|
1
|
Farhan M, Ling Z, Shah Z, Islam S, Alshehri MH, Antonescu E. A multi-layer neural network approach for the stability analysis of the Hepatitis B model. Comput Biol Chem 2024; 113:108256. [PMID: 39522485 DOI: 10.1016/j.compbiolchem.2024.108256] [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: 07/28/2024] [Revised: 10/05/2024] [Accepted: 10/15/2024] [Indexed: 11/16/2024]
Abstract
In the present study, we explore the dynamics of Hepatitis B virus infection, a significant global health issue, through a newly developed dynamics system. This model is distinguished by its inclusion of asymptomatic carriers and the impact of vaccination and treatment strategies. Compared to Hepatitis A, Hepatitis B poses a more serious health risk, with some cases progressing from acute to chronic. To diagnose and predict disease recurrence, the basic reproduction number (R0) is calculated. We investigate the stability of the disease's dynamics under different conditions, using the Lyapunov function to confirm our model's global stability. Our findings highlight the relevance of vaccination and early treatment in reducing Hepatitis B virus spread, making them a useful tool for public health efforts aiming at eradicating Hepatitis B virus. In our research, we investigate the dynamics of a specific model that is characterized by a system of differential equations. This work uses deep neural networks (DNNs) technique to improve model accuracy, proving the use of DNNs in epidemiological modeling. Additionally, we want to find the curves that suit the target solutions with the minimum residual errors. The simulations we conducted demonstrate our methodology's capability to accurately predict the behavior of systems across various conditions. We rigorously test the solutions obtained via the DNNs by comparing them to benchmark solutions and undergoing stages of testing, validation, and training. To determine the accuracy and reliability of our approach, we perform a series of analyses, including convergence studies, error distribution evaluations, regression analyses, and detailed curve fitting for each equation.
Collapse
Affiliation(s)
- Muhammad Farhan
- School of Mathematical Science, Yangzhou University, Yangzhou 225002, China
| | - Zhi Ling
- School of Mathematical Science, Yangzhou University, Yangzhou 225002, China
| | - Zahir Shah
- Department of Mathematical Sciences, University of Lakki Marwat, Lakki Marwat 28420, KPK, Pakistan.
| | - Saeed Islam
- Department of Mathematics, Abdul Wali Khan University Mardan, Khyber Pakhtunkhwa, Pakistan
| | - Mansoor H Alshehri
- Department of Mathematics, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
| | - Elisabeta Antonescu
- Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania
| |
Collapse
|
|
2
|
Domínguez A, Avellón A, Hernando V, Soldevila N, Borràs E, Martínez A, Izquierdo C, Torner N, Pericas C, Rius C, Godoy P. Hepatitis B Virus-Related Cirrhosis and Hepatocellular Carcinoma Hospital Discharge Rates from 2005 to 2021 in Spain: Impact of Universal Vaccination. Vaccines (Basel) 2024; 12:1254. [PMID: 39591157 PMCID: PMC11598889 DOI: 10.3390/vaccines12111254] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 10/25/2024] [Accepted: 11/01/2024] [Indexed: 11/28/2024] Open
Abstract
Background: The main consequences of chronic hepatitis B virus (HBV) infections are cirrhosis and hepatocellular carcinoma (HCC), both associated with frequent hospitalization. The aim of this study was to analyze the impact of universal HBV vaccination in Spain on chronic HBV-related hospital discharges from 2005 to 2021. Methods: Using data from the Minimum Basic Data Set of the Spanish National Health System, we calculated the hospital discharge rate ratio (HDRR) and 95% confidence interval (CI) values for chronic HBV-related discharges between 2005 and 2021. For comparative purposes, we calculated the HDRR and 95% confidence interval (CI) values for the early (2005-2013) and later (2014-2021) periods and the vaccinated compared with unvaccinated cohorts for the 20-39 age group. Results: The hospital discharge rate per 1,000,000 people was 3.08 in 2005 and 4.50 in 2021 for HCC, and 4.81 in 2005 and 1.92 in 2021 for cirrhosis. Comparing the early and later periods, values were higher for HCC (HDRR 1.13; 95% CI: 1.06-1.20) and lower for cirrhosis (HDRR 0.56; 95% CI: 0.51-0.60). The rate for the 20-39 age group was lower for the vaccinated compared with the unvaccinated cohorts overall (HDRR 0.53; 95% CI: 0.45-0.62), for HCC (HDRR 0.66; 95% CI: 0.53-0.82), and for cirrhosis (HDRR 0.41; 95% CI: 0.33-0.53). Conclusions: This study describes the important impact, after 25 years, of universal HBV vaccination in Spain: cirrhosis hospital discharge rate was reduced, and the vaccinated cohorts, compared with the unvaccinated cohorts in the 20-39 age group, had a lower hospital discharge rate of both HCC and cirrhosis.
Collapse
Affiliation(s)
- Angela Domínguez
- Department of Medicine, Universidad de Barcelona, 08036 Barcelona, Spain; (A.D.); (E.B.); (N.T.); (C.P.)
- CIBER Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, 28029 Madrid, Spain; (A.A.); (A.M.); (C.R.); (P.G.)
| | - Ana Avellón
- CIBER Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, 28029 Madrid, Spain; (A.A.); (A.M.); (C.R.); (P.G.)
- Hepatitis Unit, National Centre of Microbiology, Instituto de Salud Carlos III, 28222 Madrid, Spain
| | - Victoria Hernando
- Centro Nacional de Epidemiología, Instituto de Salud Carlos III, 28029 Madrid, Spain;
- CIBER Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Núria Soldevila
- Department of Medicine, Universidad de Barcelona, 08036 Barcelona, Spain; (A.D.); (E.B.); (N.T.); (C.P.)
- CIBER Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, 28029 Madrid, Spain; (A.A.); (A.M.); (C.R.); (P.G.)
| | - Eva Borràs
- Department of Medicine, Universidad de Barcelona, 08036 Barcelona, Spain; (A.D.); (E.B.); (N.T.); (C.P.)
- CIBER Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, 28029 Madrid, Spain; (A.A.); (A.M.); (C.R.); (P.G.)
- Agència de Salut Pública de Catalunya, 08005 Barcelona, Spain;
| | - Ana Martínez
- CIBER Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, 28029 Madrid, Spain; (A.A.); (A.M.); (C.R.); (P.G.)
- Agència de Salut Pública de Catalunya, 08005 Barcelona, Spain;
| | | | - Núria Torner
- Department of Medicine, Universidad de Barcelona, 08036 Barcelona, Spain; (A.D.); (E.B.); (N.T.); (C.P.)
- CIBER Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, 28029 Madrid, Spain; (A.A.); (A.M.); (C.R.); (P.G.)
| | - Carles Pericas
- Department of Medicine, Universidad de Barcelona, 08036 Barcelona, Spain; (A.D.); (E.B.); (N.T.); (C.P.)
- Agència de Salut Pública de Barcelona, 08023 Barcelona, Spain
- Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau (IRB Sant Pau), 08041 Barcelona, Spain
| | - Cristina Rius
- CIBER Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, 28029 Madrid, Spain; (A.A.); (A.M.); (C.R.); (P.G.)
- Agència de Salut Pública de Barcelona, 08023 Barcelona, Spain
- Institut de Recerca de l’Hospital de la Santa Creu i Sant Pau (IRB Sant Pau), 08041 Barcelona, Spain
- Department MELIS-UPF, Universitat Pompeu Fabra, 08002 Barcelona, Spain
| | - Pere Godoy
- CIBER Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, 28029 Madrid, Spain; (A.A.); (A.M.); (C.R.); (P.G.)
- Institut de Recerca Biomédica de Lleida (IRBLleida), 25006 Lleida, Spain
| |
Collapse
|
|
3
|
Maung ST, Decharatanachart P, Treeprasertsuk S, Chaiteerakij R. Risk Factors for Development of Cirrhosis in Chronic Viral Hepatitis B Patients Who Had Persistent Viral Suppression With Antiviral Therapy. J Clin Exp Hepatol 2024; 14:101388. [PMID: 38523735 PMCID: PMC10956063 DOI: 10.1016/j.jceh.2024.101388] [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: 09/13/2023] [Accepted: 02/24/2024] [Indexed: 03/26/2024] Open
Abstract
BACKGROUND AND AIMS Chronic viral hepatitis B (CHB)-infected patients occasionally develop cirrhosis despite having persistent viral suppression with antiviral therapy. We aimed to identify risk factors for developing cirrhosis in hepatitis B virus (HBV)-suppressed patients. METHODS We conducted a case-control study involving 120 noncirrhotic CHB-infected patients achieving viral suppression with antiviral treatment, with 40 cases developing cirrhosis and 80 age-, sex-, and Fibrosis-4 (FIB-4)-matched controls. Clinical and laboratory data at viral suppression, including body mass index (BMI), comorbidities, pretreatment HBV viral load, HBe antigen status, hepatitis C virus (HCV) and HIV coinfections, liver chemistries, and AST to Platelets Ratio Index (APRI) values, were retrospectively abstracted. Risk factors for cirrhosis post-HBV suppression were identified using Cox proportional hazard analysis. RESULTS Case and control groups had similar ages (51.4 ± 9.9 vs. 51.4 ± 10.2 years), proportions of males (80% vs. 80%), and FIB-4 values (1.32 vs. 1.31). The cirrhosis group showed significantly higher BMI (25.1 vs. 22.7, P = 0.01) and more diabetes prevalence (50.0% vs. 26.3%, P = 0.01), while other comorbidities and laboratory parameters were comparable (P > 0.05). By univariate analysis, BMI >23 kg/m2, diabetes, and APRI >0.7 were significantly associated with cirrhosis, with hazard ratios (HRs) (95%CI) of 2.99 (1.46-6.13), 2.31 (1.23-4.36), and 2.71 (1.05-6.99), P = 0.003, 0.010, and 0.039, respectively. In multivariate analyses adjusted for APRI, BMI>23 kg/m2 remained significantly associated with cirrhosis (aHR: 2.76, P = 0.006), while diabetes showed borderline significance (aHR: 1.99, P = 0.072). CONCLUSIONS In HBV-infected patients achieving viral suppression with therapy, a BMI >23 kg/m2 increases the risk of cirrhosis. Therefore, a comprehensive approach addressing metabolic factors is imperative for preventing disease progression in HBV-infected patients.
Collapse
Affiliation(s)
- Soe T. Maung
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Ma Har Myaing Hospital, Yangon, Myanmar
| | | | - Sombat Treeprasertsuk
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Roongruedee Chaiteerakij
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
- Center of Excellence for Innovation and Endoscopy in Gastrointestinal Oncology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| |
Collapse
|
|
4
|
He X, Ding Q. D-dimer-to-platelet count ratio as a novel indicator for predicting prognosis in HBV-related decompensated cirrhosis. Heliyon 2024; 10:e26585. [PMID: 38434313 PMCID: PMC10907634 DOI: 10.1016/j.heliyon.2024.e26585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2023] [Revised: 02/15/2024] [Accepted: 02/15/2024] [Indexed: 03/05/2024] Open
Abstract
Background Hepatitis B virus-related decompensated cirrhosis (HBV-DC) is a critical illness with a low survival rate. Timely identification of prognostic indicators is crucial for risk stratification and personalized management of patients. The present study aimed to investigate the potential of the D-dimer-to-platelet count ratio (DPR) as a prognostic indicator for HBV-DC. Methods A retrospective review of medical records was conducted for 164 patients diagnosed with HBV-DC. Baseline clinical and laboratory characteristics were extracted for analysis. The endpoint was 30-day mortality. Disease severity was assessed by the Model for End-stage Liver Disease (MELD) score. A multivariate logistic regression model and receiver operating characteristic curve analysis (ROC) were used to evaluate the predictive value of DPR for mortality. Results During the 30-day follow-up period, 30 (18.3%) patients died. Non-survivors exhibited significantly higher DPR values than survivors, and a high DPR had a strong association with increased mortality. Importantly, DPR was identified as an independent risk factor for mortality in HBV-DC patients after adjustments for confounding factors (Odds ratio = 1.017; 95% Confidence interval, 1.006-1.029; p = 0.003). The cut-off value of DPR as a predictor of mortality was>57.6 (sensitivity = 57%, specificity = 86%, p < 0.001). The area under ROC curve for DPR for 30-day mortality was 0.762, comparable to the MELD score (p = 0.100). Furthermore, the combined use of DPR and MELD score further increased the area under the ROC curve to 0.897. Conclusion Elevated DPR was demonstrated to have a correlation with unfavorable outcomes in HBV-DC patients, suggesting its potential utility as an effective biomarker for assessment of prognosis in these patients.
Collapse
Affiliation(s)
| | - QiuMing Ding
- Department of Clinical Laboratory, Shengzhou People's Hospital, Shengzhou Branch of the First Affiliated Hospital of Zhejiang University, Shengzhou, 312400, China
| |
Collapse
|
|
5
|
Ye X, He X, Hu Z, Zheng F, Huang X, Xie X, Chen F, Ou H, Qiu R. Metabolomic analysis identifies dysregulation of lipid metabolism in the immune clearance phase of chronic hepatitis B patients. J Pharm Biomed Anal 2024; 239:115900. [PMID: 38064772 DOI: 10.1016/j.jpba.2023.115900] [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: 09/28/2023] [Revised: 11/13/2023] [Accepted: 12/01/2023] [Indexed: 01/05/2024]
Abstract
There is an accelerated progression of liver necroinflammation and fibrosis in the liver during the immune clearance (IC) phase of Chronic hepatitis B virus (HBV) infection, which are critical indicators of antiviral treatment for chronic hepatitis B (CHB) infection. This study applied serum metabolomics to identify the potential metabolite biomarkers for differential diagnosis between the CHB immune tolerance (IT) and Immune clearance (IC) phases. A liquid chromatography-mass spectrometry (LC-MS)-based approach was applied to evaluate and compared the serum metabolic profiles of 28 patients in IT phase and 33 patients in IC phase and appropriate statistical methods with MetaboAnalystR 2.0 R package to analyze those metabolites. The differential metabolites between IT and TC groups were classified and the top altered classification were lipids and lipid-like molecules and fatty acyls, clearly indicating that there were differences in the lipid metabolomic profile of HBV-infected patients with IT vs. IR phase. We identified the top 10 potential metabolite biomarkers for differential diagnosis between IT and IR. There were four lipid metabolites among them and the AUC of two of them, octadecadienoyl-sn-glycero-3-phosphocholine and 3-Cycloheptene-l-acetic acid, were 0.983 and 0.933. octadecadienoyl-sn-glycero-3-phosphocholine is Diacylglycerol (18:2n6/18:0) and 3-Cycloheptene-l-acetic acid is hydroxy fatty acids, both of which were associated with lipid metabolism. This study not only provides the potential metabolic biomarkers but also insight into the mechanism of CHB progression during IT clearance phase.
Collapse
Affiliation(s)
- Xiangyang Ye
- Department of Infectious Diseases, The Affiliated Hospital of Putian University, Putian, Fujian 351100, China; Fujian Medical University, Fuzhou, Fujian, 350122, China
| | - Xiongzhi He
- Department of Infectious Diseases, The Affiliated Hospital of Putian University, Putian, Fujian 351100, China
| | - Zhenting Hu
- Department of Infectious Diseases, The Affiliated Hospital of Putian University, Putian, Fujian 351100, China
| | - Fengfeng Zheng
- Department of Infectious Diseases, The Affiliated Hospital of Putian University, Putian, Fujian 351100, China
| | - Xiaogang Huang
- Department of Infectious Diseases, The Affiliated Hospital of Putian University, Putian, Fujian 351100, China
| | - Xuemei Xie
- Department of Infectious Diseases, The Affiliated Hospital of Putian University, Putian, Fujian 351100, China
| | - Feihua Chen
- Department of Infectious Diseases, The Affiliated Hospital of Putian University, Putian, Fujian 351100, China
| | - Hanbing Ou
- Department of Infectious Diseases, The Affiliated Hospital of Putian University, Putian, Fujian 351100, China
| | - Rongxian Qiu
- Department of Infectious Diseases, The Affiliated Hospital of Putian University, Putian, Fujian 351100, China.
| |
Collapse
|
|
6
|
Nguyen LBL, Lemoine M, Ndow G, Ward ZJ, Hallet TB, D'Alessandro U, Thursz M, Nayagam S, Shimakawa Y. Treat All versus targeted strategies to select HBV-infected people for antiviral therapy in The Gambia, west Africa: a cost-effectiveness analysis. Lancet Glob Health 2024; 12:e66-e78. [PMID: 38097300 DOI: 10.1016/s2214-109x(23)00467-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 10/04/2023] [Accepted: 10/05/2023] [Indexed: 12/18/2023]
Abstract
BACKGROUND Global elimination of hepatitis B virus (HBV) requires expanded uptake of antiviral therapy, potentially by simplifying testing algorithms, especially in resource-limited countries. We evaluated the effectiveness, cost-effectiveness, and budget impact of three strategies that determine eligibility for anti-HBV treatment, as compared with the WHO 2015 treatment eligibility criteria, in The Gambia. METHODS We developed a microsimulation model of natural history using data from the Prevention of Liver Fibrosis and Cancer in Africa programme (known as PROLIFICA) in The Gambia, for an HBV-infected cohort of individuals aged 20 years. The algorithms included in the model were a conventional strategy using the European Association for the Study of the Liver (EASL) 2017 criteria, a simplified algorithm using hepatitis B e antigen and alanine aminotransferase (the Treatment Eligibility in Africa for the Hepatitis B Virus [TREAT-B] score), a Treat All approach for all HBV-infected individuals, and the WHO 2015 criteria. Outcomes to measure effectiveness were disability-adjusted life years (DALYs) and years of life saved (YLS), which were used to calculate incremental cost-effectiveness ratios (ICERs) with the WHO 2015 criteria as the base-case scenario. Costs were assessed from a modified social perspective. A budget impact analysis was also done. We tested the robustness of results with a range of sensitiviy analyses including probabilistic sensitivity analysis. FINDINGS Compared with the WHO criteria, TREAT-B resulted in 4877 DALYs averted and Treat All resulted in 9352 DALYs averted, whereas the EASL criteria led to an excess of 795 DALYs. TREAT-B was cost-saving, whereas the ICER for Treat All (US$2149 per DALY averted) was higher than the cost-effectiveness threshold for The Gambia (0·5 times the country's gross domestic product per capita: $352). These patterns did not change when YLS was the outcome. In a modelled cohort of 5000 adults (aged 20 years) with chronic HBV infection from The Gambia, the 5-year budget impact was $1·14 million for Treat All, $0·66 million for TREAT-B, $1·03 million for the WHO criteria, and $1·16 million for the EASL criteria. Probabilistic sensitivity analysis indicated that among the Treat All, EASL, and TREAT-B algorithms, Treat All would become the most preferred strategy only with a willingness-to-pay threshold exceeding approximately $72 000 per DALY averted or $110 000 per YLS. INTERPRETATION Although the Treat All strategy might be the most effective, it is unlikely to be cost-effective in The Gambia. A simplified strategy such as TREAT-B might be a cost-saving alternative. FUNDING UK Research and Innovation (Medical Research Council). TRANSLATION For the French translation of the abstract see Supplementary Materials section.
Collapse
Affiliation(s)
- Liem B Luong Nguyen
- Institut Pasteur, Université Paris Cité, Unité d'Épidémiologie des Maladies Émergentes, Paris, France; CIC Cochin Pasteur, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Maud Lemoine
- Department of Metabolism, Digestion and Reproduction, Division of Digestive Disease, Liver Unit, St Mary's Hospital, Imperial College London, UK; Medical Research Council Unit, London School of Hygiene & Tropical Medicine, Fajara, The Gambia
| | - Gibril Ndow
- Department of Metabolism, Digestion and Reproduction, Division of Digestive Disease, Liver Unit, St Mary's Hospital, Imperial College London, UK; Medical Research Council Unit, London School of Hygiene & Tropical Medicine, Fajara, The Gambia
| | - Zachary J Ward
- Center for Health Decision Science, Harvard TH Chan School of Public Health, Boston, MA, USA
| | - Timothy B Hallet
- Medical Research Council Centre for Global Infectious Disease Analysis, School of Public Health, Imperial College London, London, UK
| | - Umberto D'Alessandro
- Medical Research Council Unit, London School of Hygiene & Tropical Medicine, Fajara, The Gambia
| | - Mark Thursz
- Department of Metabolism, Digestion and Reproduction, Division of Digestive Disease, Liver Unit, St Mary's Hospital, Imperial College London, UK
| | - Shevanthi Nayagam
- Department of Metabolism, Digestion and Reproduction, Division of Digestive Disease, Liver Unit, St Mary's Hospital, Imperial College London, UK; Medical Research Council Centre for Global Infectious Disease Analysis, School of Public Health, Imperial College London, London, UK
| | - Yusuke Shimakawa
- Institut Pasteur, Université Paris Cité, Unité d'Épidémiologie des Maladies Émergentes, Paris, France.
| |
Collapse
|
|
7
|
STOKES CALEB, J. MELVIN ANN. Viral Infections of the Fetus and Newborn. AVERY'S DISEASES OF THE NEWBORN 2024:450-486.e24. [DOI: 10.1016/b978-0-323-82823-9.00034-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
|
8
|
Pantelidou P, Sinakos E, Germanidis G, Pagkalidou E, Haidich AB, Akriviadis E, Hytiroglou P. Assessment of histologic risk factors for hepatocellular carcinoma in patients with chronic hepatitis B of advanced stage. Pathol Res Pract 2023; 249:154741. [PMID: 37586217 DOI: 10.1016/j.prp.2023.154741] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2023] [Revised: 08/03/2023] [Accepted: 08/03/2023] [Indexed: 08/18/2023]
Abstract
Histologic markers of increased risk for hepatocellular carcinoma can provide useful information for the management of patients with chronic hepatitis B. The expression of epithelial cell adhesion molecule (EpCAM, a marker of hepatic progenitor cells), p21 (a marker of hepatocyte senescence), glutamine synthetase (a marker of perivenular hepatocytes) and CD34 (a marker of sinusoidal capillarization) were assessed by immunohistochemistry in 52 liver biopsy specimens from patients with advanced stage chronic hepatitis B. Nineteen patients developed hepatocellular carcinoma during a follow-up period of 133 months. The findings were compared with those of 18 liver biopsy specimens from patients with early-stage chronic hepatitis B and 6 liver biopsy specimens without significant pathologic findings. EpCAM expression in hepatocytes was significantly increased in specimens with advanced stage, as compared with all other specimens. EpCAM positivity in over 30 % of hepatocytes was only seen in 3 specimens from patients who subsequently developed hepatocellular carcinoma. The expression of p21, glutamine synthetase and CD34 was not associated with hepatocellular carcinoma development. Nevertheless, glutamine synthetase immunostains highlighted zonality abnormalities that were useful in chronic hepatitis B staging. In conclusion, extensive immunopositivity of hepatocytes for EpCAM in chronic hepatitis B may represent a marker of increased hepatocellular carcinoma risk. Glutamine synthetase immunostaining represents a useful adjunct in determining the stage of chronic hepatitis B in diagnostic practice.
Collapse
Affiliation(s)
- Pavlina Pantelidou
- Department of Pathology, School of Medicine, Aristotle University of Thessaloniki, Greece
| | - Emmanouil Sinakos
- Fourth Department of Internal Medicine, School of Medicine, Aristotle University of Thessaloniki, Greece
| | - Georgios Germanidis
- First Department of Internal Medicine, School of Medicine, Aristotle University of Thessaloniki, Greece
| | - Eirini Pagkalidou
- Department of Hygiene, Social-Preventive Medicine and Medical Statistics, School of Medicine, Aristotle University of Thessaloniki, Greece
| | - Anna Bettina Haidich
- Department of Hygiene, Social-Preventive Medicine and Medical Statistics, School of Medicine, Aristotle University of Thessaloniki, Greece
| | - Evangelos Akriviadis
- Fourth Department of Internal Medicine, School of Medicine, Aristotle University of Thessaloniki, Greece
| | - Prodromos Hytiroglou
- Department of Pathology, School of Medicine, Aristotle University of Thessaloniki, Greece.
| |
Collapse
|
|
9
|
Mao T, Zhang B, Yang T, Qian Y, Zhou C, He C. Evaluation of five lymphocyte-based scores for prediction of mortality in hepatitis B virus-associated decompensated cirrhosis. Heliyon 2023; 9:e18556. [PMID: 37520964 PMCID: PMC10374927 DOI: 10.1016/j.heliyon.2023.e18556] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Revised: 07/14/2023] [Accepted: 07/20/2023] [Indexed: 08/01/2023] Open
Abstract
Background Lymphocytes are generally accepted to be a key component of the immune response, and an inadequate immune response is closely associated with disease severity and adverse outcomes in hepatitis B virus (HBV)-infected patients. The present study aimed to determine and compare the prognostic values of five lymphocyte-based scores (monocyte-to-lymphocyte ratio [MLR], mean platelet volume-to-lymphocyte ratio [MPVLR], neutrophil-to-lymphocyte ratio [NLR], red cell distribution width-to-lymphocyte ratio [RLR], and C-reactive protein-to-lymphocyte ratio [CLR]) for HBV-associated decompensated cirrhosis (HBV-DC). Methods Data were extracted from an institutional database. The outcome was 30-day mortality. Receiver operating characteristic curve analyses were conducted, and the resulting area under the curve (AUC) values were used to evaluate the predictive capabilities of the five lymphocyte-based scores for mortality in HBC-DC relative to Model for End-Stage Liver Disease (MELD) score. Results The study included 273 patients, and the 30-day mortality was 20.9%. Lymphocyte counts were slightly lower in non-survivors than in survivors. The prognostic values of CLR, NLR, MLR, MPVLR, and RLR for mortality in HBV-DC were different. The predictive powers of NLR and MLR were superior to those of the other three scores and similar to that of MELD score. Multivariate analyses identified NLR, MLR, and MELD score as independent prognostic predictors. Conclusion High NLR and MLR are easily accessible and reliable indicators for predicting 30-day mortality in HBV-DC and have superior prognostic ability compared with other lymphocyte-based scores.
Collapse
Affiliation(s)
- Ting Mao
- Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Bin Zhang
- Department of Clinical Laboratory, Kunshan Hospital of Chinese Medicine, Affiliated Hospital of Yangzhou University, Kunshan, Jiangsu, China
| | - Ti Yang
- Department of Clinical Laboratory, Kunshan Hospital of Chinese Medicine, Affiliated Hospital of Yangzhou University, Kunshan, Jiangsu, China
| | - Yinyan Qian
- Department of Clinical Laboratory, Kunshan Hospital of Chinese Medicine, Affiliated Hospital of Yangzhou University, Kunshan, Jiangsu, China
| | - Chenchen Zhou
- Department of Clinical Laboratory, Kunshan Hospital of Chinese Medicine, Affiliated Hospital of Yangzhou University, Kunshan, Jiangsu, China
| | - Chunyan He
- Department of Clinical Laboratory, Kunshan Hospital of Chinese Medicine, Affiliated Hospital of Yangzhou University, Kunshan, Jiangsu, China
| |
Collapse
|
|
10
|
Kim JJ, Alsabbagh W, Wong WWL. Cost Effectiveness of Implementing a Universal Birth Hepatitis B Vaccination Program in Ontario. PHARMACOECONOMICS 2023; 41:413-425. [PMID: 36708500 DOI: 10.1007/s40273-022-01236-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 12/20/2022] [Indexed: 05/10/2023]
Abstract
BACKGROUND AND OBJECTIVE The World Health Organization recommends a universal hepatitis B vaccination within the first 24 h of birth. However, hepatitis B vaccines are given during adolescence in many jurisdictions including in Ontario, Canada. The objective of this study was to assess the cost effectiveness of shifting the hepatitis B vaccination timing from adolescence to birth. METHODS A state-transition model of 18 health states representing the natural history of acute and chronic hepatitis B was developed to conduct a cost-utility analysis. Most input parameters were obtained from the Canadian literature or publicly available provincial data. The model followed a lifetime model time horizon with health outcomes and costs being discounted at 1.5% annually. Deterministic and probabilistic sensitivity analyses were performed to test the robustness of the model. Analyses were conducted from a public-payer perspective with all costs adjusted to 2021 Canadian dollars. RESULTS Hepatitis B vaccination in newborns dominated the current strategy of adolescent vaccination. The probabilistic analysis showed that the newborn strategy was cost effective in 100% of the iterations at a willingness-to-pay threshold of $50,000/quality-adjusted life-year and cost saving in 79.39% of the iterations. A microsimulation projected that a newborn vaccination may lead to reductions in cases by 16.1% in acute hepatitis B, 43.2% in chronic hepatitis B, 48.2% in hepatocellular carcinoma, and 51.9% in hepatitis B liver-related death. CONCLUSIONS Our analysis suggests that changing the age of the hepatitis B vaccination recommendation from adolescent to newborn is cost effective and mostly a cost-saving strategy. Newborn vaccination may lead to cost and health benefits while aligning with best available evidence and guidance from the World Health Organization.
Collapse
Affiliation(s)
- John J Kim
- School of Pharmacy, Faculty of Science, University of Waterloo, 10A Victoria Street South, Kitchener, ON, N2G 1C5, Canada
| | - Wasem Alsabbagh
- School of Pharmacy, Faculty of Science, University of Waterloo, 10A Victoria Street South, Kitchener, ON, N2G 1C5, Canada
| | - William W L Wong
- School of Pharmacy, Faculty of Science, University of Waterloo, 10A Victoria Street South, Kitchener, ON, N2G 1C5, Canada.
| |
Collapse
|
|
11
|
Abstract
Hepatitis B virus (HBV) infection is a major public health problem, with an estimated 296 million people chronically infected and 820 000 deaths worldwide in 2019. Diagnosis of HBV infection requires serological testing for HBsAg and for acute infection additional testing for IgM hepatitis B core antibody (IgM anti-HBc, for the window period when neither HBsAg nor anti-HBs is detected). Assessment of HBV replication status to guide treatment decisions involves testing for HBV DNA, whereas assessment of liver disease activity and staging is mainly based on aminotransferases, platelet count, and elastography. Universal infant immunisation, including birth dose vaccination is the most effective means to prevent chronic HBV infection. Two vaccines with improved immunogenicity have recently been approved for adults in the USA and EU, with availability expected to expand. Current therapies, pegylated interferon, and nucleos(t)ide analogues can prevent development of cirrhosis and hepatocellular carcinoma, but do not eradicate the virus and rarely clear HBsAg. Treatment is recommended for patients with cirrhosis or with high HBV DNA levels and active or advanced liver disease. New antiviral and immunomodulatory therapies aiming to achieve functional cure (ie, clearance of HBsAg) are in clinical development. Improved vaccination coverage, increased screening, diagnosis and linkage to care, development of curative therapies, and removal of stigma are important in achieving WHO's goal of eliminating HBV infection by 2030.
Collapse
Affiliation(s)
- Wen-Juei Jeng
- Department of Gastroenterology and Hepatology, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - George V Papatheodoridis
- Academic Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece
| | - Anna S F Lok
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA.
| |
Collapse
|
|
12
|
Xu W, Hu Q, Chen C, Li W, Li Q, Chen L. FibroScan Predicts Liver Fibrosis Progression in Chronic HBV Infection Patients with No Clear Indication for Antiviral Therapy: A Retrospective Cohort Study. Infect Drug Resist 2023; 16:1777-1785. [PMID: 37020800 PMCID: PMC10067685 DOI: 10.2147/idr.s402990] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Accepted: 03/22/2023] [Indexed: 03/29/2023] Open
Abstract
Background and Aims Chronic hepatitis B virus (HBV) infection patients who do not fulfill the typical treatment indications should be followed up. This study aimed to evaluate the risk of liver fibrosis progression (LFP) and assess the role of noninvasive tests (NITs) of liver fibrosis in monitoring LFP in these patients. Methods A total of 116 patients with active HBV replication, persistently normal or minimally elevated alanine aminotransferase (ALT) levels, and no or mild hepatic necroinflammation or fibrosis based on liver biopsy tests at baseline and followed by a repeated liver biopsy assessment during follow-up. LFP was defined as increase in METAVIR fibrosis score by 1 score or more. Results Among 116 patients, 40 (34.5%) progressed by at least one fibrosis stage, 16 (13.8%) progressed by at least two fibrosis stages at a median follow-up interval of 27 months (IQR: 12-36). Multivariate analysis confirmed the significant association of an increase in liver stiffness measurement (LSM) value with LFP on histology (p =0.005). The AUROC of LSM value increase rate is significantly higher than that of serum-based NITs of liver fibrosis for the prediction of LFP (p < 0.05). An increase in LSM by 20% is the optimal cutoff for the prediction of LFP. Conclusion LFP is non-negligible in patients with active HBV replication, persistently normal or minimally elevated ALT, and initially no or minimal hepatic necroinflammation or fibrosis. Serial LSM tests would be more reliable in identifying LFP than serum-based NITs, and easier to obtain than serial liver biopsy tests.
Collapse
Affiliation(s)
- Wei Xu
- Department of Liver Disease, Shanghai Public Health Clinical Center, Fudan University, Shanghai, People’s Republic of China
| | - Qiankun Hu
- Department of Liver Disease, Shanghai Public Health Clinical Center, Fudan University, Shanghai, People’s Republic of China
| | - Chong Chen
- Department of Infectious Disease, Shanghai Public Health Clinical Center, Fudan University, Shanghai, People’s Republic of China
| | - Weixia Li
- Department of Infectious Disease, Shanghai Public Health Clinical Center, Fudan University, Shanghai, People’s Republic of China
| | - Qiang Li
- Department of Liver Disease, Shanghai Public Health Clinical Center, Fudan University, Shanghai, People’s Republic of China
- Correspondence: Qiang Li; Liang Chen, Email ;
| | - Liang Chen
- Department of Liver Disease, Shanghai Public Health Clinical Center, Fudan University, Shanghai, People’s Republic of China
| |
Collapse
|
|
13
|
Yu M, Huang L, Zhang S, Jiang L, Jin Y, Gu M, Liao J, Zhang J. Follow-up value of serum AFP and aminotransferases in chronic hepatitis B progression. Front Cell Infect Microbiol 2023; 13:1082390. [PMID: 36761898 PMCID: PMC9905438 DOI: 10.3389/fcimb.2023.1082390] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 01/10/2023] [Indexed: 01/26/2023] Open
Abstract
INTRODUCTION Chronic viral hepatitis (CH) is a stage prior to cirrhosis and primary cancer. Standard protocols for CH assessment during the long follow-up period are of great importance for precise treatment and living quality improvement. In this study, we aimed to analyze multiple serum indexes in chronic hepatitis B (CHB)-infected patients and to discuss their combined values in clinical applications. METHODS Total 503 lines of laboratory data from 2012 to 2021 were extracted from103 CHB patients who were followed-up in our hospital. They were divided into the remission group and the progression group according to their complete clinical information and laboratory data. A series of models of serum indexes were analyzed to illustrate the fluctuation trend of @ach index in a time-dependent manner. RESULTS The models revealed that abundant serum alpha-fetoprotein (AFP) in the remission group was characteristically associated with hepatocyte destruction markers aspartate aminotransferase (AST) and alanine aminotransferase and favored a much longer progression-free period (P 0.0001). A model-derived equation consisting of serum AFP and AST values showed a good performance (83% reliability) to distinguish the two groups. DISCUSSION This study clearly demonstrates the intrinsic quantitative relationship between serum AFP and liver aminotransferases involving antivirus treatment response. The model-based equation compensates for serum hepatitis B virus DNA detection during outpatient follow-up and it may serve as a useful laboratory tool for CHB progression assessment.
Collapse
Affiliation(s)
- Mengyao Yu
- Department of Laboratory Medicine, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
- Branch of National Clinical Research Center for Laboratory Medicine, Nanjing, China
| | - Lei Huang
- Department of Laboratory Medicine, Nanjing Medical University, Nanjing, China
| | - Shichang Zhang
- Department of Laboratory Medicine, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
- Branch of National Clinical Research Center for Laboratory Medicine, Nanjing, China
| | - Longfeng Jiang
- Department of Infectious Diseases, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Yuexinzi Jin
- Department of Laboratory Medicine, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
- Branch of National Clinical Research Center for Laboratory Medicine, Nanjing, China
| | - Min Gu
- Department of Laboratory Medicine, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
- Branch of National Clinical Research Center for Laboratory Medicine, Nanjing, China
| | - Jun Liao
- School of Science, China Pharmaceutical University, Nanjing, China
| | - Jiexin Zhang
- Department of Laboratory Medicine, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
- Branch of National Clinical Research Center for Laboratory Medicine, Nanjing, China
| |
Collapse
|
|
14
|
Kikuchi K, Fukuda K, Hayashi S, Maeda T, Takashima Y, Fujita M, Ikuta K, Anjiki K, Tachibana S, Onoi Y, Matsumoto T, Kuroda R, Matsubara T. Polyarthritis presented in a patient with untreated chronic hepatitis B infection. Mod Rheumatol Case Rep 2023; 7:320-323. [PMID: 36214605 DOI: 10.1093/mrcr/rxac075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Revised: 07/10/2022] [Accepted: 09/23/2022] [Indexed: 01/04/2023]
Abstract
Hepatitis B virus (HBV) infection can cause arthritis, but it is rarely reported. In the current report, we present a case of chronic polyarthritis in a patient with untreated HBV infection. A 63-year-old woman suffering from polyarthritis in her fingers visited our institution. She had experienced exacerbations and remissions of polyarthritis for more than 20 years. She had been diagnosed with rheumatoid arthritis and had been treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and nonsteroidal anti-inflammatory drugs by her primary care doctor, but the csDMARDs were discontinued at the request of the patient 10 years before the first visit to our hospital. The blood test showed negative for rheumatoid factor and anticyclic citrullinated peptides antibody but positive for hepatitis B surface antigen. Hepatitis B surface antigen and HBV-Deoxyribo Nucleic Acid (DNA) were increased to 312.6 (IU/ml) and 4.6 (log copies/ml), respectively. Based on the results of abdominal computed tomography and echography, she was diagnosed with liver cirrhosis. Treatment for HBV infection was begun with oral tenofovir at 25 mg/day. The polyarthritis in her fingers gradually disappeared and has not relapsed for 6 months after the initiation of treatment for HBV infection. When polyarthritis is diagnosed, the possibility that chronic HBV infection can be one of the causes of polyarthritis should be considered.
Collapse
Affiliation(s)
- Kenichi Kikuchi
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Koji Fukuda
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.,Department of Orthopaedics, Matsubara Mayflower Hospital, Kato, Japan
| | - Shinya Hayashi
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Toshihisa Maeda
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yoshinori Takashima
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Masahiro Fujita
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Kenmei Ikuta
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Kensuke Anjiki
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Shotaro Tachibana
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Yuma Onoi
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Tomoyuki Matsumoto
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Ryosuke Kuroda
- Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan
| | - Tsukasa Matsubara
- Department of Orthopaedics, Matsubara Mayflower Hospital, Kato, Japan
| |
Collapse
|
|
15
|
Ward JW, Wanlapakorn N, Poovorawan Y, Shouval D. Hepatitis B Vaccines. PLOTKIN'S VACCINES 2023:389-432.e21. [DOI: 10.1016/b978-0-323-79058-1.00027-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
|
16
|
Comparable Mortality Between Asian Patients with Chronic Hepatitis B Under Long-Term Antiviral Therapy vs Matched Control: A Population-Based Study. Am J Gastroenterol 2022:00000434-990000000-00555. [PMID: 36288330 DOI: 10.14309/ajg.0000000000002074] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2022] [Accepted: 10/06/2022] [Indexed: 12/05/2022]
Abstract
INTRODUCTION Antiviral therapy (AVT) substantially improved the prognosis for patients with chronic hepatitis B (CHB). Head-to-head comparisons of prognosis between treated patients with CHB and the general population are scarce. We directly compared the prognosis between Asian patients with CHB receiving AVT and the general population. METHODS From the South Korean National Health Insurance Service database, patients with CHB receiving AVT ≥3 years, aged 40-64 years, who underwent health examinations between 2011 and 2012 (AVT-CHB group) were recruited. As a control, propensity score-matched general population was chosen among patients without CHB. The primary outcome was all-cause mortality; secondary outcomes were cardiovascular disease (CVD), hepatocellular carcinoma (HCC), and all types of non-HCC malignancies. RESULTS During follow-up (median 7.2 years), 26,467 and 75,469 individuals in the AVT-CHB group and matched general population were analyzed. The 5- and 7-year cumulative all-cause mortality rates were 0.40% and 1.0% for the AVT-CHB group vs 0.50% and 1.0% for the matched general population (adjusted hazard ratio [aHR] 0.96, 95% confidence interval [CI] 0.83-1.10; P = 0.51). The AVT-CHB group had a lower risk of CVD than the matched general population (aHR 0.70, 95% CI: 0.62-0.79; P < 0.001). Although the AVT-CHB group was more likely to develop HCC than the matched general population (aHR 13.16, 95% CI: 10.90-15.89; P < 0.001), the non-HCC malignancy risks in the AVT-CHB group were comparable to the matched general population (aHR 1.05, 95% CI 0.98-1.13; P = 0.137). DISCUSSION The AVT-CHB group had a similar risk of all-cause mortality and non-HCC malignancies and a lower risk of CVD than the matched general population.
Collapse
|
|
17
|
Mohareb AM, Liu AF, Kim AY, Coffie PA, Kouamé MG, Freedberg KA, Boyd A, Hyle EP. Clearance of Hepatitis B e Antigen in Untreated Chronic Hepatitis B Virus Infection: A Systematic Review and Meta-analysis. J Infect Dis 2022; 226:1761-1770. [PMID: 35511194 DOI: 10.1093/infdis/jiac168] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Accepted: 04/29/2022] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND In people with hepatitis B virus (HBV) infection, persistence of hepatitis B e antigen (HBeAg) is associated with clinical progression and need for treatment. HBeAg loss represents partial immune control and is a critical event in the natural history of chronic HBV. METHODS We conducted a systematic review and meta-analysis of cohort studies that report HBeAg loss among people with untreated chronic HBV. We evaluated HBeAg loss using a random-effects model and conducted subanalysis on region. RESULTS We screened 10 560 publications, performed 196 full-text analyses, and included 26 studies for meta-analysis. The pooled rate of HBeAg loss was 6.46/100 person-years (PYs) (95% confidence interval, 5.17-8.08). Meta-regression showed that older age of participants and studies in Europe were associated with higher rate of HBeAg loss. Rates per 100 PYs were 7.43 (95% confidence interval, 6.30-8.75; 1 study) in Africa, 3.24 (2.61--4.02; 1 study) in the Eastern Mediterranean, 13.67 (11.21-16.66; 4 studies) in Europe, 7.34 (4.61--11.70; 5 studies) in North America, and 5.53 (4.05--7.55; 15 studies) in the Western Pacific. CONCLUSIONS Spontaneous HBeAg loss occurs at a rate of 6.46/100 PYs. Variations by region and age group may reflect epidemiological, immunological, or HBV genotype-related differences.
Collapse
Affiliation(s)
- Amir M Mohareb
- Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, Massachusetts, USA.,Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA.,Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
| | - Anne F Liu
- Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.,Division of Gastroenterology, Hepatology, and Endoscopy, Brigham & Women's Hospital, Boston, Massachusetts, USA
| | - Arthur Y Kim
- Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA.,Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
| | - Patrick A Coffie
- Department of Dermatology and Infectious Diseases, UFR des Sciences Médicales, Université Félix Houphouët-Boigny, Abidjan, Côte d'Ivoire.,Programme PAC-CI, ANRS Research site, Abidjan, Côte d'Ivoire
| | | | - Kenneth A Freedberg
- Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, Massachusetts, USA.,Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA.,Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.,Division of General Internal Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA
| | - Anders Boyd
- Stiching hiv monitoring, Amsterdam, the Netherlands.,Department of Infectious Diseases, Research and Prevention, Public Health Service of Amsterdam, Amsterdam, the Netherlands
| | - Emily P Hyle
- Medical Practice Evaluation Center, Massachusetts General Hospital, Boston, Massachusetts, USA.,Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA.,Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA
| |
Collapse
|
|
18
|
Serious adverse events after cessation of nucleos(t)ide analogues in individuals with chronic hepatitis B: A systematic review and meta-analysis. JHEP Rep 2022; 5:100617. [DOI: 10.1016/j.jhepr.2022.100617] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2022] [Revised: 10/12/2022] [Accepted: 10/15/2022] [Indexed: 11/30/2022] Open
|
|
19
|
Tian F, Feld JJ, Feng Z, Sander B, Wong WWL. Feasibility of hepatitis B elimination in high-income countries with ongoing immigration. J Hepatol 2022; 77:947-956. [PMID: 35483535 DOI: 10.1016/j.jhep.2022.04.014] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 04/11/2022] [Accepted: 04/13/2022] [Indexed: 02/08/2023]
Abstract
BACKGROUND & AIMS Addressing HBV is vital to meeting the World Health Organization (WHO)'s viral hepatitis elimination goals, as 47% of viral hepatitis complications can be attributed to HBV. The objective of this study is to develop an agent-based model determining which integrated strategies involving vaccination, screening, and treatment would achieve the WHO's goals. METHODS We developed an agent-based model to characterize the HBV epidemic in a high-income country with ongoing immigration. The spread of HBV was simulated through sexual networks and perinatal transmission. Model parameters were estimated from the literature and calibrated against historical HBV data. Sensitivity analyses were performed to assess the uncertainty. RESULTS We predict that under the current strategies, the incidence of acute hepatitis B, and HBV-attributable decompensated cirrhosis and hepatocellular carcinoma would decrease by 64.5%, 9.4%, and 10.5% between 2015-2030, respectively. However, the incidence of chronic hepatitis B and liver-related deaths would increase by 26.6% and 1.0% between 2015-2030, respectively. Results were sensitive to the number of immigrants and HBV prevalence in immigrants. CONCLUSIONS The results suggest that the current vaccination, screening, and treatment strategies will be inadequate to achieve WHO elimination goals. Even with extensive integrated scale-up in vaccination, screening, and treatment, the morbidity and mortality targets may not be reachable, highlighting the need for a re-evaluation of the global strategy for HBV, the importance of developing curative therapy for HBV, and of establishing tailored strategies to prevent long-term sequelae and improve health in immigrants. LAY SUMMARY We have developed a model that reflects the dynamics of hepatitis B virus (HBV) transmission in a high-income country with ongoing immigration, which enabled us to forecast the epidemiology of HBV for policy-level decision making. Our analysis suggests that current vaccination, screening, and treatment strategies are inadequate to achieve the WHO goals of eliminating chronic hepatitis B. Even with extensive integrated scale-up in vaccination, screening, and treatment, the morbidity and mortality targets may not be reachable.
Collapse
Affiliation(s)
- Feng Tian
- School of Pharmacy, University of Waterloo, Kitchener, Ontario, Canada
| | - Jordan J Feld
- Toronto Centre for Liver Disease, University Health Network, Toronto, Ontario, Canada
| | - Zeny Feng
- Department of Mathematics and Statistics, University of Guelph, Guelph, Ontario, Canada
| | - Beate Sander
- Toronto Health Economics and Technology Assessment Collaborative (THETA), University Health Network, Toronto, Ontario, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada; ICES, Toronto, Ontario, Canada; Public Health Ontario, Toronto, Ontario, Canada
| | - William W L Wong
- School of Pharmacy, University of Waterloo, Kitchener, Ontario, Canada; Toronto Health Economics and Technology Assessment Collaborative (THETA), University Health Network, Toronto, Ontario, Canada; Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada; ICES, Toronto, Ontario, Canada.
| |
Collapse
|
|
20
|
Roca TP, Villar LM, Nogueira Lima FS, Vasconcelos MPA, Borzacov LMP, Silva EDCE, do Lago BV, da Silva MTL, Botelho Souza LF, Salcedo JMV, dos Santos ADO, Vieira DS. Genomic Variability of Hepatitis B Virus Circulating in Brazilian Western Amazon. Viruses 2022; 14:v14102100. [PMID: 36298655 PMCID: PMC9611064 DOI: 10.3390/v14102100] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Revised: 08/31/2022] [Accepted: 09/01/2022] [Indexed: 12/02/2022] Open
Abstract
The emergence of clinically relevant mutations in the hepatitis B virus (HBV) genome has been a matter of great debate because of the possibility of escape from the host’s immune system, the potential to cause more severe progression of liver diseases and the emergence of treatment-resistant variants. Here we characterized the circulating variants of HBV in Rondônia State, in the north of Brazil. Serum samples of 62 chronic HBV carriers were subjected to PCR assays and clinical data were collected. Mutations and genotypes were characterized through direct sequencing. The findings show the presence of subgenotypes A1 (54.83%, 34/62), D3 (16.13%, 10/62), F2 (16.13%, 10/62), A2 (4.84%, 3/62), D2 (3.23%, 2/62), D1 (1.61%, 1/62), D4 (1.61%, 1/62) and F4 (1.61%, 1/62). Deletions in the pre-S2 region were found in 13.79% (8/58) of the samples, mutations in the S gene in 59.68% (37/62) and RT mutations in 48.39% (30/62). We found a variable genotypic distribution in different locations and important mutations related to immune escape and drug resistance in Western Amazonia, which contributed to genetic surveillance and provided important information to help control the disease.
Collapse
Affiliation(s)
- Tárcio Peixoto Roca
- Laboratory of Viral Hepatitis, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro 21040-900, Brazil
- Laboratory of Molecular Virology, Oswaldo Cruz Foundation of Rondônia—FIOCRUZ/RO, Porto Velho 76812-245, Brazil
- Correspondence: (T.P.R.); (L.M.V.)
| | - Livia Melo Villar
- Laboratory of Viral Hepatitis, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro 21040-900, Brazil
- Correspondence: (T.P.R.); (L.M.V.)
| | - Felipe Souza Nogueira Lima
- Laboratory of Molecular Virology, Oswaldo Cruz Foundation of Rondônia—FIOCRUZ/RO, Porto Velho 76812-245, Brazil
| | | | | | | | - Bárbara Vieira do Lago
- Laboratory of Viral Hepatitis, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro 21040-900, Brazil
| | - Mayara Torquato Lima da Silva
- Laboratory of Biotechnology and Structural Bioengineering, Biophysics Institute Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro 21941-901, Brazil
| | | | - Juan Miguel Villalobos Salcedo
- Laboratory of Molecular Virology, Oswaldo Cruz Foundation of Rondônia—FIOCRUZ/RO, Porto Velho 76812-245, Brazil
- Tropical Medicine Research Center of Rondônia—CEPEM/RO, Porto Velho 76812-329, Brazil
| | | | - Deusilene Souza Vieira
- Laboratory of Molecular Virology, Oswaldo Cruz Foundation of Rondônia—FIOCRUZ/RO, Porto Velho 76812-245, Brazil
- Tropical Medicine Research Center of Rondônia—CEPEM/RO, Porto Velho 76812-329, Brazil
- Postgraduate Program in Experimental Biology, Federal University of Rondônia—PGBIOEXP/UNIR, Porto Velho 76801-059, Brazil
| |
Collapse
|
|
21
|
Sun L, Ding P, Mao W, Wu J. D-Dimer-to-Albumin Ratio: A Novel Indicator to Predict Poor Outcomes in Patients with HBV-Associated Decompensated Cirrhosis. BIOMED RESEARCH INTERNATIONAL 2022; 2022:9062383. [PMID: 36147636 PMCID: PMC9489368 DOI: 10.1155/2022/9062383] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Accepted: 09/01/2022] [Indexed: 09/12/2023]
Abstract
BACKGROUND The purpose of the present study was to investigate the impact of D-dimer-to-albumin ratio (DAR) on outcomes in patients with hepatitis B virus-associated decompensated cirrhosis (HBV-DeCi). METHODS A total of 172 HBV-DeCi patients were enrolled. Logistic regression was used to explore the association between DAR and 30-day mortality. The area under the receiver operating characteristic curve (AUC) was used to evaluate the performance of DAR for predicting mortality. RESULTS The 30-day mortality was 19.8%. DAR was clearly higher in the nonsurvivors compared with the survivors, and increasing DAR was associated with an increasing risk of death. DAR was independently associated with mortality and its AUC for mortality was equivalent to that for Model for End-Stage Liver Disease score. CONCLUSIONS DAR may be a potential prognostic marker for mortality in HBV-DeCi patients.
Collapse
Affiliation(s)
- Lin Sun
- Department of Clinical Laboratory, Shengzhou People's Hospital, Shengzhou Branch of the First Affiliated Hospital of Zhejiang University, Shengzhou 312400, China
| | - PingPing Ding
- Department of Clinical Laboratory, Shengzhou People's Hospital, Shengzhou Branch of the First Affiliated Hospital of Zhejiang University, Shengzhou 312400, China
| | - WeiLin Mao
- Department of Clinical Laboratory, Shengzhou People's Hospital, Shengzhou Branch of the First Affiliated Hospital of Zhejiang University, Shengzhou 312400, China
- Department of Clinical Laboratory, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China
| | - JianPing Wu
- Department of Clinical Laboratory, Shengzhou People's Hospital, Shengzhou Branch of the First Affiliated Hospital of Zhejiang University, Shengzhou 312400, China
- Department of Clinical Laboratory, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China
| |
Collapse
|
|
22
|
Liaw YF, Chien RN. Finite nucleos(t)ide analogue therapy in hepatitis B e antigen-negative chronic hepatitis B: From an "option" to an "active recommendation". Kaohsiung J Med Sci 2022; 38:295-301. [PMID: 35262284 DOI: 10.1002/kjm2.12518] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Accepted: 01/27/2022] [Indexed: 12/12/2022] Open
Abstract
Nucleos(t)ide analogue (Nuc) including entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide may suppress hepatitis B virus (HBV) DNA profoundly but have no direct action on covalently closed circular DNA, which is a very stable template for HBV production. Therefore, decades of long-term Nuc therapy are required to maintain HBV suppression and to achieve hepatitis B surface antigen (HBsAg) loss in hepatitis B e antigen (HBeAg)-negative patients. However, there are concerns including financial burden, adherence, and willingness for indefinite long-term Nuc therapy. Patients lost to follow-up and hence not monitored may risk severe relapse that may deteriorate to hepatic decompensation or even hepatic failure. Cessation of Nuc therapy in HBeAg-negative patients was initially considered in early 2000s. Earlier findings in Asian patients that finite Nuc therapy over 2-3 years is feasible and safe have founded Asian-Pacific Association for the Study of Liver stopping rule since 2008. Subsequent studies have confirmed the feasibility and safety of the strategy of finite Nuc therapy, which has finally been accepted as "an option" by American and European liver associations since 2016. More recent large studies since 2018 have further confirmed the pivotal finding of greatly increased HBsAg loss rate (~5-year 39%) after stopping Nuc therapy. With the high HBsAg loss rate as the main justification, the paradigm shift from indefinite long-term therapy to finite Nuc therapy in HBeAg-negative patients has been changing from an "option" to an "active recommendation" aiming to achieve HBsAg loss. More studies are needed to fine-tuning the strategy, including research for the optimal duration of consolidation therapy, timing to stop, and to start retreatment.
Collapse
Affiliation(s)
- Yun-Fan Liaw
- College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Liver Research Unit, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Rong-Nan Chien
- College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Liver Research Unit, Chang Gung Memorial Hospital, Taoyuan, Taiwan.,Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan
| |
Collapse
|
|
23
|
Low Hemoglobin-to-Red Cell Distribution Width Ratio Is Associated with Mortality in Patients with HBV-Related Decompensated Cirrhosis. BIOMED RESEARCH INTERNATIONAL 2022; 2022:5754790. [PMID: 35198637 PMCID: PMC8860564 DOI: 10.1155/2022/5754790] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Revised: 01/28/2022] [Accepted: 02/02/2022] [Indexed: 12/15/2022]
Abstract
Background The prognostic role of hemoglobin-to-red blood cell distribution width ratio (HRR) in HBV-related decompensated cirrhosis (HBV-DeCi) has not been established. The present study is aimed at determining the potential of HRR as a predictive factor for the prognosis of HBV-DeCi patients. Methods The study included 177 HBV-DeCi patients. The clinical outcome was death at 30 days. Multivariate regression analysis and receiver operating characteristic curve analysis were applied to assess the predictive value of HRR for poor outcomes. Results A total of 26 patients (14.7%) had died by 30 days. Patients with unfavorable outcomes had lower HRR than patients with favorable outcomes. Multivariate analysis revealed that HRR and Model for End-Stage Liver Disease (MELD) score were independently associated with poor outcomes. Combination of HRR and MELD score may improve prognostic accuracy in HBV-DeCi. Conclusions The present findings indicate that low HRR may be a promising predictor for mortality in HBV-DeCi patients.
Collapse
|
|
24
|
Shahriar S, Araf Y, Ahmad R, Kattel P, Sah GS, Rahaman TI, Sadiea RZ, Sultana S, Islam MS, Zheng C, Hossain MG. Insights Into the Coinfections of Human Immunodeficiency Virus-Hepatitis B Virus, Human Immunodeficiency Virus-Hepatitis C Virus, and Hepatitis B Virus-Hepatitis C Virus: Prevalence, Risk Factors, Pathogenesis, Diagnosis, and Treatment. Front Microbiol 2022; 12:780887. [PMID: 35222296 PMCID: PMC8865087 DOI: 10.3389/fmicb.2021.780887] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 12/21/2021] [Indexed: 12/15/2022] Open
Abstract
Human immunodeficiency virus, hepatitis B virus, and hepatitis C virus are three blood-borne viruses that can cause major global health issues by increasing severe morbidity. There is a high risk of coinfection with these viruses in individuals because of their same transmission routes through blood using shared needles, syringes, other injection equipment, sexual transmission, or even vertical transmission. Coinfection can cause various liver-related illnesses, non-hepatic organ dysfunction, followed by death compared to any of these single infections. The treatment of coinfected patients is complicated due to the side effects of antiviral medication, resulting in drug resistance, hepatotoxicity, and a lack of required responses. On the other hand, coinfected individuals must be treated with multiple drugs simultaneously, such as for HIV either along with HBV or HCV and HBV and HCV. Therefore, diagnosing, treating, and controlling dual infections with HIV, HBV, or HCV is complicated and needs further investigation. This review focuses on the current prevalence, risk factors, and pathogenesis of dual infections with HIV, HBV, and HCV. We also briefly overviewed the diagnosis and treatment of coinfections of these three blood-borne viruses.
Collapse
Affiliation(s)
- Sagarika Shahriar
- Biotechnology Program, Department of Mathematics and Natural Sciences, BRAC University, Dhaka, Bangladesh
| | - Yusha Araf
- Department of Genetic Engineering and Biotechnology, School of Life Sciences, Shahjalal University of Science and Technology, Sylhet, Bangladesh
| | - Rasel Ahmad
- Department of Microbiology and Hygiene, Bangladesh Agricultural University, Mymensingh, Bangladesh
| | - Pravakar Kattel
- Department of Microbiology and Hygiene, Bangladesh Agricultural University, Mymensingh, Bangladesh
| | - Ganga Sagar Sah
- Department of Microbiology and Hygiene, Bangladesh Agricultural University, Mymensingh, Bangladesh
| | - Tanjim Ishraq Rahaman
- Department of Biotechnology and Genetic Engineering, Faculty of Life Sciences, Bangabandhu Sheikh Mujibur Rahman Science and Technology University, Gopalganj, Bangladesh
| | - Rahila Zannat Sadiea
- Department of Microbiology and Hygiene, Bangladesh Agricultural University, Mymensingh, Bangladesh
| | - Shahnaj Sultana
- Department of Microbiology and Hygiene, Bangladesh Agricultural University, Mymensingh, Bangladesh
| | - Md. Sayeedul Islam
- Department of Biological Sciences, Graduate School of Science, Osaka University, Osaka, Japan
| | - Chunfu Zheng
- Department of Microbiology, Immunology and Infectious Diseases, University of Calgary, Calgary, AB, Canada
| | - Md. Golzar Hossain
- Department of Microbiology and Hygiene, Bangladesh Agricultural University, Mymensingh, Bangladesh
| |
Collapse
|
|
25
|
Chang ML, Liaw YF. Hepatitis B Flare in Hepatitis B e Antigen-Negative Patients: A Complicated Cascade of Innate and Adaptive Immune Responses. Int J Mol Sci 2022; 23:ijms23031552. [PMID: 35163476 PMCID: PMC8836007 DOI: 10.3390/ijms23031552] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Revised: 01/19/2022] [Accepted: 01/26/2022] [Indexed: 12/11/2022] Open
Abstract
Chronic hepatitis B virus (HBV) infection is a dynamic process involving interactions among HBV, hepatocytes, and the host immune system. The natural course of chronic hepatitis B (CHB) is divided into four chronological phases, including the hepatitis B e antigen (HBeAg)-positive and HBeAg-negative phases. During HBV flare, alanine aminotransferase (ALT) levels abruptly rise to >5× the upper limit of normal; this is thought to occur due to the immune response against an upsurge in serum HBV DNA and antigen levels. Hepatitis flares may occur spontaneously, during or after antiviral therapy, or upon immunosuppression or chemotherapy in both HBeAg-positive and HBeAg-negative patients. The clinical spectrum of HBV flares varies from asymptomatic to hepatic decompensation or failure. HBeAg seroconversion with ≥ 1 year of consolidation therapy is accepted as an endpoint of oral antiviral therapy in HBeAg-positive patients, but recommendations for treating HBeAg-negative patients differ. Thus, the management of HBeAg-negative patients has attracted increasing interest. In the current review, we summarize various types of HBV flares and the associated complex cascade of innate and adaptive immune responses, with a focus on HBeAg-negative CHB patients. Hopefully, this review will provide insight into immunopathogenesis to improve the management of HBV flares in HBeAg-negative CHB patients.
Collapse
Affiliation(s)
- Ming-Ling Chang
- College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan;
- Division of Hepatology, Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan
- Correspondence: ; Tel.: +886-3-3281200 (ext. 8107); Fax: +886-3-3272236
| | - Yun-Fan Liaw
- College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan;
- Division of Hepatology, Department of Hepatogastroenterology, Chang Gung Memorial Hospital, Taoyuan 333423, Taiwan
| |
Collapse
|
|
26
|
Affiliation(s)
- Bin Ye
- Department of Critical Care Medicine, Shengzhou People's Hospital, Shengzhou Branch of the First Affiliated Hospital of Zhejiang University, Shengzhou, China
| | - QiuMing Ding
- Department of Clinical Laboratory, Shengzhou People's Hospital, Shengzhou Branch of the First Affiliated Hospital of Zhejiang University, Shengzhou, China
| | - Xia He
- Department of Clinical Laboratory, Shengzhou People's Hospital, Shengzhou Branch of the First Affiliated Hospital of Zhejiang University, Shengzhou, China
| | - XiaoYun Liu
- Department of Clinical Laboratory, Shengzhou People's Hospital, Shengzhou Branch of the First Affiliated Hospital of Zhejiang University, Shengzhou, China
| | - Jianjiang Shen
- Department of Clinical Laboratory, Shengzhou People's Hospital, Shengzhou Branch of the First Affiliated Hospital of Zhejiang University, Shengzhou, China
| |
Collapse
|
|
27
|
Li XP, Gul N, Khan MA, Bilal R, Ali A, Alshahrani MY, Muhammad T, Islam S. A new Hepatitis B model in light of asymptomatic carriers and vaccination study through Atangana–Baleanu derivative. RESULTS IN PHYSICS 2021; 29:104603. [DOI: 10.1016/j.rinp.2021.104603] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
|
|
28
|
Wu Q, Mao W. New prognostic factor for hepatitis B virus-related decompensated cirrhosis: Ratio of monocytes to HDL-cholesterol. J Clin Lab Anal 2021; 35:e24007. [PMID: 34545611 PMCID: PMC8605123 DOI: 10.1002/jcla.24007] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Revised: 08/22/2021] [Accepted: 09/03/2021] [Indexed: 12/14/2022] Open
Abstract
Aim Hepatitis B virus‐related decompensated cirrhosis (HBV‐DeCi) has a high mortality rate, and it remains a challenge to predict its outcomes in clinical practice. We aimed to determine the association between monocyte‐to‐HDL‐cholesterol ratio (MHR) and short‐term prognosis in HBV‐DeCi patients. Methods A total of 145 HBV‐DeCi patients were enrolled. A multivariate analysis was performed to identify predictors of mortality. The findings were validated by a receiver operating characteristic analysis using the area under the curve (AUC). Results A total of 20 (13.8%) patients had died 30 days after admission. MHR was markedly increased in the non‐survivors compared with the survivors. In the multivariate analysis, MHR was identified as an independent risk factor for mortality, with a significant predictive value (AUC = 0.825; sensitivity, 90.0%; specificity, 62.4%). Conclusions Elevated MHR is associated with increased mortality rate in HBV‐DeCi patients.
Collapse
Affiliation(s)
- Qianxia Wu
- Department of Clinical Laboratory, College of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
| | - Weilin Mao
- Department of Clinical Laboratory, College of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
| |
Collapse
|
|
29
|
Abstract
Antiviral therapy has greatly improved the survival and reduced the incidence of adverse liver events such as hepatic decompensation and hepatocellular carcinoma in chronic hepatitis B patients with cirrhosis (hepatitis B virus [HBV]-cirrhosis). However, hepatitis B surface antigen loss, regarded as the ultimate goal of therapy or functional cure, was rarely achieved during long-term indefinite nucleos(t)ide analogues (Nuc) treatment. Emerging issues such as medication adherence and loss-to-follow-up may lead to increased risk of hepatic decompensation, even catastrophic life-threatening events. Studies have shown that finite therapy is feasible and reasonably safe, even in patients with HBV-cirrhosis. This review critically assesses the scientific evidence of the pros and cons for finite Nuc therapy in HBV-cirrhosis and proposes how to stop Nuc therapy and monitor the off-therapy patients. It also proposes the perspective and unsolved issues to be investigated in the future.
Collapse
Affiliation(s)
- Wen-Juei Jeng
- Liver Research Unit, Linkou Medical Center, Chang Gung University, Chang Gung Memorial Hospital, College of Medicine, Taoyuan, Taiwan.,Department of Gastroenterology and Hepatology, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Yun-Fan Liaw
- Liver Research Unit, Linkou Medical Center, Chang Gung University, Chang Gung Memorial Hospital, College of Medicine, Taoyuan, Taiwan
| |
Collapse
|
|
30
|
Association of Low High-Density Lipoprotein Cholesterol Levels with Poor Outcomes in Hepatitis B-Associated Decompensated Cirrhosis Patients. BIOMED RESEARCH INTERNATIONAL 2021; 2021:9927330. [PMID: 34355041 PMCID: PMC8331308 DOI: 10.1155/2021/9927330] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Accepted: 07/18/2021] [Indexed: 02/02/2023]
Abstract
Background Lipid levels become decreased in cirrhotic patients and are correlated with disease severity. In the present study, we investigated the impact of serum high-density lipoprotein cholesterol (HDL-C) on prognosis in patients with HBV-associated decompensated cirrhosis (HBV-DeCi). Methods The medical records of 153 HBV-DeCi patients were analyzed. Patients were separated into survivors and nonsurvivors according to their 30-day survival. Univariate and multivariate analyses were performed to identify predictors of poor outcomes, and the performance of these predictors was evaluated by receiver operating characteristic (ROC) curve analysis. Results The 30-day mortality in the cohort was 18.9%. HDL-C levels differed markedly between survivors and nonsurvivors. On multivariate analysis, Model for End-stage Liver Disease (MELD) score and HDL-C level were identified as independent risk factors for mortality in HBV-DeCi patients. In the ROC analyses, the prognostic accuracy for mortality was similar between HDL-C (area under ROC curve: 0.785) and MELD score (area under ROC curve: 0.853). Conclusions Low HDL-C level had a significant correlation with mortality in HBV-DeCi patients and can be used as a simple marker for risk assessment and selection of therapeutic options.
Collapse
|
|
31
|
Jeng WJ, Chien RN, Liaw YF. Fibrosis in patients with chronic hepatitis B and minimally raised ALT during tenofovir therapy. THE LANCET. INFECTIOUS DISEASES 2021; 21:910-911. [PMID: 34174230 DOI: 10.1016/s1473-3099(21)00317-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Accepted: 05/14/2021] [Indexed: 11/20/2022]
Affiliation(s)
- Wen-Juei Jeng
- Liver research unit, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan 33305, Taiwan; Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan 33305, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Rong-Nan Chien
- Liver research unit, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan 33305, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan.
| | - Yun-Fan Liaw
- Liver research unit, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan 33305, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| |
Collapse
|
|
32
|
Yao K, Liu J, Wang J, Yan X, Xia J, Yang Y, Wu W, Liu Y, Chen Y, Zhang Z, Li J, Huang R, Wu C. Distribution and clinical characteristics of patients with chronic hepatitis B virus infection in the grey zone. J Viral Hepat 2021; 28:1025-1033. [PMID: 33797145 DOI: 10.1111/jvh.13511] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Revised: 03/17/2021] [Accepted: 03/18/2021] [Indexed: 12/11/2022]
Abstract
A substantial proportion of patients with chronic hepatitis B (CHB) who do not fit into any of the usual immune states are considered to be in the 'grey zone (GZ)'. We aimed to investigate the distribution and characteristics of GZ in a large cohort of CHB patients. Four thousand seven hundred and fifty-nine consecutive treatment-naïve CHB patients were enrolled. The immune states were defined based on AASLD 2018 Hepatitis B Guidance. GZ CHB patients were classified into four groups: HBeAg positive, normal ALT levels and serum HBV DNA ≤106 IU/ml (GZ-A); HBeAg positive, elevated ALT levels and serum HBV DNA ≤2 × 104 IU/ml (GZ-B); HBeAg negative, normal ALT levels and serum HBV DNA ≥2 × 103 IU/ml (GZ-C); HBeAg negative, elevated ALT levels and serum HBV DNA ≤2 × 103 IU/ml (GZ-D). The distributions of different immune states were: 233 (4.90%) patients in immune-tolerant phase, 941 (19.77%) patients in HBeAg-positive immune active phase, 1,717 (36.08%) patients in inactive phase and 546 (11.47%) patients in HBeAg-negative immune active phase. Of note, 1,322 (27.78%) patients did not fit into any of above phases and were defined as the GZ. A high proportion of patients in GZ-B had advanced fibrosis (33.3%) or cirrhosis (25.8%). Older age, HBeAg-positive status and higher ALT levels were independently risk factors of advanced disease in GZ CHB patients. Therefore, our results revealed that more than a quarter of CHB patients were classified into the GZ and a high proportion of patients in GZ-B had advanced fibrosis or even cirrhosis.
Collapse
Affiliation(s)
- Kefang Yao
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China
| | - Jiacheng Liu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Jian Wang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Xiaomin Yan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Juan Xia
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Yue Yang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Weihua Wu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Yong Liu
- Department of Laboratory Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Yuxin Chen
- Department of Laboratory Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Zhaoping Zhang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Jie Li
- Department of Infectious Disease, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
| | - Rui Huang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Chao Wu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, China.,Department of Infectious Diseases, Nanjing Drum Tower Hospital, Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.,Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| |
Collapse
|
|
33
|
Usefulness of International Normalized Ratio to Albumin Ratio for Evaluation of Mortality in Hepatitis B Virus-Associated Decompensated Cirrhosis. BIOMED RESEARCH INTERNATIONAL 2021; 2021:6664574. [PMID: 34055994 PMCID: PMC8133843 DOI: 10.1155/2021/6664574] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 04/10/2021] [Accepted: 05/03/2021] [Indexed: 11/23/2022]
Abstract
Background We sought to determine the prognostic value of prothrombin time-international normalized ratio to albumin ratio (PTAR) in patients with hepatitis B virus-associated decompensated cirrhosis (HBV-DeCi). Methods The study enrolled 166 HBV-DeCi patients. Multivariate regression analysis was performed to identify predictors associated with mortality. Results Among the 166 HBV-DeCi patients, 27 (16.3%) had died by 30 days after admission. PTAR was markedly increased in nonsurvivors compared with survivors, and had a significant positive correlation with disease severity. Multivariate analysis identified PTAR as an effective independent predictor for mortality in HBV-DeCi patients. Conclusions High PTAR was associated with poor outcomes and can act as a novel prognostic predictor for mortality in HBV-DeCi patients.
Collapse
|
|
34
|
Huang J, Cai M, He X. Serum potassium levels and prognosis in HBV-associated decompensated cirrhosis. J Clin Lab Anal 2021; 35:e23775. [PMID: 33951234 PMCID: PMC8183925 DOI: 10.1002/jcla.23775] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 03/19/2021] [Indexed: 12/14/2022] Open
Abstract
Background Serum potassium disorders are commonly seen in patients with advanced cirrhosis and have a detrimental effect on clinical outcome, but its role in HBV‐related decompensated cirrhosis (DeCi) is remained to be illustrated. We aim to assess the effects of serum potassium on outcomes in HBV‐DeCi patients. Methods Retrospective study included 155 subjects. Multivariate analysis was used to determine the independent prognostic factor. Predictive ability of mortality for variables was determined using the receiver operating characteristics curves. Results The 30‐day in‐hospital mortality was 12.9%. Serum potassium levels differed markedly between survivors and non‐survivors. On multivariate analysis, Model for End‐Stage Liver Disease (MELD) score and serum potassium level were identified as independent predictors of outcomes in HBV‐DeCi patients. The combination of serum potassium and MELD score could improve prognostic accuracy in these patients. Conclusions Our findings suggest that serum potassium is an effective predictor for poor outcomes in HBV‐DeCi patients.
Collapse
Affiliation(s)
- JianJiang Huang
- Department of Critical Care Medicine, Shengzhou People's Hospital, Shengzhou Branch of the First Affiliated Hospital of Zhejiang University, Shengzhou, China
| | - Ming Cai
- Department of Clinical Laboratory, Shengzhou People's Hospital, Shengzhou Branch of the First Affiliated Hospital of Zhejiang University, Shengzhou, China
| | - Xia He
- Department of Clinical Laboratory, Shengzhou People's Hospital, Shengzhou Branch of the First Affiliated Hospital of Zhejiang University, Shengzhou, China
| |
Collapse
|
|
35
|
Han Z, He X, Peng S. Neutrophil count to albumin ratio as a prognostic indicator for HBV-associated decompensated cirrhosis. J Clin Lab Anal 2021; 35:e23730. [PMID: 33609049 PMCID: PMC8059716 DOI: 10.1002/jcla.23730] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2021] [Revised: 01/27/2021] [Accepted: 01/28/2021] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND To explore the value of neutrophil count to albumin ratio (NAR) in predicting the outcomes of patients with HBV-associated decompensated cirrhosis (HBV-DeCi). METHODS One hundred and fifty-four HBV-DeCi patients were enrolled. The 30-day mortality was determined. Multivariate analysis was applied to identify risk factors for poor outcomes. Receiver operating characteristic curve analyses was performed to evaluate prognostic accuracy. RESULTS The 30-day mortality was 10.4%. NAR was significantly higher in non-survivors than in survivors and was an independent predictor for unfavorable prognosis. CONCLUSIONS The present results indicate that increased NAR is associated with poor survival in HBV-DeCi patients and has potential for clinical application.
Collapse
Affiliation(s)
- Zhong Han
- Department of Clinical Laboratory, Shengzhou People's Hospital, Shengzhou Branch of the First Affiliated Hospital of Zhejiang University, Shengzhou, China
| | - Xia He
- Department of Clinical Laboratory, Shengzhou People's Hospital, Shengzhou Branch of the First Affiliated Hospital of Zhejiang University, Shengzhou, China
| | - SongQing Peng
- Department of Clinical Laboratory, Shengzhou People's Hospital, Shengzhou Branch of the First Affiliated Hospital of Zhejiang University, Shengzhou, China
| |
Collapse
|
|
36
|
Hickey TE, Selth LA, Chia KM, Laven-Law G, Milioli HH, Roden D, Jindal S, Hui M, Finlay-Schultz J, Ebrahimie E, Birrell SN, Stelloo S, Iggo R, Alexandrou S, Caldon CE, Abdel-Fatah TM, Ellis IO, Zwart W, Palmieri C, Sartorius CA, Swarbrick A, Lim E, Carroll JS, Tilley WD. The androgen receptor is a tumor suppressor in estrogen receptor-positive breast cancer. Nat Med 2021; 27:310-320. [PMID: 33462444 DOI: 10.1038/s41591-020-01168-7] [Citation(s) in RCA: 143] [Impact Index Per Article: 35.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Accepted: 11/03/2020] [Indexed: 01/28/2023]
Abstract
The role of the androgen receptor (AR) in estrogen receptor (ER)-α-positive breast cancer is controversial, constraining implementation of AR-directed therapies. Using a diverse, clinically relevant panel of cell-line and patient-derived models, we demonstrate that AR activation, not suppression, exerts potent antitumor activity in multiple disease contexts, including resistance to standard-of-care ER and CDK4/6 inhibitors. Notably, AR agonists combined with standard-of-care agents enhanced therapeutic responses. Mechanistically, agonist activation of AR altered the genomic distribution of ER and essential co-activators (p300, SRC-3), resulting in repression of ER-regulated cell cycle genes and upregulation of AR target genes, including known tumor suppressors. A gene signature of AR activity positively predicted disease survival in multiple clinical ER-positive breast cancer cohorts. These findings provide unambiguous evidence that AR has a tumor suppressor role in ER-positive breast cancer and support AR agonism as the optimal AR-directed treatment strategy, revealing a rational therapeutic opportunity.
Collapse
Affiliation(s)
- Theresa E Hickey
- Dame Roma Mitchell Cancer Research Laboratories, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia
| | - Luke A Selth
- Dame Roma Mitchell Cancer Research Laboratories, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia
- Flinders Health and Medical Research Institute, Flinders University, Adelaide, South Australia, Australia
- Freemason's Foundation Centre for Men's Health, University of Adelaide, Adelaide, South Australia, Australia
| | - Kee Ming Chia
- Garvan Institute of Medical Research & St Vincent's Clinical School, University of New South Wales, Sydney, New South Wales, Australia
| | - Geraldine Laven-Law
- Dame Roma Mitchell Cancer Research Laboratories, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia
| | - Heloisa H Milioli
- Garvan Institute of Medical Research & St Vincent's Clinical School, University of New South Wales, Sydney, New South Wales, Australia
| | - Daniel Roden
- Garvan Institute of Medical Research & St Vincent's Clinical School, University of New South Wales, Sydney, New South Wales, Australia
| | - Shalini Jindal
- Dame Roma Mitchell Cancer Research Laboratories, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia
| | - Mun Hui
- Garvan Institute of Medical Research & St Vincent's Clinical School, University of New South Wales, Sydney, New South Wales, Australia
| | | | - Esmaeil Ebrahimie
- Dame Roma Mitchell Cancer Research Laboratories, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia
| | - Stephen N Birrell
- Dame Roma Mitchell Cancer Research Laboratories, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia
| | - Suzan Stelloo
- Oncode Institute, Netherlands Cancer Institute, Amsterdam, the Netherlands
- Oncode Institute, Radboud University Nijmegen, Nijmegen, the Netherlands
| | - Richard Iggo
- Dame Roma Mitchell Cancer Research Laboratories, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia
- Institut Bergonié, University of Bordeaux, Bordeaux, France
| | - Sarah Alexandrou
- Garvan Institute of Medical Research & St Vincent's Clinical School, University of New South Wales, Sydney, New South Wales, Australia
| | - C Elizabeth Caldon
- Garvan Institute of Medical Research & St Vincent's Clinical School, University of New South Wales, Sydney, New South Wales, Australia
| | | | | | - Wilbert Zwart
- Oncode Institute, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Carlo Palmieri
- Institute of Systems, Molecular and Integrative Biology, University of Liverpool & Clatterbridge Centre NHS Foundation Trust, Liverpool, UK
| | | | - Alex Swarbrick
- Garvan Institute of Medical Research & St Vincent's Clinical School, University of New South Wales, Sydney, New South Wales, Australia
| | - Elgene Lim
- Garvan Institute of Medical Research & St Vincent's Clinical School, University of New South Wales, Sydney, New South Wales, Australia
| | - Jason S Carroll
- Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
| | - Wayne D Tilley
- Dame Roma Mitchell Cancer Research Laboratories, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.
- Freemason's Foundation Centre for Men's Health, University of Adelaide, Adelaide, South Australia, Australia.
| |
Collapse
|
|
37
|
Pang N, Zhao C, Li J, Li L, Yang X, Yang M, Wu Z, Feng D. Body mass index changes after transjugular intrahepatic portosystemic shunt in individuals with cirrhosis. Nutrition 2020; 84:111095. [PMID: 33571910 DOI: 10.1016/j.nut.2020.111095] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
OBJECTIVES Liver cirrhosis is often accompanied by portal hypertension and malnutrition, two common complications that seriously affect treatment efficacy and quality of life. This study aimed to investigate the effect of transjugular intrahepatic portosystemic shunt (TIPS) on body mass index (BMI) and metabolism in individuals with cirrhotic portal hypertension, and the risk factors that affect changes of BMI. METHODS A retrospective study was performed to collect basic information before and after TIPS. This study included 77 participants. For each participant, we assayed body nutrition parameters: change of weight and BMI, routine liver and kidney function tests, and free fatty acids. In addition, we evaluated glucose and biochemical indexes. We used analysis of variance and regression analysis to investigate the effect of TIPS on BMI and metabolism in individuals with cirrhotic portal hypertension, and the risk factors that affect changes of BMI and metabolic components. RESULTS After TIPS, there was significant improvement in weight, BMI, red blood cell count, blood platelet count, hemoglobin, and Child-Pugh score in individuals with cirrhotic portal hypertension. Average weight and BMI increased after TIPS by 3.2% and 3.4%, respectively (P < 0.05). After 36 months, there were no significant differences in weight and BMI between before and after TIPS. We also observed a dose-response association of pre-TIPS blood ammonia and increased post-TIPS BMI (P = 0.05) in men. CONCLUSIONS This study suggests that individuals with cirrhosis treated with TIPS may see improvement in overall clinical and physical status, as measured by increased weight and BMI. Our data also indicate that pre-TIPS blood ammonia is positively associated with post-TIPS BMI.
Collapse
Affiliation(s)
- Ningdong Pang
- Department of Oncology and Vascular Intervention, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Chao Zhao
- Department of Oncology and Vascular Intervention, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Jinyu Li
- Department of Oncology and Vascular Intervention, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Lei Li
- Department of Oncology and Vascular Intervention, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Xiaofei Yang
- Department of Oncology and Vascular Intervention, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Minling Yang
- Department of Oncology and Vascular Intervention, First Hospital of Shanxi Medical University, Taiyuan, China
| | - Zhifeng Wu
- The Third Hospital of Shanxi Medical University, Taiyuan, China.
| | - Duiping Feng
- Department of Oncology and Vascular Intervention, First Hospital of Shanxi Medical University, Taiyuan, China.
| |
Collapse
|
|
38
|
Chidambaranathan-Reghupaty S, Fisher PB, Sarkar D. Hepatocellular carcinoma (HCC): Epidemiology, etiology and molecular classification. Adv Cancer Res 2020; 149:1-61. [PMID: 33579421 PMCID: PMC8796122 DOI: 10.1016/bs.acr.2020.10.001] [Citation(s) in RCA: 505] [Impact Index Per Article: 101.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma (HCC), the primary malignancy of hepatocytes, is a diagnosis with bleak outcome. According to National Cancer Institute's SEER database, the average five-year survival rate of HCC patients in the US is 19.6% but can be as low as 2.5% for advanced, metastatic disease. When diagnosed at early stages, it is treatable with locoregional treatments including surgical resection, Radio-Frequency Ablation, Trans-Arterial Chemoembolization or liver transplantation. However, HCC is usually diagnosed at advanced stages when the tumor is unresectable, making these treatments ineffective. In such instances, systemic therapy with tyrosine kinase inhibitors (TKIs) becomes the only viable option, even though it benefits only 30% of patients, provides only a modest (~3months) increase in overall survival and causes drug resistance within 6months. HCC, like many other cancers, is highly heterogeneous making a one-size fits all option problematic. The selection of liver transplantation, locoregional treatment, TKIs or immune checkpoint inhibitors as a treatment strategy depends on the disease stage and underlying condition(s). Additionally, patients with similar disease phenotype can have different molecular etiology making treatment responses different. Stratification of patients at the molecular level would facilitate development of the most effective treatment option. With the increase in efficiency and affordability of "omics"-level analysis, considerable effort has been expended in classifying HCC at the molecular, metabolic and immunologic levels. This review examines the results of these efforts and the ways they can be leveraged to develop targeted treatment options for HCC.
Collapse
Affiliation(s)
- Saranya Chidambaranathan-Reghupaty
- C. Kenneth and Dianne Wright Center for Clinical and Translational Research, Virginia Commonwealth University, Richmond, VA, United States
| | - Paul B Fisher
- Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States; VCU Institute of Molecular Medicine, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States; VCU Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, United States
| | - Devanand Sarkar
- Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States; VCU Institute of Molecular Medicine, Virginia Commonwealth University, School of Medicine, Richmond, VA, United States; VCU Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, United States.
| |
Collapse
|
|
39
|
Zhang J, Qiu Y, He X, Mao W, Han Z. Platelet-to-white blood cell ratio: A novel and promising prognostic marker for HBV-associated decompensated cirrhosis. J Clin Lab Anal 2020; 34:e23556. [PMID: 32893950 PMCID: PMC7755811 DOI: 10.1002/jcla.23556] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Revised: 08/11/2020] [Accepted: 08/13/2020] [Indexed: 12/14/2022] Open
Abstract
Aim The present study aimed to investigate associations of the platelet‐to‐white blood cell ratio (PWR)—a novel hematological indicator of inflammatory responses—with 30‐day outcomes in patients with HBV‐associated decompensated cirrhosis (HBV‐DeCi). Methods We recruited 131 patients with HBV‐DeCi for this retrospective study and extracted baseline clinical data and laboratory characteristics from medical records. Univariate and multivariate analyses were performed to determine major factors influencing 30‐day mortality. Area under the receiver operating characteristic curve analyses was performed to compare the predictive values of prognostic markers. Results During the 30‐day follow‐up period, 15 patients died. The PWR was significantly different between nonsurvivors and survivors. Lower PWR was found to be associated with an increased risk of mortality, and PWR was found to be an independent predictor of mortality in patients with HBV‐DeCi. Conclusions Our results demonstrate that low PWR may be a predictor of poor prognosis in patients with HBV‐DeCi, and this factor may be a useful supplement to standard approaches to enable effective management of these patients.
Collapse
Affiliation(s)
- JinFei Zhang
- Department of Clinical Laboratory, Shengzhou People's Hospital, Shengzhou Branch of the First Affiliated Hospital of Zhejiang University, Shengzhou, China
| | - YingPo Qiu
- Department of Clinical Laboratory, The Second Hospital of Yinzhou District, Ningbo, China
| | - Xia He
- Department of Clinical Laboratory, Shengzhou People's Hospital, Shengzhou Branch of the First Affiliated Hospital of Zhejiang University, Shengzhou, China
| | - WeiLin Mao
- Department of Clinical Laboratory, Shengzhou People's Hospital, Shengzhou Branch of the First Affiliated Hospital of Zhejiang University, Shengzhou, China.,Department of Clinical Laboratory, College of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
| | - Zhong Han
- Department of Clinical Laboratory, Shengzhou People's Hospital, Shengzhou Branch of the First Affiliated Hospital of Zhejiang University, Shengzhou, China
| |
Collapse
|
|
40
|
Teng CF, Wu HC, Su IJ, Jeng LB. Hepatitis B Virus Pre-S Mutants as Biomarkers and Targets for the Development and Recurrence of Hepatocellular Carcinoma. Viruses 2020; 12:v12090945. [PMID: 32859114 PMCID: PMC7552003 DOI: 10.3390/v12090945] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2020] [Revised: 08/06/2020] [Accepted: 08/25/2020] [Indexed: 12/11/2022] Open
Abstract
Chronic hepatitis B virus (HBV) infection is a major risk factor for the development of hepatocellular carcinoma (HCC), the leading cause of cancer-related death worldwide. Despite progress in the prevention and therapy of HCC, high incidence and recurrence rates of HCC remain big threats, resulting in poor patient survival. Effective biomarkers and targets of HCC are therefore urgently needed for better management and to improve patient outcomes. Pre-S mutants have been well demonstrated as HBV oncoproteins that play important roles in HCC development through activation of multiple oncogenic signal pathways in hepatocytes, in vitro and in vivo. The presence of pre-S mutants in patients with chronic HBV infection and HBV-related HCC has been associated with a significantly higher risk of HCC development and recurrence after curative surgical resection, respectively. In this review, we summarize the roles of pre-S mutants as biomarkers for predicting HBV-related HCC development and recurrence, and highlight the pre-S mutants-activated oncogenic signal pathways as potential targets for preventing HBV-related HCC development.
Collapse
Affiliation(s)
- Chiao-Fang Teng
- Graduate Institute of Biomedical Sciences, China Medical University, No.91, Hsueh-Shih Rd., Northern Dist., Taichung City 404, Taiwan
- Organ Transplantation Center, China Medical University Hospital, No.2, Yude Rd., North Dist., Taichung City 404, Taiwan
- Research Center for Cancer Biology, China Medical University, Taichung City 404, Taiwan
- Correspondence: (C.-F.T.); (I.-J.S.); (L.-B.J.); Tel.: +886-4-2205-2121 (C.-F.T. & L.-B.J.); +886-6-253-3131 (I.-J.S.); Fax: +886-4-2202-9083 (C.-F.T. & L.-B.J.); +886-6-242-5747 (I.-J.S.)
| | - Han-Chieh Wu
- National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan 350, Taiwan;
| | - Ih-Jen Su
- Department of Biotechnology, Southern Taiwan University of Science and Technology, No.1, Nantai St., Yongkang Dist., Tainan City 710, Taiwan
- Correspondence: (C.-F.T.); (I.-J.S.); (L.-B.J.); Tel.: +886-4-2205-2121 (C.-F.T. & L.-B.J.); +886-6-253-3131 (I.-J.S.); Fax: +886-4-2202-9083 (C.-F.T. & L.-B.J.); +886-6-242-5747 (I.-J.S.)
| | - Long-Bin Jeng
- Organ Transplantation Center, China Medical University Hospital, No.2, Yude Rd., North Dist., Taichung City 404, Taiwan
- Correspondence: (C.-F.T.); (I.-J.S.); (L.-B.J.); Tel.: +886-4-2205-2121 (C.-F.T. & L.-B.J.); +886-6-253-3131 (I.-J.S.); Fax: +886-4-2202-9083 (C.-F.T. & L.-B.J.); +886-6-242-5747 (I.-J.S.)
| |
Collapse
|
|
41
|
Chang ML, Cheng JS, Chien RN, Liaw YF. Hepatitis Flares Are Associated With Better Outcomes Than No Flare in Patients With Decompensated Cirrhosis and Chronic Hepatitis B Virus Infection. Clin Gastroenterol Hepatol 2020; 18:2064-2072.e2. [PMID: 31982607 DOI: 10.1016/j.cgh.2020.01.018] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2019] [Revised: 12/27/2019] [Accepted: 01/11/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Little is known about the effects of baseline hepatitis flares (level of alanine aminotransferase ≥5-fold above the upper limit of normal) on the outcomes of patients with chronic hepatitis B virus (HBV) infection with decompensated cirrhosis treated with nucleos(t)ide analogues. We aimed to investigate these effects. METHODS We performed a cohort study of 511 consecutive patients (78.1% men; 58.7% with flares at baseline) with chronic HBV infection and decompensated cirrhosis who were treated with nucleos(t)ide analogues as soon as decompensation was noted. Patients were enrolled from January 2002 to March 2018 at a tertiary care center in Taiwan and followed up for 16 years. RESULTS Patients with hepatitis flares had higher mean baseline levels of HBV DNA (6.44 ± 1.52 vs 6.08 ± 1.46 log10 IU/mL; P = .003), hepatitis B surface antigen, and total bilirubin; prolonged prothrombin time; higher platelet counts (108.0 ± 42.9 vs 83.6 ± 44.7 103/μL; P < .001); and a higher proportion were infected with HBV genotype B, compared with patients without flares. Patients with flares had lower ratios of neutrophils to lymphocytes than patients with flares (6.14 ± 9.18 vs 9.12 ± 1.36; P = .019); were less likely than patients without flares to be positive for hepatitis B e antigen, ascites, esophageal varices, or splenomegaly; and a lower proportion died or underwent liver transplantation (46.5% vs 73.2% of patients without flares; P < .001), even though the patients without flares had similar short-term (<3 mo) outcomes. Factors associated independently with baseline flares were esophageal varices (odds ratio [OR], 0.165; 95% CI, 0.067-0.406), ascites (OR, 0.415; 95% CI, 0.178-0.969), levels of total bilirubin (OR, 1.158; 95% CI, 1.041-1.269), prolonged prothrombin time (OR, 1.095; 95% CI, 1.033-1.168), and higher platelet counts (OR, 1.009; 95% CI, 1.00-1.018). After we used propensity score matching to match patients with and without baseline flares, factors associated with the cumulative incidence of death or liver transplantation were flares (hazard ratio [HR], 0.491; 95% CI, 0.317-0.76), ratio of neutrophils to lymphocytes (HR, 1.278; 95% CI, 1.027-1.591), and prolonged prothrombin time (HR, 1.223; 95% CI, 1.052-1.423). CONCLUSIONS In a 16-year study of patients with chronic HBV infection and decompensated cirrhosis treated with nucleos(t)ide analogues, a baseline flare of hepatitis was associated independently with better long-term (≥3 mo) outcomes than no flare.
Collapse
Affiliation(s)
- Ming-Ling Chang
- Liver Research Center, Division of Hepatology, Department of Gastroenterology and Hepatology, Taoyuan, Taiwan; Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
| | - Jur-Shan Cheng
- Clinical Informatics and Medical Statistics Research Center, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Emergency Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Rong-Nan Chien
- Liver Research Center, Division of Hepatology, Department of Gastroenterology and Hepatology, Taoyuan, Taiwan; Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Yun-Fan Liaw
- Liver Research Center, Division of Hepatology, Department of Gastroenterology and Hepatology, Taoyuan, Taiwan; Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| |
Collapse
|
|
42
|
Mean Platelet Volume/Lymphocyte Ratio as a Prognostic Indicator for HBV-Related Decompensated Cirrhosis. Gastroenterol Res Pract 2020; 2020:4107219. [PMID: 32714387 PMCID: PMC7352138 DOI: 10.1155/2020/4107219] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Revised: 06/09/2020] [Accepted: 06/19/2020] [Indexed: 12/30/2022] Open
Abstract
Aim To evaluate the prognostic role of the mean platelet volume/lymphocyte ratio (MPVLR) for mortality in patients with hepatitis B virus-related decompensated cirrhosis (HBV-DeCi). Methods The medical records of 101 patients with HBV-DeCi were retrospectively reviewed, and their baseline clinical and laboratory characteristics were extracted. The predictive value of the MPVLR for death was estimated using receiver operating characteristic curve analysis and a multivariate logistic regression model. Results Patients with HBV-DeCi in the high-MPVLR group exhibited significantly increased 90-day mortality compared with that of the patients within the low-MPVLR group, and MPVLR was an independent predictor of 90-day mortality in patients with HBV-DeCi. Conclusions Increased MPVLR is associated with poor outcomes in patients with HBV-DeCi and might be a useful component of future prognostic scores.
Collapse
|
|
43
|
Abstract
INTRODUCTION Hepatitis B virus (HBV) reactivation can be induced by treatments that attenuate the immunological control over HBV, leading to increased morbidity and mortality. The risk of HBV reactivation is determined by host immunity, viral factors, and the type and dose of treatments. Nevertheless, the risk of HBV reactivation for a growing number of novel therapies remains uncertain and needs to be carefully examined. Identification of patients at risk and administration of prophylactic antiviral agents are critical to prevent HBV reactivation. Early diagnosis and initiation of antiviral treatment are the keys to avoid devastating outcomes. AREA COVERED We summarized the latest evidence and recommendations for risk stratification, early diagnosis, prophylaxis, and management of HBV reactivation. EXPERT OPINION Universal screening, adequate prophylaxis, and close monitoring are essential for the prevention of HBV reactivation. Risk stratification of patients at risk with appropriate antiviral prophylaxis can prevent HBV reactivation effectively. Several emerging biomarkers have been proved to help determine the risk precisely. Early detection and timely administration of antiviral agents are crucial for management. Further studies on the precision of risk stratification as well as the optimal duration of prophylaxis and treatment are needed to establish an individualized strategy.
Collapse
Affiliation(s)
- Shang-Chin Huang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital , Taipei, Taiwan
| | - Hung-Chih Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital , Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital , Taipei, Taiwan.,Department of Microbiology, National Taiwan University College of Medicine Taipei , Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital , Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital , Taipei, Taiwan.,Department of Medical Research, National Taiwan University Hospital , Taipei, Taiwan.,Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine , Taipei, Taiwan
| |
Collapse
|
|
44
|
Ganesan M, Eikenberry A, Poluektova LY, Kharbanda KK, Osna NA. Role of alcohol in pathogenesis of hepatitis B virus infection. World J Gastroenterol 2020; 26:883-903. [PMID: 32206001 PMCID: PMC7081008 DOI: 10.3748/wjg.v26.i9.883] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Revised: 02/09/2020] [Accepted: 02/15/2020] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) and alcohol abuse often contribute to the development of end-stage liver disease. Alcohol abuse not only causes rapid progression of liver disease in HBV infected patients but also allows HBV to persist chronically. Importantly, the mechanism by which alcohol promotes the progression of HBV-associated liver disease are not completely understood. Potential mechanisms include a suppressed immune response, oxidative stress, endoplasmic reticulum and Golgi apparatus stresses, and increased HBV replication. Certainly, more research is necessary to gain a better understanding of these mechanisms such that treatment(s) to prevent rapid liver disease progression in alcohol-abusing HBV patients could be developed. In this review, we discuss the aforementioned factors for the higher risk of liver diseases in alcohol-induced HBV pathogenies and suggest the areas for future studies in this field.
Collapse
Affiliation(s)
- Murali Ganesan
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, United States
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, NE 68105, United States
| | - Allison Eikenberry
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, United States
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, NE 68105, United States
| | - Larisa Y Poluektova
- Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE 68198, United States
| | - Kusum K Kharbanda
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, United States
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, NE 68105, United States
| | - Natalia A Osna
- Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, United States
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Nebraska Medical Center, Omaha, NE 68105, United States
| |
Collapse
|
|
45
|
Tian F, Houle SKD, Alsabbagh MW, Wong WWL. Cost-Effectiveness of Tenofovir Alafenamide for Treatment of Chronic Hepatitis B in Canada. PHARMACOECONOMICS 2020; 38:181-192. [PMID: 31691902 DOI: 10.1007/s40273-019-00852-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/25/2023]
Abstract
BACKGROUND/AIM Tenofovir alafenamide (TAF) has been approved for treating chronic hepatitis B (CHB) due to a proposed better safety profile in comparison with current therapies. We evaluated the cost effectiveness of TAF and other available treatment options for hepatitis B envelope antigen (HBeAg)-positive and HBeAg-negative CHB patients from a Canadian provincial Ministry of Health perspective. METHODS A state-transition model based on the published literature was developed to compare treatment strategies involving entecavir (ETV), tenofovir disoproxil fumarate (TDF), and TAF. It adopted a lifetime time horizon. Outcomes measured were predicted number of liver-related deaths, costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS For HBeAg-positive patients, TAF followed by ETV generated an additional 0.16 QALYs/person at an additional cost of Can$14,836.18 with an ICER of Can$94,142.71/QALY compared with TDF followed by ETV. Of the iterations, 28.7% showed that it is the optimal strategy with a Can$50,000 willingness-to-pay threshold. For HBeAg-negative patients, ETV followed by TAF would prevent an additional 13 liver-related deaths per 1000 CHB patients compared with TDF, followed by ETV. It generated an additional 0.13 QALYs/person at an additional cost of Can$59,776.53 with an ICER of Can$461,162.21/QALY compared with TDF, followed by ETV. TAF-containing strategies are unlikely to be a rational choice in either case. The results were sensitive to the HBeAg seroconversion rates and viral suppression rates of the treatments. CONCLUSIONS Our analysis suggests that TAF is not cost effective at its current cost. A 33.4% reduction in price would be required to make it cost effective for HBeAg-positive patients with a Can$50,000 willingness-to-pay threshold.
Collapse
Affiliation(s)
- Feng Tian
- School of Pharmacy, Faculty of Science, University of Waterloo, 10A Victoria Street S, Kitchener, ON, N2G1C5, Canada
| | - Sherilyn K D Houle
- School of Pharmacy, Faculty of Science, University of Waterloo, 10A Victoria Street S, Kitchener, ON, N2G1C5, Canada
| | - Mhd Wasem Alsabbagh
- School of Pharmacy, Faculty of Science, University of Waterloo, 10A Victoria Street S, Kitchener, ON, N2G1C5, Canada
| | - William W L Wong
- School of Pharmacy, Faculty of Science, University of Waterloo, 10A Victoria Street S, Kitchener, ON, N2G1C5, Canada.
| |
Collapse
|
|
46
|
Zhou J, Mao W, Shen L, Huang H. Plasma D-dimer as a novel biomarker for predicting poor outcomes in HBV-related decompensated cirrhosis. Medicine (Baltimore) 2019; 98:e18527. [PMID: 31876748 PMCID: PMC6946568 DOI: 10.1097/md.0000000000018527] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
This study aim was to evaluate whether plasma D-dimer levels could serve as a novel prognostic biomarker for 1-month mortality in patients with HBV-related decompensated cirrhosis (HBV-DeCi).This was a retrospective study that enrolled 132 HBV-DeCi patients. Univariate and multivariate regression models were used to identify risk factors for mortality. The area under the receiver operating characteristic curve was calculated to estimate and compare the predictive values of different prognostic markers.In the present study, the plasma D-dimer levels were higher in the nonsurviving group than in the surviving group. Additionally, the D-dimer level was positively correlated with the model for end-stage liver disease (MELD) score. The results of multivariate analysis showed that both the MELD score and D-dimer level are independent predictors of 1-month mortality in HBV-DeCi patients (both P < .01).Plasma D-dimer can be considered a new additional prognostic marker for 1-month mortality in HBV-DeCi patients.
Collapse
Affiliation(s)
- Jing Zhou
- Department of Brain Surgery, Shengzhou People's Hospital, Shengzhou Branch of the First Affiliated Hospital of Zhejiang University, Shengzhou
| | - WeiLin Mao
- Department of Clinical Laboratory, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang
- Key Laboratory of Digestive System Diseases of Shengzhou, Shengzhou People's Hospital, Shengzhou
| | - LiangJun Shen
- Department of Brain Surgery, Shengzhou People's Hospital, Shengzhou Branch of the First Affiliated Hospital of Zhejiang University, Shengzhou
| | - HongGuang Huang
- Department of Neurosurgery, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China
| |
Collapse
|
|
47
|
Kim DJ, Cho EJ, Yu KS, Jang IJ, Yoon JH, Park T, Cho JY. Comprehensive Metabolomic Search for Biomarkers to Differentiate Early Stage Hepatocellular Carcinoma from Cirrhosis. Cancers (Basel) 2019; 11:E1497. [PMID: 31590436 PMCID: PMC6826937 DOI: 10.3390/cancers11101497] [Citation(s) in RCA: 55] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Revised: 10/02/2019] [Accepted: 10/02/2019] [Indexed: 02/06/2023] Open
Abstract
The established biomarker for hepatocellular carcinoma (HCC), serum α-fetoprotein (AFP), has suboptimal performance in early disease stages. This study aimed to develop a metabolite panel to differentiate early-stage HCC from cirrhosis. Cross-sectional metabolomic analyses of serum samples were performed for 53 and 47 patients with early HCC and cirrhosis, respectively, and 50 matched healthy controls. Results were validated in 82 and 80 patients with early HCC and cirrhosis, respectively. To retain a broad spectrum of metabolites, technically distinct analyses (global metabolomic profiling using gas chromatography time-of-flight mass spectrometry and targeted analyses using liquid chromatography with tandem mass spectrometry) were employed. Multivariate analyses classified distinct metabolites; logistic regression was employed to construct a prediction model for HCC diagnosis. Five metabolites (methionine, proline, ornithine, pimelylcarnitine, and octanoylcarnitine) were selected in a panel. The panel distinguished HCC from cirrhosis and normal controls, with an area under the receiver operating curve (AUC) of 0.82; this was significantly better than that of AFP (AUC: 0.75). During validation, the panel demonstrated significantly better predictability (AUC: 0.94) than did AFP (AUC: 0.78). Defects in ammonia recycling, the urea cycle, and amino acid metabolism, demonstrated on enrichment pathway analysis, may reliably distinguish HCC from cirrhosis. Compared with AFP alone, the metabolite panel substantially improved early-stage HCC detection.
Collapse
Affiliation(s)
- Da Jung Kim
- Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, Korea.
| | - Eun Ju Cho
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
| | - Kyung-Sang Yu
- Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, Korea.
| | - In-Jin Jang
- Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, Korea.
| | - Jung-Hwan Yoon
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul 03080, Korea.
| | - Taesung Park
- Department of Statistics, Seoul National University, Seoul 08826, Korea.
| | - Joo-Youn Cho
- Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, Korea.
| |
Collapse
|
|
48
|
Radu-Ionita F, Pyrsopoulos NT, Jinga M, Tintoiu IC, Sun Z, Bontas E. Viral Hepatitis B. LIVER DISEASES 2019:173-180. [PMCID: PMC7122759 DOI: 10.1007/978-3-030-24432-3_16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/07/2022]
Abstract
Hepatitis B virus (HBV) was first discovered on aboriginal Australians in 1963. Epidemiological studies soon recognized that HBV is a global chronic liver disease, with the highest prevalence rates in Asia and Africa. HBV is highly infectious, and in most cases transmitted from family members. Infections acquired during the perinatal period have a 90% chance of progressing to persistent HBV infection. This rate decreases to 2.3% when infection occurs at college student age. The persistent HBV infection starts with the immune tolerance phase when our immune system may recognize HBV antigens, but does not produce significant inflammation. An immune clearance reaction may develop to terminate HBV replication two to four decades later. When this immune clearance reaction successfully suppresses HBV replication, HBsAg carriers may progress to the residual phase. About 50% of HBsAg carriers ultimately clear HBsAg at age 80. Those patients unable to clear HBV replication smoothly have increased risk of chronic hepatitis, liver cirrhosis, and hepatocarcinogenesis. Current therapies decrease hepatic decompensation and increase survival rate. However, the sustained virologic response rate is lower than 40%. About 50% of patients experience a clinical flare within one year after therapy ends. Further studies will be needed to improve sustained virologic response rate.
Collapse
Affiliation(s)
- Florentina Radu-Ionita
- Faculty of Medicine, “Titu Maiorescu” University, Central Military Emergency University Hospital “Dr. Carol Davila”, Bucharest, Romania
| | | | - Mariana Jinga
- Carol Davila University of Medicine and Pharmacy, Central Military Emergency University Hospital “Dr. Carol Davila”, Bucharest, Romania
| | - Ion C. Tintoiu
- Faculty of Medicine, “Titu Maiorescu” University, Central Military Emergency University Hospital “Dr. Carol Davila”, Bucharest, Romania
| | - Zhonghua Sun
- Medical Radiation Sciences, Curtin University, Perth, WA Australia
| | - Ecaterina Bontas
- “Prof. C.C. Iliescu” Emergency Institute for Cardiovascular Diseases, Bucharest, Romania
| |
Collapse
|
|
49
|
Chen CJ, Tsay PK, Huang SF, Tsui PH, Yu WT, Hsu TH, Tai J, Tai DI. Effects of Hepatic Steatosis on Non-Invasive Liver Fibrosis Measurements Between Hepatitis B and Other Etiologies. APPLIED SCIENCES 2019; 9:1961. [DOI: 10.3390/app9091961] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Fibrosis-4 (FIB4), transient elastography (TE), and acoustic radiation force impulse (ARFI) are popular modalities to assess liver fibrosis. Their cutoff values for degrees of fibrosis vary between studies. The influence of hepatic steatosis on fibrosis measurements for different etiologies was evaluated. Data from a consecutive series of patients who received fibrosis measurement were included for the training group. An additional series with histology served as the validation group. A standardized protocol was performed for both TE and ARFI, mostly by a single technician. Patients with alcoholism, autoimmune disease, active inflammation, or who were receiving therapy were excluded. The training group included 215 patients and the validation group included 221. The correlation of liver stiffness between TE and ARFI was good (R2 linear = 0.798; p < 0.001). Different correlations between ARFI and TE were noted between high and low control attenuation parameter (CAP) values (cutoff: 290 dB/m), especially in the non-hepatitis B subgroups. Relatively lower FIB4 and TE values were seen in the high CAP versus low CAP in patients with histology-proven non-alcoholic fatty liver disease and chronic hepatitis C. FIB4 cutoff values were >25% lower among F2-F4 stages and the TE cutoff value for F4 was 8.5% lower in the high versus low CAP group. Such findings were not observed in chronic hepatitis B. Different fibrogenesis mechanisms between hepatitis B and non-B are discussed. We conclude that hepatic steatosis significantly impacts FIB4 and TE fibrosis measurements in non-hepatitis B-related liver diseases. Fibrosis grade should be interpreted with caution in severe steatosis.
Collapse
Affiliation(s)
- Cheng-Jen Chen
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Tao-Yuan 333, Taiwan
| | - Pei-Kwei Tsay
- Department of Public Health and Center of Biostatistics, Chang Gung University College of Medicine, Tao-Yuan 333, Taiwan
| | - Shiu-Feng Huang
- Division of Molecular and Genomic Medicine, National Health Research Institute, Taipei 115, Taiwan
| | - Po-Hsiang Tsui
- Department of Medical imaging and Radiological Sciences, College of Medicine, Institute for Radiological Research, Chang Gung University, Taoyuan 333, Taiwan
| | - Wan-Ting Yu
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Tao-Yuan 333, Taiwan
| | - Tse-Hwa Hsu
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Tao-Yuan 333, Taiwan
| | - Jennifer Tai
- Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou Medical Center, Tao-Yuan 333, Taiwan
| | - Dar-In Tai
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Tao-Yuan 333, Taiwan
| |
Collapse
|
|
50
|
Molecular Mechanisms Driving Progression of Liver Cirrhosis towards Hepatocellular Carcinoma in Chronic Hepatitis B and C Infections: A Review. Int J Mol Sci 2019. [PMID: 30889843 DOI: 10.3390/ijms] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Almost all patients with hepatocellular carcinoma (HCC), a major type of primary liver cancer, also have liver cirrhosis, the severity of which hampers effective treatment for HCC despite recent progress in the efficacy of anticancer drugs for advanced stages of HCC. Here, we review recent knowledge concerning the molecular mechanisms of liver cirrhosis and its progression to HCC from genetic and epigenomic points of view. Because ~70% of patients with HCC have hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection, we focused on HBV- and HCV-associated HCC. The literature suggests that genetic and epigenetic factors, such as microRNAs, play a role in liver cirrhosis and its progression to HCC, and that HBV- and HCV-encoded proteins appear to be involved in hepatocarcinogenesis. Further studies are needed to elucidate the mechanisms, including immune checkpoints and molecular targets of kinase inhibitors, associated with liver cirrhosis and its progression to HCC.
Collapse
|