|
1
|
Hong JJ, Zhang RT, Ma CL, Hu QY. Pulmonary microbial spectrum in late-stage SARS-CoV-2 infection: a case series. Eur J Clin Microbiol Infect Dis 2024; 43:2037-2046. [PMID: 39031269 DOI: 10.1007/s10096-024-04897-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Accepted: 07/08/2024] [Indexed: 07/22/2024]
Abstract
Coronavirus disease 2019 (COVID-19), a kind of respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily spreads through the respiratory tract from human to human. Its extensive and rapid spread has led to a global pandemic, causing great harm to human health and economic development all over the world. Current known evidence indicates that SARS-CoV-2 has evolved accumulating multiple mutations, with altered infectivity and viral replication capacity. A better understanding of the complications of COVID-19 and its relationship with underlying diseases is crucial for the prevention and treatment of SARS-CoV-2. This case series reviewed case data of our 4 recent patients with severe or critical COVID-19, including treatment plan, status of pulmonary infection and their microbiology workup with metagenomic next-generation sequencing with bronchoalveolar lavage fluid. This report shed light on the significance of rapid and accurate clinical diagnosis and treatment on COVID-19.
Collapse
Affiliation(s)
- Jin-Jing Hong
- School of Medicine, The First People's Hospital of Wenling (Taizhou University Affiliated Wenling Hospital), Taizhou University, 1139 Shifu Blvd, Jiaojiang District, Taizhou, Zhejiang, 318000, China
| | - Ren-Tao Zhang
- School of Medicine, The First People's Hospital of Wenling (Taizhou University Affiliated Wenling Hospital), Taizhou University, 1139 Shifu Blvd, Jiaojiang District, Taizhou, Zhejiang, 318000, China
| | - Chun-Lian Ma
- School of Medicine, The First People's Hospital of Wenling (Taizhou University Affiliated Wenling Hospital), Taizhou University, 1139 Shifu Blvd, Jiaojiang District, Taizhou, Zhejiang, 318000, China.
| | - Qiong-Ying Hu
- School of Medicine, The First People's Hospital of Wenling (Taizhou University Affiliated Wenling Hospital), Taizhou University, 1139 Shifu Blvd, Jiaojiang District, Taizhou, Zhejiang, 318000, China.
| |
Collapse
|
|
2
|
Kuroki A, Tay J, Lee GH, Yang YY. Broad-Spectrum Antiviral Peptides and Polymers. Adv Healthc Mater 2021; 10:e2101113. [PMID: 34599850 DOI: 10.1002/adhm.202101113] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Revised: 09/13/2021] [Indexed: 12/18/2022]
Abstract
As the human cost of the pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still being witnessed worldwide, the development of broad-spectrum antiviral agents against emerging and re-emerging viruses is seen as a necessity to hamper the spread of infections. Various targets during the viral life-cycle can be considered to inhibit viral infection, from viral attachment to viral fusion or replication. Macromolecules represent a particularly attractive class of therapeutics due to their multivalency and versatility. Although several antiviral macromolecules hold great promise in clinical applications, the emergence of resistance after prolonged exposure urges the need for improved solutions. In the present article, the recent advancement in the discovery of antiviral peptides and polymers with diverse structural features and antiviral mechanisms is reviewed. Future perspectives, such as, the development of virucidal peptides/polymers and their coatings against SARS-CoV-2 infection, standardization of antiviral testing protocols, and use of artificial intelligence or machine learning as a tool to accelerate the discovery of antiviral macromolecules, are discussed.
Collapse
Affiliation(s)
- Agnès Kuroki
- Yong Loo Lin School of Medicine National University of Singapore Singapore 117597 Singapore
- Institute of Bioengineering and Bioimaging 31 Biopolis Ways, The Nanos Singapore 138669 Singapore
| | - Joyce Tay
- Institute of Bioengineering and Bioimaging 31 Biopolis Ways, The Nanos Singapore 138669 Singapore
| | - Guan Huei Lee
- Yong Loo Lin School of Medicine National University of Singapore Singapore 117597 Singapore
| | - Yi Yan Yang
- Institute of Bioengineering and Bioimaging 31 Biopolis Ways, The Nanos Singapore 138669 Singapore
| |
Collapse
|
|
3
|
Goh ZY, Ren EC, Ko HL. Intracellular interferon signalling pathways as potential regulators of covalently closed circular DNA in the treatment of chronic hepatitis B. World J Gastroenterol 2021; 27:1369-1391. [PMID: 33911462 PMCID: PMC8047536 DOI: 10.3748/wjg.v27.i14.1369] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Revised: 02/23/2021] [Accepted: 03/17/2021] [Indexed: 02/06/2023] Open
Abstract
Infection with the hepatitis B virus (HBV) is still a major global health threat as 250 million people worldwide continue to be chronically infected with the virus. While patients may be treated with nucleoside/nucleotide analogues, this only suppresses HBV titre to sub-detection levels without eliminating the persistent HBV covalently closed circular DNA (cccDNA) genome. As a result, HBV infection cannot be cured, and the virus reactivates when conditions are favorable. Interferons (IFNs) are cytokines known to induce powerful antiviral mechanisms that clear viruses from infected cells. They have been shown to induce cccDNA clearance, but their use in the treatment of HBV infection is limited as HBV-targeting immune cells are exhausted and HBV has evolved multiple mechanisms to evade and suppress IFN signalling. Thus, to fully utilize IFN-mediated intracellular mechanisms to effectively eliminate HBV, instead of direct IFN administration, novel strategies to sustain IFN-mediated anti-cccDNA and antiviral mechanisms need to be developed. This review will consolidate what is known about how IFNs act to achieve its intracellular antiviral effects and highlight the critical interferon-stimulated gene targets and effector mechanisms with potent anti-cccDNA functions. These include cccDNA degradation by APOBECs and cccDNA silencing and transcription repression by epigenetic modifications. In addition, the mechanisms that HBV employs to disrupt IFN signalling will be discussed. Drugs that have been developed or are in the pipeline for components of the IFN signalling pathway and HBV targets that detract IFN signalling mechanisms will also be identified and discussed for utility in the treatment of HBV infections. Together, these will provide useful insights into design strategies that specifically target cccDNA for the eradication of HBV.
Collapse
Affiliation(s)
- Zhi Yi Goh
- Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore
- Integrative Sciences and Engineering Programme, NUS Graduate School, National University of Singapore, Singapore 119077, Singapore
| | - Ee Chee Ren
- Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore
- Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119260, Singapore
| | - Hui Ling Ko
- Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore
| |
Collapse
|
|
4
|
Hepatitis B virus drug resistance mutations in HIV/HBV co-infected children in Windhoek, Namibia. PLoS One 2020; 15:e0238839. [PMID: 32915862 PMCID: PMC7485811 DOI: 10.1371/journal.pone.0238839] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Accepted: 08/25/2020] [Indexed: 12/14/2022] Open
Abstract
In patients who are HIV infected, hepatitis B virus (HBV) infection is an important co-morbidity. However, antiretroviral options for HIV/HBV co-infected children are limited and, at the time of this study, only included lamivudine. These children may remain on this regimen for many years until late adolescence. They are at high risk of developing HBV drug resistance and uncontrolled HBV disease. The aim of this study was to characterize HBV infection in HIV/HBV co-infected children. Known HIV-infected/HBsAg-positive children, previously exposed to lamivudine monotherapy against HBV, and their mothers were recruited at the Katutura Hospital paediatric HIV clinic in Windhoek, Namibia. Dried blood spot and serum samples were collected for HBV characterization and serological testing, respectively. Fifteen children and six mothers participated in the study. Eight of the 15 children (53.3%) tested HBV DNA positive; all eight children were on lamivudine-based ART. Lamivudine-associated resistance variants, together with immune escape mutants in the surface gene, were identified in all eight children. Resistance mutations included rtL80I, rtV173L, rtL180M, rtM204I/V and the overlapping sE164D, sW182*, sI195M and sW196LS variants. HBV strains belonged to genotypes E (6/8, 75%) and D3 (2/8, 25%). Further analysis of the HBV core promoter region revealed mutations associated with reduced expression of HBeAg protein and hepatocarcinogenesis. All six mothers, on HBV-active ART containing tenofovir and lamivudine, tested HBV DNA negative. This study confirms the importance of screening HIV-infected children for HBV and ensuring equity of drug access to effective HBV treatment if co-infected.
Collapse
|
|
5
|
Zhang X, Chen X, Wei M, Zhang C, Xu T, Liu L, Xu Z. Potential resistant mutations within HBV reverse transcriptase sequences in nucleos(t)ide analogues-experienced patients with hepatitis B virus infection. Sci Rep 2019; 9:8078. [PMID: 31147594 PMCID: PMC6542804 DOI: 10.1038/s41598-019-44604-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Accepted: 05/16/2019] [Indexed: 12/17/2022] Open
Abstract
This study was performed to analyze the potential resistant mutations within HBV reverse transcriptase (RT) sequences against nucleos(t)ide analogues (NA). HBV DNA RT region spanning from amino acid 169 to 250 was amplified and sequenced from 435 HBV patients who experienced NA treatment. Among study’s cohort, genotypes B and C infected patients were 55.9% and 44.1%, respectively. Mutations were recorded in 54.7% (238/435) patients at 22 positions. Genotype C displayed significant higher frequency of potential NA resistant mutations than genotype B (63.0% vs. 48.1%, P = 0.003). Moreover, eight mutation sites, including 180, 181, 191, 200, 202, 221, 229 and 224, in genotype C showed significant higher frequencies than in genotype B. In contrast, mutation at site 236 was more common in genotype B. Notably, 11 mutations at position 169, 202, 250, 173, 180, 200, 207, 214, 237, 242 and 245 coexisted with M204I or V. Substitutions at nine non-classical mutation sites (191, 207, 213, 218, 221, 224, 229, 238 and 242) were detected in patients with virological breakthrough. Particularly, tenofovir (TDF) resistance was observed in one patient undergoing TDF monotherapy and experienced several NA treatment before. These results might provide clinical useful information under antiviral therapy.
Collapse
Affiliation(s)
- Xiaoman Zhang
- Clinical Liver Center, the 910th hospital of People's Liberation Army, Quanzhou, 362000, China
| | - Xianli Chen
- Department of Infectious and Liver Disease, Xiang'an hospital of Xiamen University, Xiamen, 361000, China
| | - Meijuan Wei
- Clinical Liver Center, the 910th hospital of People's Liberation Army, Quanzhou, 362000, China.,Clinical Liver Center, Decheng hospital of Quanzhou Affiliated of Huaqiao University, Quanzhou, 362000, China
| | - Chunyu Zhang
- Clinical Liver Center, the 910th hospital of People's Liberation Army, Quanzhou, 362000, China
| | - Tao Xu
- Clinical Liver Center, the 910th hospital of People's Liberation Army, Quanzhou, 362000, China
| | - Liguan Liu
- Clinical Liver Center, the 910th hospital of People's Liberation Army, Quanzhou, 362000, China
| | - Zhengju Xu
- Clinical Liver Center, the 910th hospital of People's Liberation Army, Quanzhou, 362000, China.
| |
Collapse
|
|
6
|
Lian JS, Zhang XL, Lu YF, Chen JY, Zhang YM, Jia HY, Zhang Z, Yang YD. Switching Lamivudine with Adefovir Dipivoxil Combination Therapy to Entecavir Monotherapy Provides Better Viral Suppression and Kidney Safety. Int J Med Sci 2019; 16:17-22. [PMID: 30662324 PMCID: PMC6332476 DOI: 10.7150/ijms.28700] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2018] [Accepted: 10/18/2018] [Indexed: 11/05/2022] Open
Abstract
Introduction: Most chronic hepatitis B (CHB) patients in China are primitively treated with a combination of lamivudine (LAM) and adefovir dipivoxil (ADV). Although antiviral resistance can be avoided with this combination therapy, using it can have harmful side effects related to ADV, specifically kidney and bone injury. This study was designed to compare viral suppression and kidney safety when switching LAM and ADV combination therapy de novo to entecavir (ETV) monotherapy in patients with CHB and compensated hepatic cirrhosis. Materials and methods: In total, 360 CHB and compensated liver cirrhosis patients who received treatment of LAM and ADV combination therapy for more than 1 year were included in this study. One hundred and eighty patients continued combination therapy to serve as a control group and the other 180 patients were switched to ETV monotherapy to serve as the experimental group. The total course of therapy was 3 years. Laboratory studies were done every 3 months to measure liver and kidney function. Studies included glomerular filtration rate (eGFR), HBV-DNA, urine β2-microglobulin (β2-M) and retinol binding protein (RBP). Results: In the experimental group, an HBV-DNA level below 20 IU/ml was found in 77.65%, 85.88%, and 94.77% in years 1, 2, and 3, respectively. In the control group, HBV-DNA levels were below 20 IU/ml in 69.66%, 75.42%, and 85.80% in years 1, 2, and 3, respectively. Low HBV-DNA levels in the experimental group were significantly less common than in the control group on the second and third year; P values were 0.009 and 0.006 for years 2 and 3, respectively. The cumulative genetic mutation rate was 3.49% in the experimental group and 8.88% in the control group (P=0.044). Decreases in eGFR more than 30% from baseline were found in 0%, 0.56%, and 1.74% of patients in the experimental group and 4.49%, 9.14% and 14.79% in patients in the control group in the first, second, and third year, respectively. Serum creatinine more than 50 μmol/L above baseline was found in 0%, 0% and 1.74% of patients in the experimental group and 1.12%, 4.00% and 5.32% of patients in the control group in years 1, 2, and 3, respectively. The urine β2-M and RBP levels were abnormal more often in the experimental group than in the control group. Conclusion: Switching to ETV monotherapy can decrease HBV-DNA levels, reduce the genetic mutation rate, and prevent renal damage caused by LAM and ADV combination therapy in patients with CHB and compensated liver cirrhosis. Patients receiving LAM and ADV combination therapy de novo should be switched to ETV monotherapy immediately.
Collapse
Affiliation(s)
- Jiang-Shan Lian
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University. Hangzhou 310003, China
| | - Xiao-Lin Zhang
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University. Hangzhou 310003, China.,Shanghai Public Health Clinical Center, Shanghai Public Health Clinical Center Affiliated to Fudan University
| | - Ying-Feng Lu
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University. Hangzhou 310003, China
| | - Jian-Yang Chen
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University. Hangzhou 310003, China
| | - Yi-Min Zhang
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University. Hangzhou 310003, China
| | - Hong-Yu Jia
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University. Hangzhou 310003, China
| | - Zhe Zhang
- Urology Department, The First Affiliated Hospital of Zhejiang University, School of Medicine, Zhejiang University. Hangzhou 310003, China
| | - Yi-Da Yang
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Department of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University. Hangzhou 310003, China
| |
Collapse
|
|
7
|
Song M, Sun Y, Tian J, He W, Xu G, Jing Z, Li W. Silencing Retinoid X Receptor Alpha Expression Enhances Early-Stage Hepatitis B Virus Infection In Cell Cultures. J Virol 2018; 92:e01771-17. [PMID: 29437960 PMCID: PMC5874418 DOI: 10.1128/jvi.01771-17] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2017] [Accepted: 01/12/2018] [Indexed: 12/23/2022] Open
Abstract
Multiple steps of the life cycle of hepatitis B virus (HBV) are known to be coupled to hepatic metabolism. However, the details of involvement of the hepatic metabolic milieu in HBV infection remain incompletely understood. Hepatic lipid metabolism is controlled by a complicated transcription factor network centered on retinoid X receptor alpha (RXRα). Here, we report that RXRα negatively regulates HBV infection at an early stage in cell cultures. The RXR-specific agonist bexarotene inhibits HBV in HepG2 cells expressing the sodium taurocholate cotransporting polypeptide (NTCP) (HepG2-NTCP), HepaRG cells, and primary Tupaia hepatocytes (PTHs); reducing RXRα expression significantly enhanced HBV infection in the cells. Transcriptome sequencing (RNA-seq) analysis of HepG2-NTCP cells with a disrupted RXRα gene revealed that reduced gene expression in arachidonic acid (AA)/eicosanoid biosynthesis pathways, including the AA synthases phospholipase A2 group IIA (PLA2G2A), is associated with increased HBV infection. Moreover, exogenous treatment of AA inhibits HBV infection in HepG2-NTCP cells. These data demonstrate that RXRα is an important cellular factor in modulating HBV infection and implicate the participation of AA/eicosanoid biosynthesis pathways in the regulation of HBV infection.IMPORTANCE Understanding how HBV infection is connected with hepatic lipid metabolism may provide new insights into virus infection and its pathogenesis. By a series of genetic studies in combination with transcriptome analysis and pharmacological assays, we here investigated the role of cellular retinoid X receptor alpha (RXRα), a crucial transcription factor for controlling hepatic lipid metabolism, in de novo HBV infection in cell cultures. We found that silencing of RXRα resulted in elevated HBV covalently closed circular DNA (cccDNA) formation and viral antigen production, while activation of RXRα reduced HBV infection efficiency. Our results also showed that silencing phospholipase A2 group IIA (PLA2G2A), a key enzyme of arachidonic acid (AA) synthases, enhanced HBV infection efficiency in HepG2-NTCP cells and that exogenous AA treatment reduced de novo HBV infection in the cells. These findings unveil RXRα as an important cellular factor in modulating HBV infection and may point to a new strategy for host-targeted therapies against HBV.
Collapse
Affiliation(s)
- Mei Song
- Graduate Program, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- National Institute of Biological Sciences, Beijing, China
| | - Yinyan Sun
- National Institute of Biological Sciences, Beijing, China
| | - Ji Tian
- National Institute of Biological Sciences, Beijing, China
- Graduate Program, School of Life Science, Tsinghua University, Beijing, China
| | - Wenhui He
- National Institute of Biological Sciences, Beijing, China
| | - Guangwei Xu
- National Institute of Biological Sciences, Beijing, China
| | - Zhiyi Jing
- National Institute of Biological Sciences, Beijing, China
| | - Wenhui Li
- Graduate Program, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- National Institute of Biological Sciences, Beijing, China
| |
Collapse
|
|
8
|
Guo X, Wu J, Wei F, Ouyang Y, Li Q, Liu K, Wang Y, Zhang Y, Chen D. Trends in hepatitis B virus resistance to nucleoside/nucleotide analogues in North China from 2009-2016: A retrospective study. Int J Antimicrob Agents 2018; 52:201-209. [PMID: 29654894 DOI: 10.1016/j.ijantimicag.2018.04.002] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2017] [Revised: 03/29/2018] [Accepted: 04/04/2018] [Indexed: 12/13/2022]
Abstract
Nucleos(t)ide analogues (NAs) are widely used in anti-hepatitis B virus (anti-HBV) therapy for effective inhibition of HBV replication. However, HBV resistance to NAs has emerged, resulting in virus reactivation and disease recurrence. Data on the current dynamics of HBV resistance are still rare in China. This study analysed 4491 plasma samples with HBV primary genotypic resistance mutations representative of the general HBV resistance situation in northern China from 2009-2016. We found that entecavir (ETV), representing 57.6% (12 713/22 060) of NA users in North China in 2016, has become the major NA for treating Chinese patients infected with HBV. Despite >50% of M204I/V±L180M among all HBV resistance cases annually and extensive exposure of patients to lamivudine (LAM), telbivudine (LdT) and adefovir dipivoxil (ADV), ETV resistance also showed a dramatically increased incidence, which rose to 17.1% in 2016. Moreover, A181T/V, ETV resistance mutations and multidrug resistance mutations were found more frequently in HBV genotype C compared with genotype B (21.2% vs. 8.5%, 12.4% vs. 7.9% and 5.9% vs. 3.0%, respectively), whereas M204I and N236T were more predominant in genotype B than genotype C (40.3% vs. 20.8% and 11.3% vs. 1.8%, respectively). In conclusion, we report the dynamic changes of HBV NA resistance mutation patterns and the current NA usage profile for anti-HBV treatment in North China over the past 8 years. These data provide valuable information on HBV NA resistance that is an important reference for clinicians to devise more effective treatment regimens for individual patients.
Collapse
Affiliation(s)
- Xianghua Guo
- Beijing You An Hospital, Capital Medical University, Beijing 100069, China; Beijing Institute of Hepatology, Beijing 100069, China; Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
| | - Jushan Wu
- Beijing You An Hospital, Capital Medical University, Beijing 100069, China
| | - Feili Wei
- Beijing You An Hospital, Capital Medical University, Beijing 100069, China; Beijing Institute of Hepatology, Beijing 100069, China; Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
| | - Yabo Ouyang
- Beijing You An Hospital, Capital Medical University, Beijing 100069, China; Beijing Institute of Hepatology, Beijing 100069, China; Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
| | - Qing Li
- Beijing You An Hospital, Capital Medical University, Beijing 100069, China
| | - Kai Liu
- Beijing You An Hospital, Capital Medical University, Beijing 100069, China; Beijing Institute of Hepatology, Beijing 100069, China; Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
| | - Yanjun Wang
- Beijing You An Hospital, Capital Medical University, Beijing 100069, China; Beijing Institute of Hepatology, Beijing 100069, China; Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China
| | - Yulin Zhang
- Beijing You An Hospital, Capital Medical University, Beijing 100069, China.
| | - Dexi Chen
- Beijing You An Hospital, Capital Medical University, Beijing 100069, China; Beijing Institute of Hepatology, Beijing 100069, China; Beijing Precision Medicine and Transformation Engineering Technology Research Center of Hepatitis and Liver Cancer, Beijing 100069, China; Organ Transplantation Center, The Affiliated Hospital of Qingdao University, Qingdao City, Shandong Province 266003, China.
| |
Collapse
|
|
9
|
Evolution of drug-resistant mutations in HBV genomes in patients with treatment failure during the past seven years (2010-2016). Virus Genes 2017; 54:41-47. [PMID: 29119303 DOI: 10.1007/s11262-017-1518-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2017] [Accepted: 11/01/2017] [Indexed: 02/06/2023]
Abstract
The objective of this study was to analyze the prevalence of drug-resistant HBV mutants in patients with treatment failure during the past seven years (2010-2016). 4055 HBV-infected patients who underwent HBV polymerase gene mutation test from 2010 to 2016 were enrolled. The nucleos(t)ide analogues (NAs) resistance mutation positions, including rtL180, rtA181, rtT184, rtS202, rtM204, rtI233, rtN236, rtI169, rtV173, and rtM250 were analyzed. Genotypic resistance mutations were detected in 30.8% (1248/4055) of the patients with treatment failure. Rates of drug-resistant mutations associated with LAM, ADV, ETV, and multidrug were 27.23% (1104/4055), 9.67% (392/4055), 3.69% (150/4055), and 0.79% (32/4055). Among the primary NA-resistant mutations, rtM204I (13.44%, 545/4055) occurred more frequently, followed by rtM204V, rtN236T, rtA181T, and rtA181V. For single-base mutations, rtL180M and rtA181V increased gradually during the past seven years, while rtM204I/V and rtN236T decreased after 2015. The development of drug-resistant mutations positively correlated with the consumption of ETV (r = 0.964, P = 0.002), and weakly correlated with that of LAM (r = 0.679, P = 0.109) and ADV (r = 0.429, P = 0.354). Moreover, single-base mutation rtA181V and multi-base mutations (rtL180M + M204I and rtL180M + M204V + M204I) were more common in HBV genotype C than those in genotype B (1.94% vs. 0.66%, 1.84% vs. 0.16%, 1.02% vs. 0.16%, respectively). NA-related mutations in HBV RT region increased in the past seven years, especially for LAM. Frequencies of rtL180M and rtA181T/V increased gradually in the past seven years, to which we should pay more attention.
Collapse
|
|
10
|
Mabeya SN, Ngugi C, Lihana RW, Khamadi SA, Nyamache AK. Predominance of Hepatitis B Virus Genotype A Among Treated HIV Infected Patients Experiencing High Hepatitis B Virus Drug Resistance in Nairobi, Kenya. AIDS Res Hum Retroviruses 2017; 33:966-969. [PMID: 28316253 DOI: 10.1089/aid.2017.0019] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Hepatitis B virus (HBV)-HIV coinfections are becoming common with information on HBV genetic diversity and drug resistance still remaining elusive. To evaluate the HBV genetic diversity and drug resistance-associated mutations among drug-experienced HIV patients, the genetic analysis of the partial HBV-pol-reverse trancriptase gene was successfully sequenced from 13 samples. Analysis of the sequences showed that all (11) the sequences belonged to genotype A. Nucleos(t)ide drug resistance mutations were found in 6 patients. Five subjects had rtV173L, rtL180M, and rtM204V and one with rtL180M and rtM204V major mutations. HBV genotype A remains the most predominant genotype circulating in Nairobi city with detected high level of HBV drug resistance to lamivudine, telbivudine, and emtricitabine. The detected circulating HBV genotype A in Nairobi reflects its possible spread in the population with its origin being within the country. We suggest that patients should not be on lamivudine monotherapy. These individuals should be managed on combination of tenofovir plus lamivudine or emtricitabine therapy to prevent the emergence of HBV drug resistant variants alongside a continuous surveillance monitoring of drug resistance and HBV genotypes.
Collapse
Affiliation(s)
- Sepha Nyatichi Mabeya
- Department of Medical Microbiology, Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya
| | - Caroline Ngugi
- Department of Medical Microbiology, Jomo Kenyatta University of Agriculture and Technology, Nairobi, Kenya
| | | | | | | |
Collapse
|
|
11
|
Zhang ZH, Wu CC, Chen XW, Li X, Li J, Lu MJ. Genetic variation of hepatitis B virus and its significance for pathogenesis. World J Gastroenterol 2016; 22:126-144. [PMID: 26755865 PMCID: PMC4698480 DOI: 10.3748/wjg.v22.i1.126] [Citation(s) in RCA: 76] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2015] [Revised: 09/25/2015] [Accepted: 11/13/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) has a worldwide distribution and is endemic in many populations. Due to its unique life cycle which requires an error-prone reverse transcriptase for replication, it constantly evolves, resulting in tremendous genetic variation in the form of genotypes, sub-genotypes, and mutations. In recent years, there has been considerable research on the relationship between HBV genetic variation and HBV-related pathogenesis, which has profound implications in the natural history of HBV infection, viral detection, immune prevention, drug treatment and prognosis. In this review, we attempted to provide a brief account of the influence of HBV genotype on the pathogenesis of HBV infection and summarize our current knowledge on the effects of HBV mutations in different regions on HBV-associated pathogenesis, with an emphasis on mutations in the preS/S proteins in immune evasion, occult HBV infection and hepatocellular carcinoma (HCC), mutations in polymerase in relation to drug resistance, mutations in HBV core and e antigen in immune evasion, chronicalization of infection and hepatitis B-related acute-on-chronic liver failure, and finally mutations in HBV x proteins in HCC.
Collapse
|
|
12
|
Gupta N, Goyal M, Wu CH, Wu GY. The Molecular and Structural Basis of HBV-resistance to Nucleos(t)ide Analogs. J Clin Transl Hepatol 2014; 2:202-11. [PMID: 26357626 PMCID: PMC4548360 DOI: 10.14218/jcth.2014.00021] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2014] [Revised: 07/26/2014] [Accepted: 07/27/2014] [Indexed: 02/06/2023] Open
Abstract
Infection with hepatitis B virus (HBV) is a worldwide health problem. Chronic hepatitis B can lead to fibrosis, liver cirrhosis, and hepatocellular carcinoma (HCC). Management of the latter two conditions often requires liver transplantation. Treatment with conventional interferon or pegylated interferon alpha can clear the virus, but the rates are very low. The likelihood, however, of viral resistance to interferon is minimal. The main problems with this therapy are the frequency and severity of side effects. In contrast, nucleos(t)ide analogs (NAs) have significantly lower side effects, but require long term treatment as sustained virological response rates are extremely low. However, long term treatment with NAs increases the risk for the development of anti-viral drug resistance. Only by understanding the molecular basis of resistance and using agents with multiple sites of action can drugs be designed to optimally prevent the occurrence of HBV antiviral resistance.
Collapse
Affiliation(s)
- Nidhi Gupta
- Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Heath Center, Farmington, USA
| | - Milky Goyal
- Department of Microbiology, College of Basic Sciences and Humanities, Punjab Agriculture University, Ludhiana, Punjab, India
| | - Catherine H. Wu
- Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Heath Center, Farmington, USA
| | - George Y. Wu
- Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Heath Center, Farmington, USA
- Correspondence to: George Y. Wu, Department of Medicine, Division of Gastroenterology-Hepatology, University of Connecticut Health Center, Farmington, CT 06030, USA. Tel: +1-800-535-6232. E-mail:
| |
Collapse
|
|
13
|
Grizzi F, Desmet VJ. Liver biopsy interpretation & the regression of hepatitis B virus related cirrhosis. Indian J Med Res 2014; 140:160-162. [PMID: 25297346 PMCID: PMC4216487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Affiliation(s)
- Fabio Grizzi
- Department of Immunology and Inflammation Humanitas Clinical and Research Center Via Manzoni 56 - 20089 Rozzano, Milan, Italy
| | | |
Collapse
|