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1
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Pondé RADA. Unusual serological profile in hepatitis B virus (HBV) infection associated with a probable clinical case of acute exacerbation of pre-existing chronic HBV infection. Mol Biol Rep 2023; 50:6435-6443. [PMID: 37326752 DOI: 10.1007/s11033-023-08546-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Accepted: 05/22/2023] [Indexed: 06/17/2023]
Abstract
BACKGROUND Acute or chronic HBV infection in an individual can be laboratory characterized according to the serological profile of the viral markers in the bloodstream, and the dynamics monitoring of these markers is necessary to assess the disorder course and the infection outcome. However, under certain circumstances unusual or atypical serological profiles may be observed in both acute and chronic HBV infection. They are considered as such because they do not properly characterize the form or infection clinical phase or because they seem inconsistent, considering the viral markers dynamics in both clinical contexts. This manuscript comprises the analysis of an unusual serological profile in HBV infection. METHODS AND RESULTS This clinical-laboratory study, had as reference a patient who presented clinical profile suggestive of acute HBV infection after recent exposure, whose laboratory data were initially compatible with this clinical presentation. However, the serological profile analysis and its monitoring demonstrated unusual pattern of viral markers expression, which has been observed in several clinical contexts, and is often associated a number of agent- or host-related factors. CONCLUSION The serological profile analyzed here, associated with the biochemical markers serum levels found, is indicative of active chronic infection, consequence of viral reactivation. This finding suggests that in the event of unusual serological profiles in HBV infection, if the influence of agent- or host-related factors is not properly considered and neither the viral markers dynamics properly analyzed, there may be mistake in the infection clinical diagnosis, especially when the patient's clinical and epidemiological history is unknown.
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Affiliation(s)
- Robério Amorim de Almeida Pondé
- Secretaria de Estado da Saúde -SES/Superintendência de Vigilância em Saúde-SUVISA/GO, Gerência de Vigilância Epidemiológica de Doenças Transmissíveis-GVEDT/Coordenação de Análises e Pesquisas-CAP, Goiânia, Brazil.
- Laboratory of Human Virology, Institute of Tropical Pathology and Public Health, Federal University of Goiás, Goiânia, Goiás, Brazil.
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Risk Factors and Outcomes in Critically Ill Patients with Hematological Malignancies Complicated by Hospital-Acquired Infections. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:medicina59020214. [PMID: 36837416 PMCID: PMC9960080 DOI: 10.3390/medicina59020214] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/04/2022] [Revised: 01/11/2023] [Accepted: 01/11/2023] [Indexed: 01/24/2023]
Abstract
Background and objectives: Patients admitted to the intensive care unit (ICU) have an increased risk of hospital-acquired infection (HAI). A diagnosis of cancer alone increases the risk of sepsis three-five-fold, which further increases the risk of nosocomial infection, subsequently deteriorates results, and leads to high mortality. In this study, we aimed to assess the mortality rate among hematologic oncologic patients with suspected infection who were subsequently admitted to the ICU and the predictive factors that are associated with high ICU mortality. Materials and Methods: This retrospective cohort study was conducted in the hematological oncology critical care unit of a tertiary care hospital between November 2017 and February 2021. We analyzed anonymized medical records of hospitalized hematologic oncologic patients who were suspected or proven to have infection in the hematology-oncology department and were subsequently transferred to the ICU. Results: Both shorter hospitalization and shorter ICU stay length were observed in survivors [9.2 (7.7-10.4)] vs. non-survivors [10 (9.1-12.9), p = 0.004]. Sepsis had the highest hazard ratio (7.38) among all other factors, as patients with sepsis had higher mortality rates (98% among ICU non-survivors and 57% among ICU survivors) than those who had febrile neutropenia. Conclusions: The overall ICU mortality in patients with hematologic malignancies was 66%. Sepsis had the highest hazard ratio among all other predictive factors, as patients with sepsis had higher mortality rates than those who had febrile neutropenia. Chronic hepatitis (HBV and HCV) was significantly associated with higher ICU mortality.
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3
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Jiang S, Wang X, Chen K, Yang P. Establishment of an inducible cell line for Hepatitis B virus genotype C2 and its pharmacological responses to interferons. Pharmacol Res 2022; 178:106142. [PMID: 35218895 DOI: 10.1016/j.phrs.2022.106142] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2021] [Revised: 02/17/2022] [Accepted: 02/22/2022] [Indexed: 11/16/2022]
Abstract
Hepatitis B virus (HBV) genotype C is closely associated with poor prognosis, contributing greatly to heavy chronic hepatitis B (CHB)-related liver disease burden in China and worldwide. However, the mechanistic studies on genotype C of HBV remain largely limited, partially because of a long-term lack of genotype C HBV-based stable cell tools. According to a bioinformatic analysis on the sub-genotype C2 HBV that is predominantly endemic in China, we selected 17.3 strain as a representative isolate. With a Tet-off gene expression system, an inducible viral replication and virion production of genotype C2 HBV were achieved in a cell line carrying persistent rcDNA-cccDNA recycling, termed HepG2-17.3, can be useful for virological studies on genotype C2 HBV. Additionally, this cell line has been formatted into cell-based assay that permits particular pharmacological screening of drug candidates, such as interferon regimens, for evaluations of the inhibitory effects on genotype C2 HBV replication.
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Affiliation(s)
- Shaodong Jiang
- CAS Key Laboratory of Infection and Immunity, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Xin Wang
- CAS Key Laboratory of Infection and Immunity, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
| | - Kaili Chen
- CAS Key Laboratory of Infection and Immunity, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China
| | - Pengyuan Yang
- CAS Key Laboratory of Infection and Immunity, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
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4
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van Santen DK, Boyd A, Bruisten S, Sonder GJ, Prins M, van Houdt R. Frequent delayed spontaneous seroclearance of hepatitis B virus after incident HBV infection among adult high-risk groups. J Viral Hepat 2020; 27:81-87. [PMID: 31520430 DOI: 10.1111/jvh.13205] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Revised: 08/06/2019] [Accepted: 08/13/2019] [Indexed: 01/26/2023]
Abstract
High rates (~25%) of developing chronic hepatitis B virus (HBV) infection (hepatitis B surface antigen (HBsAg)-positive for > 6 months following infection) have been observed in people who use drugs (PWUD) and men who have sex with men (MSM). We aimed to estimate the frequency of delayed HBsAg seroclearance, along with its determinants, and time to delayed HBsAg seroclearance. Data were used from MSM and PWUD enrolled in the Amsterdam Cohort Studies (1985-2002) who had anti-hepatitis B core antibody seroconversion. Potential determinants for standard HBsAg seroclearance, delayed HBsAg seroclearance and chronic HBV were examined using multinominal logistic regression. Time to HBsAg seroclearance was estimated using Kaplan-Meier curves. A total of 147 incident HBV infections occurred during follow-up. On initial HBsAg testing after infection (6-12 months), 42 (29%) were HBsAg-positive and 105 (71%) were HBsAg-negative ('standard HBsAg seroclearance'). Of the 42 initially HBsAg-positive individuals, 22 subsequently tested HBsAg-negative (of whom 7 (31.8%) were HBV DNA positive at last visit, suggesting occult HBV). Overall, 15 became HBsAg-negative and HBV DNA-negative ('delayed HBsAg seroclearance'), while 27 remained HBsAg and/or HBV DNA-positive ('chronic HBV'). The 5-year cumulative probability of delayed HBsAg seroclearance was 41.6% for initially HBsAg-positive individuals. Delayed HBsAg seroclearance and remaining chronically infected were associated with younger age and HIV/hepatitis C virus (HCV)-co-infection. In conclusion, delayed HBsAg seroclearance is common in these key adult populations at-risk for HBV, while proportion developing HBV chronicity (18%) is still higher compared to the general population (~5%). Given the proportion of individuals with occult HBV infection and that HCV direct-acting antivirals can lead to HBV reactivation, HBV DNA testing in HCV co-infected MSM/PWUD are warranted prior to treatment initiation.
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Affiliation(s)
- Daniela K van Santen
- Department of Infectious Diseases, Public Health Service of Amsterdam, Amsterdam, The Netherlands
| | - Anders Boyd
- Department of Infectious Diseases, Public Health Service of Amsterdam, Amsterdam, The Netherlands.,INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Saint Antoine Hospital, AP-HP, Sorbonne Université, Paris, France
| | - Sylvia Bruisten
- Department of Infectious Diseases, Public Health Service of Amsterdam, Amsterdam, The Netherlands.,Department of Infectious Diseases, Amsterdam Infection and Immunity Institute (AI&II), Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Gerard Jb Sonder
- Department of Infectious Diseases, Public Health Service of Amsterdam, Amsterdam, The Netherlands.,Department of Infectious Diseases, Amsterdam Infection and Immunity Institute (AI&II), Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Maria Prins
- Department of Infectious Diseases, Public Health Service of Amsterdam, Amsterdam, The Netherlands.,Department of Infectious Diseases, Amsterdam Infection and Immunity Institute (AI&II), Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
| | - Robin van Houdt
- Department of Medical Microbiology and Infection Control, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
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5
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Early initiation of antiviral therapy contributes to a rapid and significant loss of serum HBsAg in infantile-onset hepatitis B. J Hepatol 2019; 71:1263-1264. [PMID: 31561911 DOI: 10.1016/j.jhep.2019.07.022] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Accepted: 07/26/2019] [Indexed: 12/04/2022]
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6
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Fujiwara K, Yasui S, Haga Y, Nakamura M, Yonemitsu Y, Arai M, Kanda T, Oda S, Yokosuka O, Kato N. Early Combination Therapy with Corticosteroid and Nucleoside Analogue Induces Rapid Resolution of Inflammation in Acute Liver Failure due to Transient Hepatitis B Virus Infection. Intern Med 2018; 57:1543-1552. [PMID: 29321429 PMCID: PMC6028684 DOI: 10.2169/internalmedicine.9670-17] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Objective Patients with acute hepatitis B sometimes develop acute liver failure (ALF), which has a poor prognosis. The efficacy of nucleoside analogue (NA) monotherapy for ALF due to transient hepatitis B virus infection (HBV-ALF) remains controversial. Further investigations are necessary in nations with a shortage of donor livers for liver transplantation. In the present study, we aimed to clarify the efficacy of combination therapy with corticosteroid (CS) and NA in the treatment HBV-ALF. Patients We examined the clinical and biochemical features of 19 patients with HBV-ALF who were treated in the early stage of the disease between 2000 and 2015. Results Fourteen patients received CS and NA (CS + NA group) and 5 received NA monotherapy (NA group). Eleven patients (58%) survived and 8 (42%) died. The survival rates in the CS + NA and NA groups were 64% and 40%, respectively (p=0.60). The mean alanine aminotransferase (ALT) levels declined significantly at week 2 in both groups. The mean PT activities improved significantly at weeks 1 and 2 in the CS + NA group (p<0.05) but not in the NA group. None of the surviving patients developed persistent infection. Conclusion Combination therapy with CS and NA induces the rapid resolution of inflammation leading to a rapid recovery of the liver function. When it is administered at a sufficiently early stage, it would have a survival benefit and prevent persistent infection in HBV-ALF.
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Affiliation(s)
- Keiichi Fujiwara
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Japan
| | - Shin Yasui
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Japan
| | - Yuuki Haga
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Japan
| | - Masato Nakamura
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Japan
| | - Yutaka Yonemitsu
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Japan
| | - Makoto Arai
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Japan
| | - Tatsuo Kanda
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Japan
| | - Shigeto Oda
- Department of Emergency and Critical Care Medicine, Graduate School of Medicine, Chiba University, Japan
| | - Osamu Yokosuka
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Japan
| | - Naoya Kato
- Department of Gastroenterology, Graduate School of Medicine, Chiba University, Japan
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Abstract
Various viral kinetics among patients with acute hepatitis B (AHB) have been observed in clinical practice. This study investigated the virological, biochemical, and serological characteristics of AHB in adults.A total of 192 adult patients with AHB were recruited between December 2010 and January 2014. The quantification of biochemical and serologic markers for hepatitis B virus (HBV) infection was monitored from the onset.Of the 192 patients, 113 patients were followed up. One patient died due to acute liver failure, 2 developed chronic HBV infection. Clinical recovery was observed in 110 patients; 92.7% (102/110) achieved clinical recovery within 24 weeks, and 7.3% (8/110) between 24 and 44 weeks. There were 3 different viral kinetics patterns among the patients with AHB: the clearance of HBV DNA preceded hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg), the clearance of HBeAg preceded HBV DNA and HBsAg, the clearance of HBsAg preceded HBV DNA and HBeAg.In the absence of HBV DNA clearance within 13 weeks, the risk of development of chronic HBV infection increased. The serologic HBV markers clearance occurred between 24 and 44 weeks (6-11 months) from the onset in 8 of the AHB patients, which was longer than 6 months. Thus, AHB may be redefined as HBV DNA undetectable, HBsAg and HBeAg seroconversion within 44 weeks.
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8
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Ma H, Gao M, Li J, Zhou L, Guo J, Liu J, Han X, Zhai L, Wu T. Re-recognizing serological change patterns and antiviral therapy opportunity of patients with acute hepatitis B through highly sensitive detection technology. Clin Res Hepatol Gastroenterol 2016; 40:584-589. [PMID: 27055389 DOI: 10.1016/j.clinre.2016.02.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2015] [Revised: 01/31/2016] [Accepted: 02/11/2016] [Indexed: 02/04/2023]
Abstract
OBJECTIVE This study was conducted to re-recognize serological change patterns of patients with acute hepatitis B (AHB) by a highly sensitive detection technology, as well as to explore methods to select the optimal treatment opportunity. METHODS The biochemical and virological parameters of 558 AHB patients were analyzed retrospectively. The serological markers of hepatitis B virus and HBV DNA were detected by electrochemiluminescence immunoassay and automatic real-time fluorescent quantitative PCR, respectively. RESULTS At baseline, the positive rate of hepatitis B surface antigen (HBsAg) (86.2%) was significantly higher than the positive rate of HBV DNA (51.9%). Among the 58 patients with HBsAg-negative AHB, 16 were detected with trace amounts of HBV DNA at baseline. At 12 weeks, the HBsAg of 43 cases remained positive, and the mean level of HBsAg was 587.5IU/mL±313.4IU/mL. A total of 18 patients with HBsAg levels greater than 1500IU/mL at 12 weeks received interferon α-1b treatment and achieved HBsAg clearance within 24 weeks. CONCLUSIONS Unlike traditional changing patterns, the clearance of HBV DNA in peripheral circulation for a few patients with AHB occurred later than HBsAg clearance. Detection of HBV DNA in peripheral circulation by highly sensitive detection technology could provide a diagnostic basis for those AHB patients who rapidly achieved HBsAg clearance before achieving HBV DNA clearance in their peripheral circulation and prevent misdiagnosis. Dynamic monitoring of the changes in HBsAg levels through highly sensitive detection technology could be used as a guide for the timely adoption of antiviral treatment with interferon and then AHB chronicity would be prevented.
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Affiliation(s)
- Haixia Ma
- Graduate School, Tianjin Medical University, Tianjin, China; Tianjin Second People's Hospital, Tianjin Institute of Hepatology, No. 75, Sudi Road, 300192 Nankai District, Tianjin, China
| | - Min Gao
- Tianjin Second People's Hospital, Tianjin Institute of Hepatology, No. 75, Sudi Road, 300192 Nankai District, Tianjin, China
| | - Jia Li
- Tianjin Second People's Hospital, Tianjin Institute of Hepatology, No. 75, Sudi Road, 300192 Nankai District, Tianjin, China.
| | - Li Zhou
- Tianjin Second People's Hospital, Tianjin Institute of Hepatology, No. 75, Sudi Road, 300192 Nankai District, Tianjin, China
| | - Jie Guo
- Tianjin Second People's Hospital, Tianjin Institute of Hepatology, No. 75, Sudi Road, 300192 Nankai District, Tianjin, China
| | - Junjuan Liu
- Tianjin Second People's Hospital, Tianjin Institute of Hepatology, No. 75, Sudi Road, 300192 Nankai District, Tianjin, China
| | - Xu Han
- Tianjin Second People's Hospital, Tianjin Institute of Hepatology, No. 75, Sudi Road, 300192 Nankai District, Tianjin, China
| | - Lu Zhai
- Tianjin Second People's Hospital, Tianjin Institute of Hepatology, No. 75, Sudi Road, 300192 Nankai District, Tianjin, China
| | - Ting Wu
- Graduate School, Tianjin Medical University, Tianjin, China; Tianjin Second People's Hospital, Tianjin Institute of Hepatology, No. 75, Sudi Road, 300192 Nankai District, Tianjin, China
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9
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Inoue J, Kondo Y, Umetsu T, Yamamoto T, Miura M, Mano Y, Kobayashi T, Obara N, Niitsuma H, Kogure T, Nakagome Y, Kimura O, Iwata T, Morosawa T, Fujisaka Y, Shimosegawa T. Shifting hepatitis B virus genotypes of acute hepatitis B patients in northeast Japan. J Med Virol 2016; 88:69-78. [PMID: 26113372 DOI: 10.1002/jmv.24309] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/23/2015] [Indexed: 12/17/2022]
Abstract
It has been reported that acute hepatitis B (AHB) patients with genotype A HBV (HBV/A) have been increasing since the 1990s in metropolitan areas in Japan. However, little is known about the trends of HBV genotypes in AHB patients in northeast Japan where genotype B HBV (HBV/B) prevails more than in other areas. In this study, we aimed to clarify the changes in the HBV genotypes and clinical characteristics of AHB patients in this area. HBV genotypes were determined by direct sequencing (n = 125) or enzyme immunoassay (n = 9) using serum samples from AHB patients including fulminant hepatitis in 1987-2014. Among 134 patients, 26 (19%), 33 (25%), and 75 (56%) patients were infected with HBV of genotypes A, B, and C, respectively. HBV/A emerged from 2001 and the percentage was increased gradually up to 48% in 2010-2014, whereas HBV/B was reduced from 40% in 1987-1994 to 10% in 2010-2014. Phylogenetic analysis showed that three major subgenotype A2 strains had come into this area serially. The levels of HBV DNA and prothrombin time were higher in HBV/A patients than other genotypes. This study could not show significant difference in the HBsAg-positive period among genotypes nor the effect of nucleoside analogues to shorten the HBsAg-positive period. A higher level of initial HBV DNA was associated with late disappearance of HBsAg. In conclusion, the percentage of HBV/A in AHB patients has been increasing in northeast Japan since 2001, which is later than metropolitan areas, whereas that of HBV/B is decreasing.
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Affiliation(s)
- Jun Inoue
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Yasuteru Kondo
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Teruyuki Umetsu
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Takeshi Yamamoto
- Department of Gastroenterology, Tohoku Pharmaceutical University Hospital, Sendai, Japan
| | - Masahito Miura
- Department of Gastroenterology, South Miyagi Medical Center, Miyagi, Japan
| | - Yutaka Mano
- Department of Gastroenterology, Sendai Medical Center, Sendai, Japan
| | - Tomoo Kobayashi
- Department of Hepatology, Tohoku Rosai Hospital, Sendai, Japan
| | - Noriyuki Obara
- Department of Gastroenterology, Iwate Prefectural Central Hospital, Morioka, Japan
| | - Hirofumi Niitsuma
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Takayuki Kogure
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Yu Nakagome
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Osamu Kimura
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Tomoaki Iwata
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Tatsuki Morosawa
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Yasuyuki Fujisaka
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
| | - Tooru Shimosegawa
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
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10
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Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HLY, Chen CJ, Chen DS, Chen HL, Chen PJ, Chien RN, Dokmeci AK, Gane E, Hou JL, Jafri W, Jia J, Kim JH, Lai CL, Lee HC, Lim SG, Liu CJ, Locarnini S, Al Mahtab M, Mohamed R, Omata M, Park J, Piratvisuth T, Sharma BC, Sollano J, Wang FS, Wei L, Yuen MF, Zheng SS, Kao JH. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int 2016; 10:1-98. [PMID: 26563120 PMCID: PMC4722087 DOI: 10.1007/s12072-015-9675-4] [Citation(s) in RCA: 1921] [Impact Index Per Article: 213.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2015] [Accepted: 09/14/2015] [Indexed: 02/06/2023]
Abstract
Worldwide, some 240 million people have chronic hepatitis B virus (HBV), with the highest rates of infection in Africa and Asia. Our understanding of the natural history of HBV infection and the potential for therapy of the resultant disease is continuously improving. New data have become available since the previous APASL guidelines for management of HBV infection were published in 2012. The objective of this manuscript is to update the recommendations for the optimal management of chronic HBV infection. The 2015 guidelines were developed by a panel of Asian experts chosen by the APASL. The clinical practice guidelines are based on evidence from existing publications or, if evidence was unavailable, on the experts' personal experience and opinion after deliberations. Manuscripts and abstracts of important meetings published through January 2015 have been evaluated. This guideline covers the full spectrum of care of patients infected with hepatitis B, including new terminology, natural history, screening, vaccination, counseling, diagnosis, assessment of the stage of liver disease, the indications, timing, choice and duration of single or combination of antiviral drugs, screening for HCC, management in special situations like childhood, pregnancy, coinfections, renal impairment and pre- and post-liver transplant, and policy guidelines. However, areas of uncertainty still exist, and clinicians, patients, and public health authorities must therefore continue to make choices on the basis of the evolving evidence. The final clinical practice guidelines and recommendations are presented here, along with the relevant background information.
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Affiliation(s)
- S K Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
| | - M Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - G K Lau
- Division of Gastroenterology and Hepatology, Humanity and Health Medical Centre, Hong Kong SAR, China
- The Institute of Translational Hepatology, Beijing, China
| | - Z Abbas
- Department of Hepatogastroenterlogy, Sindh Institute of Urology and Transplantation, Karachi, Pakistan
| | - H L Y Chan
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - C J Chen
- Genomics Research Center, Academia Sinica, National Taiwan University, Taipei, Taiwan
| | - D S Chen
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - H L Chen
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - P J Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - R N Chien
- Liver Research Unit, Chang Gung Memorial Hospital and University, Chilung, Taiwan
| | - A K Dokmeci
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
| | - Ed Gane
- New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand
| | - J L Hou
- Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Guangzhou, China
| | - W Jafri
- Department of Medicine, Aga Khan University, Karachi, Pakistan
| | - J Jia
- Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | | | - C L Lai
- Department of Medicine, University of Hong Kong, Hong Kong, China
| | - H C Lee
- Internal Medicine Asan Medical Center, Seoul, Korea
| | - S G Lim
- Division of Gastroenterology and Hepatology, National University Health System, Singapore, Singapore
| | - C J Liu
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - S Locarnini
- Research and Molecular Development, Victorian Infectious Diseases Reference Laboratory, Melbourne, Australia
| | - M Al Mahtab
- Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - R Mohamed
- Department of Medicine, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia
| | - M Omata
- Yamanashi Hospitals (Central and Kita) Organization, 1-1-1 Fujimi, Kofu-shi, Yamanashi, 400-8506, Japan
| | - J Park
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - T Piratvisuth
- NKC Institute of Gastroenterology and Hepatology, Prince of Songkla University, Songkhla, Thailand
| | - B C Sharma
- Department of Gastroenterology, G.B. Pant Hospital, New Delhi, India
| | - J Sollano
- Department of Medicine, University of Santo Tomas, Manila, Philippines
| | - F S Wang
- Treatment and Research Center for Infectious Diseases, Beijing 302 Hospital, Beijing, China
| | - L Wei
- Peking University Hepatology Institute, Beijing, China
| | - M F Yuen
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Hong Kong, Pofulam, Hong Kong
| | - S S Zheng
- Department of Hepatobiliary and Pancreatic Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, Zhejiang Province, China
| | - J H Kao
- Graduate Institute of Clinical Medicine and Hepatitis Research Center, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
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11
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Pondé RAA. Acute hepatitis B virus infection or acute exacerbation of chronic hepatitis B infection: the differential serological diagnosis. Eur J Clin Microbiol Infect Dis 2015; 35:29-40. [PMID: 26581426 DOI: 10.1007/s10096-015-2522-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2015] [Accepted: 11/02/2015] [Indexed: 12/15/2022]
Abstract
Acute exacerbations of chronic hepatitis B are common, and may even be the first presentation of hepatitis B virus (HBV) infection. Sometimes, patients involved in these scenarios may have mistaken diagnosis of acute hepatitis B. The reason for the confusion is that the two forms of infection manifestation resemble remarkably in clinical, biochemical, and serological features, such as apparent rapid onset of severe disease, advanced grades of encephalopathy, high aminotransferases and prolonged international normalized ratios (INRs), as well as positivity for HBsAg and for IgM anti-HBc antibodies and DNA detection. Therefore, these two entities cannot be distinguished easily without historical information of HBV-associated chronic infection or recent HBV exposure, information that is often inaccurate. Considering the different prognoses, treatment strategies, and the epidemiological impact in the public health context, the correct diagnosis is extremely important. Despite the lack of effective and reliable tests to differentiate between acute infection and acute exacerbation of chronic HBV infection, the expression and kinetic evaluation of viral markers present in the circulation of individuals infected, the observation of physical-chemical properties of specific antibodies, and the combination of these findings represent some strategies in serology that could assist in differentiating between the two entities, or at least in the guidance for the correct diagnosis.
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Affiliation(s)
- R A A Pondé
- Laboratory of Human Virology, Institute of Tropical Pathology and Public Health, Federal University of Goiás, Goiânia, Goiás, Brazil. .,Central Goiana de Sorologia, Imuno-hematologia e Biologia Molecular, Goiânia, Goiás, Brazil. .,SUVISA-Superintendência de Vigilância em Saúde, Secretaria Estadual de Saúde, Coordenação Estadual de Controle das Hepatites Virais (CECHV), Goiânia, Goiás, Brazil. .,, Rua 7A Edifício RIOL, Nº 158, 1º andar, sala 101, setor aeroporto, Goiânia, Goiás, 74-075-030, Brazil.
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12
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Characterization of Acute and Chronic Hepatitis B Virus Genotypes in Canada. PLoS One 2015; 10:e0136074. [PMID: 26406309 PMCID: PMC4583310 DOI: 10.1371/journal.pone.0136074] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2015] [Accepted: 07/26/2015] [Indexed: 12/11/2022] Open
Abstract
Objective The prevalence and distribution of hepatitis B virus (HBV) genotypes in Canada is not known. Genotypic analysis may contribute to a better understanding of HBV strain distribution and transmission risk. Methods HBV surface antigen (HBsAg) positive samples of acute (n = 152) and chronic (n = 1533) HBV submitted for strain analysis or reference genotype testing between 2006 and 2012 were analyzed. The HBsAg coding region was amplified to determine the HBV genotype by INNO-LiPA assay or sequence analysis. Single and multivariate analyses were used to describe genotypes’ associations with known demographic and behavioral risk factors for 126 linked cases of acute HBV. Results Nine genotypes were detected (A to I), including mixed infections. Genotype C (HBV/C) dominated within chronic infections while HBV/D and A prevailed among acute HBV cases. History of incarceration and residing with a chronic HBV carrier or injection drug user were the most frequently reported risks for acute HBV infection. Over time, HBV/A increased among both acute and chronic infections, and HBV/C and HBV/D decreased among chronic infections. Conclusion Chronic and acute HBV genotypes in Canada differ in the relative distribution and their associations with known risk factors, suggesting different routes of transmission and clinical progression of infection.
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13
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Croagh CMN, Lubel JS. Natural history of chronic hepatitis B: phases in a complex relationship. World J Gastroenterol 2014; 20:10395-404. [PMID: 25132755 PMCID: PMC4130846 DOI: 10.3748/wjg.v20.i30.10395] [Citation(s) in RCA: 84] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2013] [Revised: 02/24/2014] [Accepted: 04/27/2014] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis B (CHB) is a condition of global prevalence and its sequelae include cirrhosis and hepatocellular carcinoma. The natural history of CHB is a complex interplay of virological, environmental and host factors. The dynamic relationship between the virus and host evolves over the duration of the infection and different phases of the disease have been observed and described. These have been conceptualized in terms of the state of balance between the host immune system and the hepatitis B virus and have been given the labels immune tolerant, immune clearance, immune control and immune escape although other nomenclature is also used. Host factors, such as age at infection, determine progression to chronicity. Virological factors including hepatitis B viral load, mutations and genotype also have an impact on the adverse outcomes of the infection, as do hepatotoxic cofactors such as alcohol. Our understanding of the natural history of CHB has evolved significantly over the past few decades and characterizing the phase of disease of CHB remains an integral part of managing this virus in the clinic.
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Okamoto D, Nakayama H, Ikeda T, Ikeya S, Nagashima S, Takahashi M, Sugai Y, Okamoto H. Molecular analysis of the interspousal transmission of hepatitis B virus in two Japanese patients who acquired fulminant hepatitis B after 50 and 49 years of marriage. J Med Virol 2014; 86:1851-60. [PMID: 25132075 DOI: 10.1002/jmv.24040] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/11/2014] [Indexed: 12/13/2022]
Abstract
A 71-year-old (C1I) and 69-year-old (C2I) Japanese female contracted fulminant hepatitis B after 50 and 49 years of marriage, respectively. Both index cases exhibited high levels of anti-HBc IgM antibodies (24.2 and 31.5 S/CO, respectively), suggestive of acute hepatitis B virus (HBV) infection, although they had no discernible risk factors for HBV infection, except for chronically HBV-infected spouses with detectable HBV DNA (3.3 log copies/ml [C1S: 72-year-old] and 7.2 log copies/ml [C2S: 71-year-old]). The HBV genotype/subgenotype was identical in each couple (B/B1 or C/C2). The HBV isolates from the index cases and spouses shared a nucleotide sequence identity of 99.5% and 99.7%, respectively, over the entire genome, and these four isolates had the highest nucleotide sequence identity of only 97% to HBV isolates deposited in DNA databases. Phylogenetic trees confirmed a close relationship of the HBV isolates between C1I and C1S and between C2I and C2S, supported by a high bootstrap value of 100% within each couple, indicating the transfer of HBV infection between spouses. These four isolates shared a precore mutation of G1896A known to be associated with fulminant hepatitis B. Although the history of sexual contact within a reasonable incubation period was obscure for one stable, monogamous couple (C1I and C1S), the other couple had a monogamous sexual relationship within six months prior to disease onset. This study indicates that two elderly Japanese patients with fulminant hepatitis B acquired HBV infection via interspousal (most likely sexual) transmission during long-lasting marriages.
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Affiliation(s)
- Daisuke Okamoto
- Department of Internal Medicine, Iwaki Kyoritsu General Hospital, Fukushima-Ken, Japan
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15
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Yamada N, Shigefuku R, Sugiyama R, Kobayashi M, Ikeda H, Takahashi H, Okuse C, Suzuki M, Itoh F, Yotsuyanagi H, Yasuda K, Moriya K, Koike K, Wakita T, Kato T. Acute hepatitis B of genotype H resulting in persistent infection. World J Gastroenterol 2014; 20:3044-3049. [PMID: 24659896 PMCID: PMC3961985 DOI: 10.3748/wjg.v20.i11.3044] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2013] [Revised: 11/18/2013] [Accepted: 12/06/2013] [Indexed: 02/07/2023] Open
Abstract
A 47-year-old man presented with general fatigue and dark urine. The laboratory data showed increased levels of hepatic transaminases. The patient was positive for hepatitis B virus (HBV) markers and negative for anti-human immunodeficiency virus. The HBV-DNA titer was set to 7.7 log copies/mL. The patient was diagnosed with acute hepatitis B. The HBV infection route was obscure. The serum levels of hepatic transaminases decreased to normal ranges without any treatment, but the HBV-DNA status was maintained for at least 26 mo, indicating the presence of persistent infection. We isolated HBV from the acute-phase serum and determined the genome sequence. A phylogenetic analysis revealed that the isolated HBV was genotype H. In this patient, the elevated peak level of HBV-DNA and the risk alleles at human genome single nucleotide polymorphisms s3077 and rs9277535 in the human leukocyte antigen-DP locus were considered to be risk factors for chronic infection. This case suggests that there is a risk of persistent infection by HBV genotype H following acute hepatitis; further cases of HBV genotype H infection must be identified and characterized. Thus, the complete determination of the HBV genotype may be essential during routine clinical care of acute hepatitis B outpatients.
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Mayerat C, Mantegani A, Frei PC. Does hepatitis B virus (HBV) genotype influence the clinical outcome of HBV infection? Infection 1999; 43:431-41. [PMID: 10607244 DOI: 10.1007/s15010-015-0747-0] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2014] [Accepted: 02/06/2015] [Indexed: 02/06/2023]
Abstract
Between 5 and 10% of adults infected with the hepatitis B virus (HBV) develop a chronic infection lasting longer than 6 months, which may lead to advanced liver disease. HBV can be classified into six genotypic families: A, B, C, D, E and F, but only genotypes A and D are significantly represented in western Europe, where they account for some 90% of cases of infection with HBV. In the present study, we investigated a possible association between HBV genotype A or D and clinical outcome of the infection. We compared the prevalence of these genotypes in a group of patients with chronic active hepatitis to that of a group with acute resolving hepatitis. In patients with chronic active hepatitis, genotype A was found in 28 of 35 patients and genotype D in only four. The remaining three patients were infected with genotype non-A, non-D. In contrast, genotype D was found in 24 of 30 patients with acute hepatitis, whilst genotype A was found in only three patients of this group. Three were infected with genotype non-A, non-D. Our results show a clear association between genotype A and chronic outcome (Ficher's exact test: two-sided P-value, P < 0.0001). They suggest that HBV genotypes may play a role in the virus-host relationship. Possible mechanisms for such a role are discussed.
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Affiliation(s)
- C Mayerat
- Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland
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