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Patil VS, Harish DR, Charla R, Bhandare VV, Gujarathi SS, Beerwala FA, Patil PP, Jalalpure SS, Hegde HV, Roy S. Flavonoids of Andrographis paniculata regulate hepatitis B virus replication and hepatocellular carcinoma progression: evidence from computational and experimental studies. BMC Complement Med Ther 2025; 25:95. [PMID: 40057777 PMCID: PMC11889761 DOI: 10.1186/s12906-025-04807-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2024] [Accepted: 02/03/2025] [Indexed: 05/13/2025] Open
Abstract
BACKGROUND The HBx protein of hepatitis B virus (HBV) plays a crucial role in HBV pathogenesis, yet current treatments like HIV reverse transcriptase (RT) inhibitors, which target HBV RT due to similar active sites, have severe side effects, risk of drug resistance, and high costs. The present study investigates the anti-hepatitis B virus (HBV) properties of Andrographis paniculata (AP) and Thespesia populnea (TP) on HBV expressing HepG2.2.15 cells and by computational analysis. METHODS In vitro cytotoxicity, reverse transcriptase inhibitory, DNA and pgRNA quantification by qRT-PCR, time course analysis of HBsAg and HBeAg, and HBX-HBXIP interaction inhibition studies were conducted. The interaction of HBX with HBXIP, and phytocompounds' interaction with HBx was analyzed through molecular docking and dynamics studies. RESULTS AP exhibits lower cytotoxicity (CC50 = 832.915 µg/mL) than TP (CC50 = 593.122 µg/mL) after 24 h, with Tenofovir disoproxil fumarate (TDF) showing minimal cytotoxicity (CC50 > 500 µM). Both AP and TP significantly decreased intracellular HBV DNA with a > 25 fold reduction at higher concentrations (125-500 µg/mL) but had no significant effect on pgRNA level. AP and TP 500 µg/mL effectively inhibited HBsAg secretion (95% and 80% inhibition, respectively), over 120 h. AP also showed inhibition of HBeAg secretion (75-82%), while TP exhibited a higher inhibition of 90% at 24 h. TDF showed consistent but lower inhibitory effects on HBsAg and HBeAg. The HBx-HBXIP interaction inhibition assay showed AP's greater inhibitory capacity (IC50 < 62.5 µg/mL) compared to TP (IC50 = 806.69 µg/mL). Computational studies further validated these findings, showing stable binding interactions of AP compounds (flavonoids) with HBx protein (with Arg138 and His139, Lys140, and Trp141 residues participating in the interaction with HBXIP), corroborating their potential in disrupting HBV replication. Molecular dynamics simulations confirmed the stability of these interactions over 100ns. CONCLUSIONS AP exhibits potent anti-HBV activities, making it a promising candidate for further therapeutic development.
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Affiliation(s)
- Vishal S Patil
- ICMR-National Institute of Traditional Medicine, Nehru Nagar, Belagavi, Karnataka, 590010, India
- KLE College of Pharmacy, Belagavi, KLE Academy of Higher Education and Research, Nehru Nagar, Belagavi,, Karnataka, 590010, India
| | - Darasaguppe R Harish
- ICMR-National Institute of Traditional Medicine, Nehru Nagar, Belagavi, Karnataka, 590010, India.
| | - Rajitha Charla
- ICMR-National Institute of Traditional Medicine, Nehru Nagar, Belagavi, Karnataka, 590010, India
| | | | - Swarup S Gujarathi
- ICMR-National Institute of Traditional Medicine, Nehru Nagar, Belagavi, Karnataka, 590010, India
| | - Faizan A Beerwala
- ICMR-National Institute of Traditional Medicine, Nehru Nagar, Belagavi, Karnataka, 590010, India
- KLE College of Pharmacy, Belagavi, KLE Academy of Higher Education and Research, Nehru Nagar, Belagavi,, Karnataka, 590010, India
| | - Priyanka P Patil
- ICMR-National Institute of Traditional Medicine, Nehru Nagar, Belagavi, Karnataka, 590010, India
- KLE College of Pharmacy, Belagavi, KLE Academy of Higher Education and Research, Nehru Nagar, Belagavi,, Karnataka, 590010, India
| | - Sunil S Jalalpure
- ICMR-National Institute of Traditional Medicine, Nehru Nagar, Belagavi, Karnataka, 590010, India.
| | - Harsha V Hegde
- ICMR-National Institute of Traditional Medicine, Nehru Nagar, Belagavi, Karnataka, 590010, India
| | - Subarna Roy
- ICMR-National Institute of Traditional Medicine, Nehru Nagar, Belagavi, Karnataka, 590010, India
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Lai JCT, Colombatto P, Wong GLH, Brunetto MR. Why and when could nucleos(t)ide analogues treatment be withdrawn? Dig Liver Dis 2025; 57:558-563. [PMID: 39472177 DOI: 10.1016/j.dld.2024.10.012] [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: 09/18/2024] [Accepted: 10/14/2024] [Indexed: 01/03/2025]
Abstract
Oral antiviral therapy to hepatitis B virus (HBV) with nucleos(t)ide analogues (NUCs) is effective in suppressing the viral load leading to improved clinical outcomes. However, functional cure of HBV, indicated by hepatitis B surface antigen (HBsAg) clearance from the serum, is rare. Although safety and adherence may represent minor issues in long-term treatment with the available NUCs, more efficacious treatments with finite treatment duration for patients with chronic hepatitis B (CHB) are currently undergoing active clinical investigation. Available data suggest that HBsAg loss can be achieved in 10% to 20% of patients after NUC discontinuation, at the cost of about 50% to 80% virological relapse and 40% to 55% retreatment with NUC. With this, NUC treatment in patients with cirrhosis should not be stopped to avoid detrimental risk of hepatic decompensation and death. Viral and immune biomarkers, which may be potentially useful in stratifying the patients at risk of relapse after stopping NUC therapy, are under investigation. In the era of personalized medicine aided by artificial intelligence tools, tight monitoring of viral kinetics and algorithmic modeling appear a promising strategy to assist in individualized decision and conclude the optimal timing of the NUC treatment discontinuation.
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Affiliation(s)
- Jimmy Che-To Lai
- Medical Data Analytics Centre, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China
| | - Piero Colombatto
- Liver Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses of Pisa University Hospital
| | - Grace Lai-Hung Wong
- Medical Data Analytics Centre, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China; State Key Laboratory of Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China.
| | - Maurizia Rossana Brunetto
- Liver Unit and Laboratory of Molecular Genetics and Pathology of Hepatitis Viruses of Pisa University Hospital; Department of Clinical and Experimental Medicine, University of Pisa, Italy; Institute of Biostructure and Bioimaging, National Research Council, Naples, Italy.
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Mak L, Yee LJ, Wong RJ, Ramers CB, Frenette C, Hsu Y. Hepatocellular carcinoma among patients with chronic hepatitis B in the indeterminate phase. J Viral Hepat 2024; 31 Suppl 2:27-35. [PMID: 38717914 PMCID: PMC11619554 DOI: 10.1111/jvh.13914] [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: 10/30/2023] [Accepted: 12/15/2023] [Indexed: 12/06/2024]
Abstract
Hepatitis B virus (HBV) infection is a dynamic disease where patients progress through several stages defined by HBV e-antigen (HBeAg) status, HBV-DNA levels and transaminase elevations, with antiviral therapy indicated only in specific stages. However, some patients cannot be classified into one of the stages and are said to fall into an 'indeterminate phase' or 'grey zone'. Exact definitions of the indeterminate phase vary from guideline to guideline as a result of different cut-off values for biomarker measurements. Data suggest that as many as 50% of HBV patients may be in an indeterminate phase and may not rapidly transition out of this phase. Clinical data that suggest these patients are at increased risk of hepatocellular carcinoma (HCC) are complemented by molecular evidence of integrations of HBV-DNA into the host genome, chromosomal translocations and immune activation despite liver enzymes that may suggest lack of inflammation. Antiviral therapy reduces these hepatocarcinogenic mechanisms and is reflected in a reduction of fibrosis and HCC risk. We review key data on patients in the indeterminate phase, with emphasis on HCC as an outcome. We take a holistic approach and link new biological data with clinical observations as well as examine the potential role of antiviral therapy in reducing HCC risk among patients in the indeterminate phase. With the availability of safe and effective oral antivirals, consideration must be given as to how much residual risk of HCC should be tolerated among patients in the indeterminate phase.
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Affiliation(s)
- Lung‐Yi Mak
- Department of Medicine, Queen Mary HospitalThe University of Hong KongHong KongSpecial Administrative RegionChina
| | | | - Robert J. Wong
- Division of Gastroenterology and HepatologyStanford University School of MedicinePalo AltoCaliforniaUSA
- Division of Gastroenterology and HepatologyVeterans Affairs Palo Alto Health Care SystemPalo AltoCaliforniaUSA
| | - Christian B. Ramers
- Laura Rodriguez Research InstituteFamily Health Centers of San DiegoSan DiegoCaliforniaUSA
- University of CaliforniaSan Diego School of MedicineLa JollaCaliforniaUSA
| | | | - Yao‐Chun Hsu
- Division of Gastroenterology and HepatologyE‐Da HospitalKaohsiungTaiwan
- School of Medicine, College of MedicineI‐Shou UniversityKaohsiungTaiwan
- Institute of Biomedical InformaticsNational Yang Ming Chiao Tung UniversityTaipeiTaiwan
- Division of Gastroenterology and HepatologyFu‐Jen Catholic University HospitalNew TaipeiTaiwan
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Zhang Y, Xu W, Deng Z, Wang L, Zheng X, Zhu X, Li X, Li J, Shu X, Lai J, Peng L, Xie C. Long-term efficacy and safety of tenofovir alafenamide, tenofovir disoproxil fumarate, and entecavir in treating hepatitis B virus-related acute-on-chronic liver failure: A 144-week data analysis. LIVER RESEARCH 2024; 8:295-303. [PMID: 39958923 PMCID: PMC11771274 DOI: 10.1016/j.livres.2024.10.001] [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] [Received: 03/13/2024] [Revised: 06/12/2024] [Accepted: 10/17/2024] [Indexed: 02/18/2025]
Abstract
Background and aims Antiviral therapy is essential for hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). No data are available on the long-term prognosis or safety of tenofovir alafenamide (TAF), tenofovir disoproxil fumarate (TDF), or entecavir (ETV) in treating HBV-ACLF globally. This study was conducted to investigate the long-term efficacy and safety of the three nucleos(t)ide analogs in the treatment of HBV-ACLF. Methods In this prospective, real-world cohort study, patients with HBV-ACLF were assigned to the TAF, TDF, and ETV groups. A total of 199 patients completed the 144-week follow-up. After propensity score matching (PSM), 44 patients remained in each group for further analysis of survival status, incidence of hepatocellular carcinoma (HCC), virological response, and liver and renal function indicators. Results In the original cohort, HCC developed in one patient in each group. No serious drug-related adverse events were observed. In the PSM cohort, the 144-week survival rates were 56.82%, 75.00%, and 59.09% in the TAF, TDF, and ETV groups, respectively (P = 0.118). When stratified into noncirrhosis and cirrhosis subgroups at baseline, the survival rate of the ETV group was slightly lower than that of the TAF and TDF group in noncirrhosis patients (P = 0.338), and the survival rate of the TAF group was slightly lower than that of the TDF and ETV group in cirrhosis patients (P = 0.052), but the differences were not statistically significant. The long-term overall survival rates in the TAF, TDF, and ETV groups were comparable. After 144 weeks, no significant difference in the virological response rate or liver or renal function indicators was found among the three groups, except for the level of aspartate aminotransferase, which was significantly higher in the TDF group than in the ETV group at week 144 (P = 0.001). Conclusions There were no significant differences in the survival rate, incidence of HCC, efficacy or safety associated with the use of these three nucleos(t)ide analogs in treating HBV-ACLF. Trial registration ClinicalTrials.gov NCT03920618.
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Affiliation(s)
- Yeqiong Zhang
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Wenxiong Xu
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Zhexuan Deng
- Department of Intensive Care Medicine, Jiangxi Provincial Hospital of Integrated Chinese and Western Medicine, Nanchang, Jiangxi, China
| | - Lu Wang
- Department of Diagnostics, Second School of Clinical Medicine, Binzhou Medical University, Yantai, Shandong, China
| | - Xingrong Zheng
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Xiang Zhu
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Xuejun Li
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Jianguo Li
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Xin Shu
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Jing Lai
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Liang Peng
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Chan Xie
- Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
- Guangdong Provincial Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
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Zhang H, Huang J, Zhu W, Feng W, Zeng Y. Does long-term use of tenofovir disoproxil fumarate affect fracture risk in patients with chronic hepatitis B? J Hepatol 2024; 81:e199-e200. [PMID: 38879174 DOI: 10.1016/j.jhep.2024.05.040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2024] [Revised: 05/14/2024] [Accepted: 05/30/2024] [Indexed: 07/27/2024]
Affiliation(s)
- Haitao Zhang
- Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Jin Huang
- Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou 730050, Gansu, China
| | - Wenhao Zhu
- Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Wenjun Feng
- The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong, China.
| | - Yirong Zeng
- The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong, China.
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Zhu M, Jia L, Wang Y, Zhang Y, Lv S. Comparative evaluation of adverse drug reactions for tenofovir alafenamide and tenofovir disoproxil fumarate using the FAERS Database: a disproportionality analysis. Expert Opin Drug Saf 2024:1-10. [PMID: 39129454 DOI: 10.1080/14740338.2024.2391496] [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: 04/02/2024] [Revised: 06/05/2024] [Accepted: 06/27/2024] [Indexed: 08/13/2024]
Abstract
BACKGROUND Tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) are widely used nucleoside reverse transcriptase inhibitors (NRTIs), necessitating a thorough understanding of their safety profiles to ensure optimal patient care and treatment adherence. METHODS We employed statistical methods including the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Item Gamma Poisson Shrinker (MGPS) to compare and evaluate the safety profiles of these NRTIs. RESULTS TAF was significantly associated with weight increase (ROR: 6.43; 95% CI: 5.93-6.96) and specific psychiatric disorders. TDF showed a notable signal for renal disorders and product-related issues, including product dose omission (ROR: 3.53; 95% CI: 3.22-3.87). Additionally, the study highlighted differences in safety signals related to pregnancy outcomes, with TAF having a higher ROR for maternal exposure (ROR: 7.83; 95% CI: 7.06-8.69) and TDF for fetal exposure (ROR: 4.51; 95% CI: 3.93-5.18), underscoring the need for cautious use in pregnant women. The comparative analysis also identified signals for osteonecrosis (ROR: 108.81; 95% CI: 106.25-111.43) and bone loss (ROR: 714; 95% CI: 685.49-743.68) for TAF and TDF, respectively, highlighting the importance of bone health considerations in treatment plans. CONCLUSION These findings underscore the importance of personalized antiviral therapy and patient safety.
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Affiliation(s)
- Meng Zhu
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Lingjuan Jia
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Yike Wang
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Yongsheng Zhang
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Shengxia Lv
- School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
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Johannessen A, Reikvam DH, Aleman S, Berhe N, Weis N, Desalegn H, Stenstad T, Heggelund L, Samuelsen E, Karlsen LN, Lindahl K, Pettersen FO, Iversen J, Kleppa E, Bollerup S, Winckelmann AA, Brugger-Synnes P, Simonsen HE, Svendsen J, Kran AMB, Holmberg M, Olsen IC, Rueegg CS, Dalgard O. Clinical trial: An open-label, randomised trial of different re-start strategies after treatment withdrawal in HBeAg negative chronic hepatitis B. Aliment Pharmacol Ther 2024; 60:434-445. [PMID: 38970293 DOI: 10.1111/apt.18147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 04/20/2024] [Accepted: 06/26/2024] [Indexed: 07/08/2024]
Abstract
BACKGROUND Stopping nucleos(t)ide analogue (NA) therapy in patients with chronic hepatitis B (CHB) may trigger a beneficial immune response leading to HBsAg loss, but clinical trials on re-start strategies are lacking. AIM To assess whether it is beneficial to undergo a prolonged flare after NA cessation. METHODS One-hundred-and-twenty-seven patients with HBeAg negative, non-cirrhotic CHB with at least 24 months of viral suppression on NA therapy were included. All study participants stopped antiviral therapy and were randomised to either low-threshold (ALT > 80 U/L and HBV DNA > 2000 IU/mL) or high-threshold (ALT > 100 U/L for >4 months, or ALT > 400 U/L for >2 months) for the re-start of therapy. The primary endpoint was HBsAg loss within 36 months of stopping antiviral treatment. The primary analysis was based on intention-to-treat allocation with last observation carried forward. RESULTS There was a numerical but not statistically significant difference in HBsAg loss between the low-threshold (3 of 64; 4.7%) and the high-threshold (8 of 63; 12.7%) group (risk difference: 8.0%, 95% CI: -2.3 to 19.6, p = 0.123). None of the patients with end-of-treatment HBsAg > 1000 IU/mL achieved HBsAg loss; among those with end-of-treatment HBsAg < 1000 IU/mL, 8 of 15 (53.3%) achieved HBsAg loss in the high-threshold group compared to 3 of 26 (11.5%) in the low-threshold group. CONCLUSIONS We could not confirm our hypothesis that a higher threshold for restart of therapy after NA withdrawal improves the likelihood of HBsAg loss within 36 months in patients with HBeAg negative CHB. Further studies including only patients with HBsAg level <1000 IU/mL and/or larger sample size and longer follow-up duration are recommended.
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Affiliation(s)
- Asgeir Johannessen
- Department of Infectious Diseases, Vestfold Hospital Trust, Tønsberg, Norway
- Department of Infectious Diseases, Regional Advisory Unit for Imported and Tropical Diseases, Oslo University Hospital, Oslo, Norway
- Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Dag Henrik Reikvam
- Department of Infectious Diseases, Regional Advisory Unit for Imported and Tropical Diseases, Oslo University Hospital, Oslo, Norway
- Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Soo Aleman
- Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - Nega Berhe
- Department of Infectious Diseases, Vestfold Hospital Trust, Tønsberg, Norway
- Department of Infectious Diseases, Regional Advisory Unit for Imported and Tropical Diseases, Oslo University Hospital, Oslo, Norway
- Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia
| | - Nina Weis
- Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Hvidovre, Denmark
- Faculty of Health and Medical Sciences, Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Hailemichael Desalegn
- Department of Infectious Diseases, Vestfold Hospital Trust, Tønsberg, Norway
- Medical Department, St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia
| | - Tore Stenstad
- Department of Infectious Diseases, Vestfold Hospital Trust, Tønsberg, Norway
| | - Lars Heggelund
- Vestre Viken Hospital Trust, Drammen Hospital, Drammen, Norway
| | - Ellen Samuelsen
- Department of Infectious Diseases, Akershus University Hospital, Lørenskog, Norway
| | - Lars Normann Karlsen
- Department of Gastroenterology, Stavanger University Hospital, Stavanger, Norway
| | - Karin Lindahl
- Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden
| | - Frank Olav Pettersen
- Department of Infectious Diseases, Regional Advisory Unit for Imported and Tropical Diseases, Oslo University Hospital, Oslo, Norway
| | - Jonas Iversen
- Department of Infectious Diseases, Regional Advisory Unit for Imported and Tropical Diseases, Oslo University Hospital, Oslo, Norway
| | - Elisabeth Kleppa
- Department of Infectious Diseases, Regional Advisory Unit for Imported and Tropical Diseases, Oslo University Hospital, Oslo, Norway
| | - Signe Bollerup
- Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Hvidovre, Denmark
| | - Anni Assing Winckelmann
- Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Hvidovre, Denmark
| | | | | | - Jan Svendsen
- Vestre Viken Hospital Trust, Bærum Hospital, Drammen, Norway
| | - Anne-Marte Bakken Kran
- Norwegian Institute of Public Health, Oslo, Norway
- Department of Microbiology, Oslo University Hospital, Oslo, Norway
| | - Marte Holmberg
- Department of Infectious Diseases, Vestfold Hospital Trust, Tønsberg, Norway
| | - Inge Christoffer Olsen
- Oslo Centre for Biostatistics and Epidemiology, Oslo University Hospital, Oslo, Norway
- Department of Research Support for Clinical Trials, Oslo University Hospital, Oslo, Norway
| | - Corina Silvia Rueegg
- Oslo Centre for Biostatistics and Epidemiology, Oslo University Hospital, Oslo, Norway
| | - Olav Dalgard
- Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Infectious Diseases, Akershus University Hospital, Lørenskog, Norway
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Nam H, Han JW, Lee SK, Yang H, Lee HL, Sung PS, Song MJ, Kwon JH, Jang JW, Chang UI, Kim CW, Nam SW, Bae SH, Choi JY, Yoon SK, Yang JM, Kim HY. Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in virologically suppressed patient with chronic hepatitis B. J Gastroenterol Hepatol 2024; 39:1673-1683. [PMID: 38690711 DOI: 10.1111/jgh.16593] [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: 11/05/2023] [Revised: 01/25/2024] [Accepted: 04/15/2024] [Indexed: 05/02/2024]
Abstract
BACKGROUND AND AIM Our study evaluated the outcomes of switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) in patients with chronic hepatitis B (CHB). We assessed viral and biochemical responses as well as changes in the estimated glomerular filtration rate (eGFR) and bone mineral density (BMD). METHODS This retrospective multicenter study included CHB patients who achieved virologic response (VR) (HBV DNA < 20 IU/mL) while on TDF and were subsequently switched to TAF between April 2018 and October 2021. RESULTS This study included 309 patients with a median age of 59 years, and 42.1% were male. The mean duration of TDF and TAF administration were 54.0 and 37.5 months, respectively. All patients maintained VR after switching to TAF. Alanine aminotransferase (ALT) normalization rate significantly increased 6 months after switching (74.8%-83.5%; P = 0.008). Adjusted eGFR significantly improved at 6 months (+5.55 ± 10.52 mL/min/1.73 m2; P < 0.001) and 12 months (+6.02 ± 10.70 mL/min/1.73 m2; P < 0.001) after switching. In the subgroup of patients with renal impairment (eGFR < 60 mL/min/1.73 m2), significant improvement in renal function was observed at 6 months (+0.6 ± 10.5 mL/min/1.73 m2; P < 0.001) and 12 months (+1.0 ± 10.7 mL/min/1.73 m2; P < 0.001) after switching to TAF. In patients with osteoporosis (n = 182), switching to TAF resulted in significant improvement in spine and hip BMD at 12 months, with increases of 9.7% (95% CI: 7.0-12.5) and 9.4% (95% CI: 7.0-11.8), respectively. CONCLUSION In this real-world study, switching to TAF was effective and safe in patients, with notable improvements in ALT levels, renal function, and BMD.
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Affiliation(s)
- Heechul Nam
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Division of Hepatology, Department of Internal Medicine, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Bucheon-si, Republic of Korea
| | - Ji Won Han
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Division of Hepatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Soon Kyu Lee
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Division of Hepatology, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, Republic of Korea
| | - Hyun Yang
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Division of Hepatology, Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Hae Lim Lee
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Division of Hepatology, Department of Internal Medicine, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Bucheon-si, Republic of Korea
| | - Pil Soo Sung
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Division of Hepatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Myeong Jun Song
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Division of Hepatology, Department of Internal Medicine, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Daejeon, Republic of Korea
| | - Jung Hyun Kwon
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Division of Hepatology, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, Republic of Korea
| | - Jeong Won Jang
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Division of Hepatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - U-Im Chang
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Division of Hepatology, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Bucheon-si, Republic of Korea
| | - Chang Wook Kim
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Division of Hepatology, Department of Internal Medicine, Uijeongbu St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Bucheon-si, Republic of Korea
| | - Soon Woo Nam
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Division of Hepatology, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Incheon, Republic of Korea
| | - Si Hyun Bae
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Division of Hepatology, Department of Internal Medicine, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jong Young Choi
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Division of Hepatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Seung Kew Yoon
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Division of Hepatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
| | - Jin Mo Yang
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Division of Hepatology, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Bucheon-si, Republic of Korea
| | - Hee Yeon Kim
- The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- Division of Hepatology, Department of Internal Medicine, Bucheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Bucheon-si, Republic of Korea
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9
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Chinese Society of Infectious Diseases, Chinese Medical Association, Chinese Society of Hepatology, Chinese Medical Association, Group of Infectious Diseases, Chinese Pediatric Society, Chinese Medical Association, National Clinical Research Center for Infectious Diseases (Beijing). Expert Consensus on the Prevention and Treatment of Chronic Hepatitis B in Children. INFECTIOUS DISEASES & IMMUNITY 2024; 4:106-120. [DOI: 10.1097/id9.0000000000000122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/27/2024]
Abstract
Abstract
The aim of this consensus is to standardize the prevention, diagnosis, and treatment of chronic hepatitis B in children and to achieve the goal of “eliminating viral hepatitis as a major public health threat by 2030” issued by the World Health Organization. Formulated by organized experts of the Chinese Society of Infectious Diseases and Chinese Society of Hepatology, Chinese Medical Association; Group of Infectious Diseases, Chinese Pediatric Society, Chinese Medical Association; and the National Clinical Research Center for Infectious Diseases (Beijing), the consensus provides the latest evidence and recommendations for the prevention, diagnosis, and treatment of chronic hepatitis B in children.
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10
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Yip TCF, Lai JCT, Yam TF, Tse YK, Hui VWK, Lai MSM, Chan HLY, Wong VWS, Wong GLH. Long-term use of tenofovir disoproxil fumarate increases fracture risk in elderly patients with chronic hepatitis B. J Hepatol 2024; 80:553-563. [PMID: 38101755 DOI: 10.1016/j.jhep.2023.12.001] [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: 09/21/2023] [Revised: 11/30/2023] [Accepted: 12/04/2023] [Indexed: 12/17/2023]
Abstract
BACKGROUND & AIMS The use of tenofovir disoproxil fumarate (TDF) is associated with a reduction in bone mineral density and an increase in bone metabolism biomarkers. However, data on clinical bone fractures remain limited. We evaluated the impact of TDF compared to entecavir on the risk of fracture in elderly patients with chronic hepatitis B (CHB). METHODS Patients with CHB aged ≥60 years receiving entecavir or TDF between January 2008 and December 2022 were identified using a territory-wide database in Hong Kong. The risk of incident fracture in entecavir- and TDF-treated patients before and after month 24 were compared after propensity score matching. RESULTS A total of 41,531 patients with CHB (mean age 69.8±7.8 years, 61.6% male) receiving entecavir (n = 39,897 [96.1%]) and TDF (n = 1,634 [3.9%]) were analysed. At a median follow-up of 25.3 (9.1-58.5) months, 1,733 (4.2%) patients developed incident fracture. Patients with incident fracture were more likely to have diabetes, hypertension, congestive heart failure, rheumatoid arthritis, osteoporosis, and a history of fracture. Compared with propensity score-matched entecavir-treated patients, the risk of incident fracture in TDF-treated patients was comparable in the first 24 months (weighted subdistribution hazard ratio [sHR] 0.99, 95% CI 0.56-1.73, p = 0.960) but increased after month 24 (weighted sHR 1.80, 95% CI 1.11-2.93, p = 0.019). The 24-, 60-, and 96-month cumulative incidences (95% CI) of fracture in TDF-treated and entecavir-treated patients were 2.3% (1.6%-3.4%) vs. 2.6% (1.9%-3.5%), 6.4% (5.0%-8.2%) vs. 4.7% (3.8%-6.0%), and 10.2% (8.3%-12.6%) vs. 6.8% (5.4%-8.5%), respectively. CONCLUSIONS The risk of fracture increased with TDF treatment for ≥24 months in elderly patients with CHB. Selection of nucleos(t)ide analogues should be individualised based on age and comorbidities. IMPACT AND IMPLICATIONS Previous literature suggested that the use of tenofovir disoproxil fumarate (TDF) is associated with a decrease in bone mineral density. However, data on the impact of TDF on long-term incident clinical fracture remains scarce. In this real-world territory-wide study of 41,531 treated patients with chronic hepatitis B in Hong Kong, patients who received TDF were at a higher risk of fracture after 2 years of treatment than those who received entecavir. Given the ageing population of patients with chronic hepatitis B and the rising prevalence of comorbidities, our findings support the current treatment guidelines that recommend selecting antiviral treatment based on age and comorbidities.
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Affiliation(s)
- Terry Cheuk-Fung Yip
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Jimmy Che-To Lai
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Tsz-Fai Yam
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Yee-Kit Tse
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Vicki Wing-Ki Hui
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Mandy Sze-Man Lai
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Henry Lik-Yuen Chan
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Internal Medicine, Union Hospital, Hong Kong SAR, China
| | - Vincent Wai-Sun Wong
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Grace Lai-Hung Wong
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong SAR, China; Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China; State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China.
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11
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Quintieri P, Speranza R, Russo M, Dono F, Onofrj M, Sensi SL. A case of benign recurrent abducens nerve palsy associated with chronic HBV infection. Neurol Sci 2024; 45:361-363. [PMID: 37796370 DOI: 10.1007/s10072-023-07100-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2023] [Accepted: 09/27/2023] [Indexed: 10/06/2023]
Affiliation(s)
- P Quintieri
- Department of Neuroscience, Imaging and Clinical Sciences, "G. d'Annunzio" University of Chieti-Pescara, Via Luigi Polacchi 11/13, Chieti, Italy
| | - R Speranza
- Department of Neuroscience, Imaging and Clinical Sciences, "G. d'Annunzio" University of Chieti-Pescara, Via Luigi Polacchi 11/13, Chieti, Italy
| | - M Russo
- Department of Neuroscience, Imaging and Clinical Sciences, "G. d'Annunzio" University of Chieti-Pescara, Via Luigi Polacchi 11/13, Chieti, Italy.
- CAST - Center for Advanced Studies and Technologies, "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy.
| | - F Dono
- Department of Neuroscience, Imaging and Clinical Sciences, "G. d'Annunzio" University of Chieti-Pescara, Via Luigi Polacchi 11/13, Chieti, Italy
- CAST - Center for Advanced Studies and Technologies, "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy
| | - M Onofrj
- Department of Neuroscience, Imaging and Clinical Sciences, "G. d'Annunzio" University of Chieti-Pescara, Via Luigi Polacchi 11/13, Chieti, Italy
- CAST - Center for Advanced Studies and Technologies, "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy
| | - S L Sensi
- Department of Neuroscience, Imaging and Clinical Sciences, "G. d'Annunzio" University of Chieti-Pescara, Via Luigi Polacchi 11/13, Chieti, Italy.
- CAST - Center for Advanced Studies and Technologies, "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy.
- ITAB - Institute for Advanced Biomedical Technologies, "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy.
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12
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Wei T, Zhou BY, Wu XH, Liu XA, Huo MW, Huang XX, Shi LZ, Shi LL, Cao QR. Development of Polyvinyl Alcohol/Polyethylene Glycol Copolymer-based Orodispersible Films Loaded with Entecavir: Formulation and In vitro Characterization. Curr Drug Deliv 2024; 21:1362-1374. [PMID: 37929732 DOI: 10.2174/0115672018261294231024093926] [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: 05/22/2023] [Revised: 08/08/2023] [Accepted: 09/06/2023] [Indexed: 11/07/2023]
Abstract
PURPOSE The aim of the study is to prepare entecavir (ETV)-loaded orodispersible films (ODFs) using polyvinyl alcohol (PVA)/polyethylene glycol (PEG) graft copolymer (Kollicoat® IR) as a film-forming agent, and further to evaluate the dissolution rate, mechanical and physicochemical properties of films. METHODS ETV-ODFs were prepared by a solvent casting method. The amount of film-forming agent, plasticizer, and disintegrating agent was optimized in terms of the appearance, thickness, disintegration time and mechanical properties of ODFs. The compatibility between the drug and each excipient was conducted under high temperature (60 °C), high humidity (RH 92.5%), and strong light (4500 Lx) for 10 days. The dissolution study of optimal ODFs compared with the original commercial tablet (Baraclude®) was performed using a paddle method in pH 1.0, pH 4.5, pH 6.8, and pH 7.4 media at 37 °C. The morphology of ODFs was observed via scanning electron microscopy (SEM). The mechanical properties such as tensile strength (TS), elastic modulus (EM), and percentage elongation (E%) of ODFs were evaluated using the universal testing machine. The physicochemical properties of ODFs were investigated using X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FT-IR). RESULTS The related substances were less than 0.5% under high temperature, high humidity, and strong light for 10 days when ETV was mixed with excipients. The optimal formulation of ODFs was set as the quality ratio of Kollicoat® IR, glycerol, sodium alginate (ALG-Na): TiO2: MCC+CMC-Na: ETV was 60:9:12:1:1:1. The drug-loaded ODFs were white and translucent with excellent stripping property. The thickness, disintegration time, EM, TS, and E% were 103.33±7.02 μm, 25.31±1.95 s, 25.34±8.69 Mpa, 2.14±0.26 Mpa, and 65.45±19.41 %, respectively. The cumulative drug release from ODFs was more than 90% in four different media at 10 min. The SEM showed that the drug was highly dispersible in ODFs, and the XRD, DSC, and FT-IR results showed that there occurred some interactions between the drug and excipients. CONCLUSION In conclusion, the developed ETV-loaded ODFs showed relatively short disintegration time, rapid drug dissolution, and excellent mechanical properties. This might be an alternative to conventional ETV Tablets for the treatment of chronic hepatitis B.
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Affiliation(s)
- Teng Wei
- College of Pharmaceutical Sciences, Soochow University, Suzhou, People's Republic of China
| | - Bing-Yu Zhou
- Dongliao People's Hospital, Liaoyuan, People's Republic of China
| | - Xin-Hong Wu
- College of Pharmaceutical Sciences, Soochow University, Suzhou, People's Republic of China
| | - Xue-Ai Liu
- College of Pharmaceutical Sciences, Soochow University, Suzhou, People's Republic of China
| | - Ming-Wei Huo
- College of Pharmaceutical Sciences, Soochow University, Suzhou, People's Republic of China
| | - Xiang-Xiang Huang
- College of Pharmaceutical Sciences, Soochow University, Suzhou, People's Republic of China
| | - Ling-Zhi Shi
- College of Pharmaceutical Sciences, Soochow University, Suzhou, People's Republic of China
| | - Li-Li Shi
- College of Medicine, Jiaxing University, Jiaxing, People's Republic of China
| | - Qin-Ri Cao
- College of Pharmaceutical Sciences, Soochow University, Suzhou, People's Republic of China
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13
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You H, Wang F, Li T, Xu X, Sun Y, Nan Y, Wang G, Hou J, Duan Z, Wei L, Jia J, Zhuang H. Guidelines for the Prevention and Treatment of Chronic Hepatitis B (version 2022). J Clin Transl Hepatol 2023; 11:1425-1442. [PMID: 37719965 PMCID: PMC10500285 DOI: 10.14218/jcth.2023.00320] [Citation(s) in RCA: 77] [Impact Index Per Article: 38.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2023] [Revised: 08/02/2023] [Accepted: 08/03/2023] [Indexed: 09/19/2023] Open
Abstract
To facilitate the achieving of the goal of "eliminating viral hepatitis as a major public health threat by 2030" set by the World Health Organization, the Chinese Society of Hepatology together with the Chinese Society of Infectious Diseases (both are branches of the Chinese Medical Association) organized a panel of experts and updated the guidelines for prevention and treatment of chronic hepatitis B in China (version 2022). With the support of available evidence, this revision of the guidelines focuses on active prevention, large scale testing, and expansion of therapeutic indication of chronic hepatitis B with the aim of reducing the hepatitis B related disease burden.
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Affiliation(s)
- Hong You
- Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Fusheng Wang
- The Fifth Medical Center of PLA General Hospital, Beijing, China
| | - Taisheng Li
- Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Xiaoyuan Xu
- Peking University First Hospital, Beijing, China
| | - Yameng Sun
- Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Yuemin Nan
- Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
| | | | - Jinlin Hou
- Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Zhongping Duan
- Beijing You-An Hospital, Capital Medical University, Beijing, China
| | - Lai Wei
- Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Jidong Jia
- Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Hui Zhuang
- Peking University Health Science Center, Beijing, China
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14
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Peng WT, Jiang C, Yang FL, Zhou NQ, Chen KY, Liu JQ, Peng SF, Fu L. Tenofovir amibufenamide vs tenofovir alafenamide for treating chronic hepatitis B: A real-world study. World J Gastroenterol 2023; 29:5907-5918. [PMID: 38111506 PMCID: PMC10725562 DOI: 10.3748/wjg.v29.i44.5907] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2023] [Revised: 10/29/2023] [Accepted: 11/14/2023] [Indexed: 11/27/2023] Open
Abstract
BACKGROUND The efficacy and safety profile of tenofovir amibufenamide (TMF) in chronic hepatitis B (CHB) patients is not well-established. AIM To compare the efficacy and safety of TMF and tenofovir alafenamide (TAF) over a 48-wk period in patients with CHB. METHODS A total of 215 subjects meeting the inclusion criteria were enrolled and divided into two groups: TMF group (n = 106) and the TAF group (n = 109). The study included a comparison of virological response (VR): Undetectable hepatitis B virus DNA levels, alanine transaminase (ALT) normalization rates, renal function parameters, and blood lipid profiles. RESULTS At 24 and 48 wk, VR rates for the TMF group were 53.57% and 78.57%, respectively, compared with 48.31% and 78.65% for the TAF group (P > 0.05). The VR rates were also similar in both groups among patients with low-level viremia, both hepatitis B e antigen (HBeAg)-positive and HBeAg-negative subgroups. The TMF cohort showed ALT normalization and renal safety profiles similar to the TAF group. There was a notable increase in total cholesterol levels in the TAF group (P = 0.045), which was not observed in the TMF group (P > 0.05). In patients with liver cirrhosis, both groups exhibited comparable VR and ALT normalization rates and renal safety profiles. However, the fibrosis 4 score at 48 wk showed a significant reduction in the TAF group as compared to the TMF group within the liver cirrhosis subgroup. CONCLUSION Our study found TMF is as effective as TAF in treating CHB and has a comparable safety profile. However, TAF may be associated with worsening lipid profiles.
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Affiliation(s)
- Wen-Ting Peng
- Department of Infectious Diseases, Xiangya Hospital Central South University, Changsha 410008, Hunan Province, China
| | - Chuan Jiang
- Department of Infectious Diseases, Xiangya Hospital Central South University, Changsha 410008, Hunan Province, China
| | - Fei-Lan Yang
- Department of Infectious Diseases, Xiangya Hospital Central South University, Changsha 410008, Hunan Province, China
| | - Nian-Qi Zhou
- Department of Infectious Diseases, Xiangya Hospital Central South University, Changsha 410008, Hunan Province, China
| | - Ke-Yu Chen
- Department of Infectious Diseases, Xiangya Hospital Central South University, Changsha 410008, Hunan Province, China
| | - Jin-Qing Liu
- Department of Infectious Diseases, Xiangya Hospital Central South University, Changsha 410008, Hunan Province, China
| | - Shi-Fang Peng
- Department of Infectious Diseases, Xiangya Hospital Central South University, Changsha 410008, Hunan Province, China
| | - Lei Fu
- Department of Infectious Diseases, Xiangya Hospital Central South University, Changsha 410008, Hunan Province, China
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15
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Wang N, He S, Zheng Y, Wang L. Efficacy and safety of tenofovir disoproxil fumarate versus entecavir in the treatment of acute-on-chronic liver failure with hepatitis B: a systematic review and meta-analysis. BMC Gastroenterol 2023; 23:388. [PMID: 37957546 PMCID: PMC10642028 DOI: 10.1186/s12876-023-03024-7] [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: 04/06/2023] [Accepted: 10/31/2023] [Indexed: 11/15/2023] Open
Abstract
BACKGROUND Oral nucleoside (acid) analogues (NAs) are recommended for patients with acute-on-chronic liver failure (ACLF) associated with hepatitis B virus (HBV-ACLF). The efficacy and safety of tenofovir (TDF) and entecavir (ETV) in these patients remain unclear. METHODS A comprehensive literature search in PubMed, Web of Science, The Cochrane Library, and Embase database was conducted to select studies published before December 2022 on TDF or ETV for HBV-ACLF. The primary outcomes were survival rates at 4, 12, and 48 weeks. Secondary outcomes were virologic and biochemical responses, serum antigen conversion, liver function score, and safety. RESULTS Four prospective and one retrospective cohort studies were selected. The overall analysis showed comparable survival rates at 4, 12, and 48 weeks for all patients receiving TDF or ETV (4-week: RR = 1.17, 95% CI: 0.90-1.51, p = 0.24; 12-week: RR = 1.00, 95% CI: 0.88-1.13, p = 0.94; 48-week: RR = 0.96, 95% CI: 0.58-1.57, p = 0.86). Child-Turcotte-Pugh (CTP) score and model for end-stage liver disease (MELD) score at 12 weeks were comparable in both groups but lower than baseline (CTP: SMD = -0.75, 95% CI:-2.81-1.30, p = 0.47; MELD: SMD = -1.10, 95% CI:-2.29-0.08, p = 0.07). At 48 weeks, estimated glomerular filtration rate (eGFR) levels were found to decrease to different degrees from baseline in both the TDF and ETV groups, and the decrease was greater in the TDF group than in the ETV group. No significant differences were found in biochemical, virologic response, and serum antigen conversion between the two groups during the observation period. CONCLUSION TDF treatment of HBV-ACLF is similar to ETV in improving survival, liver function, and virologic response but the effects on renal function in two groups in the long term remain unclear. More and larger long-term clinical trials are required to confirm these findings.
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Affiliation(s)
- Neng Wang
- Center of Infectious Disease, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China
| | - Sike He
- West China School of Medicine, Sichuan University, Chengdu, Sichuan, People's Republic of China
| | - Yu Zheng
- Center of Infectious Disease, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China
| | - Lichun Wang
- Center of Infectious Disease, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China.
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16
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Peng W, Gu H, Cheng D, Chen K, Wu C, Jiang C, Liu J, Peng S, Fu L. Tenofovir alafenamide versus entecavir for treating hepatitis B virus-related acute-on-chronic liver failure: real-world study. Front Microbiol 2023; 14:1185492. [PMID: 37303805 PMCID: PMC10249370 DOI: 10.3389/fmicb.2023.1185492] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Accepted: 05/05/2023] [Indexed: 06/13/2023] Open
Abstract
Background and aims Real-world data regarding hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) patients receiving tenofovir alafenamide (TAF) as an antiviral drug are limited. Hence, we evaluated the efficacy and kidney safety of TAF among this population. Methods A total of 272 HBV-related ACLF patients hospitalized at Xiangya Hospital of Central South University were enrolled in this retrospective research. All patients received antiviral therapy with TAF (n = 100) or ETV (n = 172) and comprehensive medical treatments. Results Through 1:1 propensity score matching, 100 patients were finally included in each group. At week 48, the survival rates without transplantation of the TAF group and ETV group were 76.00 and 58.00%, separately (P = 0.007). After 4 weeks of treatment, the TAF treatment group exhibited a significantly decline in HBV DNA viral load (P = 0.029). The mean estimated glomerular filtration rate was apparently improved in the TAF group compared with the ETV group (TAF 5.98 ± 14.46 vs. ETV 1.18 ± 18.07 ml/min/1.73 m2) (P < 0.05). There were 6 patients in TAF group and 21 patients in ETV group with chronic kidney disease (CKD) stage progression ≥ 1. By contrast, the ETV treatment group has a greater risk of renal function progression in CKD 1 stage patients (P < 0.05). Conclusion This real-world clinical study showed that TAF is more effective than ETV in reducing viral load and improving survival rate in HBV-ACLF patients and the risk of renal function decline is lower. Clinical trial registration https://ClinicalTrials.gov, identifier NCT05453448.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Lei Fu
- *Correspondence: Lei Fu, ; orcid.org/0001-7550-1254
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17
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Cheng T, Li G, Mao X, Hao L, Cheng X, Ning H. Impact of Hepatitis B virus infection on postoperative complications and length of stay in elderly patients with hip fracture: A retrospective cohort study. Injury 2023:S0020-1383(23)00453-9. [PMID: 37198044 DOI: 10.1016/j.injury.2023.05.043] [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: 08/14/2022] [Revised: 03/28/2023] [Accepted: 05/10/2023] [Indexed: 05/19/2023]
Abstract
BACKGROUND Osteoporosis and subsequent fractures are common in the chronic hepatitis B (CHB) population, especially in the elderly. This study investigated the effects of hepatitis B virus (HBV) infection on postoperative outcomes following hip fracture surgery. METHODS The study identified elderly patients who underwent hip fracture surgery at three academic tertiary care centres between January 2014 and December 2020. Propensity score matching was performed to compare the outcomes of 1,046 patients with HBV infection to 1,046 controls. RESULTS The seroprevalence of HBV among elderly patients undergoing hip surgery was 4.94%. The HBV cohort had significantly higher rates of medical complications (28.1 vs. 22.7%, p = 0.005), surgical complications (14.0 vs. 9.7%, p = 0.003), and unplanned readmissions (18.9 vs. 14.5%, p = 0.03) within 90 days of surgery. Patients with HBV infection were more likely to have increased length of stay (6.2 vs. 5.9 days, p = 0.009) and in-hospital charges (¥52,231 vs. ¥49,832, p < 0.00001). Multivariate logistic regression suggested that liver fibrosis and thrombocytopenia were independent risk factors for major complications and extended LOS. CONCLUSION Patients with HBV infection were at greater risk of adverse postoperative outcomes. We should pay more attention to the considerable burden of perioperative management of CHB patients. Due to the high proportion of undiagnosed patients in the Chinese elderly population, universal HBV screening should be considered preoperatively.
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Affiliation(s)
- Tao Cheng
- Department of Orthopaedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, The People's Republic of China.
| | - Guoyong Li
- Department of Orthopaedic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, The People's Republic of China
| | - Xin Mao
- Department of Orthopaedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, The People's Republic of China
| | - Liang Hao
- Department of Orthopaedic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, The People's Republic of China.
| | - Xigao Cheng
- Department of Orthopaedic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, The People's Republic of China
| | - Huiming Ning
- Department of Infectious Disease, Shanghai Eighth People's Hospital, Shanghai, The People's Republic of China
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18
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Jia H, Mai J, Wu M, Chen H, Li X, Li C, Liu J, Liu C, Hu Y, Zhu X, Jiang X, Hua B, Xia T, Liu G, Deng A, Liang B, Guo R, Lu H, Wang Z, Chen H, Zhang Z, Zhang H, Niu J, Ding Y. Safety, tolerability, pharmacokinetics, and antiviral activity of the novel core protein allosteric modulator ZM-H1505R (Canocapavir) in chronic hepatitis B patients: a randomized multiple-dose escalation trial. BMC Med 2023; 21:98. [PMID: 36927420 PMCID: PMC10022191 DOI: 10.1186/s12916-023-02814-w] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 03/06/2023] [Indexed: 03/18/2023] Open
Abstract
BACKGROUND Hepatitis B virus (HBV) core protein-targeting antivirals (CpTAs) are promising therapeutic agents for treating chronic hepatitis B (CHB). In this study, the antiviral activity, pharmacokinetics (PK), and tolerability of ZM-H1505R (Canocapavir), a chemically unique HBV CpTA, were evaluated in patients with CHB. METHODS This study was a double-blind, randomized, placebo-controlled phase 1b trial in Chinese CHB patients. Noncirrhotic and treatment-naive CHB patients were divided into three cohorts (10 patients per cohort) and randomized within each cohort in a ratio of 4:1 to receive a single dose of 50, 100, or 200 mg of Canocapavir or placebo once a day for 28 consecutive days. RESULTS Canocapavir was well tolerated, with the majority of adverse reactions being grade I or II in severity. There were no serious adverse events, and no patients withdrew from the study. Corresponding to 50, 100, and 200 mg doses of Canocapavir, the mean plasma trough concentrations of the drug were 2.7-, 7.0-, and 14.6-fold of its protein-binding adjusted HBV DNA EC50 (135 ng/mL), respectively, with linear PK and a low-to-mild accumulation rate (1.26-1.99). After 28 days of treatment, the mean maximum HBV DNA declines from baseline were -1.54, -2.50, -2.75, and -0.47 log10 IU/mL for the 50, 100, and 200 mg of Canocapavir or placebo groups, respectively; and the mean maximum pregenomic RNA declines from baseline were -1.53, -2.35, -2.34, and -0.17 log10 copies/mL, respectively. CONCLUSIONS Canocapavir treatment is tolerated with efficacious antiviral activity in CHB patients, supporting its further development in treating HBV infection. TRIAL REGISTRATION ClinicalTrials.gov, number NCT05470829).
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Affiliation(s)
- Haiyan Jia
- Phase I Clinical Research Center, The First Hospital of Jilin University, No. 1 Xinmin Street, Changchun, Jilin Province, China
- Gynecology and Obstetrics Center, the First Hospital of Jilin University, Changchun, China
| | - Jiajia Mai
- Phase I Clinical Research Center, The First Hospital of Jilin University, No. 1 Xinmin Street, Changchun, Jilin Province, China
| | - Min Wu
- Phase I Clinical Research Center, The First Hospital of Jilin University, No. 1 Xinmin Street, Changchun, Jilin Province, China
| | - Hong Chen
- Phase I Clinical Research Center, The First Hospital of Jilin University, No. 1 Xinmin Street, Changchun, Jilin Province, China
| | - Xiaojiao Li
- Phase I Clinical Research Center, The First Hospital of Jilin University, No. 1 Xinmin Street, Changchun, Jilin Province, China
| | - Cuiyun Li
- Phase I Clinical Research Center, The First Hospital of Jilin University, No. 1 Xinmin Street, Changchun, Jilin Province, China
| | - Jingrui Liu
- Phase I Clinical Research Center, The First Hospital of Jilin University, No. 1 Xinmin Street, Changchun, Jilin Province, China
| | - Chengjiao Liu
- Phase I Clinical Research Center, The First Hospital of Jilin University, No. 1 Xinmin Street, Changchun, Jilin Province, China
| | - Yue Hu
- Phase I Clinical Research Center, The First Hospital of Jilin University, No. 1 Xinmin Street, Changchun, Jilin Province, China
| | - Xiaoxue Zhu
- Phase I Clinical Research Center, The First Hospital of Jilin University, No. 1 Xinmin Street, Changchun, Jilin Province, China
| | - Xiuhong Jiang
- Shanghai Zhimeng Biopharma, Inc, 1976 Gaoke Middle Road, Suite A-302, Pudong District, Shanghai, China
| | - Bo Hua
- Shanghai Zhimeng Biopharma, Inc, 1976 Gaoke Middle Road, Suite A-302, Pudong District, Shanghai, China
| | - Tian Xia
- Shanghai Zhimeng Biopharma, Inc, 1976 Gaoke Middle Road, Suite A-302, Pudong District, Shanghai, China
| | - Gang Liu
- Shanghai Zhimeng Biopharma, Inc, 1976 Gaoke Middle Road, Suite A-302, Pudong District, Shanghai, China
| | - Aiyun Deng
- Shanghai Zhimeng Biopharma, Inc, 1976 Gaoke Middle Road, Suite A-302, Pudong District, Shanghai, China
| | - Bo Liang
- Shanghai Zhimeng Biopharma, Inc, 1976 Gaoke Middle Road, Suite A-302, Pudong District, Shanghai, China
| | - Ruoling Guo
- Shanghai Zhimeng Biopharma, Inc, 1976 Gaoke Middle Road, Suite A-302, Pudong District, Shanghai, China
| | - Hui Lu
- Shanghai Zhimeng Biopharma, Inc, 1976 Gaoke Middle Road, Suite A-302, Pudong District, Shanghai, China
| | - Zhe Wang
- Shanghai Zhimeng Biopharma, Inc, 1976 Gaoke Middle Road, Suite A-302, Pudong District, Shanghai, China
| | - Huanming Chen
- Shanghai Zhimeng Biopharma, Inc, 1976 Gaoke Middle Road, Suite A-302, Pudong District, Shanghai, China
| | - Zhijun Zhang
- Shanghai Zhimeng Biopharma, Inc, 1976 Gaoke Middle Road, Suite A-302, Pudong District, Shanghai, China
| | - Hong Zhang
- Phase I Clinical Research Center, The First Hospital of Jilin University, No. 1 Xinmin Street, Changchun, Jilin Province, China.
| | - Junqi Niu
- Department of Hepatology, Center of Infectious Disease and Pathogen Biology, The First Hospital of Jilin University, Changchun, China.
| | - Yanhua Ding
- Phase I Clinical Research Center, The First Hospital of Jilin University, No. 1 Xinmin Street, Changchun, Jilin Province, China.
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Kao WY, Tan ECH, Lee HL, Huang YH, Huo TI, Chang CC, Chiou JF, Hou MC, Wu JC, Su CW. Entecavir versus tenofovir on prognosis of hepatitis B virus-related hepatocellular carcinoma after curative hepatectomy. Aliment Pharmacol Ther 2023; 57:1299-1312. [PMID: 36914943 DOI: 10.1111/apt.17438] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 01/27/2023] [Accepted: 02/15/2023] [Indexed: 03/16/2023]
Abstract
BACKGROUND There is still controversy about whether tenofovir disoproxil fumarate (TDF) and entecavir (ETV) have different effects on the outcomes of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). AIMS The aim of this study was to compare the prognoses between ETV and TDF treatment among patients with HBV-related HCC after hepatectomy. METHODS An analysis was done on data from the Taiwan Cancer Registry, which was linked to Taiwan National Health Insurance Research Database, for the years 2011-2016. We identified 7107 patients with HBV-related HCC after curative hepatectomy, and 25.3% of them used ETV or TDF after surgery. After propensity score overlap weighting, 1797 patients treated with ETV (n = 1365) or TDF (n = 432) were included for analyses. Cox proportional hazards models were used to compare the efficacy of ETV and TDF for recurrence and overall survival (OS). RESULTS After hepatectomy, the recurrence rate per 100 person-years was 14.87 for the ETV group and 9.25 for the TDF group. The risk of recurrence was similar in the TDF group and the ETV group (HR [95% CI]: 0.91 [0.69-1.19; p = 0.479]), as was the risk of all-cause mortality (HR [95% CI]: 0.67 [0.42-1.07]; p = 0.091). When considering early recurrence (<2 years) and late recurrence (≧2 years), the TDF and ETV groups showed no significant differences. Subgroup analyses and sensitivity analyses demonstrated consistent results. CONCLUSION Both TDF and ETV showed similar health benefits in terms of recurrence and OS in patients with HBV-related HCC patients after hepatectomy.
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Affiliation(s)
- Wei-Yu Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.,Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.,TMU Research Center for Digestive Medicine, Taipei Medical University, Taipei, Taiwan
| | - Elise Chia-Hui Tan
- Department of Health Service Administration, College of Public Health, China Medical University, Taichung, Taiwan
| | - Hsin-Lun Lee
- Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.,Department of Radiation Oncology, Taipei Medical University Hospital, Taipei, Taiwan.,Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Department of Internal Medicine, School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Teh-Ia Huo
- Division of Basic Research, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.,Institute of Pharmacology, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chun-Chao Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan.,Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.,TMU Research Center for Digestive Medicine, Taipei Medical University, Taipei, Taiwan
| | - Jeng-Fong Chiou
- Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.,Department of Radiation Oncology, Taipei Medical University Hospital, Taipei, Taiwan.,Department of Radiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Ming-Chih Hou
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Department of Internal Medicine, School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Jaw-Ching Wu
- Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chien-Wei Su
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Department of Internal Medicine, School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Division of Holistic and Multidisciplinary Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
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20
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Cheng T, Li G, Ning H, Hao L. Antiviral Therapy for Chronic Hepatitis B Infection Improves Outcomes After Total Hip Arthroplasty: A Multicenter Retrospective Study. J Arthroplasty 2023; 38:300-306. [PMID: 35963280 DOI: 10.1016/j.arth.2022.08.005] [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: 05/16/2022] [Revised: 08/03/2022] [Accepted: 08/04/2022] [Indexed: 02/03/2023] Open
Abstract
BACKGROUND Previous studies have shown that chronic hepatitis B virus (HBV) infection may place patients at increased risk of postoperative adverse events. However, there is limited information on the effects of antiviral treatment (AVT) on postoperative outcomes following total hip arthroplasties (THAs). METHODS A multicenter retrospective database query was used to identify patients infected with HBV undergoing THAs between 2012 and 2017. All eligible patients were divided into 2 cohorts on the basis of AVT before surgery: the treated group and the untreated group. The treated cohort was matched at a ratio of 1:3 to the untreated cohort by propensity score matching. Operating times, blood losses, all-type complications, surgical complications, lengths of stay, 90-day readmissions, unplanned reoperations, and implant revisions were compared between the 2 cohorts. After these patients were further stratified by liver fibrosis status, multivariate logistic analyses were performed by controlling for differences in demographics and comorbidities. In total, 918 patients chronically infected with HBV were identified. Over four-fifths of these patients (83.0%) did not receive preoperative AVT. Of interest, more than half of the untreated patients (54.1%) were previously undiagnosed. RESULTS The untreated group had significantly longer mean operating time (82 versus 76 minutes, P = .007) and higher mean blood loss (515 versus 465 mL, P = .03) than the treated group. Moreover, they were more prone to experiencing surgical complications (25.4% versus 16.7%, P = .01), longer lengths of stay (6.2 versus 5.4 days, P = .0005), readmissions (12.4% versus 5.8%, P = .02), reoperations (16.7% versus 9.6%, P = .03), and revisions (11.1% versus 4.5%, P = .02). Multivariate regression analyses found that AVT significantly decreased all-type complications, reoperations, and revisions in patients with significant fibrosis (all P < .05). CONCLUSION The AVT of HBV infection prior to THAs could reduce the risk of developing postoperative complications, regardless of the presence of liver fibrosis. This finding emphasizes that surgeons should recommend HBV screening and treatment integrated into preoperative medical optimization.
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Affiliation(s)
- Tao Cheng
- Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, The People's Republic of China
| | - Guoyong Li
- Department of Orthopaedic Surgery, The Fourth Affiliated Hospital of Nanchang University, Nanchang, The People's Republic of China; Department of Orthopaedic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, The People's Republic of China
| | - Huiming Ning
- Department of Infectious Disease, Shanghai Eighth People's Hospital, Shanghai, The People's Republic of China
| | - Liang Hao
- Department of Orthopaedic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, The People's Republic of China
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21
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Peng MJ, Guo XQ, Zhang WL, Chen J, Kang W, Yang XF, Guo Y, Zhang Y. Effect of pegylated interferon-α2b add-on therapy on renal function in chronic hepatitis B patients: A real-world experience. Front Microbiol 2022; 13:980250. [PMID: 36329842 PMCID: PMC9622795 DOI: 10.3389/fmicb.2022.980250] [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: 06/28/2022] [Accepted: 10/03/2022] [Indexed: 01/03/2025] Open
Abstract
BACKGROUND AND AIM Controversy remains as to pegylated interferon-α (PEG-IFNα) antiviral therapy to renal function in chronic hepatitis B (CHB) patients. The aim of this study was to evaluate the influence of PEG-IFNα2b (Y shape, 40 kD) add-on treatment for renal function in CHB patients who received entecavir therapy. METHODS This was a retrospective observational study to investigate factors related to renal function in 114 CHB patients who received PEG-IFNα2b add-on therapy to entecavir for 48 weeks. Changes of blood urea nitrogen (BUN), serum creatinine (sCr), and estimated glomerular filtration rate (eGFR), which was calculated with both Chronic Kidney Disease Epidemiology Collaboration and Modification of Diet in Renal Disease (MDRD) formulas, were analyzed by one-way analysis of variance. A linear mixed effects model for repeated measures was used to assess the correlation between baseline information and eGFR changes at 24 and 48 weeks of therapy. The model considered the baseline age, gender, body weight, viral load, hepatitis B surface antigen, BUN, sCr, and treatment strategy as fixed effects and incorporated random effects for individual subjects. RESULTS BUN and sCr was decreased, while eGFR was increased at 12 weeks of therapy. Only eGFR maintained at 24 and 48 weeks of therapy. Patients with female gender, age ≥ 40 years, and baseline HBsAg level < 250 IU/mL showed significant improvement of renal function with PEG-IFNα2b add-on therapy. The linear mixed effects model revealed that female gender, baseline sCr, and PEG-IFNα2b add-on were significant positive predictors for eGFR elevation at 24 and 48 weeks of therapy. CONCLUSION In real-world experience, PEG-IFNα2b add-on therapy might be associated with increased eGFR in CHB patients.
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Affiliation(s)
- Mei-Juan Peng
- Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi’an, China
| | - Xiao-Qing Guo
- Department of Hepatology, The Third People’s Hospital of Taiyuan, Taiyuan, China
| | - Wei-Lu Zhang
- Department of Epidemiology, School of Public Health, Fourth Military Medical University, Xi’an, China
| | - Jing Chen
- Xiamen Amoytop Biotech Co., Ltd., Xiamen, China
| | - Wen Kang
- Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi’an, China
| | - Xiao-Fei Yang
- Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi’an, China
| | - Ying Guo
- Department of Hepatology, The Third People’s Hospital of Taiyuan, Taiyuan, China
| | - Ye Zhang
- Department of Infectious Diseases, Tangdu Hospital, Fourth Military Medical University, Xi’an, China
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22
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Sinakos E, Panas P, Fragkou N, Antoniadis N, Katsanos G, Tsakni E, Oikonomou T, Notopoulos A, Tsoulfas G, Goulis I, Akriviadis E. Tenofovir alafenamide prophylaxis post-liver transplantation: a real-world study in patients with chronic kidney disease. Acta Gastroenterol Belg 2022; 85:331-337. [PMID: 35709777 DOI: 10.51821/85.2.9577] [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] [Indexed: 11/21/2022]
Abstract
BACKGROUND & AIMS Tenofovir alafenamide fumarate (TAF) was shown equally efficacious in suppressing hepatitis B virus (HBV) but with less renal toxicity than tenofovir disoproxil fumarate (TDF). The aim of this real-world study was to evaluate renal function in post-liver transplantation (LT) patients that changed TDF with TAF. METHODS The TAF group (n=17) included patients who switched to TAF due to low (<60 ml/min/1.73m2) Glomerular Filtration Rate (GFR). The control group included patients that remained on TDF (n=30), although some (n= 14) had chronic kidney disease (CKD) (TDF-CKD group). GFR was assessed using: i) MDRD-6 variable; ii) CKD-EPI formula; iii) radionuclide technique (rGFR). RESULTS There were no significant differences between the two groups except for the presence of diabetes and follow-up period, which were more common and shorter, respectively, in the TAF group (35% vs. 10%, p=0.03; 13.7 vs. 35.5 months, p<0.001). At the end of follow-up there were no significant changes in renal function between the TAF and the TDF group or TDF-CKD group, although the numerical change in rGFR in the latter comparison was greater in the TAF group (ΔrGFR 3 vs. -2.14 ml/min, p=0.26). The use of everolimus was associated with improvement in renal function (ΔrGFR 2 vs. -7.75 ml/min, p=0.06 [TAF vs. TDF group]; 2 vs. -12 ml/min, p=0.01 [TAF vs. TDF-CKD group]). There were no TAF- related side effects or cases of HBV recurrence. CONCLUSION Conversion to TAF in post-LT patients who develop CKD does not lead to improvement of kidney function after a period of one year.
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Affiliation(s)
- E Sinakos
- 4th Medical Department, Hippokratio Hospital, Aristotle University of Thessaloniki, Greece
| | - P Panas
- 4th Medical Department, Hippokratio Hospital, Aristotle University of Thessaloniki, Greece
| | - N Fragkou
- 4th Medical Department, Hippokratio Hospital, Aristotle University of Thessaloniki, Greece
| | - N Antoniadis
- Department of Transplant Surgery, Hippokratio Hospital, Aristotle University of Thessaloniki, Greece
| | - G Katsanos
- Department of Transplant Surgery, Hippokratio Hospital, Aristotle University of Thessaloniki, Greece
| | - E Tsakni
- Department of Transplant Surgery, Hippokratio Hospital, Aristotle University of Thessaloniki, Greece
| | - T Oikonomou
- 4th Medical Department, Hippokratio Hospital, Aristotle University of Thessaloniki, Greece
| | - A Notopoulos
- Department of Nuclear Medicine, Hippokratio Hospital, Thessaloniki, Greece
| | - G Tsoulfas
- Department of Transplant Surgery, Hippokratio Hospital, Aristotle University of Thessaloniki, Greece
| | - I Goulis
- 4th Medical Department, Hippokratio Hospital, Aristotle University of Thessaloniki, Greece
| | - E Akriviadis
- 4th Medical Department, Hippokratio Hospital, Aristotle University of Thessaloniki, Greece
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23
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Kumar M, Abbas Z, Azami M, Belopolskaya M, Dokmeci AK, Ghazinyan H, Jia J, Jindal A, Lee HC, Lei W, Lim SG, Liu CJ, Li Q, Al Mahtab M, Muljono DH, Niriella MA, Omata M, Payawal DA, Sarin SK, Ségéral O, Tanwandee T, Trehanpati N, Visvanathan K, Yang JM, Yuen MF, Zheng Y, Zhou YH. Asian Pacific association for the study of liver (APASL) guidelines: hepatitis B virus in pregnancy. Hepatol Int 2022; 16:211-253. [PMID: 35113359 DOI: 10.1007/s12072-021-10285-5] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Accepted: 12/06/2021] [Indexed: 12/11/2022]
Abstract
Hepatitis B virus (HBV) infection still remains a major public health issue in the Asia-Pacific region. Most of the burden of HBV-related disease results from infections acquired in infancy through perinatal or early childhood exposure to HBV in Asia-Pacific. Hepatitis B during pregnancy presents unique management issues for both the mother and fetus. These APASL guidelines provide a comprehensive review and recommendations based on available evidence in the literature, for the management of females with HBV infection through every stage of pregnancy and postpartum. These also address the concerns, management challenges, and required follow-up of children born to hepatitis B-positive mothers.
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Affiliation(s)
- Manoj Kumar
- Department of Hepatology and Liver Transplantation, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, 110070, India.
| | - Zaigham Abbas
- Department of Medicine, Ziauddin University Hospital, Karachi, Pakistan
| | - Milad Azami
- Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran
| | | | - A K Dokmeci
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
| | - Hasmik Ghazinyan
- Department of Hepatology, Nork Clinical Hospital of Infectious Disease, Yerevan, Armenia
| | - Jidong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medial University, Beijing, China
| | - Ankur Jindal
- Department of Hepatology and Liver Transplantation, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, 110070, India
| | - Han Chu Lee
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Wei Lei
- Hepatopancreatobiliary Center, School of Clinical Medicine, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, China
| | - Seng Gee Lim
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Chun-Jen Liu
- Department of Internal Medicine and Hepatitis Research Center, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei City, Taiwan
| | - Qiang Li
- Division of Liver Diseases Jinan Infectious Disease Hospital, Shandong University, Jinan, China
| | - Mamun Al Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | | | - Madunil Anuk Niriella
- Department of Medicine, Faculty of Medicine, University of Kelaniya, Ragama, Colombo, Sri Lanka
| | - Masao Omata
- Department of Gastroenterology, Yamanashi Central Hospital, Yamanashi, Japan
- University of Tokyo, Tokyo, Japan
| | - Diana A Payawal
- Fatima University Medical Center Manila, Manila, Philippines
| | - Shiv K Sarin
- Department of Hepatology and Liver Transplantation, Institute of Liver and Biliary Sciences, D1 Vasant Kunj, New Delhi, 110070, India.
| | - Olivier Ségéral
- French Agency for Research on AIDS and Viral Hepatitis, University of Health Science, Phnom Penh, Cambodia
| | - Tawesak Tanwandee
- Division of Gastroenterology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Nirupma Trehanpati
- Department of Molecular and Cellular Medicine, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Kumar Visvanathan
- Department of Medicine, University of Melbourne, Melbourne, VIC, Australia
| | - Jin Mo Yang
- Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea
| | - Man-Fung Yuen
- Li Shu Fan Medical Foundation Professor in Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong
| | - Yingjie Zheng
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Y H Zhou
- Department of Laboratory Medicine, Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
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24
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Yip TCF, Gill M, Wong GLH, Liu K. Management of hepatitis B virus reactivation due to treatment of COVID-19. Hepatol Int 2022; 16:257-268. [PMID: 35235148 PMCID: PMC8889512 DOI: 10.1007/s12072-022-10306-x] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2021] [Accepted: 01/25/2022] [Indexed: 01/08/2023]
Abstract
The world has made significant progress in developing novel treatments for COVID-19 since the pandemic began. Some treatments target the patient's dysregulated inflammatory response during COVID-19 infection and may cause hepatitis B reactivation (HBVr) in patients with current or past hepatitis B virus (HBV) infection. This review summarizes the risk and management of HBVr due to different treatments of COVID-19 in patients who have current or past HBV infection. Abnormal liver function tests are common during COVID-19 infection. Current evidence suggests that current or past HBV infection is not associated with an increased risk of liver injury and severe disease in COVID-19 patients. Among patients who received high-dose corticosteroids, various immunosuppressive monoclonal antibodies and inhibitors of Janus kinase, the risk of HBVr exists, especially among those without antiviral prophylaxis. Data, however, remain scarce regarding the specific use of immunosuppressive therapies in COVID-19 patients with HBV infection. Some results are mainly extrapolated from patients receiving the same agents in other diseases. HBVr is a potentially life-threatening event following profound immunosuppression by COVID-19 therapies. Future studies should explore the use of immunosuppressive therapies in COVID-19 patients with HBV infection and the impact of antiviral prophylaxis on the risk of HBVr.
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Affiliation(s)
- Terry Cheuk-Fung Yip
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, 9/F Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, Hong Kong SAR, China
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong SAR, China
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Madeleine Gill
- AW Morrow Gastroenterology and Liver Unit, Royal Prince Alfred Hospital, University of Sydney, Sydney, NSW Australia
- Sydney Medical School, University of Sydney, Sydney, NSW Australia
| | - Grace Lai-Hung Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, 9/F Prince of Wales Hospital, 30-32 Ngan Shing Street, Shatin, Hong Kong SAR, China
- Medical Data Analytics Centre, The Chinese University of Hong Kong, Hong Kong SAR, China
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Ken Liu
- AW Morrow Gastroenterology and Liver Unit, Royal Prince Alfred Hospital, University of Sydney, Sydney, NSW Australia
- Sydney Medical School, University of Sydney, Sydney, NSW Australia
- Centenary Institute of Cancer Medicine and Cell Biology, The University of Sydney, Sydney, NSW Australia
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Prognosis Comparison Between Chronic Hepatitis B Patients Receiving a Finite Course of Tenofovir and Entecavir Treatment: A Nationwide Cohort Study in Taiwan. Clin Ther 2022; 44:403-417.e6. [DOI: 10.1016/j.clinthera.2022.01.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Revised: 01/13/2022] [Accepted: 01/14/2022] [Indexed: 11/20/2022]
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Chauhan S, Jain K, Naqvi S. Dendrimers and its theranostic applications in infectious diseases. NANOTHERANOSTICS FOR TREATMENT AND DIAGNOSIS OF INFECTIOUS DISEASES 2022:199-228. [DOI: 10.1016/b978-0-323-91201-3.00004-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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27
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Lai JCT, Wong VWS, Yip TCF, Hui VWK, Tse YK, Lee HW, Liang LY, Lui GCY, Chan HLY, Wong GLH. Secular trend of treatment uptake in patients with chronic hepatitis B: A territory-wide study of 135 395 patients from 2000 to 2017. J Gastroenterol Hepatol 2021; 36:3487-3499. [PMID: 34404113 DOI: 10.1111/jgh.15664] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Revised: 07/22/2021] [Accepted: 08/10/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND AIMS The uptake of antiviral treatment for patients with chronic hepatitis B (CHB) has been suboptimal. We aimed to determine the secular trend of treatment uptake in the territory-wide CHB cohort in Hong Kong from 2000 to 2017 and the factors for no treatment despite fulfilling treatment criteria. METHODS Chronic hepatitis B patients under public clinics and hospitals were identified through electronic medical records. The treatment indications were defined according to the Asian-Pacific guidelines published at the time of patients' first appearance in four periods: 2000-2004, 2005-2009, 2010-2013, and 2014-2017. RESULTS There were 135 395 CHB patients were included; 1493/12472 (12.0%), 7416/43426 (17.1%), 10 129/46559 (21.8%), 8051/32 938 (24.4%) patients fulfilled treatment criteria in the four periods, respectively. The treatment uptake rate increased with time: 35.1%, 43.4%, 60.2%, and 68.6% respectively. High fibrosis indices (APRI, FIB-4, and Forns indices) appeared to be the main factors for treatment indication in non-cirrhotic patients, with over 90% fulfilling treatment criteria due to high fibrosis indices alone. Of those fulfilling treatment criteria by high fibrosis indices, less than 60% of patients (25.2%, 36.1%, 46.0%, and 58.9%, respectively) had antiviral treatment initiated. Normal platelet count (odds ratio 0.42, P < 0.001) was the independent factor associated with not initiating antiviral treatment in patients fulfilling treatment criteria. CONCLUSIONS Treatment uptake rates have been increasing over time. Normal platelet count, which reflects less advanced liver disease, precludes patients from receiving antiviral treatment even if treatment indication is fulfilled. Hence, the importance to identify non-cirrhotic patients with significant liver fibrosis should be emphasized.
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Affiliation(s)
- Jimmy C-T Lai
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
- Medical Data Analytics Centre (MDAC), The Chinese University of Hong Kong, Hong Kong
| | - Vincent W-S Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
- Medical Data Analytics Centre (MDAC), The Chinese University of Hong Kong, Hong Kong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - Terry C-F Yip
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
- Medical Data Analytics Centre (MDAC), The Chinese University of Hong Kong, Hong Kong
| | - Vicki W-K Hui
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
- Medical Data Analytics Centre (MDAC), The Chinese University of Hong Kong, Hong Kong
| | - Yee-Kit Tse
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
- Medical Data Analytics Centre (MDAC), The Chinese University of Hong Kong, Hong Kong
| | - Hye-Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Lilian Y Liang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
| | - Grace C-Y Lui
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
| | - Henry L-Y Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
- Medical Data Analytics Centre (MDAC), The Chinese University of Hong Kong, Hong Kong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
| | - Grace L-H Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
- Medical Data Analytics Centre (MDAC), The Chinese University of Hong Kong, Hong Kong
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong
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Liu Z, Jin Q, Zhang Y, Gong G, Wu G, Yao L, Wen X, Gao Z, Huang Y, Yang D, Chen E, Mao Q, Lin S, Shang J, Gong H, Zhong L, Yin H, Wang F, Hu P, Xiao L, Li C, Wu Q, Sun C, Niu J, Hou J, the TMF Study Group. Randomised clinical trial: 48 weeks of treatment with tenofovir amibufenamide versus tenofovir disoproxil fumarate for patients with chronic hepatitis B. Aliment Pharmacol Ther 2021; 54:1134-1149. [PMID: 34587302 PMCID: PMC9292801 DOI: 10.1111/apt.16611] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Revised: 06/10/2021] [Accepted: 09/07/2021] [Indexed: 12/28/2022]
Abstract
BACKGROUND Tenofovir amibufenamide (TMF) can provide more efficient delivery than tenofovir disoproxil fumarate (TDF). AIM To compare the efficacy and safety of TMF and TDF for 48 weeks in patients with chronic hepatitis B (CHB). METHODS We performed a randomised, double-blind, non-inferiority study at 49 sites in China. Patients with CHB were assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo. The primary efficacy endpoint was the proportion of patients with hepatitis B virus (HBV) DNA less than 20 IU/mL at week 48. We also assessed safety, particularly bone, renal and metabolic abnormalities. RESULTS We randomised 1002 eligible patients. The baseline characteristics were well balanced between groups. After a median 48 weeks of treatment, the non-inferiority criterion was met in all analysis sets. In the HBeAg-positive population, 50.2% of patients receiving TMF and 53.7% receiving TDF achieved HBV DNA less than 20 IU/mL. In the HBeAg-negative population, 88.9% and 87.8%, respectively, achieved HBV DNA less than 20 IU/mL in the TMF and TDF groups. Patients receiving TMF had significantly less decrease in bone mineral density at both hip (P < 0.001) and spine (P < 0.001), and a smaller increase in serum creatinine at week 48 (P < 0.05). Other safety results were similar between groups. CONCLUSION TMF was non-inferior to TDF in terms of anti-HBV efficacy and showed better bone and renal safety. (NCT03903796).
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29
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Wang G, Duan Z. Guidelines for Prevention and Treatment of Chronic Hepatitis B. J Clin Transl Hepatol 2021; 9:769-791. [PMID: 34722192 PMCID: PMC8516840 DOI: 10.14218/jcth.2021.00209] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2021] [Revised: 07/20/2021] [Accepted: 08/03/2021] [Indexed: 12/12/2022] Open
Abstract
To achieve the goal of the World Health Organization to eliminate viral hepatitis as a major public health threat by 2030, the Chinese Society of Infectious Diseases and the Chinese Society of Hepatology convened an expert panel in 2019 to update the guidelines for the prevention and treatment of chronic hepatitis B (CHB). The current guidelines cover recent advances in basic, clinical, and preventive studies of CHB infection and consider the actual situation in China. These guidelines are intended to provide support for the prevention, diagnosis, and treatment of CHB.
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Affiliation(s)
- Guiqiang Wang
- Center for Liver Diseases, Department of Infectious Diseases, Peking University First Hospital; Department of Infectious and Liver Diseases, Peking University International Hospital, Beijing, China
| | - Zhongping Duan
- Center for Difficult and Complicated Liver Diseases and Artificial Liver, Beijing YouAn Hospital, Capital Medical University, Beijing, China
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30
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Higuera-de-la-Tijera F, Castro-Narro GE, Velarde-Ruiz Velasco JA, Cerda-Reyes E, Moreno-Alcántar R, Aiza-Haddad I, Castillo-Barradas M, Cisneros-Garza LE, Dehesa-Violante M, Flores-Calderón J, González-Huezo MS, Márquez-Guillén E, Muñóz-Espinosa LE, Pérez-Hernández JL, Ramos-Gómez MV, Sierra-Madero J, Sánchez-Ávila JF, Torre-Delgadillo A, Torres R, Marín-López ER, Kershenobich D, Wolpert-Barraza E. Asociación Mexicana de Hepatología A.C. Clinical guideline on hepatitis B. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2021; 86:403-432. [PMID: 34483073 DOI: 10.1016/j.rgmxen.2021.04.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Accepted: 04/14/2021] [Indexed: 12/24/2022]
Abstract
Hepatitis B virus (HBV) infection continues to be a worldwide public health problem. In Mexico, at least three million adults are estimated to have acquired hepatitis B (total hepatitis B core antibody [anti-HBc]-positive), and of those, 300,000 active carriers (hepatitis B surface antigen [HBsAg]-positive) could require treatment. Because HBV is preventable through vaccination, its universal application should be emphasized. HBV infection is a major risk factor for developing hepatocellular carcinoma. Semi-annual liver ultrasound and serum alpha-fetoprotein testing favor early detection of that cancer and should be carried out in all patients with chronic HBV infection, regardless of the presence of advanced fibrosis or cirrhosis. Currently, nucleoside/nucleotide analogues that have a high barrier to resistance are the first-line therapies.
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Affiliation(s)
- F Higuera-de-la-Tijera
- Departamento de Gastroenterología, Hospital General de México "Dr. Eduardo Liceaga", Mexico City, Mexico
| | - G E Castro-Narro
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Mexico City, Mexico.
| | - J A Velarde-Ruiz Velasco
- Departamento de Gastroenterología, Hospital Civil de Guadalajara "Fray Antonio Alcalde", Guadalajara, Jalisco, Mexico
| | - E Cerda-Reyes
- Departamento de Gastroenterología, Hospital Central Militar, Mexico City, Mexico
| | - R Moreno-Alcántar
- Departamento de Gastroenterología, Hospital de Especialidades del Centro Médico Nacional Siglo XXI, IMSS, Mexico City, Mexico
| | - I Aiza-Haddad
- Clínica de Enfermedades Hepáticas, Hospital Ángeles Lomas, Mexico City, Mexico
| | - M Castillo-Barradas
- Departamento de Gastroenterología, Hospital de Especialidades del Centro Médico Nacional "La Raza", IMSS, Mexico City, Mexico
| | - L E Cisneros-Garza
- Centro de Enfermedades Hepáticas, Hospital San José, Nuevo León, Monterrey, Mexico
| | - M Dehesa-Violante
- Fundación Mexicana para la Salud Hepática A.C. (FUNDHEPA), Mexico City, Mexico
| | - J Flores-Calderón
- Departamento de Gastroenterología, Hospital de Pediatría del Centro Médico Nacional Siglo XXI, IMSS, Mexico City, Mexico
| | - M S González-Huezo
- Servicio de Gastroenterología y Endoscopia Gastrointestinal, ISSSEMYM, Metepec, Estado de México, Mexico
| | - E Márquez-Guillén
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Mexico City, Mexico
| | - L E Muñóz-Espinosa
- Clínica de Hígado, Departamento de Medicina Interna, Hospital Universitario "Dr. José E. González", Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico
| | - J L Pérez-Hernández
- Departamento de Gastroenterología, Hospital General de México "Dr. Eduardo Liceaga", Mexico City, Mexico
| | - M V Ramos-Gómez
- Departamento de Gastroenterología, Centro Médico Nacional "20 de Noviembre", ISSSTE, Mexico City, Mexico
| | - J Sierra-Madero
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Mexico City, Mexico
| | - J F Sánchez-Ávila
- Tecnológico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Mexico City, Mexico
| | - A Torre-Delgadillo
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Mexico City, Mexico
| | - R Torres
- Hospital de Infectología del Centro Médico Nacional "La Raza", IMSS, Mexico City, Mexico
| | | | - D Kershenobich
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Mexico City, Mexico
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Higuera-de-la-Tijera F, Castro-Narro GE, Velarde-Ruiz Velasco JA, Cerda-Reyes E, Moreno-Alcántar R, Aiza-Haddad I, Castillo-Barradas M, Cisneros-Garza LE, Dehesa-Violante M, Flores-Calderón J, González-Huezo MS, Márquez-Guillén E, Muñóz-Espinosa LE, Pérez-Hernández JL, Ramos-Gómez MV, Sierra-Madero J, Sánchez-Ávila JF, Torre-Delgadillo A, Torres R, Marín-López ER, Kershenobich D, Wolpert-Barraza E. Asociación Mexicana de Hepatología A.C. Clinical guideline on hepatitis B. REVISTA DE GASTROENTEROLOGIA DE MEXICO (ENGLISH) 2021; 86:S0375-0906(21)00061-6. [PMID: 34384668 DOI: 10.1016/j.rgmx.2021.04.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Revised: 04/11/2021] [Accepted: 04/14/2021] [Indexed: 02/07/2023]
Abstract
Hepatitis B virus (HBV) infection continues to be a worldwide public health problem. In Mexico, at least three million adults are estimated to have acquired hepatitis B (total hepatitis B core antibody [anti-HBc]-positive), and of those, 300,000 active carriers (hepatitis B surface antigen [HBsAg]-positive) could require treatment. Because HBV is preventable through vaccination, its universal application should be emphasized. HBV infection is a major risk factor for developing hepatocellular carcinoma. Semi-annual liver ultrasound and serum alpha-fetoprotein testing favor early detection of that cancer and should be carried out in all patients with chronic HBV infection, regardless of the presence of advanced fibrosis or cirrhosis. Currently, nucleoside/nucleotide analogues that have a high barrier to resistance are the first-line therapies.
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Affiliation(s)
- F Higuera-de-la-Tijera
- Departamento de Gastroenterología, Hospital General de México «Dr. Eduardo Liceaga», Ciudad de México, México
| | - G E Castro-Narro
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición «Salvador Zubirán», Ciudad de México, México.
| | - J A Velarde-Ruiz Velasco
- Departamento de Gastroenterología, Hospital Civil de Guadalajara «Fray Antonio Alcalde», Guadalajara, Jalisco, México
| | - E Cerda-Reyes
- Departamento de Gastroenterología, Hospital Central Militar, Ciudad de México, México
| | - R Moreno-Alcántar
- Departamento de Gastroenterología, Hospital de Especialidades del Centro Médico Nacional Siglo XXI, IMSS, Ciudad de México, México
| | - I Aiza-Haddad
- Clínica de Enfermedades Hepáticas, Hospital Ángeles Lomas, Ciudad de México, México
| | - M Castillo-Barradas
- Departamento de Gastroenterología, Hospital de Especialidades del Centro Médico Nacional «La Raza», IMSS, Ciudad de México, México
| | - L E Cisneros-Garza
- Centro de Enfermedades Hepáticas, Hospital San José, Nuevo León, Monterrey, México
| | - M Dehesa-Violante
- Fundación Mexicana para la Salud Hepática A.C. (FUNDHEPA), Ciudad de México, México
| | - J Flores-Calderón
- Departamento de Gastroenterología, Hospital de Pediatría del Centro Médico Nacional Siglo XXI, IMSS, Ciudad de México, México
| | - M S González-Huezo
- Servicio de Gastroenterología y Endoscopia Gastrointestinal, ISSSEMYM, Metepec, Estado de México, México
| | - E Márquez-Guillén
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición «Salvador Zubirán», Ciudad de México, México
| | - L E Muñóz-Espinosa
- Clínica de Hígado, Departamento de Medicina Interna, Hospital Universitario «Dr. José E. González», Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, México
| | - J L Pérez-Hernández
- Departamento de Gastroenterología, Hospital General de México «Dr. Eduardo Liceaga», Ciudad de México, México
| | - M V Ramos-Gómez
- Departamento de Gastroenterología, Centro Médico Nacional «20 de Noviembre», ISSSTE, Ciudad de México, México
| | - J Sierra-Madero
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición «Salvador Zubirán», Ciudad de México, México
| | - J F Sánchez-Ávila
- Tecnológico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Ciudad de México, México
| | - A Torre-Delgadillo
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición «Salvador Zubirán», Ciudad de México, México
| | - R Torres
- Hospital de Infectología del Centro Médico Nacional «La Raza», IMSS, Ciudad de México, México
| | | | - D Kershenobich
- Departamento de Gastroenterología, Instituto Nacional de Ciencias Médicas y Nutrición «Salvador Zubirán», Ciudad de México, México
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Honda T, Yamada N, Murayama A, Shiina M, Aly HH, Kato A, Ito T, Ishizu Y, Kuzuya T, Ishigami M, Murakami Y, Tanaka T, Moriishi K, Nishitsuji H, Shimotohno K, Ishikawa T, Fujishiro M, Muramatsu M, Wakita T, Kato T. Amino Acid Polymorphism in Hepatitis B Virus Associated With Functional Cure. Cell Mol Gastroenterol Hepatol 2021; 12:1583-1598. [PMID: 34352407 PMCID: PMC8536788 DOI: 10.1016/j.jcmgh.2021.07.013] [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] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Revised: 07/23/2021] [Accepted: 07/26/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS To provide an adequate treatment strategy for chronic hepatitis B, it is essential to know which patients are expected to have a good prognosis and which patients do not require therapeutic intervention. Previously, we identified the substitution of isoleucine to leucine at amino acid 97 (I97L) in the hepatitis B core region as a key predictor among patients with stable hepatitis. In this study, we attempted to identify the point at which I97L affects the hepatitis B virus (HBV) life cycle and to elucidate the underlying mechanisms governing the stabilization of hepatitis. METHODS To confirm the clinical features of I97L, we used a cohort of hepatitis B e antigen-negative patients with chronic hepatitis B infected with HBV-I97 wild-type (wt) or HBV-I97L. The effects of I97L on viral characteristics were evaluated by in vitro HBV production and infection systems with the HBV reporter virus and cell culture-generated HBV. RESULTS The ratios of reduction in hepatitis B surface antigen and HBV DNA were higher in patients with HBV-I97L than in those with HBV-I97wt. HBV-I97L exhibited lower infectivity than HBV-I97wt in both infection systems with reporter HBV and cell culture-generated HBV. HBV-I97L virions exhibiting low infectivity primarily contained a single-stranded HBV genome. The lower efficiency of cccDNA synthesis was demonstrated after infection of HBV-I97L or transfection of the molecular clone of HBV-I97L. CONCLUSIONS The I97L substitution reduces the level of cccDNA through the generation of immature virions with single-stranded genomes. This I97L-associated low efficiency of cccDNA synthesis may be involved in the stabilization of hepatitis.
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Affiliation(s)
- Takashi Honda
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya
| | - Norie Yamada
- Department of Virology II, National Institute of Infectious Diseases, Tokyo
| | - Asako Murayama
- Department of Virology II, National Institute of Infectious Diseases, Tokyo
| | - Masaaki Shiina
- Department of Virology II, National Institute of Infectious Diseases, Tokyo
| | - Hussein Hassan Aly
- Department of Virology II, National Institute of Infectious Diseases, Tokyo
| | - Asuka Kato
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya
| | - Takanori Ito
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya
| | - Yoji Ishizu
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya
| | - Teiji Kuzuya
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya
| | - Masatoshi Ishigami
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya
| | - Yoshiki Murakami
- Department of Molecular Pathology, Tokyo Medical University, Tokyo
| | - Tomohisa Tanaka
- Department of Microbiology, Graduate School of Medicine, University of Yamanashi, Yamanashi
| | - Kohji Moriishi
- Department of Microbiology, Graduate School of Medicine, University of Yamanashi, Yamanashi
| | - Hironori Nishitsuji
- Genome Medical Sciences Project, National Center for Global Health and Medicine, Ichikawa, Japan
| | - Kunitada Shimotohno
- Genome Medical Sciences Project, National Center for Global Health and Medicine, Ichikawa, Japan
| | - Tetsuya Ishikawa
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya
| | | | - Takaji Wakita
- Department of Virology II, National Institute of Infectious Diseases, Tokyo
| | - Takanobu Kato
- Department of Virology II, National Institute of Infectious Diseases, Tokyo,Correspondence Address correspondence to: Takanobu Kato, MD, PhD, Toyama 1-23-1, Shinjuku-ku, Tokyo 162-8640, Japan. fax: +81-3-5285-1161.
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Zhang ZQ, Shi BS, Lu W, Huang D, Wang YB, Feng YL. Quantitative serum HBV markers in predicting phases of natural history of chronic HBV infection. J Virol Methods 2021; 296:114226. [PMID: 34217779 DOI: 10.1016/j.jviromet.2021.114226] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2021] [Revised: 06/29/2021] [Accepted: 06/29/2021] [Indexed: 12/14/2022]
Abstract
BACKGROUND Clinical importance of commercially available quantitative HBV markers has not been fully investigated. OBJECTIVE To choice and to evaluate clinically valuable HBV markers for predicting phases of natural history with chronic HBV infection. METHODS 472 naïve patients with chronic HBV infection were enrolled, in which 21 and 220 were confirmed as HBeAg-positive inactive and active hepatitis (EPIH and EPAH), respectively, and 106 and 125 were confirmed as HBeAg-negative inactive and active hepatitis (ENIH and ENAH), respectively. HBsAg, HBcrAg and anti- HBc were measured using chemiluminescent immunoassay, and HBV DNA was measured using PCR-fluorescence probing assay. RESULTS There were all statistical differences in medians of HBsAg, anti-HBc, HBcrAg and HBV DNA between EPIH and EPAH and between ENIH and ENAH (all P < 0.01). According to binary logistic stepwise regressions, HBsAg and anti-HBc were preferred variables for predicting EPAH, and HBcrAg and HBV DNA were preferred variables for predicting ENAH. Based on normalization for coefficients of preferred variables entering regression equations, a handy model of MEPAH for predicting EPAH and of MENAH for predicting ENAH was constructed, respectively. Area under receiver operating characteristic curves of MEPAH and MENAH for predicting EPAH and ENAH were 0.882 and 0.931, respectively. With standard of MEPAH ≤ 5.997 and MENAH > 10.535, sensitivity or specificity of which for predicting EPAH and ENAH were about 81.0 % and 87.0 %, respectively. CONCLUSION HBsAg and anti-HBc for predicting EPAH and HBcrAg and HBV DNA for predicting ENAH are dependable markers; MEPAH for predicting EPAH and MENAH for predicting ENAH have very good performance.
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Affiliation(s)
- Zhan-Qing Zhang
- Department of Hepatobiliary Medicine, Shanghai Public Health Clinical Center of Fudan University, China.
| | - Bi-Sheng Shi
- Scientific Research Center, Shanghai Public Health Clinical Center of Fudan University, China.
| | - Wei Lu
- Department of Hepatobiliary Medicine, Shanghai Public Health Clinical Center of Fudan University, China.
| | - Dan Huang
- Department of Hepatobiliary Medicine, Shanghai Public Health Clinical Center of Fudan University, China.
| | - Yan-Bing Wang
- Department of Hepatobiliary Medicine, Shanghai Public Health Clinical Center of Fudan University, China.
| | - Yan-Ling Feng
- Department of Clinical Pathology, Shanghai Public Health Clinical Center of Fudan University, China.
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Chen WY, Lin PY, Lai CH, Chen YL. Evaluation of Clinical Neuropathy After Living Donor Liver Transplant. EXP CLIN TRANSPLANT 2021; 19:664-670. [PMID: 34085916 DOI: 10.6002/ect.2020.0392] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
OBJECTIVES Neurologic complications are more common in liver transplants than in other solid-organ transplants. One such neurologic complication, peripheral neuropathy, may cause functional limitations for recipients and have a negative effect on posttransplant quality of life. We aimed to examine the risk factors associated with the occurrence of clinical neuropathy after liver transplant and to investigate the frequency of sensory deficits. MATERIALS AND METHODS In this case-control study, we analyzed factors from medical records of 63 recipients who underwent living donor liver transplant during the period from January 2010 to December 2016. A neuropathy symptom score was assigned to identify the patients who had clinical neuropathy (case group) and the patients without clinical neuropathy (control group). Quantitative sensory testing was performed to measure the warm and cold detection thresholds, and the difference between the 2 groups was examined. RESULTS Compared with controls, patients with clinical neuropathy were older (61.0 vs 55.4 years; P = .028), had higher rates of diabetes (46.2% vs 16.0%; P = .03), and were taking antiviral agents against hepatitis B (100% vs 62%; P = .006). Patients with neuropathic symptoms had significantly increased frequencies of impairment of warm and cold detection thresholds. In addition, the greater severity of symptoms showed higher detection thresholds of warm (control, 40.7℃; mild-to-moderate, 43.8 ℃; severe, 46.0 ℃; P = .007) and cold (control, 28.8℃ ; mild-to-moderate, 27.0 ℃; severe, 21.8 ℃ ; P = .008). CONCLUSIONS Our findings show that older age, diabetes, and treatment with oral antiviral agents against hepatitis B virus were more likely to be associated with the occurrence of clinical neuropathy after liver transplant. Early awareness and careful monitoring are warranted.
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Affiliation(s)
- Wen-Yuan Chen
- From the Department of Pharmacy, Changhua Christian Hospital, Changhua, Taiwan
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Prifti GM, Moianos D, Giannakopoulou E, Pardali V, Tavis JE, Zoidis G. Recent Advances in Hepatitis B Treatment. Pharmaceuticals (Basel) 2021; 14:417. [PMID: 34062711 PMCID: PMC8147224 DOI: 10.3390/ph14050417] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 04/22/2021] [Accepted: 04/23/2021] [Indexed: 01/10/2023] Open
Abstract
Hepatitis B virus infection affects over 250 million chronic carriers, causing more than 800,000 deaths annually, although a safe and effective vaccine is available. Currently used antiviral agents, pegylated interferon and nucleos(t)ide analogues, have major drawbacks and fail to completely eradicate the virus from infected cells. Thus, achieving a "functional cure" of the infection remains a real challenge. Recent findings concerning the viral replication cycle have led to development of novel therapeutic approaches including viral entry inhibitors, epigenetic control of cccDNA, immune modulators, RNA interference techniques, ribonuclease H inhibitors, and capsid assembly modulators. Promising preclinical results have been obtained, and the leading molecules under development have entered clinical evaluation. This review summarizes the key steps of the HBV life cycle, examines the currently approved anti-HBV drugs, and analyzes novel HBV treatment regimens.
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Affiliation(s)
- Georgia-Myrto Prifti
- Department of Pharmacy, Division of Pharmaceutical Chemistry, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771 Athens, Greece; (G.-M.P.); (D.M.); (E.G.); (V.P.)
| | - Dimitrios Moianos
- Department of Pharmacy, Division of Pharmaceutical Chemistry, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771 Athens, Greece; (G.-M.P.); (D.M.); (E.G.); (V.P.)
| | - Erofili Giannakopoulou
- Department of Pharmacy, Division of Pharmaceutical Chemistry, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771 Athens, Greece; (G.-M.P.); (D.M.); (E.G.); (V.P.)
| | - Vasiliki Pardali
- Department of Pharmacy, Division of Pharmaceutical Chemistry, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771 Athens, Greece; (G.-M.P.); (D.M.); (E.G.); (V.P.)
| | - John E. Tavis
- Molecular Microbiology and Immunology, Saint Louis University, Saint Louis, MO 63104, USA;
| | - Grigoris Zoidis
- Department of Pharmacy, Division of Pharmaceutical Chemistry, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimiopolis Zografou, 15771 Athens, Greece; (G.-M.P.); (D.M.); (E.G.); (V.P.)
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Zhao J, Feng WG, Wei Z, Zhou J, Chen XY, Zhang ZL. Follow-Up of Adefovir Dipivoxil Induced Osteomalacia: Clinical Characteristics and Genetic Predictors. Front Pharmacol 2021; 12:636352. [PMID: 33995038 PMCID: PMC8113870 DOI: 10.3389/fphar.2021.636352] [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: 12/19/2020] [Accepted: 04/16/2021] [Indexed: 11/13/2022] Open
Abstract
Adefovir dipivoxil (ADV) is widely used for chronic hepatitis B therapy in China. To explore the clinical features and prognosis of ADV-induced osteomalacia and to analyze the association between osteomalacia and genetic variants in 51 drug transporters genes. Clinical and follow-up data of the ADV-treated patients were collected. Target capture sequencing was used to identify genetic variations of 51 drug transporter genes. A total of 193 hepatitis B patients treated with ADV were enrolled, of whom 140 had osteomalacia. The other 53 without osteomalacia were included in the control group. The median duration of ADV treatment before the onset of osteomalacia was 6.5 years (range:1.5–7 years). We found that most patients with osteomalacia had hypophosphatemia, high serum alkaline phosphatase levels, hypouricemia, nondiabetic glycosuria, proteinuria. Stopping ADV administration, supplementing calcitriol and calcium were effective treatments. During 3–6 months of follow-up, the clinical symptoms and biochemical indicators of patients with osteomalacia have been significantly improved. There was no significant difference in duration of adefovir treatment in patients with or without osteomalacia (p = 0.791). Through regression analysis, we found that age was a risk factor for osteomalacia [per 1 year, odds ratio (OR), 1.053; 95% confidence interval (95% CI), 1.020–1.087; p = 0.015]. 1992 single nucleotide variants were found using target capture sequencing. However, the associations of genetic variants of 51 drug transporter genes and the risk of osteomalacia were negligible. Osteomalacia is prone to occur in patients with chronic hepatitis B treated with long-term ADV at a therapeutic dose. After standard treatment, the prognosis is mostly good. We failed to find genetic variants that can predict the risk of ADV-induced osteomalacia.
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Affiliation(s)
- Jiao Zhao
- Shanghai Clinical Research Center of Bone Disease, Department of Osteoporosis and Bone Disease, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Wei-Guang Feng
- Department of Hepatology, The Fourth People's Hospital of Huai'an, Huai'an, China
| | - Zhe Wei
- Shanghai Clinical Research Center of Bone Disease, Department of Osteoporosis and Bone Disease, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Jian Zhou
- Department of Hepatology, The Fourth People's Hospital of Huai'an, Huai'an, China
| | - Xiao-Yun Chen
- Department of Rheumatology, Shanghai University of Traditional Chinese Medicine Affiliated LongHua Hospital, Shanghai, China
| | - Zhen-Lin Zhang
- Shanghai Clinical Research Center of Bone Disease, Department of Osteoporosis and Bone Disease, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, China
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Zhang Y, Xu W, Zhu X, Li X, Li J, Shu X, Lai J, Xie J, Xie C, Peng L. The 48-week safety and therapeutic effects of tenofovir alafenamide in hbv-related acute-on-chronic liver failure: A prospective cohort study. J Viral Hepat 2021; 28:592-600. [PMID: 33423348 DOI: 10.1111/jvh.13468] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2020] [Accepted: 12/30/2020] [Indexed: 12/23/2022]
Abstract
Tenofovir alafenamide (TAF) has been available in China for a short time, little is known about its safety and efficacy in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (HBV-ACLF). We conducted this study to further verify the safety and efficacy of TAF in these patients. Eighty-eight eligible subjects were included and divided into three groups: TAF group, TDF group and ETV group. Clinical and laboratory test results were collected and the survival status, virus suppression status and liver and renal function improvement were observed during follow-up. No drug-related adverse events were observed within a 48-week observation period. At week 48, the survival rates of the three groups were 56.5%, 78.3% and 59.5% (p = 0.262). HBV DNA undetectable rates were similar (80.0% vs.75.0% vs.84.6%, respectively, p = 0.863). Liver function improved in all the three groups over time. Compared with the other two groups, patients in the TAF group had a greater decrease in serum creatinine (CR) and an increase in estimated glomerular filtration rate (eGFR), especially at week 12. At week 48, the median changes of CR were -0.7 (IQR -3.0, 13.0) vs. 15.0 (IQR -3.0, 21.0) vs. 5.0 (IQR -9.0, 14.0), respectively (p = 0.334), while the median changes of eGFR were -2.12 (IQR -13.87, 1.44) vs. -10.43 (IQR -20.21, 3.18) vs. -5.31 (IQR -14.72, 5.44) ml/min/1.73 m2 , respectively (p = 0.592). In this real-world clinical study, TAF is as effective as TDF and ETV, and may be more beneficial in protecting renal function in the early stages of antiviral therapy.
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Affiliation(s)
- Yeqiong Zhang
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.,Guangdong Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Wenxiong Xu
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.,Guangdong Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Xiang Zhu
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.,Guangdong Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Xuejun Li
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.,Guangdong Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Jianguo Li
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.,Guangdong Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Xin Shu
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.,Guangdong Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Jing Lai
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.,Guangdong Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Junqiang Xie
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.,Guangdong Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Chan Xie
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.,Guangdong Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Liang Peng
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.,Guangdong Key Laboratory of Liver Disease Research, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
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Li MS, Hou ZH, Yao GZ, Tan DM. The strategy and efficacy of prophylaxis against hepatitis B virus recurrence after liver transplantation for HBV-related diseases in the era of potent nucleos(t)ide analogues: A meta-analysis. J Dig Dis 2021; 22:91-101. [PMID: 33128339 DOI: 10.1111/1751-2980.12959] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2020] [Revised: 10/04/2020] [Accepted: 10/27/2020] [Indexed: 12/11/2022]
Abstract
OBJECTIVES This meta-analysis aimed to evaluate the clinical outcome of liver transplant (LT) recipients under potent nucleoside or nucleotide analogue (NA)-based regimens and investigate different prophylactic schemes. METHODS We followed PRISMA statement to conduct this study. Two reviewers independently searched relevant literature via PubMed, Embase, Ovid MEDLINE, Web of Science and Insightmeme. Studies were included if they evaluated hepatitis B virus (HBV) recurrence under potent NA-based regimens in patients who received HBV-related LT. Primary and secondary outcomes were HBV recurrence, hepatocellular carcinoma (HCC) recurrence, all-cause and HBV recurrence-related mortality. Incidences with 95% confidence intervals were calculated and assessed by fixed and random effects models. Subgroup analyses were used to examine the impact of different treatment strategies. RESULTS Altogether 25 studies (N = 2327) were included, with a pooled HBV recurrence rate of 1.01% (95% CI 0.53%-1.59%). HBV viremia or hepatitis D virus superinfection did not influence HBV recurrence significantly (P = 0.23 and 0.71, respectively). The recurrence rate under an indefinite combination of potent NA and hepatitis B immunoglobulin (HBIG) was lower than that under potent NA monotherapy (P = 0.000) and similar to that under NA plus a finite course of HBIG (P = 0.48). The pooled HCC recurrence rate was 5.34% (95% CI 0.78%-12.48%). HBV recurrence-related mortality and all-cause mortality were 0% and 6.95% (95% CI 4.30%-10.08%), respectively. CONCLUSIONS Potent NA-based regimens provide satisfactory HBV antiviral prophylaxis and improve long-term outcomes for LT recipients. A finite combination of potent NA and HBIG is an alternative to life-long dual therapy.
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Affiliation(s)
- Ming Shu Li
- Xiangya School of Public Health, Central South University, Changsha, Hunan Province, China
| | - Zhou Hua Hou
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
| | - Guo Zhu Yao
- School of Mathematics and Statistics, Changsha University of Science and Technology, Changsha, Hunan Province, China
| | - De Ming Tan
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, Hunan Province, China
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Maternal hepatitis B or C carrier status and long-term risk for offspring neurological morbidity: a population-based cohort study. J Dev Orig Health Dis 2021; 13:115-119. [PMID: 33472720 DOI: 10.1017/s2040174420001397] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Hepatitis B and hepatitis C (HBV/HCV) are important global public health concerns. We aimed to evaluate the association between maternal HBV/HCV carrier status and long-term offspring neurological hospitalisations. A population-based cohort analysis compared the risk for long-term childhood neurological hospitalisations in offspring born to HBV/HCV carrier vs. non-carrier mothers in a large tertiary medical centre between 1991 and 2014. Childhood neurological diseases, such as cerebral palsy, movement disorders or developmental disorders, were pre-defined based on ICD-9 codes as recorded in hospital medical files. Offspring with congenital malformations and multiple gestations were excluded from the study. A Kaplan-Meier survival curve was constructed to compare cumulative neurological hospitalisations over time, and a Cox proportional hazards model was used to control for confounders. During the study period (1991-2014), 243,682 newborns met the inclusion criteria, and 777 (0.3%) newborns were born to HBV/HCV mothers. The median follow-up was 10.51 years (0-18 years). The offspring from HBV/HCV mothers had higher incidence of neurological hospitalisations (4.5 vs. 3.1%, hazard ratio (HR) = 1.91, 95% CI 1.37-2.67). Similarly, the cumulative incidence of neurological hospitalisations was higher in children born to HBV/HCV carrier mothers (Kaplan-Meier survival curve log-rank test p < 0.001). The increased risk remained significant in a Cox proportional hazards model, which adjusted for gestational age, mode of delivery and pregnancy complications (adjusted HR = 1.40, 1.01-1.95, p = 0.049). We conclude that maternal HBV or HCV carrier status is an independent risk factor for the long-term neurological hospitalisation of offspring regardless of gestational age and other adverse perinatal outcomes.
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Gu J, Yu G, Zhang X, Zhang S, Cai H, Ye C, Yang Y, Li D, Tong Z, Shen H, Chen H, Ding F, Lai X, Liu J, Xu M, Wu W. Cross-sectional retrospective analysis of clinical characteristics of chronic hepatitis B patients with oral antiviral treatment in eastern China. Virol J 2021; 18:19. [PMID: 33441170 PMCID: PMC7805123 DOI: 10.1186/s12985-021-01491-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2020] [Accepted: 01/06/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND In China, more than 20 million patients with chronic hepatitis B need antiviral treatment. Side effects of antiviral treatment such as renal complications can be problematic, particularly in an aging population. METHODS The data were retrospectively extracted from the hospital medical charts of five centers in eastern China from January 1 to December 31, 2018. RESULTS A total of 8309 patients with CHB was enrolled in this study. The median age of the patients was 46 years. The prevalence of diabetes mellitus, hypertension, and hepatic cirrhosis was respectively 3.49%, 4.42%, and 23.72%. The prevalence of these comorbidities increased with age (P < 0.001). Of the patients with CHB, 5332 had complete renal function results. Among them, patients with an estimated glomerular filtration rate of < 60 mL/min/1.73m2 accounted for 4.14%, and those with proteinuria for 8.33%. According to the definition of chronic kidney disease, the proportion of patients with chronic kidney disease was 11.37%. The prevalence of chronic kidney disease increased with age (P < 0.001). In a multivariate analysis, age group [odds ratio (OR) = 2.387], diabetes mellitus (OR = 1.486), hypertension (OR = 2.557), hepatic cirrhosis (OR = 1.295), and a history of exposure to adefovir dipivoxil (OR = 1.644) were significantly associated with CKD (P < 0.05). Among patients with CKD, 17.66% (107/606) had a history of lamivudine exposure, and 34.65% (210/606) had a history of nucleotide analogue exposure CONCLUSION: The management of Chinese patients with CHB should take into consideration age, previous medication history, and renal impairment.
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Affiliation(s)
- Jueqing Gu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University School of Medicine First Affiliated Hospital, Hangzhou, 310031, CN, China
| | - Guodong Yu
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University School of Medicine First Affiliated Hospital, Hangzhou, 310031, CN, China
| | - Xiaoli Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University School of Medicine First Affiliated Hospital, Hangzhou, 310031, CN, China
| | - Shanyan Zhang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University School of Medicine First Affiliated Hospital, Hangzhou, 310031, CN, China
| | - Huan Cai
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University School of Medicine First Affiliated Hospital, Hangzhou, 310031, CN, China
| | - Chanyuan Ye
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University School of Medicine First Affiliated Hospital, Hangzhou, 310031, CN, China
| | - Yida Yang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University School of Medicine First Affiliated Hospital, Hangzhou, 310031, CN, China.
| | - Dezhou Li
- Department of Infectious Diseases, Ningbo No 2 Hospital, Ningbo, China
| | - Zhaowei Tong
- Department of Infectious Diseases, Huzhou Central Hospital, Huzhou, China
| | - Huajiang Shen
- Department of Infectious Diseases, Affiliated Hospital of Shaoxing University, Shaoxing, China
| | - Huazhong Chen
- Department of Infectious Diseases, WenZhou Medical College Affiliated Taizhou Hospital, Wenzhou, China
| | - Feng Ding
- Department of Infectious Diseases, Affiliated Hospital of Shaoxing University, Shaoxing, China
| | - Xijie Lai
- Department of Infectious Diseases, Ningbo No 2 Hospital, Ningbo, China
| | - Junyan Liu
- Department of Infectious Diseases, WenZhou Medical College Affiliated Taizhou Hospital, Wenzhou, China
| | - Meiling Xu
- Department of Infectious Diseases, Huzhou Central Hospital, Huzhou, China
| | - Weiti Wu
- Department of Infectious Diseases, WenZhou Medical College Affiliated Taizhou Hospital, Wenzhou, China
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CSOG MFM Committee Guideline: Management of Hepatitis B During Pregnancy and Prevention of Mother-to-Child Transmission of Hepatitis B Virus (2020). MATERNAL-FETAL MEDICINE 2021. [DOI: 10.1097/fm9.0000000000000087] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
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Cui X, Wang J, Li Y, Couse ZG, Risoleo TF, Moayeri M, Leppla SH, Malide D, Yu ZX, Eichacker PQ. Bacillus anthracis edema toxin inhibits hypoxic pulmonary vasoconstriction via edema factor and cAMP-mediated mechanisms in isolated perfused rat lungs. Am J Physiol Heart Circ Physiol 2021; 320:H36-H51. [PMID: 33064559 PMCID: PMC7847081 DOI: 10.1152/ajpheart.00362.2020] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Revised: 10/15/2020] [Accepted: 10/15/2020] [Indexed: 12/31/2022]
Abstract
Bacillus anthracis edema toxin (ET) inhibited lethal toxin-stimulated pulmonary artery pressure (Ppa) and increased lung cAMP levels in our previous study. We therefore examined whether ET inhibits hypoxic pulmonary vasoconstriction (HPV). Following baseline hypoxic measures in isolated perfused lungs from healthy rats, compared with diluent, ET perfusion reduced maximal Ppa increases (mean ± SE percentage of maximal Ppa increase with baseline hypoxia) during 6-min hypoxic periods (FIO2 = 0%) at 120 min (16 ± 6% vs. 51 ± 6%, P = 0.004) and 180 min (11.4% vs. 55 ± 6%, P = 0.01). Protective antigen-mAb (PA-mAb) and adefovir inhibit host cell edema factor uptake and cAMP production, respectively. In lungs perfused with ET following baseline measures, compared with placebo, PA-mAb treatment increased Ppa during hypoxia at 120 and 180 min (56 ± 6% vs. 10 ± 4% and 72 ± 12% vs. 12 ± 3%, respectively, P ≤ 0.01) as did adefovir (84 ± 10% vs. 16.8% and 123 ± 21% vs. 26 ± 11%, respectively, P ≤ 0.01). Compared with diluent, lung perfusion with ET for 180 min reduced the slope of the relationships between Ppa and increasing concentrations of endothelin-1 (ET-1) (21.12 ± 2.96 vs. 3.00 ± 0.76 × 108 cmH2O/M, P < 0.0001) and U46619, a thromboxane A2 analogue (7.15 ± 1.01 vs. 3.74 ± 0.31 × 107 cmH2O/M, P = 0.05) added to perfusate. In lungs isolated from rats after 15 h of in vivo infusions with either diluent, ET alone, or ET with PA-mAb, compared with diluent, the maximal Ppa during hypoxia and the slope of the relationship between change in Ppa and ET-1 concentration added to the perfusate were reduced in lungs from animals challenged with ET alone (P ≤ 0.004) but not with ET and PA-mAb together (P ≥ 0.73). Inhibition of HPV by ET could aggravate hypoxia during anthrax pulmonary infection.NEW & NOTEWORTHY The most important findings here are edema toxin's potent adenyl cyclase activity can interfere with hypoxic pulmonary vasoconstriction, an action that could worsen hypoxemia during invasive anthrax infection with lung involvement. These findings, coupled with other studies showing that lethal toxin can disrupt pulmonary vascular integrity, indicate that both toxins can contribute to pulmonary pathophysiology during infection. In combination, these investigations provide a further basis for the use of antitoxin therapies in patients with worsening invasive anthrax disease.
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Affiliation(s)
- Xizhong Cui
- Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland
| | - Jeffrey Wang
- Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland
| | - Yan Li
- Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland
| | - Zoe G Couse
- Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland
| | - Thomas F Risoleo
- Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland
| | - Mahtab Moayeri
- Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland
| | - Stephen H Leppla
- Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland
| | - Daniela Malide
- National Heart, Lung, and Blood Institute, Bethesda, Maryland
| | - Zu-Xi Yu
- National Heart, Lung, and Blood Institute, Bethesda, Maryland
| | - Peter Q Eichacker
- Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, Maryland
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Inoue J, Akahane T, Kobayashi T, Obara N, Umetsu T, Kakazu E, Ninomiya M, Iwata T, Sano A, Tsuruoka M, Sato K, Masamune A. Switching to tenofovir disoproxil fumarate in entecavir-treated chronic hepatitis B patients: A pilot randomized controlled study. Biomed Rep 2020; 14:20. [PMID: 33335726 PMCID: PMC7739848 DOI: 10.3892/br.2020.1396] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Accepted: 10/16/2020] [Indexed: 12/27/2022] Open
Abstract
Although hepatitis B surface antigen (HBsAg) removal is considered the goal of chronic hepatitis B treatment, it can rarely be achieved with nucleos(t)ide analogues (NAs). It has been reported that tenofovir disoproxil fumarate (TDF) is superior in reducing HBsAg compared with entecavir (ETV) in treatment-naïve patients; however, the effect of TDF in patients who have received NAs is still unclear. The aim of the present study was to evaluate the efficacy of switching from ETV to TDF in patients who were already receiving ETV. A pilot randomized controlled study for 2 years in patients who had been treated with ETV for >1 year and did not exhibit drug resistance was performed (Clinical trial registration: UMIN000021948, UMIN-CTR, May 1, 2016). A total of 20 patients were enrolled and 19 patients were randomized into 2 groups, a TDF-switching group (n=12) or an ETV-continuing group (n=7). The mean change in HBsAg levels after 2 years was greater in the TDF group compared with the ETV group, but the difference was not significant (-0.25 vs. -0.06 log IU/ml). In the TDF group, hepatitis B e antigen (HBeAg)-positive patients at baseline showed significantly greater changes in HBsAg (-0.63 vs. -0.03 log IU/ml; P=0.030). In contrast, no difference between HBeAg-positive and HBeAg-negative patients was observed in the ETV group. No significant differences of estimated glomerular filtration rate and inorganic phosphorus changes were observed among the TDF and ETV groups. In conclusion, a significant HBsAg decrease was not achieved after switching from ETV to TDF in the overall analysis, but HBeAg-positive patients showed a larger HBsAg decrease after switching treatment.
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Affiliation(s)
- Jun Inoue
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8574, Japan
| | - Takehiro Akahane
- Department of Gastroenterology, Japanese Red Cross Ishinomaki Hospital, Ishinomaki, Miyagi 986-8522, Japan
| | - Tomoo Kobayashi
- Department of Hepatology, Tohoku Rosai Hospital, Sendai, Miyagi 981-8563, Japan
| | - Noriyuki Obara
- Department of Gastroenterology, Japan Community Health care Organization Sendai Hospital, Sendai, Miyagi 981-8501, Japan
| | - Teruyuki Umetsu
- Department of Internal Medicine, Kesen-numa City Hospital, Kesennuma, Miyagi 988-0181, Japan
| | - Eiji Kakazu
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8574, Japan
| | - Masashi Ninomiya
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8574, Japan
| | - Tomoaki Iwata
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8574, Japan
| | - Akitoshi Sano
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8574, Japan
| | - Mio Tsuruoka
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8574, Japan
| | - Kosuke Sato
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8574, Japan
| | - Atsushi Masamune
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980-8574, Japan
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44
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Hui VWK, Chan SL, Wong VWS, Liang LY, Yip TCF, Lai JCT, Yuen BWY, Luk HWS, Tse YK, Lee HW, Chan HLY, Wong GLH. Increasing antiviral treatment uptake improves survival in patients with HBV-related HCC. JHEP Rep 2020; 2:100152. [PMID: 33024950 PMCID: PMC7530304 DOI: 10.1016/j.jhepr.2020.100152] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/08/2020] [Revised: 07/13/2020] [Accepted: 07/17/2020] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND & AIMS Antiviral treatment is known to improve survival in patients with chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC). Yet, the treatment uptake in CHB patients remains low. We aimed to report the secular trend in antiviral treatment uptake from 2007-2017, and to compare the effect of different nucleos(t)ide analogue (NA) initiation times (before vs. after HCC diagnosis) on survival. METHODS A 3-month landmark analysis was used to compare overall survival in patients not receiving NA treatment (i.e. no NA), patients receiving NAs after their first HCC treatment (i.e. post-HCC NA), and patients receiving NAs ≤3 months before their first HCC treatment (i.e. pre-HCC NA). A propensity score-weighted Cox proportional hazards model was used to balance clinical characteristics between the 3 groups and to estimate hazard ratios (HRs). RESULTS The uptake of antiviral treatment in HCC patients increased from 47.3% in 2007 to 98.3% in 2017. The pre-HCC NA group contributed mostly to the uptake rate, which increased from 72.7% to 96.0% in the past decade. In addition, 3,843 CHB patients (407 no NA; 2,932 pre-HCC NA; 504 post-HCC NA) with HCC, receiving at least 1 type of HCC treatment, were included in the analysis. Lack of NA treatment at the time of HCC diagnosis increased the risk of death (weighted HR 3.05; 95% CI 2.70-3.44; p <0.001). The impact of the timing of NA treatment was insignificant (weighted HR 0.90; 95% CI 0.78-1.04; p = 0.161). CONCLUSIONS The uptake of antiviral treatment in HCC patients increased over the past decade. NA treatment, regardless of whether it was initiated before or after HCC diagnosis, improved survival. It is never too late to initiate NA treatment, even after HCC diagnosis. LAY SUMMARY More and more patients who have hepatitis B-related liver cancer received antiviral treatment over the past decade. The timing of starting antiviral treatment, regardless of whether it was before or after liver cancer happens, does not really matter in terms of survival benefits.
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Key Words
- AFP, alpha-fetoprotein
- ALT, alanine aminotransferase
- ASMD, absolute standardised mean difference
- CDARS, Clinical Data Analysis and Reporting System
- CHB, chronic hepatitis B
- Entecavir
- GGT, gamma-glutamyl transpeptidase
- HCC, hepatocellular carcinoma
- HR, hazard ratio
- Hazard ratio
- ICD-9-CM, International Classification of Diseases, Ninth Revision, Clinical Modification
- IPTW, inverse probability of treatment weighting
- IQR, inter-quartile range
- KS, Kolmogorov-Smirnov
- Lamivudine
- Local ablative therapy
- MICE, multivariate imputation by chained equations
- NA, nucleos(t)ide analogue
- PS, propensity score
- Propensity scores
- Surgical resection
- TACE, transarterial chemoembolisation
- TDF, tenofovir disoproxil fumarate
- Transarterial chemoembolisation
- aHR, adjusted hazard ratio
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Affiliation(s)
- Vicki Wing-Ki Hui
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
- Medical Data Analytic Centre, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Stephen Lam Chan
- Department of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
- Medical Data Analytic Centre, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Lilian Yan Liang
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Terry Cheuk-Fung Yip
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
- Medical Data Analytic Centre, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Jimmy Che-To Lai
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Becky Wing-Yan Yuen
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Hester Wing-Sum Luk
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Yee-Kit Tse
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
- Medical Data Analytic Centre, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Hye-Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Henry Lik-Yuen Chan
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
- Medical Data Analytic Centre, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Grace Lai-Hung Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong SAR, China
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China
- Medical Data Analytic Centre, The Chinese University of Hong Kong, Hong Kong SAR, China
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45
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Yip TCF, Lai JCT, Wong GLH. Secondary prevention for hepatocellular carcinoma in patients with chronic hepatitis B: are all the nucleos(t)ide analogues the same? J Gastroenterol 2020; 55:1023-1036. [PMID: 32974760 PMCID: PMC7567686 DOI: 10.1007/s00535-020-01726-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Accepted: 08/24/2020] [Indexed: 02/04/2023]
Abstract
Reducing the incidence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) is the key ultimate goal set in essentially all treatment guidelines. There has been solid evidence supporting the relationship between serum hepatitis B virus (HBV) DNA level and risk of HCC. Antiviral treatment with oral nucleos(t)ide analogues (NAs) leads to sustained viral suppression and hence is often adopted as the secondary prevention for HCC in CHB patients. The first-generation NA, lamivudine, reduced the risk of HCC at 3 years compared to placebo; yet, its high emergence of antiviral resistance has made it no longer recommended in the international guidelines. Recent heated debate is about the two current first-line NAs-entecavir and tenofovir disoproxil fumarate (TDF)-Are they just as good to reduce HCC risk in CHB patients? A handful of cohort studies show two different kinds of observations-TDF is better than entecavir in lowering HCC risk, or these two NAs have led to similarly low risk of HCC. Tenofovir alafenamide (TAF), a modified version of TDF higher rate of ALT normalization, would be another potent nucleotide analogue is the treatment of choice for secondary prevention for HCC.
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Affiliation(s)
- Terry Cheuk-Fung Yip
- Department of Medicine and Therapeutics, 9/F Prince of Wales Hospital, 30-32 NganShing Street, Shatin, Hong Kong SAR, China
- Medical Data Analytic Centre (MDAC), Hong Kong SAR, China
- Institute of Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Jimmy Che-To Lai
- Department of Medicine and Therapeutics, 9/F Prince of Wales Hospital, 30-32 NganShing Street, Shatin, Hong Kong SAR, China
- Medical Data Analytic Centre (MDAC), Hong Kong SAR, China
- Institute of Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China
| | - Grace Lai-Hung Wong
- Department of Medicine and Therapeutics, 9/F Prince of Wales Hospital, 30-32 NganShing Street, Shatin, Hong Kong SAR, China.
- Medical Data Analytic Centre (MDAC), Hong Kong SAR, China.
- Institute of Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
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46
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Yip TCF, Wong GLH. HCC risk reduction with oral nucleos(t)ide analogues in patients with chronic hepatitis B: Not perfect, not good enough. J Gastroenterol Hepatol 2020; 35:1661-1662. [PMID: 33043509 DOI: 10.1111/jgh.15249] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Accepted: 09/07/2020] [Indexed: 12/09/2022]
Affiliation(s)
- Terry Cheuk-Fung Yip
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
- Medical Data Analytic Centre (MDAC), The Chinese University of Hong Kong, Hong Kong
- Institute of Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong
| | - Grace Lai-Hung Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong
- Medical Data Analytic Centre (MDAC), The Chinese University of Hong Kong, Hong Kong
- Institute of Digestive Disease, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong
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47
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Lin CL, Chien RN, Chu YD, Liang KH, Huang YH, Ke PY, Lin KH, Lin YH, Yeh CT. Hepatitis B virus X gene mutants emerge during antiviral therapy and increase cccDNA levels to compensate for replication suppression. Hepatol Int 2020; 14:973-984. [PMID: 32770306 DOI: 10.1007/s12072-020-10079-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Accepted: 07/22/2020] [Indexed: 12/20/2022]
Abstract
BACKGROUND Hepatitis B virus (HBV) X gene (HBx) mutants can develop during the natural course of chronic HBV infection. However, little is known about whether the emergence of HBx mutants during long-term antiviral therapy is an adaptation of HBV to antiviral stress. This study was to identify HBx mutants that emerged in patients experiencing Lamivudine resistance or suboptimal treatment. METHODS Forty-six Lamivudine-resistant patients and 46 patients with suboptimal treatment responses to Entecavir were enrolled in this study. HBx mutants were identified by sequence analysis and their roles in the HBV replication cycle were characterized. RESULTS We show that deletion/truncation/insertion mutations were only detected in the Lamivudine resistance group, while synonymous mutations were found in both groups. Follow-up analyses revealed that five patients in the Lamivudine group developed hepatocellular carcinoma, while patients in the Entecavir group did not. These mutants were characterized by a significant decrease in transactivation of the pre-S1 promoter, and varying effects on transactivation of the X promoter. Co-transfection of HBx-mutant plasmid and HBV replication-competent clone into HepG2 cells resulted in increased nuclear-to-cytoplamic HBV core antigen, HBV-DNA ratios, and nuclear covalently closed circular DNA (cccDNA). Antiviral drug sensitivity assays revealed that these mutants exhibited a compensatory effect to counteract antiviral drug suppression, resulting in elevated secretory HBV-DNA levels. CONCLUSIONS Our study demonstrates that HBx mutants can emerge during Lamivudine or Entecavir therapy. These mutants exhibit altered transactivation of the HBV pre-S1 and X promoters, leading to increased cccDNA levels to compensate for replication suppression.
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Affiliation(s)
- Chih-Lang Lin
- Liver Research Unit, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan.,Liver Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.,College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Community Medicine Research Center, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Rong-Nan Chien
- Liver Research Unit, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan.,Liver Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.,College of Medicine, Chang Gung University, Taoyuan, Taiwan.,Community Medicine Research Center, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Yu-De Chu
- Liver Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
| | - Kung-Hao Liang
- Medical Research Department, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Ya-Hui Huang
- Liver Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.,College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Po-Yuan Ke
- Department of Biochemistry, Chang Gung University, Taoyuan, Taiwan
| | - Kwang-Huei Lin
- Department of Biochemistry, Chang Gung University, Taoyuan, Taiwan
| | - Yang-Hsiang Lin
- Liver Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan. .,College of Medicine, Chang Gung University, Taoyuan, Taiwan.
| | - Chau-Ting Yeh
- Liver Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan. .,College of Medicine, Chang Gung University, Taoyuan, Taiwan. .,Medical Research Department, Taipei Veterans General Hospital, Taipei, Taiwan. .,Department of Biochemistry, Chang Gung University, Taoyuan, Taiwan.
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48
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Lee J, Park JY, Yang SJ, Lee JY, Kim DG, Joo DJ, Kim MS, Kim SI, Lee JG. Renal safety of tenofovir disoproxil fumarate and entecavir with hepatitis B immunoglobulin in liver transplant patients. J Viral Hepat 2020; 27:818-825. [PMID: 32302037 DOI: 10.1111/jvh.13291] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Revised: 02/25/2020] [Accepted: 02/26/2020] [Indexed: 01/05/2023]
Abstract
Potent nucleos(t)ide analogues and hepatitis B immunoglobulin combinations are recommended after liver transplantation to prevent the recurrence of hepatitis B virus (HBV). Despite its proven efficacy, the renal safety of tenofovir disoproxil fumarate (TDF) has not been well established in liver transplant recipients. We aimed to assess the impacts of TDF and entecavir (ETV) on tubular and glomerular functions. We analysed 206 liver transplant patients treated with TDF (n = 102) or ETV (n = 104) plus hepatitis B immunoglobulin. Serum creatinine, phosphate and uric acid levels were measured. Proximal tubular dysfunction was defined as the presence of hypophosphatemia (<2 mg/dL) and hypouricemia (<2 mg/dL). Glomerular dysfunction was defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2 accompanied by a ≥25% eGFR decline from baseline. During a median follow-up of 42.5 months, 48 patients developed proximal tubular dysfunction (30.4% and 16.3% in the TDF and ETV groups; P = .017). Serum levels of phosphate and uric acid were significantly lower in the TDF group post-LT. TDF (OR, 2.34; 95% CI, 1.16-4.69; P = .017) and low body mass index (OR, 2.11; 95% CI, 1.06-4.21; P = .034) were independent risk factors for proximal tubular dysfunction. The prevalence of glomerular dysfunction was not significantly different between the two groups (TDF 51.0% and ETV 54.8%; P = .582). TDF significantly increased the risk of proximal tubular dysfunction. Although the effect of TDF on glomerular function was comparable to that of ETV, glomerular dysfunction was common after liver transplant.
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Affiliation(s)
- Juhan Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Seok Jeong Yang
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Jee Youn Lee
- Department of Surgery, Gangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Deok Gie Kim
- Department of Surgery, Wonju College of Medicine, Wonju Severance Christian Hospital, Yonsei University, Wonju, Korea
| | - Dong Jin Joo
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Myoung Soo Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Soon Il Kim
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
| | - Jae Geun Lee
- Department of Surgery, Yonsei University College of Medicine, Seoul, Korea
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49
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Wong GLH, Wong VWS, Thompson A, Jia J, Hou J, Lesmana CRA, Susilo A, Tanaka Y, Chan WK, Gane E, Ong-Go AK, Lim SG, Ahn SH, Yu ML, Piratvisuth T, Chan HLY. Management of patients with liver derangement during the COVID-19 pandemic: an Asia-Pacific position statement. Lancet Gastroenterol Hepatol 2020; 5:776-787. [PMID: 32585136 PMCID: PMC7308747 DOI: 10.1016/s2468-1253(20)30190-4] [Citation(s) in RCA: 62] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2020] [Revised: 05/25/2020] [Accepted: 05/26/2020] [Indexed: 02/06/2023]
Abstract
The COVID-19 pandemic has spread rapidly worldwide. It is common to encounter patients with COVID-19 with abnormal liver function, either in the form of hepatitis, cholestasis, or both. The clinical implications of liver derangement might be variable in different clinical scenarios. With growing evidence of its clinical significance, it would be clinically helpful to provide practice recommendations for various common clinical scenarios of liver derangement during the COVID-19 pandemic. The Asia-Pacific Working Group for Liver Derangement during the COVID-19 Pandemic was formed to systematically review the literature with special focus on the clinical management of patients who have been or who are at risk of developing liver derangement during this pandemic. Clinical scenarios covering the use of pharmacological treatment for COVID-19 in the case of liver derangement, and assessment and management of patients with chronic hepatitis B or hepatitis C, non-alcoholic fatty liver disease, liver cirrhosis, and liver transplantation during the pandemic are discussed.
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Affiliation(s)
- Grace Lai-Hung Wong
- Department of Medicine and Therapeutics, and Medical Data Analytic Centre, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, and Medical Data Analytic Centre, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China
| | - Alex Thompson
- Department of Gastroenterology, St Vincent's Hospital Melbourne, University of Melbourne, Melbourne, VIC, Australia
| | - Jidong Jia
- Liver Research Centre, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Jinlin Hou
- Hepatology Unit and Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Cosmas Rinaldi Adithya Lesmana
- Department of Gastroenterology, Dr Cipto Mangunkusumo National General Hospital, Universitas Indonesia, Jakarta, Indonesia
| | - Adityo Susilo
- Division of Tropical Medicine and Infection, Department of Internal Medicine, Dr Cipto Mangunkusumo National General Hospital, Universitas Indonesia, Jakarta, Indonesia
| | - Yasuhito Tanaka
- Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Wah-Kheong Chan
- Department of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Ed Gane
- New Zealand Liver Transplant Unit, Auckland City Hospital, University of Auckland, Auckland, New Zealand
| | - Arlinking K Ong-Go
- Department of Gastroenterology, Metropolitan Medical Center, Manila, Philippines
| | - Seng-Gee Lim
- Department of Medicine, National University of Singapore, Singapore
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Taiwan
| | - Teerha Piratvisuth
- Department of Gastroenterology, NKC Institute of Gastroenterology and Hepatology, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
| | - Henry Lik-Yuen Chan
- Department of Medicine and Therapeutics, and Medical Data Analytic Centre, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.
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50
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Lim TS, Lee JS, Kim BK, Lee HW, Jeon MY, Kim SU, Park JY, Kim DY, Han KH, Ahn SH. An observational study on long-term renal outcome in patients with chronic hepatitis B treated with tenofovir disoproxil fumarate. J Viral Hepat 2020; 27:316-322. [PMID: 31639240 DOI: 10.1111/jvh.13222] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Revised: 09/02/2019] [Accepted: 10/01/2019] [Indexed: 12/13/2022]
Abstract
In patients with chronic hepatitis B (CHB), long-term effects of tenofovir disoproxil fumarate (TDF) on renal function have been controversial. This study aimed to analyse the real-world long-term effects of TDF on renal function in Korean patients with CHB. We analysed a cohort of 640 treatment-naïve patients with CHB who were treated with TDF between May 2012 and December 2015 at Severance Hospital, Seoul, Republic of Korea. The mean age was 48.3 years old, and 59.5% were male. The proportions of hypertension and diabetes mellitus (DM) were 11.6% and 14.2%, respectively, and that of liver cirrhosis was 20.8%. During the 5-year follow-up, using a linear mixed model, serum creatinine increased from 0.77 ± 0.01 mg/dL to 0.85 ± 0.02 mg/dL (P < .001), and eGFR decreased from 102.6 ± 0.6 mL/min/1.73 m2 to 93.4 ± 1.4 mL/min/1.73 m2 (P < .001). In subgroup analysis, eGFR was statistically more decreased in patients with age > 60 than ≦60 years old (P = .027), and in patients with diuretic use than without diuretic use (P = .008). In multivariate analysis, the independent risk factors for eGFR decrease > 20% were baseline eGFR < 60mL/min/1.73 m2 (P = .034) and the use of diuretics (P < .001). CHB patients on TDF experienced greater reduction in renal function with age > 60 and with diuretic use compared to those without these characteristics. Baseline eGFR < 60 mL/min/1.73 m2 and use of diuretics were independent risk factors of eGFR decline of more than 20% on TDF therapy.
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Affiliation(s)
- Tae Seop Lim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
- Division of Gastroenterology, Department of Internal Medicine, Mediplex Sejong Hospital, Incheon, Korea
| | - Jae Seung Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Mi Young Jeon
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Kwang-Hyub Han
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
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