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Pharmacokinetic Comparison of Eight Major Compounds of Lonicerae japonicae flos after Oral Administration in Normal Rats and Rats with Liver Injury. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27238211. [PMID: 36500304 PMCID: PMC9739780 DOI: 10.3390/molecules27238211] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 11/17/2022] [Accepted: 11/22/2022] [Indexed: 11/27/2022]
Abstract
Traditional Chinese medicine considers Lonicerae japonicae flos to have antibacterial detoxification, liver protection, and gallbladder protection. At present, studies have proven that Lonicerae japonicae flos has a good therapeutic effect on liver injury. Therefore, to confirm the clinical applicability of Lonicerae japonicae flos in the treatment of liver injury, we were the first to compare the pharmacokinetics of an oral ethanol extract of Lonicerae japonicae flos in normal rats and carbon tetrachloride-induced liver injury model rats. A method was developed for the simultaneous determination of 3-caffeoylquinic acid, 4-caffeoylquinic acid, 5-caffeoylquinic acid, 3,5-dicaffeoylquinic acid, 4,5-dicaffeoylquinic acid, protocatechuic acid, Sweroside, and Secoxyloganin in rat plasma by ultra-performance liquid chromatography tandem mass spectrometry. The results show that the method is reliable and reproducible and can be used for quantitative determination of biological samples. The pharmacokinetic parameters showed that the area under the concentration-time curve of eight compounds in the model group was significantly increased. The results showed that the total absorption of the active components of Lonicerae japonicae flos in the blood increased, the clearance rate slowed down, and the bioavailability of Lonicerae japonicae flos increased in liver injury diseases.
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Ao M, Li X, Liao Y, Zhang C, Fan S, Hu C, Chen Z, Yu L. Curcumae Radix: a review of its botany, traditional uses, phytochemistry, pharmacology and toxicology. J Pharm Pharmacol 2021; 74:779-792. [PMID: 34633034 DOI: 10.1093/jpp/rgab126] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Accepted: 08/06/2021] [Indexed: 12/27/2022]
Abstract
OBJECTIVES Curcumae Radix, the medicinal part is radix, commonly called as Yujin (Chinese:), is a widely used traditional Chinese medicine for its high medicinal value and health benefits. Curcumae Radix has been used to treat conditions such as syndrome of heat disease and unconsciousness, epilepsy and internal stagnation of phlegm, qi stagnation and blood stasis, dysmenorrhoea, jaundice, cholelithiasis caused by dampness heat of liver and gallbladder. This review aims to summarize the botany, traditional usages, processing, phytochemistry, quality control, pharmacology and toxicology of Curcumae Radix to better understand its therapeutic potential. KEY FINDINGS So far, a variety of chemical constituents have been isolated and identified from Curcumae Radix, mainly including volatile oil and diphenylheptanes. Modern research shows that the extracts and compounds from Curcumae Radix possess wide-ranging pharmacological effects, including anti-tumour, hepatoprotective, anti-inflammatory and analgesic, anti-thrombosis, as well as effects on the nervous system and others. SUMMARY Curcumae Radix holds an important position in traditional system of medicine. It is cost-effective and an important plant with curative application in contemporary medicine. However, further in-depth studies are also needed to determine the medical uses of this plant and its chemical constituents, pharmacological activity, quality control and toxicology.
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Affiliation(s)
- Mingyue Ao
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.,State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, China
| | - Xing Li
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.,State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, China
| | - Yujiao Liao
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.,State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, China
| | - Chunling Zhang
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.,State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, China
| | - Shunming Fan
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.,State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, China
| | - Changjiang Hu
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.,State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, China
| | - Zhimin Chen
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.,State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, China
| | - Lingying Yu
- College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.,State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu, China
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Na JH, Kim JH, Choe WH, Kwon SY, Yoo BC. Changes in the Hepatitis B Surface Antigen Level According to the HBeAg Status and Drug Used in Long-term Nucleos(t)ide Analog-treated Chronic Hepatitis B Patients. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2021; 77:285-293. [PMID: 34158448 DOI: 10.4166/kjg.2021.043] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Revised: 06/02/2021] [Accepted: 06/04/2021] [Indexed: 12/19/2022]
Abstract
Backgrounds/Aims The HBsAg levels have been used to monitor the chronic hepatitis B (CHB) treatment response to antiviral therapy. On the other hand, it is unclear if the HBsAg quantification levels at each treatment point differ according to the HBeAg status and drug in CHB patients. This study compared the changes in HBsAg in CHB patients according to the HBeAg status and treatment drugs. Methods CHB patients with at least 1 year of follow-up treatment with one drug, either entecavir (ETV) or tenofovir (TDF), were enrolled in this study. The mean HBsAg levels were measured annually for up to 6 years. A linear mixed model was used to compare the HBsAg quantification levels during the follow-up period. An independent samples t-test was used to analyze the differences in the HBsAg quantification levels at each treatment time point. Results Ninety-seven patients were enrolled in this study; 59 among them were HBeAg-positive. Two patients in the TDF group achieved HBsAg seroconversion. The HBsAg level decreased during the follow-up in the ETV and TDF groups. The HBsAg level was lower in the TDF group than the ETV group during the follow-up. On the other hand, subgroup analysis showed that this trend was the same only in the HBeAg-negative patients, not in the HBeAg-positive patients. In the HBeAg-negative patients, HBsAg level in the TDF group was significantly lower than that in the ETV group at 36, 48, and 72 months. The change in HBsAg level from the baseline increased at a decreasing rate during the follow-up in both groups. Furthermore, the change in the HBsAg level in the TDF group was significantly larger than that of the ETV group at 36 months in the HBeAg-negative patients. Conclusions Although TDF might be more efficient than ETV in reducing the HBsAg level in HBeAg-negative patients in a few years, HBsAg seroconversion occurred very rarely. A further large-scale, long-term study will be needed to confirm the antiviral effects on the HBsAg level.
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Affiliation(s)
- Jong Hwa Na
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Jeong Han Kim
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Won Hyeok Choe
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - So Young Kwon
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
| | - Byung Chul Yoo
- Department of Internal Medicine, Konkuk University School of Medicine, Seoul, Korea
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Use of HBsAg quantification in the natural history and treatment of chronic hepatitis B. Hepatol Int 2019; 14:35-46. [PMID: 31745711 DOI: 10.1007/s12072-019-09998-5] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Accepted: 10/19/2019] [Indexed: 02/07/2023]
Abstract
In patients with chronic hepatitis B (CHB) infection, it is important to monitor the natural history, assess treatment response, and predict the risk of liver-related complications. Quantification of serum hepatitis B surface antigen (HBsAg) has gained wide interests since the last decade. It is secreted from hepatocytes in both hepatitis B e antigen (HBeAg)-positive and HBeAg-negative phases of the disease, and can be transcribed and translated from different sources of viral genome [ccc DNA or integrated hepatitis B virus (HBV) DNA]. In untreated patients, it declines slowly through the natural course and remains stable for a long time after HBeAg seroconversion. In patients treated with nucleos(t)ide analogues (NA), it also declines very slowly, even though serum hepatitis B DNA has been rendered negative. Low serum HBsAg may predict either spontaneous or treatment-induced HBsAg seroclearance, and potentially selects out HBeAg-negative patients who can safely stop NA. High serum HBsAg is associated with high risk of hepatocellular carcinoma in untreated population, and predicts treatment failure in patients receiving pegylated interferon. These potential roles of HBsAg quantification are applicable to selected populations only. There is also a need for novel markers to study the effect of emerging antiviral therapies targeting various parts of the HBV cycle to reflect their distinct mechanistic effects. Several agents measuring HBsAg levels have shown rapid and significant decline. Ongoing studies are required to demonstrate the sustainability of HBsAg suppression by these novel agents.
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Zhao W, Zhao G, Zhang S, Wang X, Yu X, Wang B. Clearance of HBeAg and HBsAg of HBV in mice model by a recombinant HBV vaccine combined with GM-CSF and IFN-α as an effective therapeutic vaccine adjuvant. Oncotarget 2018; 9:34213-34228. [PMID: 30344938 PMCID: PMC6188151 DOI: 10.18632/oncotarget.25789] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2017] [Accepted: 10/30/2017] [Indexed: 12/19/2022] Open
Abstract
Chronic hepatitis B virus (CHB) infection is a significant public threat. Current interferon-α (IFN-α) based therapies and anti-viral drugs have failed to clear the infection in the majority of CHB patients and animal models. In our previous study, we established a combined protocol that employed a 3-day pretreatment with granulocyte-macrophage colony stimulating factor (GM-CSF) prior to a standard HBV vaccine. It achieved a 90% reduction of HBsAg level in the HBsAg transgenic mouse model. This protocol, while effective, remains too complex for clinical use. In this study, we formulated a new regimen by combining GM-CSF, IFN-α and a recombinant HBV vaccine (GM-CSF/IFN-α/VACCINE) into a single preparation and tested its efficacy in a HBV infection model. After four vaccinations, both serum HBeAg and HBsAg were cleared, accompanied by a 95% reduction of HBV+ hepatocytes and the presence of a large number of infiltrating CD8+ T cells in the liver. Mechanistically these robust responses were initiated by a vaccine-induced conversion of CCR2-dependent CD11b+Ly6Chi monocytes into CD11b+CD11c+ DCs. This finding sheds light on the potential mechanism of action of the GM-CSF-based vaccine adjuvant and provides definable markers for clinical assessment during future testing of such highly potent vaccine protocols in HBV patients.
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Affiliation(s)
- Weidong Zhao
- Key Laboratory of Medical Molecular Virology of The Ministry of Health and Ministry of Education, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Gan Zhao
- Key Laboratory of Medical Molecular Virology of The Ministry of Health and Ministry of Education, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Shuren Zhang
- Key Laboratory of Medical Molecular Virology of The Ministry of Health and Ministry of Education, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Xianzheng Wang
- Key Laboratory of Medical Molecular Virology of The Ministry of Health and Ministry of Education, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Xueping Yu
- Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Bin Wang
- Key Laboratory of Medical Molecular Virology of The Ministry of Health and Ministry of Education, School of Basic Medical Sciences, Fudan University, Shanghai, China
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Zhu MY, Zou X, Li Q, Yu DM, Yang ZT, Huang D, Chen J, Gong QM, Zhang DH, Zhang Y, Chen L, Chen PZ, Zhang XX. A novel noninvasive algorithm for the assessment of liver fibrosis in patients with chronic hepatitis B virus infection. J Viral Hepat 2017; 24:589-598. [PMID: 28130852 DOI: 10.1111/jvh.12682] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2016] [Accepted: 12/19/2016] [Indexed: 02/06/2023]
Abstract
Several noninvasive blood biomarkers have been established for the assessment of liver fibrosis in patients with chronic hepatitis B virus (HBV) infection, but their clinical performance remains inconclusive. Here, we compared the diagnostic performance of these biomarkers and developed a novel algorithm for assessing liver fibrosis. Six hundred and sixteen chronically HBV-infected and treatment-naïve patients who underwent liver biopsy were enrolled and randomly divided into training (N=410) and internal validation cohorts (N=206). One hundred and fifty-nine patients from another centre were recruited as an external validation cohort. Receiver operating characteristic (ROC) curves were used to analyse the performance of the gamma-glutamyltransferase-to-platelet ratio (GPR), red cell volume distribution width-to-platelet ratio (RPR), FIB-4 index, aspartate aminotransferase-to-platelet ratio index (APRI) and HBV DNA level against liver histology, and a novel algorithm was developed using the recursive partitioning and regression tree (RPART) method. In the training cohort, the area under the ROC curve of FIB-4 was significantly higher than that of APRI (P=.038) but was comparable to those of GPR, RPR and HBV DNA; however, the performance of the biomarkers was similar among the validation cohort. The established RPR-HBV DNA algorithm performed better in the training cohort than any individual blood biomarker, and the corresponding sensitivity, specificity, positive predictive value and negative predictive value were 63%, 90%, 72% and 80%, respectively. In the internal and external validation cohorts, the performance of the algorithm in assessing liver fibrosis was also superior to that of other biomarkers. These results suggest that the established RPR-HBV DNA algorithm might improve the diagnostic accuracy of liver fibrosis in treatment-naïve patients with chronic HBV infection, although additional studies are warranted to confirm these findings.
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Affiliation(s)
- M-Y Zhu
- Department of Infectious Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - X Zou
- Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China
| | - Q Li
- Department of Hepatitis, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - D-M Yu
- Department of Infectious Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Z-T Yang
- Pôle Sino-Français de Recherches en Science du Vivant et Génomique, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - D Huang
- Department of Infectious Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - J Chen
- Department of Infectious Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Q-M Gong
- Department of Infectious Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - D-H Zhang
- Department of Infectious Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Y Zhang
- Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China.,Collaborative Innovation Center of Systems Biomedicine, Shanghai, China
| | - L Chen
- Department of Hepatitis, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - P-Z Chen
- Translational Medicine Research Center, Ruijin Hospital North, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - X-X Zhang
- Department of Infectious Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.,Translational Medicine Research Center, Ruijin Hospital North, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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Thibault V, Servant-Delmas A, Ly TD, Roque-Afonso AM, Laperche S. Performance of HBsAg quantification assays for detection of Hepatitis B virus genotypes and diagnostic escape-variants in clinical samples. J Clin Virol 2017; 89:14-21. [DOI: 10.1016/j.jcv.2017.02.001] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2016] [Revised: 02/01/2017] [Accepted: 02/03/2017] [Indexed: 12/17/2022]
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Cuomo G, Borghi V, Andreone P, Massari M, Villa E, Pietrangelo A, Verucchi G, Ferrari C. Missed treatment in an Italian HBV infected patients cohort: HBV RER. Dig Liver Dis 2016; 48:1346-1350. [PMID: 27498074 DOI: 10.1016/j.dld.2016.07.016] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2016] [Revised: 06/16/2016] [Accepted: 07/13/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Very little is known about the access to treatment for Chronic Hepatitis B in the real clinical practice and the characteristics of the patients who do not receive antiviral therapy. METHODS HBV-RER is an observational multicenter network that collected data of patients with HBV infection during a 3 years observational period (2009-2012). RESULTS Among 2527 HBsAg positive patients, 1099 were never treated (NT); only 280 were included in the analysis due to different exclusion causes A minority was HBeAg-positive. The median age was 42. At liver biopsy most patients had Metavir score of F0-F1. Univariate analysis between 280 NT patients and the 290 naïve to treatment showed that NT patients were mostly female (P=0.002), not Italian (P=0.044), younger (P<0.001). Metavir score was lower in NT (P0.002), such as the Fib4 score (P<0.001). HBV DNA level was significantly higher in NT. At multivariate analysis, independent variables associated with no-treatment were younger age, female gender, Metavir score F0-F1, Fib4 lower than 1.6 and lower blood level of HBV-DNA. CONCLUSIONS There is a large number of patients eligible to treatment who do not receive it. A younger age and a less severe disease seem to be associated to deferral of treatment.
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Affiliation(s)
- Gianluca Cuomo
- Infectious Disease, Azienda Ospedaliero Universitaria di Modena, Modena, Italy.
| | - Vanni Borghi
- Infectious Disease, Azienda Ospedaliero Universitaria di Modena, Modena, Italy
| | - Pietro Andreone
- Internal Medicine, Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy
| | - Marco Massari
- Infectious Disease, IRCCS - ASMN Reggio Emilia, Reggio Emilia, Italy
| | - Erica Villa
- Gastroenterology, Azienda Ospedaliero Universitaria di Modena, Italy
| | | | - Gabriella Verucchi
- Infectious Disease, Azienda Ospedaliero Universitaria di Bologna, Bologna, Italy
| | - Carlo Ferrari
- Infectious Disease and Hepatology, Azienda Ospedaliero Universitaria di Parma, Parma, Italy
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Liu YP, Yao CY. Rapid and quantitative detection of hepatitis B virus. World J Gastroenterol 2015; 21:11954-11963. [PMID: 26576084 PMCID: PMC4641117 DOI: 10.3748/wjg.v21.i42.11954] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2015] [Revised: 07/29/2015] [Accepted: 09/14/2015] [Indexed: 02/06/2023] Open
Abstract
Despite availability of a universal vaccine, hepatitis B virus (HBV) infection has a huge impact on public health worldwide. Accurate and timely diagnosis of HBV infection is needed. Rapid developments have been made in the diagnostic and monitoring methods for HBV infection, including serological and molecular assays. In clinical practice, qualitative hepatitis B surface antigen (HBsAg) testing has long served as a diagnostic marker for individuals infected with HBV. More recently, HBsAg level has been used to predict treatment outcome when determined early during treatment or at baseline. However, identification of HBV DNA positive cases that do not have detectable HBsAg has encouraged the application of molecular tests. Hence, combination of quantitative detection of HBV DNA and HBsAg can be used to discriminate patients during the course of HBV infection and to monitor therapy. This article reviews the most commonly used quantitative methods for HBsAg and HBV DNA.
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Hepatitis B surface antigen seroclearance: Relationship to hepatitis B e-antigen seroclearance and hepatitis B e-antigen-negative hepatitis. Am J Gastroenterol 2014; 109:1764-70. [PMID: 25244963 DOI: 10.1038/ajg.2014.301] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2014] [Accepted: 07/02/2014] [Indexed: 12/11/2022]
Abstract
OBJECTIVES The objective of this study was to determine factors associated with hepatitis B surface antigen (HBsAg) seroclearance after hepatitis B e-antigen (HBeAg) seroclearance. METHODS This is a cohort study of HBeAg-positive patients with HBeAg seroclearance. Factors associated with subsequent HBsAg seroclearance were examined. RESULTS A total of 775 patients were included. At 1, 5, 10, 15, 20, and 25 years after HBeAg seroclearance, the HBsAg seroclearance rate was 0.3, 1.3, 3.0, 8.9, 15.7, and 23.6%, respectively. The rate of HBsAg seroclearance was highest in those who underwent spontaneous HBeAg seroclearance and required no treatment afterward (group 1), compared with those who underwent treatment-induced HBeAg seroclearance (group 2), and those who required antiviral therapy after spontaneous HBeAg seroclearance (group 3). At 25 years after HBeAg seroclearance, the HBsAg seroclearance rate was 38.0, 14.9, and 0% in groups 1, 2, and 3, respectively (P<0.001). There was no difference in the rate of HBsAg seroclearance between those who received interferon-based therapy compared with nucleos(t)ide analogs. The median HBV DNA level was similar between those with and without HBsAg seroclearance. The median HBsAg level was significantly lower in those who had HBsAg seroclearance compared with those who did not achieve loss of HBsAg (2.81 vs. 3.52 log IU/ml, respectively, P=0.009). The area under receiver operating characteristic curve for HBsAg at 1 year after HBeAg seroclearance for predicting HBsAg seroclearance was 0.742, with an optimal cutoff of 751 IU/ml. CONCLUSIONS Spontaneous HBeAg seroclearance without need for subsequent antiviral therapy was associated with the highest rate of subsequent HBsAg seroclearance. Lower HBsAg levels were also associated with higher chance of HBsAg seroclearance.
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Al-Qahtani A, Al-Anazi M, Viswan NA, Khalaf N, Abdo AA, Sanai FM, Al-Ashgar H, Al-Ahdal M. Role of single nucleotide polymorphisms of KIF1B gene in HBV-associated viral hepatitis. PLoS One 2012; 7:e45128. [PMID: 23028799 PMCID: PMC3445584 DOI: 10.1371/journal.pone.0045128] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2012] [Accepted: 08/13/2012] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND/AIM Kinesin family member 1B (KIF1B) gene resides in the chromosomal region 1p36.22 and has been reported to have frequent deletions in a variety of human cancers. A recent genome wide association study (GWAS) study conducted on a Chinese population has reported the involvement of a KIF1B genetic variant in Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). This study aims to investigate the significance of KIF1B genetic variations in HBV-associated hepatitis in patients of Saudi Arabian ethnicity. METHODS TaqMan genotyping assay was used to investigate the association of three SNPs (rs17401966, rs12734551, and rs3748578) in 584 normal healthy controls and 660 HBV-infected patients. The patients were categorized into inactive carriers (Case I), active carriers (Case II), Cirrhosis (Case III) and Cirrhosis-HCC (Case IV) sub-groups. RESULTS Since SNPs rs12734551 and rs3748578 are in strong linkage disequilibrium (LD) with rs17401966, only results for the latter SNP are reported. Therefore, the allele frequency of rs17401966 among HBV-infected patients and healthy controls were comparable and therefore, no significant association was observed (P=0.2811, Odds Ratio (OR) 0.897). A similar analysis was performed among the different sub-groups in order to determine whether KIF1B SNPs were associated with the advancement of the disease. No significant differences were observed in any of the comparisons performed. CONCLUSION Polymorphisms at KIF1B gene locus investigated in this study showed no significant association with HBV infection or with HBV-associated diseases such as liver cirrhosis or HCC.
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Affiliation(s)
- Ahmed Al-Qahtani
- Department of Infection and Immunity, Research Center, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.
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Seto WK, Wong DKH, Fung J, Hung IFN, Fong DYT, Yuen JCH, Tong T, Lai CL, Yuen MF. A large case-control study on the predictability of hepatitis B surface antigen levels three years before hepatitis B surface antigen seroclearance. Hepatology 2012; 56:812-9. [PMID: 22422518 DOI: 10.1002/hep.25718] [Citation(s) in RCA: 78] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2011] [Accepted: 03/01/2012] [Indexed: 12/12/2022]
Abstract
UNLABELLED The kinetics of hepatitis B surface antigen (HBsAg) levels preceding spontaneous HBsAg seroclearance has not been fully investigated. The kinetics of HBsAg and hepatitis B virus (HBV) DNA of 203 treatment-naïve, hepatitis B e antigen (HBeAg)-negative patients with spontaneous HBsAg seroclearance were compared with 203 age- and sex-matched HBeAg-negative controls. Serum samples at 3 years, 2 years, 1 year, and 6 months before HBsAg seroclearance and at the time of HBsAg loss were tested. Median HBsAg levels at these respective time points before HBsAg seroclearance were 23.5, 3.51, 0.524, and 0.146 IU/mL. For all time points, patients with HBsAg seroclearance had significantly lower median HBsAg and HBV DNA levels, compared to those of the controls (all P < 0.001). Median HBsAg and HBV DNA levels declined significantly until HBsAg seroclearance (P < 0.001). Although median HBsAg levels also decreased significantly with time (P = 0.006) in controls, median HBV DNA levels remained similar (P = 0.414). Serum HBsAg levels, followed by HBsAg log reduction, were the best predictors of HBsAg seroclearance, with an area under the receiving operator characteristic (AUROC) of 0.833 (95% confidence interval [CI]: 0.792-0.873) and 0.803 (95% CI: 0.755-0.849), respectively. The optimal cut-off HBsAg level and HBsAg reduction to predict HBsAg seroclearance were <200 IU/mL (sensitivity, 84.2%; specificity, 73.4%) and 0.5 log IU/mL/year (sensitivity, 62.8%; specificity, 88.7%), respectively. For patients with HBsAg levels ≥ 200 IU/mL, an annual 0.5-log reduction was highly predictive of subsequent HBsAg seroclearance (AUROC, 0.867; 95% CI: 0.778-0.956). CONCLUSION To conclude, serum HBsAg <200 IU/mL and 0.5-log reduction in HBsAg were predictive of HBsAg seroclearance within 3 years of follow-up. These parameters may serve as good indicators for the consideration of treatment duration and cessation for chronic hepatitis B.
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Affiliation(s)
- Wai-Kay Seto
- Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong
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Seto WK, Wong DKH, Fung J, Ip PPC, Yuen JCH, Hung IFN, Lai CL, Yuen MF. High hepatitis B surface antigen levels predict insignificant fibrosis in hepatitis B e antigen positive chronic hepatitis B. PLoS One 2012; 7:e43087. [PMID: 22916211 PMCID: PMC3423440 DOI: 10.1371/journal.pone.0043087] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2012] [Accepted: 07/16/2012] [Indexed: 12/14/2022] Open
Abstract
Introduction There is no data on the relationship between hepatitis B surface antigen (HBsAg) levels and liver fibrosis in hepatitis B e antigen (HBeAg)-positive patients with chronic hepatitis B (CHB). Methods Serum HBsAg and HBV DNA levels in HBeAg-positive CHB patients with liver biopsies were analyzed. The upper limit of normal (ULN) of alanine aminotransferase (ALT) was 30 and 19 U/L for men and women respectively. Histologic assessment was based on Ishak fibrosis staging for fibrosis and Knodell histologic activity index (HAI) for necroinflammation. Results 140 patients (65% male, median age 32.7 years) were recruited. 56 (40%) had ALT ≤2×ULN. 72 (51.4%) and 42 (30%) had fibrosis score ≤1 and necroinflammation grading ≤4 respectively. Patients with fibrosis score ≤1, when compared to patients with fibrosis score >1, had significantly higher median HBsAg levels (50,320 and 7,820 IU/mL respectively, p<0.001). Among patients with ALT ≤2×ULN, serum HBsAg levels achieved an area under receiver operating characteristic curve of 0.869 in predicting fibrosis score ≤1. HBsAg levels did not accurately predict necroinflammation score. HBsAg ≥25,000 IU/mL was independently associated with fibrosis score ≤1 (p = 0.025, odds ratio 9.042).Using this cut-off HBsAg level in patients with ALT ≤2×ULN, positive and negative predictive values for predicting fibrosis score ≤1 were 92.7% and 60.0% respectively. HBV DNA levels had no association with liver histology. Conclusion Among HBeAg-positive patients with ALT ≤2×ULN, high serum HBsAg levels can accurately predict fibrosis score ≤1, and could potentially influence decisions concerning treatment commencement and reduce the need for liver biopsy.
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Affiliation(s)
- Wai-Kay Seto
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong
| | - Danny Ka-Ho Wong
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong
| | - James Fung
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong
| | - Philip P. C. Ip
- Department of Pathology, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong
| | - John Chi-Hang Yuen
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong
| | - Ivan Fan-Ngai Hung
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong
| | - Ching-Lung Lai
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong
- State Key Laboratory for Liver Research, University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong
| | - Man-Fung Yuen
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong
- State Key Laboratory for Liver Research, University of Hong Kong, Queen Mary Hospital, Hong Kong, Hong Kong
- * E-mail:
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Serum hepatitis B surface antigen (HBsAg) kinetics in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B. Hepatol Int 2012; 7:119-26. [PMID: 24466363 PMCID: PMC3895190 DOI: 10.1007/s12072-012-9373-4] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2012] [Accepted: 04/19/2012] [Indexed: 12/22/2022]
Abstract
Background We investigated the differences in HBsAg kinetics at different levels of viremia in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB). Methods We compared HBsAg levels among HBeAg-negative CHB patients with persistently undetectable HBV DNA (≤20 IU/mL; Group A, n = 100), HBV DNA 20–2,000 IU/mL (Group B, n = 100), and HBV DNA >2,000 IU/mL (Group C, n = 100). HBsAg and HBV DNA levels were measured at three consecutive time points during follow-up (median 21.4 months). Results Median HBsAg levels were significantly lower in Group A than in Groups B and C at all time points (p < 0.001). HBV DNA and HBsAg levels were weakly correlated (r = 0.180 and 0.151 for Groups B and C, respectively). Among patients with HBsAg <100 IU/mL, Group A patients had the greatest median serum HBsAg reduction (0.341 log IU/mL/year; Group B, 0.122 log IU/mL/year; Group C, 0.057 log IU/mL/year; p = 0.002). Among Group A patients with HBsAg <100 IU/mL, baseline HBsAg achieved an AUROC of 0.876 in predicting >1 log annual HBsAg reduction; 10–100 IU/mL HBsAg was the optimal level for prediction (sensitivity 90 %; specificity 74.6 %). Serum HBsAg/HBV DNA ratios were significantly higher in Group B than in Groups A and C (p < 0.05). Conclusions HBV DNA and HBsAg were weakly correlated. Only patients with undetectable HBV DNA showed decline in HBsAg levels during follow-up. The greatest reduction in HBsAg levels occurred in patients with baseline HBsAg <100 IU/mL.
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Seto WK, Tanaka Y, Wong DKH, Lai CL, Shinkai N, Yuen JCH, Tong T, Fung J, Hung IFN, Yuen MF. Evidence of serologic activity in chronic hepatitis B after surface antigen (HBsAg) seroclearance documented by conventional HBsAg assay. Hepatol Int 2012; 7:98-105. [PMID: 24014110 PMCID: PMC3758508 DOI: 10.1007/s12072-012-9354-7] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2011] [Accepted: 02/21/2012] [Indexed: 02/07/2023]
Abstract
BACKGROUND Possible serologic activity after hepatitis B surface antigen (HBsAg) seroclearance documented by conventional assays in chronic hepatitis B (CHB) has not been thoroughly investigated. METHODS We determined the levels of serum hepatitis B virus (HBV) DNA, hepatitis B core-related antigen (HBcrAg), and linearized HBsAg (CLEIA prototype) in 329 CHB patients (72.0% male) after HBsAg seroclearance was documented by a conventional HBsAg assay. RESULTS The median interval between presentation and HBsAg seroclearance was 69.4 months. The median age at HBsAg seroclearance was 50 years. Assays for serum HBV DNA, HBcrAg, and linearized HBsAg were performed at a median time interval of 11.2 months after HBsAg loss. Linearized HBsAg and HBcrAg were detectable in 85 (25.8%) and 69 (21%) patients, respectively, and one or both serologic markers were detectable in 133 patients (40.4%). Serum HBV DNA was detectable in only 7 patients (2.1%). There was no correlation between linearized HBsAg and HBcrAg levels (r = 0.095, p = 0.924). The incidences of detectable linearized HBsAg and HBcrAg did not differ between patient samples taken at 6-12 and >12 months after HBsAg seroclearance (p = 0.146 and 0.079, respectively). Among patients with detectable serologic markers, median levels of linearized HBsAg (p = 0.581) and HBcrAg (p = 0.951) did not significantly change with time after HBsAg seroclearance. CONCLUSION Using novel HBcrAg and linearized HBsAg assays, viral serologic activity after HBsAg seroclearance was demonstrated in more than 40% of CHB patients. These tests have potential applications in diagnosing and prognosticating CHB patients with HBsAg seroclearance.
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Affiliation(s)
- Wai-Kay Seto
- />Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam Road, Hong Kong, China
| | - Yasuhito Tanaka
- />Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Danny Ka-Ho Wong
- />Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam Road, Hong Kong, China
| | - Ching-Lung Lai
- />Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam Road, Hong Kong, China
- />State Key Laboratory for Liver Research, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
| | - Noboru Shinkai
- />Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - John Chi-Hang Yuen
- />Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam Road, Hong Kong, China
| | - Teresa Tong
- />Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam Road, Hong Kong, China
| | - James Fung
- />Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam Road, Hong Kong, China
| | - Ivan Fan-Ngai Hung
- />Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam Road, Hong Kong, China
| | - Man-Fung Yuen
- />Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam Road, Hong Kong, China
- />State Key Laboratory for Liver Research, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China
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Abbas Z, Siddiqui AR. Management of hepatitis B in developing countries. World J Hepatol 2011; 3:292-299. [PMID: 22216369 PMCID: PMC3246547 DOI: 10.4254/wjh.v3.i12.292] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2011] [Revised: 09/26/2011] [Accepted: 10/03/2011] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B is one of the leading causes of chronic hepatitis in developing countries, with 5% to 15% of the population carrying virus. The high prevalence is due to failure to adopt appropriate measure to confine the spread of infection. Most hepatitis B patients present with advanced diseases. Although perinatal transmission is believed to be an important mode, most infections in the developing world occur in childhood and early adulthood. Factors in developing countries associated with the progression of chronic hepatitis B (CHB) include co-infections with human immunodeficiency virus, delta hepatitis virus, hepatitis C virus, alcohol intake and aflatoxin. Treatment protocols extrapolated from developed countries may need modifications according to the resources available. There is some controversy as to when to start treatment, with what medication and for how long? There is now enough evidence to support that hepatitis B patients should be considered for treatment if they show persistently elevated abnormal aminotransferase levels in the last 6 mo, checked on at least three separate occasions, and a serum hepatitis B virus DNA level of > 2000 IU/mL. Therapeutic agents that were approved by Pure Food and Drug Administration are now available in many developing countries. These include standard interferon (INF)-α, pegylated INF-α, lamivudine, adefovir, entecavir and telbivudine. Drug resistance has emerged as a major challenge in the management of patients with CHB. The role of the universal vaccination program for effective control of hepatitis B cannot be emphasized enough.
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Affiliation(s)
- Zaigham Abbas
- Zaigham Abbas, Adeel R Siddiqui, Department of Hepatogastroenterology, Sindh Institute of Urology and Transplantation, Karachi 74200, Pakistan
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Kim YJ, Cho HC, Choi MS, Lee JH, Koh KC, Yoo BC, Paik SW. The change of the quantitative HBsAg level during the natural course of chronic hepatitis B. Liver Int 2011; 31:817-23. [PMID: 21645212 DOI: 10.1111/j.1478-3231.2011.02516.x] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
BACKGROUND There is insufficient information about HBsAg levels and their correlation with serum hepatitis B virus (HBV) DNA in chronic hepatitis B (CHB). AIMS We aimed to describe HBsAg levels during various phases of CHB and to investigate the correlation with serum HBV DNA levels. METHODS A total of 645 treatment-naïve Korean CHB patients were included in this retrospective cross-sectional study. They were categorized into immune tolerance (IT, n=56), HBeAg-positive hepatitis (EPH, n=150), inactive carrier (IC, n=274) and HBeAg-negative hepatitis (ENH, n=165). The baseline HBsAg and HBV DNA levels were measured. RESULTS The mean HBsAg titres (log IU/ml) differed (P<0.001): IT 4.29, EPH 3.64, IC 2.05 and ENH 3.23. In 645 patients, HBsAg and HBV DNA showed a significant correlation (r=0.693, P<0.001), and this was also observed in the IT, EPH and IC groups (r=0.664, r=0.541, r=0.505, respectively, all P<0.001), but not in the ENH group (r=0.093, P=0.321). Age had a negative correlation with HBsAg (r=-0.451, P<0.001). The cirrhotic patients had a significantly lower HBsAg level than the non-cirrhotic patients (2.41 ± 1.36 vs. 3.02 ± 1.21 log IU/ml, P<0.001). CONCLUSIONS The HBsAg level varied significantly in different phases of CHB and was correlated with HBV DNA during the IT, EPH and IC phases. These findings can provide additional information to understand the natural course and pathogenesis of CHB.
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Affiliation(s)
- Yu J Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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