection and host factors, such as concomitant medications, liver disease stage and renal function. Conclusions Patients who start antiviral treatment for chronic hepatitis C require a thorough clinical evaluation. There is a need for assessing factors that impact on the treatment schedule and duration or affect the pharmacokinetics of direct‐acting antivirals.
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Affiliation(s)
- Alessio Aghemo
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy.,Division of Internal Medicine and Hepatology, Humanitas Clinical and Research Center, Rozzano, Milan, Italy
| | - Lionel Piroth
- Infectious Diseases Department, University Hospital, INSERM, Dijon, France
| | - Sanjay Bhagani
- Department of Infectious Diseases/HIV Medicine, Royal Free London Foundation Trust, Research Department of Infection, UCL, London, UK
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25
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Nishida T, Matsubara T, Yakushijin T, Inada M. Prediction and clinical implications of HBV reactivation in lymphoma patients with resolved HBV infection: focus on anti-HBs and anti-HBc antibody titers. Hepatol Int 2019; 13:407-415. [PMID: 31290069 DOI: 10.1007/s12072-019-09966-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2019] [Accepted: 06/25/2019] [Indexed: 12/15/2022]
Abstract
Hepatitis B virus (HBV) reactivation (HBV-R) and hepatitis related to HBV-R are well-recognized complications that occur in patients who have undergone cytotoxic chemotherapy or immunosuppressive therapy. The degree of HBV-R in this population varies from self-limited or asymptomatic hepatitis to acute liver failure, which may lead to life-threatening events. However, no established treatment or standard surveillance method exists for monitoring patients to predict the development of HBV-R during or after chemotherapy or immunosuppressive therapy, particularly regarding resolved HBV infection. Prophylactic antiviral agents and regular monitoring of HBV-DNA levels are known to be useful methods for preventing HBV-R; however, these methods require considerable financial resources, and such resources are limited in the endemic areas of HBV infection. Most patients with resolved HBV infection do not develop a hepatitis flare or self-limited HBV-R with only an increase in HBV DNA. However, some patients may develop HBV-R even 1 year or more after the last chemotherapy treatment. Therefore, predicting the development of HBV-R and its timing is difficult, and exploring markers that could help predict whether or when HBV reactivation occurs is necessary. In this review, we address the predictive risk factors for HBV-R in patients with resolved HBV infection, focusing on the ability of anti-HBs and anti-HBc to predict HBV-R. We conclude that the combination of anti-HBc and anti-HBs titers may be a reliable and useful predictor for managing HBV-R.
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Affiliation(s)
- Tsutomu Nishida
- Department of Gastroenterology, Toyonaka Municipal Hospital, 4-14-1 Shibahara, Toyonaka, Osaka, 560-8565, Japan.
| | - Tokuhiro Matsubara
- Department of Gastroenterology, Toyonaka Municipal Hospital, 4-14-1 Shibahara, Toyonaka, Osaka, 560-8565, Japan
| | - Takayuki Yakushijin
- Department of Gastroenterology and Hepatology, Osaka General Medical Center, 3-1-56, Bandaihigashi, Sumiyoshi-ku, Osaka, 558-0056, Japan
| | - Masami Inada
- Department of Gastroenterology, Toyonaka Municipal Hospital, 4-14-1 Shibahara, Toyonaka, Osaka, 560-8565, Japan
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26
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Issues Meriting Further Study in Preventing Mother-to-Infant Transmission of Hepatitis B by Antiviral Therapy During Pregnancy. MATERNAL-FETAL MEDICINE 2019. [DOI: 10.1097/fm9.0000000000000012] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022] Open
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27
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KASL clinical practice guidelines for management of chronic hepatitis B. Clin Mol Hepatol 2019; 25:93-159. [PMID: 31185710 PMCID: PMC6589848 DOI: 10.3350/cmh.2019.1002] [Citation(s) in RCA: 165] [Impact Index Per Article: 27.5] [Reference Citation Analysis] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Accepted: 03/25/2019] [Indexed: 02/06/2023] Open
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28
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Rong X, Wang H, Ma J, Pan S, Wang H, Jing S, Su Y, Wang L, Zhao C. Chronic hepatitis B virus infection is associated with a poorer prognosis in diffuse large B-cell lymphoma: a meta-analysis and systemic review. J Cancer 2019; 10:3450-3458. [PMID: 31293649 PMCID: PMC6603406 DOI: 10.7150/jca.31033] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2018] [Accepted: 05/06/2019] [Indexed: 12/11/2022] Open
Abstract
Accumulating evidence from clinical trials indicates chronic hepatitis B virus (HBV) infection is associated with the incidence of diffuse large B-cell lymphoma (DLBCL) and may be associated with the prognosis of DLBCL, though this suggestion remains controversial. We performed a meta-analysis to assess whether HBV infection is associated with prognosis and response to chemotherapy in DLBCL. After a strict literature search strategy, a total of 809 HBV surface antigen (HBsAg) seropositive patients with DLBCL and 2849 HBsAg seronegative patients with DLBCL from twelve trials were included. DLBCL patients with chronic HBV infection had significantly poorer 2- and 5-year overall survival (OS) (HR 1.54, 95% CI 1.23-1.92, P<0.001 and 1.79, 1.48-2.17, P<0.001) and 2- and 5-year progression-free survival (PFS) (HR 1.44, 95% CI 1.14-1.81, P=0.002 and HR 1.34, 95% CI 1.02-1.75, P=0.03). HBsAg-seronegative patients also had a lower complete response (CR) rate (OR 0.48, 95% CI 0.34-0.68, P<0.001), higher progressive disease (PD) rate (OR 2.08, 95% CI 1.34-3.24, P=0.001), and more advanced clinical features. This meta-analysis indicates HBV infection leads to a poorer prognosis and poorer response to standard chemotherapy.
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Affiliation(s)
- Xingyu Rong
- MOE/NHC/CAMS Key Lab of Medical Molecular Virology, School of Basic Medical Sciences & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, 200032, P.R. China
- Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital, Shanghai, 200040, P.R. China
| | - Hai Wang
- MOE/NHC/CAMS Key Lab of Medical Molecular Virology, School of Basic Medical Sciences & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, 200032, P.R. China
- Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital, Shanghai, 200040, P.R. China
| | - Jiexian Ma
- Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital, Shanghai, 200040, P.R. China
| | - Shaokun Pan
- MOE/NHC/CAMS Key Lab of Medical Molecular Virology, School of Basic Medical Sciences & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, 200032, P.R. China
| | - Huijing Wang
- Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital, Shanghai, 200040, P.R. China
- Laboratory of Neuropsychopharmacology, College of Fundamental Medicine, Shanghai University of Medicine & Health Science, 201318, P.R. China
| | - Sha Jing
- MOE/NHC/CAMS Key Lab of Medical Molecular Virology, School of Basic Medical Sciences & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, 200032, P.R. China
- Institute for Basic Research on Aging and Medicine, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, 200032, P.R. China
| | - Yu Su
- MOE/NHC/CAMS Key Lab of Medical Molecular Virology, School of Basic Medical Sciences & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, 200032, P.R. China
| | - Lancui Wang
- MOE/NHC/CAMS Key Lab of Medical Molecular Virology, School of Basic Medical Sciences & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, 200032, P.R. China
| | - Chao Zhao
- MOE/NHC/CAMS Key Lab of Medical Molecular Virology, School of Basic Medical Sciences & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, 200032, P.R. China
- Shanghai Key Laboratory of Clinical Geriatric Medicine, Huadong Hospital, Shanghai, 200040, P.R. China
- Institute for Basic Research on Aging and Medicine, School of Basic Medical Sciences, Shanghai Medical College of Fudan University, Shanghai, 200032, P.R. China
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Luo J, You X, Chong Y, Wu Y, Gong J, Jie Y, Li X, Xi S, Zhang Z, Zhang Y, Xie D, Li Z, Li X. Efficacy of long-term treatment with tenofovir in Chinese nucleos(t)ide-naïve chronic hepatitis B patients regardless of baseline viral load. Exp Ther Med 2019; 18:260-268. [PMID: 31258661 DOI: 10.3892/etm.2019.7547] [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: 09/20/2018] [Accepted: 03/26/2019] [Indexed: 01/10/2023] Open
Abstract
The aim of the present study was to analyze the efficacy and safety of tenofovir (TDF) treatment for up to 5 years in nucleos(t)ide-naïve chronic hepatitis B (CHB) patients, particularly those with a high viral load, a in real-life scenario. A total of 144 nucleos(t)ide-naïve CHB patients who received TDF monotherapy for at least 3 months were retrospectively analyzed. The primary endpoint measure was the achievement of virological response (VR; undetectable serum HBV DNA, <100 IU/ml). The secondary endpoints were alanine aminotransferase (ALT) normalization (ALT < upper limit of normal), hepatitis B e antigen (HBeAg) seroconversion and safety. The median follow-up period was 120 weeks (range, 12-264 weeks). In total, 144, 130, 114, 78, 67, 40 and 13 patients were followed up for at least 12, 24, 48, 96, 144, 192 and 240 weeks, respectively. An incremental trend was observed in the rate of VR: 73.1, 91.3, 98.1, 100, 100 and 100% of the patients exhibited VR at 24, 48, 96, 144, 192 and 240 weeks, respectively. Furthermore, 29 patients with hepatitis B virus (HBV) DNA ≥8 log10 IU/ml at baseline achieved VR during the follow-up period. The proportions of patients achieving normal ALT levels were 72.1, 78.6, 91.2, 95, 96 and 100%, at 24, 48, 96, 144, 192 and 240 weeks, respectively. The rate of HBeAg loss reached 35.6% at week 240. Among the 130 patients, HBV DNA was detectable [partial VR (PVR)] in 35 patients at 24 weeks of follow-up, and 30 of those 35 patients (85.7%) required >24 weeks of further TDF therapy to achieve VR. No serious adverse events were reported. In conclusion, long-term TDF treatment of nucleos(t)ide-naïve chronic hepatitis B patients, regardless of high viral load at baseline, was effective and safe in a real-life scenario. Adjustment of TDF monotherapy may be unnecessary in nucleos(t)ide-naïve patients with PVR at 24 weeks.
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Affiliation(s)
- Jie Luo
- Department of Hepatology, The Third Affiliated Hospital of Shenzhen University, Shenzhen Luohu People's Hospital, Shenzhen, Guangdong 518000, P.R. China
| | - Xu You
- Department of Clinical Laboratory, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong 510630, P.R. China
| | - Yutian Chong
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, P.R. China
| | - Yuankai Wu
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, P.R. China
| | - Jiao Gong
- Department of Clinical Laboratory, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, P.R. China
| | - Yusheng Jie
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, P.R. China
| | - Xinhua Li
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, P.R. China
| | - Sujuan Xi
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, P.R. China
| | - Zhiwei Zhang
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, P.R. China
| | - Yufeng Zhang
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, P.R. China
| | - Dongying Xie
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, P.R. China
| | - Zhanyi Li
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, P.R. China
| | - Xiangyong Li
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, P.R. China
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Ito H, Kanbe A, Hara A, Ishikawa T. Induction of humoral and cellular immune response to HBV vaccine can be up-regulated by STING ligand. Virology 2019; 531:233-239. [PMID: 30928701 DOI: 10.1016/j.virol.2019.03.013] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2018] [Revised: 03/18/2019] [Accepted: 03/20/2019] [Indexed: 02/06/2023]
Abstract
A persistent hepatitis B virus (HBV) infection is characterized by a lack of or a weak immune response to HBV. Efficient induction of the HBV-specific immune response leads to the clearance of HBV. Stimulator of interferon (IFN) genes (STING) is a cytoplasmic sensor of intracellular DNA from microbes and host cells. In the present study, we examined the efficacy of cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) that is a ligand of the STING pathway as an HBV vaccine adjuvant. Wild-type (WT) mice and HBV-transgenic (HBV-Tg) mice were immunized with hepatitis B surface antigen (HBsAg) and cGAMP. The vaccination with HBsAg and cGAMP significantly enhanced the humoral and cellular immune response to HBsAg in WT and HBV-Tg mice. Cytokine production related to Th1 and Th2 responses and the activation of antigen-presenting cells in lymphoid tissues were induced by cGAMP. Vaccination using cGAMP may overcome tolerance in patients with chronic HBV infection.
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Affiliation(s)
- Hiroyasu Ito
- Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.
| | - Ayumu Kanbe
- Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan
| | - Akira Hara
- Department of Tumor Pathology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan
| | - Tetsuya Ishikawa
- Department of Medical Technology, Nagoya University School of Health Sciences, 1-20 Daikominami-1-chome, Higashi-ku, Nagoya, Aichi 461-8673, Japan
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Zheng J, Ou Z, Xu Y, Xia Z, Lin X, Jin S, Liu Y, Wu J. Hepatitis B virus-specific effector CD8 + T cells are an important determinant of disease prognosis: A meta-analysis. Vaccine 2019; 37:2439-2446. [PMID: 30935741 DOI: 10.1016/j.vaccine.2019.03.058] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2017] [Revised: 03/22/2019] [Accepted: 03/25/2019] [Indexed: 12/21/2022]
Abstract
BACKGROUND Hepatitis B virus (HBV)-specific effector CD8+ T cells are critical for viral clearance. To determine the effects of HBV-specific effector CD8+ T cells on HBV infection, we performed a meta-analysis of the available literature. METHODS Electronic database searches identified appropriately designed studies that detected specific CD8+ T cells in HBV-infected patients. Our main endpoints were the course of infection, seroconversion of HBV "e" antigen (HBeAg), the level of HBVDNA, and alanine aminotransferase (ALT) activity. We used a fixed/random model for analysis, according to the results of a heterogeneity test (P value of Q-squared, I2). RESULTS Our searches found five eligible articles. Pooled estimation of the reported results showed that levels of specific CD8+ T cells were significantly higher in patients with acute hepatitis B than in patients with chronic hepatitis B (odds ratio [OR] = 76.30, 95% confidence interval [CI]: 15.37-378.70). With respect to chronic hepatitis B, patients with <107 copies/ml HBVDNA had higher levels of specific CD8+ T cells relative to patients with >107 copies/ml HBVDNA, but the difference had no statistics significance (OR: 3.89, 95% CI: 0.71-21.33). Patients with negative HBeAg or positive anti-HBeAg antibody (anti-HBe) results had significantly higher levels of specific CD8+ T cells versus patients with positive HBeAg results (OR: 5.82, 95% CI: 1.41-24.13). There were no significant associations between the levels of specific CD8+ T cells and serum ALT activity (OR = 0.86, 95% CI: 0.01-74.15). CONCLUSION HBV-specific effector CD8+ T cells influence the disease activity in HBV-infected patients in various ways and determine prognosis by eliminating the virus. Therefore, efforts of studying HBV-specific effector CD8+ T cells focused vaccine are potentially needed.
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Affiliation(s)
- Juzeng Zheng
- Department of Gastroenterology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
| | - Zhanfan Ou
- Department of Gastroenterology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
| | - Yilun Xu
- Department of Gastroenterology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
| | - Ziqiang Xia
- Department of Gastroenterology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
| | - Xianfan Lin
- Department of Gastroenterology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
| | - Sisi Jin
- Department of Gastroenterology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
| | - Yang Liu
- Department of Gastroenterology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
| | - Jinming Wu
- Department of Gastroenterology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China.
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Loglio A, Viganò M, Grossi G, Labanca S, Goldaniga M, Pompa A, Farina L, Rumi M, Corradini P, Facchetti F, Lunghi G, Baldini L, Lampertico P. Lamivudine prophylaxis prevents hepatitis B virus reactivation in anti-HBc positive patients under rituximab for non-Hodgkin lymphoma. Dig Liver Dis 2019; 51:419-424. [PMID: 30316785 DOI: 10.1016/j.dld.2018.08.024] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2018] [Revised: 07/04/2018] [Accepted: 08/23/2018] [Indexed: 02/08/2023]
Abstract
BACKGOUND A significant proportion of hepatitis B surface antigen (HBsAg) negative/anti-hepatitis B core antigen (anti-HBc) positive patients with non-Hodgkin lymphoma (NHL) undergoing rituximab-based chemotherapy (R-CT) may suffer hepatitis B virus (HBV) reactivation. AIMS We wanted to assess efficacy and safety of lamivudine (LMV) prophylaxis to prevent this complication. METHODS Eighty-five consecutive HBsAg negative/anti-HBc positive NHL patients (71 years, 100% serum HBV DNA undetectable, 74% anti-HBs positive) received LMV coadministered with R-CT and for 18 months after the end of R-CT. Serum ALT, HBsAg, anti-HBs and HBV DNA were assessed every 4 months during and after end of LMV. RESULTS During 39 (2-108) months of study period, including 21 months of LMV and 27 additional months after LMV discontinuation, one patient (2%) had HBV reactivation, 31 months after stopping LMV and during administration of new immunosuppressive regimens, without LMV prophylaxis, owing to incomplete oncological response. A 50% decline of anti-HBs titers occurred in 22/63 (35%) patients, including 12 who became anti-HBs seronegative. Five (6%) patients had ALT increase during R-CT but none required R-CT discontinuation. Seventeen (20%) patients died, all for tumour progression. CONCLUSION LMV prophylaxis is safe and effective in preventing HBV reactivation in HBsAg negative/anti-HBc positive NHL patients receiving R-CT.
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Affiliation(s)
- Alessandro Loglio
- CRC "A. M. and A. Migliavacca" Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Mauro Viganò
- Division of Hepatology, Ospedale San Giuseppe, Università degli Studi di Milano, Milan, Italy
| | - Glenda Grossi
- CRC "A. M. and A. Migliavacca" Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Sara Labanca
- Division of Hepatology, Ospedale San Giuseppe, Università degli Studi di Milano, Milan, Italy
| | - Maria Goldaniga
- Department of Oncohematology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Alessandra Pompa
- Department of Oncohematology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Lucia Farina
- Department of Hematology and Pediatric Onco-Hematology, IRCCS Istituto Nazionale dei Tumori, Università degli Studi di Milano, Milan, Italy
| | - Mariagrazia Rumi
- Division of Hepatology, Ospedale San Giuseppe, Università degli Studi di Milano, Milan, Italy
| | - Paolo Corradini
- Department of Hematology and Pediatric Onco-Hematology, IRCCS Istituto Nazionale dei Tumori, Università degli Studi di Milano, Milan, Italy
| | - Floriana Facchetti
- CRC "A. M. and A. Migliavacca" Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Giovanna Lunghi
- Virology Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Luca Baldini
- Department of Oncohematology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Pietro Lampertico
- CRC "A. M. and A. Migliavacca" Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy.
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Morillas RM, López Sisamón D. Reactivación de la hepatitis B asociada a agentes inmunodepresores y a quimioterapia. Historia natural, factores de riesgo y recomendaciones para prevenirla. Med Clin (Barc) 2019; 152:107-114. [DOI: 10.1016/j.medcli.2018.08.018] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2018] [Revised: 08/30/2018] [Accepted: 08/31/2018] [Indexed: 02/07/2023]
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Teegen EM, Maurer MM, Globke B, Pratschke J, Eurich D. Liver transplantation for Hepatitis-B-associated liver disease - Three decades of experience. Transpl Infect Dis 2018; 21:e12997. [PMID: 30203903 DOI: 10.1111/tid.12997] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Revised: 08/24/2018] [Accepted: 09/02/2018] [Indexed: 12/16/2022]
Abstract
BACKGROUND Hepatitis B (HBV)-associated end-stage liver disease used to be a relevant indication for liver transplantation (LT). After transplantation, HBV-reinfection remains a serious issue. Different strategies to prevent HBV-reinfection range from the single application of immunoglobulins (HBIG), to the use of modern nucleoside/nucleotide analogues (NUC) in combination with HBIG, followed by HBIG-discontinuation. The aim of this analysis was to compare different strategies and to sum up the results of 30 years at a high-volume transplant center and deliver additional information on the histopathological level. METHODS Data of 372 liver transplantations performed for the HBV-induced liver disease in 352 patients were extracted from a prospectively organized database. HBV-reinfection was determined in the entire cohort, according to the mode of HBV-prophylaxis. Differences in survival rates were analyzed in patients with successful prophylaxis, untreated and controlled HBV-reinfection. Histopathological results were obtained from protocol biopsies in 151 patients. RESULTS HBV-reinfection was significantly associated with the type of prophylaxis, presence of HBs-Antigen at the moment of LT, transplant year and influencing the overall survival before 2005. After the introduction of modern NUCs, HBV-reinfection stopped to impact HBV-associated transplant loss and survival. Controlled HBV-infection prevents from HBV-associated transplant hepatitis and fibrosis development. The role of HBIG declines in favor of NUCs. CONCLUSIONS Uncontrolled HBV-reinfection does not occur any more. Even in the presence of Hbs-antigen, transplant fibrosis does not develop. The most reliable mode to prevent HBV-recurrence remains the combination of NUCs with a high genetic barrier and HBIG. However, HBIG can safely be discontinued after LT.
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Affiliation(s)
- Eva Maria Teegen
- Department of Surgery, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Max Magnus Maurer
- Department of Surgery, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Brigitta Globke
- Department of Surgery, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Johann Pratschke
- Department of Surgery, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Dennis Eurich
- Department of Surgery, Charité - Universitätsmedizin Berlin, Berlin, Germany
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Self-reported patient history to assess hepatitis B virus serological status during a large screening campaign. Epidemiol Infect 2018; 147:e16. [PMID: 30264683 PMCID: PMC6518477 DOI: 10.1017/s0950268818002650] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
When assessing hepatitis B virus (HBV) status in clinical settings, it is unclear whether self-reports on vaccination history and previous HBV-test results have any diagnostic capacity. Of 3997 participants in a multi-centre HBV-screening study in Paris, France, 1090 were asked questions on their last HBV-test result and vaccination history. Discordance between self-reported history compared with infection status (determined by serology) was calculated for participants claiming ‘negative’, ‘effective vaccine’, ‘past infection’, or ‘chronic infection’ HBV-status. Serological testing revealed that 320 (29.4%) were non-immunised, 576 (52.8%) were vaccinated, 173 (15.9%) had resolved the infection and 21 (1.9%) were hepatitis B surface antigen positive. In total 208/426 (48.8%) participants with a self-reported history of ‘negative’ infection had a discordant serological result, in whom 128 (61.5%) were vaccinated and 74 (35.6%) had resolved infections. A total of 153/599 (25.5%) participants self-reporting ‘effective vaccine’ had a discordant serological result, in whom 100 (65.4%) were non-immunised and 50 (32.7%) were resolved infections. Discordance for declaring ‘past’ or ‘chronic infection’ occurred in 9/55 (16.4%) and 3/10 (30.0%) individuals, respectively. In conclusion, self-reported HBV-status based on participant history is partially inadequate for determining serological HBV-status, especially between negative/vaccinated individuals. More adapted patient education about HBV-status might be helpful for certain key populations.
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Papatheodoridis GV, Manolakopoulos S, Su TH, Siakavellas S, Liu CJ, Kourikou A, Yang HC, Kao JH. Significance of definitions of relapse after discontinuation of oral antivirals in HBeAg-negative chronic hepatitis B. Hepatology 2018; 68:415-424. [PMID: 28859219 DOI: 10.1002/hep.29497] [Citation(s) in RCA: 48] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/29/2017] [Revised: 08/13/2017] [Accepted: 08/21/2017] [Indexed: 12/11/2022]
Abstract
UNLABELLED Relapses are observed in most hepatitis B e antigen (HBeAg)-negative chronic hepatitis B patients who discontinue treatment with nucleos(t)ide analogues (NAs); however, the rates of relapse vary widely among studies, and whether all patients with relapse need retreatment is unclear. The aim of this study was to assess the impact of different definitions on the rates of posttreatment relapse and therefore on the probability of retreatment in patients who have discontinued effective long-term NA therapy. In total, 130 HBeAg-negative chronic hepatitis B patients without cirrhosis and before NA treatment were included. All had on-therapy virological remission for ≥24 months and close follow-up for ≥12 months after stopping NA treatment or until retreatment, which started on stringent predefined criteria. Relapses rates based on several predetermined definitions of virological and perhaps biochemical criteria were assessed. The median duration of therapy was 60 months and the median duration of on-therapy virological remission was 43 months. During a median off-NAs follow-up of 15 months, no patient experienced liver decompensation or died. Cumulative relapse rates were 2%-49%, 4%-73%, 11%-82%, and 16%-90% at 3, 6, 12, and 24 months, respectively, whereas cumulative retreatment rates were 15%, 22%, and 40% at 6, 12, and 24 months, respectively, after discontinuation of NA therapy. No patient characteristic was independently associated with the probability of relapse based on at least two definitions or of retreatment. CONCLUSION In HBeAg-negative chronic hepatitis B patients who discontinue NA therapy, the definition of relapse has a great impact on off-NAs relapse rates and potentially on the probability of retreatment. Regardless of definition, off-NAs relapses cannot be easily predicted by patient characteristics. A substantial proportion of such patients may not require retreatment if stringent criteria are adopted. (Hepatology 2017).
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Affiliation(s)
- George V Papatheodoridis
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece
| | - Spilios Manolakopoulos
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece.,2nd Department of Internal Medicine, Medical School of National and Kapodistrian University of Athens, Hippokratio General Hospital, Athens, Greece
| | - Tung-Hung Su
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Spyros Siakavellas
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece
| | - Chun-Jen Liu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Anastasia Kourikou
- 2nd Department of Internal Medicine, Medical School of National and Kapodistrian University of Athens, Hippokratio General Hospital, Athens, Greece
| | - Hung-Chih Yang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Jia-Horng Kao
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
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Serum miRNAs Predicting Sustained HBs Antigen Reduction 48 Weeks after Pegylated Interferon Therapy in HBe Antigen-Negative Patients. Int J Mol Sci 2018; 19:ijms19071940. [PMID: 30004437 PMCID: PMC6073286 DOI: 10.3390/ijms19071940] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2018] [Revised: 06/23/2018] [Accepted: 06/29/2018] [Indexed: 12/12/2022] Open
Abstract
The therapeutic goal for hepatitis B virus (HBV) infection is HBs antigen (HBsAg) seroclearance, which is achieved through 48-week pegylated interferon (Peg-IFN) therapy. This study aimed to identify predictive biomarkers for sustained HBsAg reduction by analyzing serum microRNAs. Twenty-two consecutive chronic HBV infection patients negative for HBe antigen (HBeAg) with HBV-DNA levels <5 log copies/mL, alanine aminotransferase (ALT) <100 U/L, and compensated liver functions, were enrolled. The patients were subcutaneously injected with Peg-IFNα-2a weekly for 48 weeks (treatment period), followed by the 48-week observation period. HBsAg 1-log drop relative to baseline levels recorded at the end of the observation period was considered effective. Sera were obtained at weeks 0 and 24 during the treatment period analyzed for microRNAs. The microRNA (miRNA) antiviral activity was evaluated in vitro using Huh7/sodium taurocholate cotransporting polypeptide (NTCP) cells. As a result, six patients achieved the HBsAg 1-log drop after the observation periods. Comparison of serum microRNA levels demonstrated that high miR-6126 levels at week 24 predicted HBsAg 1-log drop. Furthermore, miR-6126 reduced HBsAg in culture medium supernatants and intracellular HBV-DNA quantities in Huh7/NTCP cells. In conclusion, high serum miR-6126 levels during Peg-IFN therapy predicted the HBsAg 1-log drop 48 weeks after the completion of therapy. In vitro assays revealed that miR-6126 was able to suppress HBsAg production and HBV replication.
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Papatheodoridis GV, Sypsa V, Dalekos G, Yurdaydin C, van Boemmel F, Buti M, Goulis J, Calleja JL, Chi H, Manolakopoulos S, Loglio A, Siakavellas S, Gatselis N, Keskın O, Lehretz M, Savvidou S, de la Revilla J, Hansen BE, Kourikou A, Vlachogiannakos I, Galanis K, Idilman R, Colombo M, Esteban R, Janssen HLA, Berg T, Lampertico P. Eight-year survival in chronic hepatitis B patients under long-term entecavir or tenofovir therapy is similar to the general population. J Hepatol 2018; 68:1129-1136. [PMID: 29427727 DOI: 10.1016/j.jhep.2018.01.031] [Citation(s) in RCA: 87] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2017] [Revised: 01/21/2018] [Accepted: 01/28/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS The effects of long-term antiviral therapy on survival have not been adequately assessed in chronic hepatitis B (CHB). In this 10-centre, ongoing cohort study, we evaluated the probability of survival and factors affecting survival in Caucasian CHB patients who received long-term entecavir/tenofovir therapy. METHODS We included 1,951 adult Caucasians with CHB, with or without compensated cirrhosis and without hepatocellular carcinoma (HCC) at baseline, who received entecavir/tenofovir for ≥12 months (median, six years). Kaplan-Meier estimates of cumulative survival over time were obtained. Standardized mortality ratios (SMRs) were calculated by comparing death rates with those in the Human Mortality Database. RESULTS The one-, five-, and eight-year cumulative probabilities were 99.7, 95.9, and 94.1% for overall survival, 99.9, 98.3, and 97.4% for liver-related survival, and 99.9, 97.8, and 95.8% for transplantation-free liver-related survival, respectively. Overall mortality was independently associated with older age and HCC development, liver-related mortality was associated with HCC development only, and transplantation-free liver-related mortality was independently associated with HCC development and lower platelet levels at baseline. Baseline cirrhosis was not independently associated with any type of mortality. Compared with the general population, in all CHB patients mortality was not significantly different (SMR 0.82), whereas it was lower in patients without HCC regardless of baseline cirrhosis (SMR 0.58) and was higher in patients who developed HCC (SMR 3.09). CONCLUSION Caucasian patients with CHB and compensated liver disease who receive long-term entecavir/tenofovir therapy have excellent overall and liver-related eight-year survival, which is similar to that of the general population. HCC is the main factor affecting their overall mortality, and is the only factor affecting their liver-related mortality. LAY SUMMARY Caucasian patients with chronic hepatitis B with or without compensated cirrhosis who receive long-term entecavir or tenofovir therapy have excellent overall eight-year survival, which is similar to that of the general population. Hepatocellular carcinoma is the main factor affecting their overall mortality, and is the only factor affecting liver-related mortality in this setting.
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Affiliation(s)
- George V Papatheodoridis
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece.
| | - Vana Sypsa
- Department of Hygiene, Epidemiology and Medical Statistics, Medical School of National and Kapodistrian University of Athens, Athens, Greece
| | - George Dalekos
- Department of Internal Medicine, Thessalia University Medical School, Larissa, Greece
| | - Cihan Yurdaydin
- Department of Gastroenterology, University of Ankara Medical School, Ankara, Turkey
| | - Florian van Boemmel
- Section of Hepatology, Clinic for Gastroenterology and Rheumatology, University Clinic Leipzig, Leipzig, Germany
| | - Maria Buti
- Liver Unit, Hospital General Universitario Valle Hebron and Ciberehd, Barcelona, Spain
| | - John Goulis
- 4th Department of Internal Medicine, Αristotle University of Thessaloniki Medical School, Thessaloniki, Greece
| | - Jose Luis Calleja
- Department of Gastroenterology, Hospital U Puerta de Hierro, IDIPHIM CIBERehd, Madrid, Spain
| | - Heng Chi
- Department of Gastroenterology & Hepatology, Erasmus MC, University Medical Center, Rotterdam, Netherlands
| | - Spilios Manolakopoulos
- 2nd Department of Internal Medicine, Medical School of National and Kapodistrian University of Athens, Athens, Greece
| | - Alessandro Loglio
- CRC "AM e A Migliavacca" Center for Liver Disease, Division of Gastrotnerology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Spyros Siakavellas
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece
| | - Nikolaos Gatselis
- Department of Internal Medicine, Thessalia University Medical School, Larissa, Greece
| | - Onur Keskın
- Department of Gastroenterology, University of Ankara Medical School, Ankara, Turkey
| | - Maria Lehretz
- Section of Hepatology, Clinic for Gastroenterology and Rheumatology, University Clinic Leipzig, Leipzig, Germany
| | - Savvoula Savvidou
- 4th Department of Internal Medicine, Αristotle University of Thessaloniki Medical School, Thessaloniki, Greece
| | - Juan de la Revilla
- Department of Gastroenterology, Hospital U Puerta de Hierro, IDIPHIM CIBERehd, Madrid, Spain
| | - Bettina E Hansen
- Department of Gastroenterology & Hepatology, Erasmus MC, University Medical Center, Rotterdam, Netherlands
| | - Anastasia Kourikou
- 2nd Department of Internal Medicine, Medical School of National and Kapodistrian University of Athens, Athens, Greece
| | - Ioannis Vlachogiannakos
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece
| | - Kostantinos Galanis
- Department of Internal Medicine, Thessalia University Medical School, Larissa, Greece
| | - Ramazan Idilman
- Department of Gastroenterology, University of Ankara Medical School, Ankara, Turkey
| | - Massimo Colombo
- Hepatology Translational Research Center, Humanitas Clinical and Research Centre, Rozzano, Italy
| | - Rafael Esteban
- Liver Unit, Hospital General Universitario Valle Hebron and Ciberehd, Barcelona, Spain
| | - Harry L A Janssen
- Department of Gastroenterology & Hepatology, Erasmus MC, University Medical Center, Rotterdam, Netherlands; Liver Clinic, Toronto Western and General Hospital, University Health Network, Toronto, ON, Canada
| | - Thomas Berg
- Section of Hepatology, Clinic for Gastroenterology and Rheumatology, University Clinic Leipzig, Leipzig, Germany
| | - Pietro Lampertico
- CRC "AM e A Migliavacca" Center for Liver Disease, Division of Gastrotnerology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
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Nam JY, Chang Y, Cho H, Kang SH, Cho YY, Cho EJ, Lee JH, Yu SJ, Yoon JH, Kim YJ. Delayed viral suppression during antiviral therapy is associated with increased hepatocellular carcinoma rates in HBeAg-positive high viral load chronic hepatitis B. J Viral Hepat 2018; 25:552-560. [PMID: 29194870 DOI: 10.1111/jvh.12838] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2017] [Accepted: 10/26/2017] [Indexed: 12/26/2022]
Abstract
The treatment option in chronic hepatitis B (CHB) patients with persistent low-level viremia despite entecavir or tenofovir monotherapy is unclear. This study investigated the development of hepatocellular carcinoma (HCC) or cirrhosis in hepatitis B e antigen (HBeAg)-positive high viral load CHB patients, according to the time needed to achieve complete viral suppression. A total of 325 HBeAg-positive CHB patients with high viral load who were recently started on antiviral therapy with entecavir or tenofovir were included. The enrolled patients were divided into 2 groups with 4 separate criteria based on the time needed to achieve complete viral suppression: within 1, 2, 3 or 4 years of therapy initiation. The outcomes were development of HCC and cirrhosis. The cumulative incidence of HCC was significantly higher in patients failing complete viral suppression within 1 year (hazard ratio (HR), 4.54; 95% confidence interval (CI), 1.03-19.93; P = .045) or 2 years (HR, 3.38; 95% CI, 1.24-9.23; P = .018), than patients who achieved complete viral suppression within 1 or 2 years, respectively. Cumulative incidence of cirrhosis was also significantly higher in patients failing suppression within 1 year (HR, 1.95; 95% CI, 1.04-3.66; P = .037) or 2 years (HR, 2.44; 95% CI, 1.41-4.22; P = .001). When the time for achieving viral suppression exceeded 2 years, the cumulative incidence of HCC or cirrhosis was not different regardless of viral suppression. Complete hepatitis B virus suppression within 2 years of antiviral therapy initiation is associated with risk reduction in HCC or cirrhosis development.
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Affiliation(s)
- J Y Nam
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Y Chang
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - H Cho
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - S H Kang
- Department of Internal Medicine, Wonju Severance Christian Hospital, Yonsei University, Wonju College of Medicine, Wonju-si, Korea
| | - Y Y Cho
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - E J Cho
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - J-H Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - S J Yu
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - J-H Yoon
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Y J Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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Dolman GE, Koffas A, Mason WS, Kennedy PT. Why, who and when to start treatment for chronic hepatitis B infection. Curr Opin Virol 2018; 30:39-47. [PMID: 29655092 DOI: 10.1016/j.coviro.2018.03.006] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2018] [Revised: 03/16/2018] [Accepted: 03/23/2018] [Indexed: 02/07/2023]
Abstract
Chronic hepatitis B remains a major global health challenge due to morbidity and mortality from hepatocellular carcinoma and complications of liver cirrhosis. Current treatment regimens are non-curative and, once initiated, treatment is of indefinite duration for the majority. The decision to initiate treatment decisions is based on risk stratification. Advances in our understanding of the natural history of chronic hepatitis B have led to a paradigm shift in recommendations for treatment. Emerging non-invasive biomarkers of disease activity will further enhance disease stratification. In this review, we summarise the guidance from major international societies on treatment for chronic hepatitis B and explore some of the novel approaches to disease assessment.
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Affiliation(s)
- Grace E Dolman
- Barts Liver Centre, Blizard Institute, Barts and the London School of Medicine and Dentistry, London, UK
| | - Apostolos Koffas
- Gastroenterology Unit, University Hospital of Larisa, Thessaly, Greece
| | | | - Patrick Tf Kennedy
- Barts Liver Centre, Blizard Institute, Barts and the London School of Medicine and Dentistry, London, UK.
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Galmozzi E, Facchetti F, Grossi G, Loglio A, Viganò M, Lunghi G, Colombo M, Lampertico P. IFNL4 rs368234815 and rs117648444 variants predict off-treatment HBsAg seroclearance in IFN-treated HBeAg-negative chronic hepatitis B patients. Liver Int 2018; 38:417-423. [PMID: 28732143 DOI: 10.1111/liv.13526] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2017] [Accepted: 07/14/2017] [Indexed: 12/11/2022]
Abstract
BACKGROUND & AIM Robust baseline predictors of interferon (IFN) response in HBeAg-negative chronic hepatitis B (CHB) patients are not currently available. The recently described rs368234815 TT/ΔG dinucleotide and rs117648444 nonsynonymous P70S polymorphisms in IFN lambda 4 (IFNL4) gene, which are strongly associated with response to IFN in hepatitis C virus (HCV) infection, could be also useful in IFN-treated CHB patients. Here we assessed whether IFNL4 rs368234815 and rs117648444 polymorphisms predict IFN-induced HBsAg clearance in CHB patients. METHODS We sequenced the IFNL4 gene on genomic DNA collected from 126 HBeAg-negative CHB patients treated with IFN and followed up for a median of 11 (1-23) years. RESULTS The 15-year cumulative probability of HBsAg loss in the 62 carriers of the rs368234815 TT/TT genotype, which abolishes the IFNλ4 protein production, was comparable to that of 19 patients carrying the rs117648444 T allele predicted to produce an impaired IFNλ4-S70 protein (39% vs 42%, P = .827). In contrast, these 81 patients, either not producing IFNλ4 or producing an impaired IFNλ4-S70 protein, had a significantly higher 15-year probability of HBsAg loss compared to the 45 subjects predicted to encode only the fully functional IFNλ4-P70 (42% vs 11% P = .003). At multivariate analysis, combination of the rs368234815 and rs117648444 genotypes strongly predicted HBsAg clearance (HR 5.90, 95% CI 1.70-20.9, P = .006) together with pretreatment serum HBV DNA levels (HR 0.57, 95% CI 0.39-0.83, P = .003). CONCLUSION IFNL4 rs368234815 and rs117648444 functional variants are worth to be investigated as pretreatment combined predictors of IFN response in HBeAg-negative CHB patients.
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Affiliation(s)
- Enrico Galmozzi
- A. M. e A. Migliavacca Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Floriana Facchetti
- A. M. e A. Migliavacca Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Glenda Grossi
- A. M. e A. Migliavacca Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Alessandro Loglio
- A. M. e A. Migliavacca Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Mauro Viganò
- Liver Unit, Ospedale San Giuseppe, Università degli Studi di Milano, Milan, Italy
| | - Giovanna Lunghi
- Virology Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Massimo Colombo
- Humanitas Clinical and Research Center, Humanitas Research Hospital, Rozzano, Italy
| | - Pietro Lampertico
- A. M. e A. Migliavacca Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
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Vlachogiannakos J, Papatheodoridis GV. Hepatitis B: Who and when to treat? Liver Int 2018; 38 Suppl 1:71-78. [PMID: 29427495 DOI: 10.1111/liv.13631] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2017] [Accepted: 11/08/2017] [Indexed: 12/12/2022]
Abstract
As current treatment options almost never achieve eradication of hepatitis B virus (HBV), the most realistic goal for HBV treatment is persistent inhibition of viral replication and ALT normalization. Thus, the decision to start treatment should be based on careful patient selection and individualized decisions. Treatment is generally indicated in chronic hepatitis B patients with HBV DNA >2000 IU/mL, elevated ALT and/or at least moderate histological lesions, while all patients with cirrhosis and detectable HBV DNA should be treated. Patients with HBV DNA >20 000 IU/mL and ALT >2xULN (upper limit of normal), HBV DNA >2000 IU/mL and liver stiffness >9 or >12 kPa in case of normal or ≤5xULN, HBV DNA >2000 IU/mL and a family history of cirrhosis and/or HCC as well as HBeAg-positive patients with HBV DNA >20 000 IU/mL and over 30 years old can begin treatment whatever the liver histology. Moreover, patients with HBV DNA >2000 IU/mL and at least moderate histological lesions can begin treatment whatever the ALT levels. Prophylactic treatment is indicated in HBV-related liver transplantation patients to prevent recurrence, in the last trimester of pregnancy in women with high viraemia to prevent vertical transmission and in patients receiving immunosuppression/chemotherapy to prevent the reactivation of HBV. Treatment is also indicated in patients with co-infections, extrahepatic manifestations and severe acute hepatitis B, or healthcare workers with viraemia. These treatment indications can only change if HBV eradication or at least HBsAg clearance can be achieved in the future in a significant proportion of patients.
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Affiliation(s)
- Jiannis Vlachogiannakos
- Department of Gastroenterology, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, Athens, Greece
| | - George V Papatheodoridis
- Department of Gastroenterology, Laiko General Hospital, Medical School of National and Kapodistrian University of Athens, Athens, Greece
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Staging liver fibrosis with DWI: is there an added value for diffusion kurtosis imaging? Eur Radiol 2018; 28:3041-3049. [PMID: 29383522 DOI: 10.1007/s00330-017-5245-6] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2017] [Revised: 11/29/2017] [Accepted: 12/05/2017] [Indexed: 12/21/2022]
Abstract
OBJECTIVES To assess liver fibrosis in patients with chronic liver disease using diffusion kurtosis imaging (DKI) in comparison with conventional diffusion-weighted imaging, with histology as reference standard. METHODS This prospective study included 81 patients and DKI with b-values of 0, 200, 500, 1,000, 1,500, 2,000 s/mm2 were performed. Mean diffusivity (MD), mean kurtosis (MK) and apparent diffusion coefficient (ADC) maps were calculated. The diagnostic efficacy of MD, MK and ADC for predicting stage 2 fibrosis or greater, and stage 3 fibrosis or greater were compared. RESULTS The MD (rho=-0.491, p<0.001), MK (rho=0.537, p<0.001) and ADC (rho=-0.496, p<0.001) correlated significantly with fibrosis stages, and ADC exhibited a strong negative correlation with MK (rho=-0.968; p<0.001) and a moderate association with MD (rho=0.601, p<0.001). Areas under the curves (AUCs) for predicting stage 2 fibrosis or greater were not significantly different (p>0.05) between MK (0.809) and ADC (0.797) as well as between MD (0.715) and ADC. AUCs were also similar for MD (0.710), MK (0.768) and ADC (0.747) for predicting stage 3 fibrosis or greater. CONCLUSION Although DKI is feasible for predicting liver fibrosis in patients with chronic liver disease, MD and MK offer similar diagnostic performance to ADC values. KEY POINTS • Diffusion kurtosis imaging is feasible for staging liver fibrosis. • Diffusion kurtosis and monoexponential model are highly correlated. • The kurtosis model offers no added value to the conventional, monoexponential model.
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Hou J, Wang G, Wang F, Cheng J, Ren H, Zhuang H, Sun J, Li L, Li J, Meng Q, Zhao J, Duan Z, Jia J, Tang H, Sheng J, Peng J, Lu F, Xie Q, Wei L, Chinese Society of Hepatology, Chinese Medical Association, Chinese Society of Infectious Diseases, Chinese Medical Association. Guideline of Prevention and Treatment for Chronic Hepatitis B (2015 Update). J Clin Transl Hepatol 2017; 5:297-318. [PMID: 29226097 PMCID: PMC5719188 DOI: 10.14218/jcth.2016.00019] [Citation(s) in RCA: 165] [Impact Index Per Article: 20.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2016] [Revised: 01/14/2017] [Accepted: 01/16/2017] [Indexed: 02/05/2023] Open
Affiliation(s)
- Jinlin Hou
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
- *Correspondence to: Jinlin Hou, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, No. 1838 North Guangzhou avenue, Guangzhou 510515, China. E-mail: ; Lai Wei, Peking University People’s Hospital, Peking University Hepatology Institute, No. 11 Xizhimen South Street, Beijing 100044, China. E-mail:
| | - Guiqiang Wang
- Department of Infectious Diseases, Center for Liver Diseases, Peking University First Hospital, Beijing, China
| | - Fusheng Wang
- The Institute of Translational Hepatology, 302 Hospital of PLA, Peking University, Beijing, China
| | - Jun Cheng
- Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Hong Ren
- Institute for Viral Hepatitis, the Key Laboratory of Molecular Biology for Infectious Diseases, the second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Hui Zhuang
- Department of Microbiology of Peking University Health Science Center, Beijing, China
| | - Jian Sun
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Jie Li
- Department of Microbiology of Peking University Health Science Center, Beijing, China
| | - Qinghua Meng
- Serious Illness Medicine Inpatient Area, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Jingmin Zhao
- Department of Pathology, 302 Hospital of PLA, Peking University, Beijing, China
| | - Zhongping Duan
- Artificial Liver Center, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Jidong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Hong Tang
- Center of Infectious Diseases, West China Hospital of Sichuan University, Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, China
| | - Jifang Sheng
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Jie Peng
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Fengmin Lu
- Department of Microbiology of Peking University Health Science Center, Beijing, China
| | - Qing Xie
- Department of Infectious Diseases, Shanghai Jiao Tong University School of Medicine Affiliated Ruijin Hospital, Shanghai, China
| | - Lai Wei
- Hepatology Institute, Peking University People’s Hospital, Beijing, China
- *Correspondence to: Jinlin Hou, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, No. 1838 North Guangzhou avenue, Guangzhou 510515, China. E-mail: ; Lai Wei, Peking University People’s Hospital, Peking University Hepatology Institute, No. 11 Xizhimen South Street, Beijing 100044, China. E-mail:
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De Clercq E. Role of tenofovir alafenamide (TAF) in the treatment and prophylaxis of HIV and HBV infections. Biochem Pharmacol 2017; 153:2-11. [PMID: 29225131 DOI: 10.1016/j.bcp.2017.11.023] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2017] [Accepted: 11/28/2017] [Indexed: 02/07/2023]
Abstract
Tenofovir (TFV) is the cornerstone of the treatment and prophylaxis of HIV infections. It has been routinely used in its prodrug form TDF (tenofovir disoproxil fumarate) combined with emtricitabine ((-)FTC) and other antiretroviral agents. TDF has now been replaced by TAF (tenofovir alafenamide) which allows better uptake by the lymphoid tissue. In combination with elvitegravir (E), cobicistat (C), emtricitabine (F), TAF can be advocated as an STR (single tablet regimen, Genvoya®) for the treatment of HIV infections. In this combination, E and C may in the future be replaced by bictegravir. The prophylaxis of HIV infection is momentarily based upon Truvada®, the combination of F with TDF, which in the future may also be replaced by TAF. TAF (Vemlidy®) has also replaced TDF (Viread®) for the treatment of hepatitis B virus (HBV) infections. Both TDF and TAF offer little or no risk for virus-drug resistance. As compared to TDF, TAF limits the risk for nephrotoxicity and loss of bone mineral density. What remains to be settled, however, before the universal use of TAF could be recommended, is its safety during pregnancy and its applicability in the treatment of tuberculosis, in combination with rifampicin.
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Affiliation(s)
- Erik De Clercq
- KU Leuven, Department of Microbiology and Immunology, Rega Institute for Medical Research, Herestraat 49, B-3000 Leuven, Belgium.
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Gentile I, Buonomo AR, Scotto R, Zappulo E, Borgia G. Infections worsen prognosis of patients with cirrhosis irrespective of the liver disease stage. Eur J Intern Med 2017; 46:e45-e47. [PMID: 28918985 DOI: 10.1016/j.ejim.2017.09.014] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2017] [Revised: 09/07/2017] [Accepted: 09/11/2017] [Indexed: 02/06/2023]
Affiliation(s)
- Ivan Gentile
- Department of Clinical Medicine and Surgery - Section of Infectious Disease, University "Federico II" of Naples, Italy
| | - Antonio Riccardo Buonomo
- Department of Clinical Medicine and Surgery - Section of Infectious Disease, University "Federico II" of Naples, Italy.
| | - Riccardo Scotto
- Department of Clinical Medicine and Surgery - Section of Infectious Disease, University "Federico II" of Naples, Italy
| | - Emanuela Zappulo
- Department of Clinical Medicine and Surgery - Section of Infectious Disease, University "Federico II" of Naples, Italy
| | - Guglielmo Borgia
- Department of Clinical Medicine and Surgery - Section of Infectious Disease, University "Federico II" of Naples, Italy
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Wang ML, Chen EQ, Zhang DM, Du LY, Yan LB, Zhou TY, Lei XZ, Lei BJ, Lu JJ, Liao J, Tang H. Efficacy and safety of three adefovir-based combination therapies in HBeAg-positive chronic hepatitis B patients with suboptimal response to adefovir monotherapy. J Viral Hepat 2017; 24 Suppl 1:21-28. [PMID: 29082645 DOI: 10.1111/jvh.12792] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/17/2017] [Accepted: 08/24/2017] [Indexed: 02/05/2023]
Abstract
Although high potent nucleos(t)ide analogues are strongly recommended as first-line therapy for chronic hepatitis B (CHB) in China, some patients are still being treated with adefovir disoproxil (ADV), especially those low-income patients whose health insurance could not reimburse the drug cost. Therefore, the management of patients who have failed ADV therapy or who sustained renal damage during ADV therapy remains an important clinical problem in China. This retrospective study aimed to compare the efficacy and safety of lamivudine (LAM), telbivudine (LdT) or entecavir (ETV) add-on strategies to optimize the treatment of patients with prior suboptimal response to ADV monotherapy. A total of 277 eligible patients were included in this study, and the baseline characteristics were similar among the LAM + ADV (n = 116), LdT + ADV (n = 72) and ETV + ADV (n = 89) groups. At week 96, both the proportion of undetectable HBV DNA (81.03% for LAM + ADV, 84.72% for LdT + ADV and 88.76% for ETV + ADV; P = .317) and ALT elevation (5.17% for LAM + ADV, 4.17% for LdT + ADV and 4.49% for ETV + ADV; P = 1.000) were similar among the three groups; also, a significant decline in liver stiffness was observed in each group from baseline to week 96. At week 96, the rate of HBeAg seroconversion was significantly higher in LdT + ADV than in LAM + ADV (26.39% vs 13.79%, P = .031) and ETV + ADV (26.39% vs 10.11%, P = .007). During the 96 weeks, no obvious renal injury was reported in any of the three groups, but an improvement in eGFR was found in LdT + ADV compared with LAM + ADV and ETV + ADV. In summary, all three combination strategies provide good control of virus replication, but the LdT + ADV combination therapy may yield better HBeAg seroconversion and eGFR improvement.
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Affiliation(s)
- M-L Wang
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - E-Q Chen
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - D-M Zhang
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - L-Y Du
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - L-B Yan
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - T-Y Zhou
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - X-Z Lei
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - B-J Lei
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - J-J Lu
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - J Liao
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
| | - H Tang
- Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China
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Papatheodoridis GV, Idilman R, Dalekos GN, Buti M, Chi H, van Boemmel F, Calleja JL, Sypsa V, Goulis J, Manolakopoulos S, Loglio A, Siakavellas S, Keskın O, Gatselis N, Hansen BE, Lehretz M, de la Revilla J, Savvidou S, Kourikou A, Vlachogiannakos I, Galanis K, Yurdaydin C, Berg T, Colombo M, Esteban R, Janssen HLA, Lampertico P. The risk of hepatocellular carcinoma decreases after the first 5 years of entecavir or tenofovir in Caucasians with chronic hepatitis B. Hepatology 2017. [PMID: 28622419 DOI: 10.1002/hep.29320] [Citation(s) in RCA: 225] [Impact Index Per Article: 28.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
UNLABELLED Whether there is a change of hepatocellular carcinoma (HCC) incidence in chronic hepatitis B patients under long-term therapy with potent nucleos(t)ide analogues is currently unclear. We therefore assessed the HCC incidence beyond year 5 of entecavir/tenofovir (ETV/TDF) therapy and tried to determine possible factors associated with late HCC occurrence. This European, 10-center, cohort study included 1,951 adult Caucasian chronic hepatitis B patients without HCC at baseline who received ETV/TDF for ≥1 year. Of them, 1,205 (62%) patients without HCC within the first 5 years of therapy have been followed for 5-10 (median, 6.8) years. HCCs have been diagnosed in 101/1,951 (5.2%) patients within the first 5 years and 17/1,205 (1.4%) patients within 5-10 years. The yearly HCC incidence rate was 1.22% within and 0.73% after the first 5 years (P = 0.050). The yearly HCC incidence rate did not differ within and after the first 5 years in patients without cirrhosis (0.49% versus 0.47%, P = 0.931), but it significantly declined in patients with cirrhosis (3.22% versus 1.57%, P = 0.039). All HCCs beyond year 5 developed in patients older than 50 years at ETV/TDF onset. Older age, lower platelets at baseline and year 5, and liver stiffness ≥12 kPa at year 5 were independently associated with more frequent HCC development beyond year 5 in multivariable analysis. No patient with low Platelets, Age, Gender-Hepatitis B score at baseline or year 5 developed HCC. CONCLUSION The HCC risk decreases beyond year 5 of ETV/TDF therapy in Caucasian chronic hepatitis B patients, particularly in those with compensated cirrhosis; older age (especially ≥50 years), lower platelets, and liver stiffness ≥12 kPa at year 5 represent the main risk factors for late HCC development. (Hepatology 2017;66:1444-1453).
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Affiliation(s)
- George V Papatheodoridis
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece
| | - Ramazan Idilman
- Department of Gastroenterology, University of Ankara Medical School, Ankara, Turkey
| | - George N Dalekos
- Department of Medicine and Research Laboratory of Internal Medicine, University of Thessaly, Larissa, Greece
| | - Maria Buti
- Hospital General Universitario Valle Hebron and Ciberehd, Barcelona, Spain
| | - Heng Chi
- Department of Gastroenterology & Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | | | | | - Vana Sypsa
- Department of Hygiene, Epidemiology & Medical Statistics, Medical School of National and Kapodistrian University of Athens, Athens, Greece
| | - John Goulis
- 4th Department of Internal Medicine, Αristotle University of Thessaloniki Medical School, Thessaloniki, Greece
| | - Spilios Manolakopoulos
- 2nd Department of Internal Medicine, Medical School of National and Kapodistrian University of Athens, Hippokratio General Hospital of Athens, Athens, Greece
| | - Alessandro Loglio
- "A. M. and A. Migliavacca" Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
| | - Spyros Siakavellas
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece
| | - Onur Keskın
- Department of Gastroenterology, University of Ankara Medical School, Ankara, Turkey
| | - Nikolaos Gatselis
- Department of Medicine and Research Laboratory of Internal Medicine, University of Thessaly, Larissa, Greece
| | - Bettina E Hansen
- Department of Gastroenterology & Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
| | - Maria Lehretz
- Section of Hepatology, University Clinic Leipzig, Leipzig, Germany
| | | | - Savvoula Savvidou
- 4th Department of Internal Medicine, Αristotle University of Thessaloniki Medical School, Thessaloniki, Greece
| | - Anastasia Kourikou
- 2nd Department of Internal Medicine, Medical School of National and Kapodistrian University of Athens, Hippokratio General Hospital of Athens, Athens, Greece
| | - Ioannis Vlachogiannakos
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece
| | - Kostantinos Galanis
- Department of Medicine and Research Laboratory of Internal Medicine, University of Thessaly, Larissa, Greece
| | - Cihan Yurdaydin
- Department of Gastroenterology, University of Ankara Medical School, Ankara, Turkey
| | - Thomas Berg
- Section of Hepatology, University Clinic Leipzig, Leipzig, Germany
| | | | - Rafael Esteban
- Hospital General Universitario Valle Hebron and Ciberehd, Barcelona, Spain
| | - Harry L A Janssen
- Department of Gastroenterology & Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.,Liver Clinic, Toronto Western & General Hospital, University Health Network, Toronto, ON, Canada
| | - Pietro Lampertico
- "A. M. and A. Migliavacca" Center for Liver Disease, Division of Gastroenterology and Hepatology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
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Halegoua-De Marzio D, Fenkel JM, Doria C. Hepatitis B in Solid-Organ Transplant Procedures Other Than Liver. EXP CLIN TRANSPLANT 2017; 15:130-137. [PMID: 28338458 DOI: 10.6002/ect.2016.0195] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
Transplant is often the best treatment available for patients with end-stage organ failure. Hepatitis B virus infection in transplant procedures other than liver is a major concern because it can be a significant cause of morbidity and mortality after transplant. Due to the increased risk of hepatic complications, such as fibrosing cholestatic hepatitis or histologic deterioration after transplant, systematic use of nucleoside or nucleotide analogues shortly before or at the time of transplant is recommended (tenofovir or entecavir are preferable to lamivudine) in all patients, whatever the baseline histologic evaluation. Sustained viral suppression may result in regression of fibrosis, which in turn may lead to decreased disease-related morbidity and improved survival. Finally, due to the high mortality after nonliver transplant procedures, decompensated cirrhosis from chronic hepatitis B should be considered as a contraindication to nonliver transplant but an indication to combined organ transplant (ie, liver-kidney transplant). Because of the high prevalence of hepatitis B virus exposure in allograft donors and recipients, hepatitis B virus status must be considered during organ allocation. Prevention of hepatitis B virus-related complications in transplant recipients starts with vaccination and donor-recipient matching.
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Affiliation(s)
- Dina Halegoua-De Marzio
- Department of Medicine, Division of Gastroenterology and Hepatology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA
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Clinical Course of Partial Virologic Response with Prolonged Tenofovir Therapy in Nuclos(t)ides-Naïve Patients with Chronic Hepatitis B. Dig Dis Sci 2017; 62:2908-2914. [PMID: 28871337 DOI: 10.1007/s10620-017-4737-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2017] [Accepted: 08/24/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND/AIMS The clinical course of chronic hepatitis B (CHB) patients with partial virologic response (PVR) during tenofovir disoproxil fumarate (TDF) therapy remains unclear. METHODS We retrospectively investigated the long-term clinical outcomes of TDF treatment in nucleos(t)ides-naïve CHB patients, particularly in those with PVR. RESULTS A total of 391 patients treated with TDF therapy for more than 12 months were included. Virologic response (VR) was achieved in 341 patients (87.2%). PVR was evident in 127 (45.3%) of the 391 patients. Multivariate logistic regression analysis using selected baseline factors identified absolute HBV DNA levels at baseline (OR 0.496; 95% CI 1.369-1.969) and HBeAg positivity (OR 0.622; 95% CI 1.096-3.167) as factors significantly associated with PVR. During continuous prolonged TDF therapy, 127 (71.8%) of 177 patients with PVR achieved VR. The cumulative rates of VR in patients with PVR at 12, 24, and 36 months were 42.4, 79.7, and 90.2%, respectively. Serum HBV DNA level at week 24 was significantly associated with VR in patients with PVR. CONCLUSIONS The vast majority of CHB patients with PVR achieved VR through prolonged TDF therapy, although the time to achieve VR was delayed in those with PVR. This suggests that adjustment of TDF therapy in patients with PVR is unnecessary.
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