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Han K, Youssef AS, Magee M, Hood S, Tracey H, Kwoh J, Theodore D, Paff M, Nader A. Lack of Pharmacokinetic Drug-Drug Interactions Between Bepirovirsen and Nucleos(t)ide Analogs. Clin Pharmacol Drug Dev 2025; 14:281-291. [PMID: 39950613 PMCID: PMC11975176 DOI: 10.1002/cpdd.1518] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Accepted: 01/22/2025] [Indexed: 04/08/2025]
Abstract
Bepirovirsen is an antisense oligonucleotide currently in Phase 3 development to treat chronic hepatitis B virus (HBV) infection. Given the importance of coadministration of bepirovirsen and standard-of-care nucleos(t)ide analogs (NAs), we evaluated drug-drug interactions (DDIs) between bepirovirsen, entecavir (ETV), and tenofovir (TFV) using in vitro and clinical data obtained through innovative study design and sampling strategy. Static models employing in vitro data indicated that bepirovirsen is not a direct inhibitor or inducer of most drug-metabolizing enzymes or an inhibitor or substrate of drug transporters and poses no clinical DDI risk against NAs. Bepirovirsen plasma pharmacokinetic parameters and concentration-time profiles in patients with chronic HBV in the CS3 study (NCT02981602) were similar with or without ETV or TFV coadministration, indicating no effect of NA coadministration on bepirovirsen pharmacokinetics. In patients with chronic HBV receiving both bepirovirsen and ETV or TFV in the B-Clear study (NCT04449029), NA plasma concentrations and pharmacokinetic parameters were similar to those published without bepirovirsen coadministration, suggesting no effect of bepirovirsen coadministration on NA pharmacokinetics. This analysis demonstrated no DDI potential between bepirovirsen and NAs, suggesting that dedicated clinical DDI studies are not required. Bepirovirsen is currently being evaluated in Phase 3 studies in combination with NA.
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Affiliation(s)
- Kelong Han
- GSK, Clinical Pharmacology Modeling and SimulationCollegevillePennsylvaniaUSA
| | - Amir S. Youssef
- GSK, Clinical Pharmacology Modeling and SimulationCollegevillePennsylvaniaUSA
| | - Mindy Magee
- GSK, Clinical Pharmacology Modeling and SimulationCollegevillePennsylvaniaUSA
| | - Steve Hood
- GSK, DMPK ‐ Disposition & BiotransformationStevenageHertfordshireUK
| | - Helen Tracey
- GSK, PBPK Modelling, DMPK, Preclinical Sciences, Research Technologies, R&DStevenageHertfordshireUK
| | - Jesse Kwoh
- Ionis Pharmaceuticals Inc.CarlsbadCaliforniaUSA
| | | | - Melanie Paff
- GSK, Development MedicineCollegevillePennsylvaniaUSA
| | - Ahmed Nader
- GSK, Clinical Pharmacology Modeling and SimulationCollegevillePennsylvaniaUSA
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Chen D, Yu R, Yin S, Qiu W, Fang J, Peng XE. Hepatitis B virus infection as a risk factor for chronic kidney disease: a systematic review and meta-analysis. BMC Infect Dis 2024; 24:620. [PMID: 38909191 PMCID: PMC11193185 DOI: 10.1186/s12879-024-09546-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Accepted: 06/20/2024] [Indexed: 06/24/2024] Open
Abstract
BACKGROUND Currently, several studies have observed that chronic hepatitis B virus infection is associated with the pathogenesis of kidney disease. However, the extent of the correlation between hepatitis B virus infection and the chronic kidney disease risk remains controversial. METHODS In the present study, we searched all eligible literature in seven databases in English and Chinese. The random effects model was used to conduct a meta-analysis. Quality of included studies was assessed using the Newcastle-Ottawa Quality Scale. RESULTS In this analysis, a total of 31 studies reporting the association between hepatitis B virus infection and chronic kidney disease risk were included. The results showed a significant positive association between hepatitis B virus infection and the risk of chronic kidney disease (pooled OR, 1.20; 95% CI, 1.12-1.29), which means that hepatitis B virus increases the risk of developing chronic kidney disease. CONCLUSION This study found that hepatitis B virus infection was associated with a significantly increased risk of chronic kidney disease. However, the current study still cannot directly determine this causal relationship. Thus, more comprehensive prospective longitudinal studies are needed in the future to provide further exploration and explanation of the association between hepatitis B virus and the risk of developing chronic kidney disease.
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Affiliation(s)
- Danjing Chen
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, 350122, People's Republic of China
| | - Rong Yu
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, 350122, People's Republic of China
| | - Shuo Yin
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, 350122, People's Republic of China
| | - Wenxin Qiu
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, 350122, People's Republic of China
| | - Jiangwang Fang
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, 350122, People's Republic of China
| | - Xian-E Peng
- Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, 350122, People's Republic of China.
- Department of Epidemiology and Health Statistics, Key Laboratory of Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Ministry of Education, Fujian Medical University, Xuefu North Road 1st, Shangjie Town, Minhou Country, Fuzhou, Fujian, 350108, China.
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Sharma P, Sawtell R, Wang Q, Sise ME. Management of Hepatitis C Virus and Hepatitis B Virus Infection in the Setting of Kidney Disease. ADVANCES IN KIDNEY DISEASE AND HEALTH 2023; 30:343-355. [PMID: 37657881 PMCID: PMC10479952 DOI: 10.1053/j.akdh.2023.04.003] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 04/04/2023] [Accepted: 04/19/2023] [Indexed: 09/03/2023]
Abstract
Treatment of chronic hepatitis C virus (HCV) and hepatitis B virus (HBV) infection poses unique challenges in patients with kidney disease. Direct-acting antivirals have been a major breakthrough in eradicating HCV infection, and several pangenotypic regimens are available for patients with chronic kidney disease or end-stage kidney disease requiring dialysis with high cure rates and no need for dose adjustment. Direct-acting antiviral therapy alone can treat HCV-associated cryoglobulinemic glomerulonephritis; concurrent antiviral and immunosuppressive therapy is needed for cases of severe, organ-threatening manifestations of cryoglobulinemia. Immunosuppression may be needed for HBV-associated kidney disease (polyarteritis nodosa or membranous nephropathy) when there is evidence of severe immune-mediated injury while weighing the risk of potential viral activation. Most HBV antiviral agents need to be dose-adjusted in patients with chronic kidney disease or end-stage kidney disease requiring dialysis, and drug-drug interactions need to be carefully evaluated in patients with kidney transplants. Considerations for accepting HCV- and HBV-infected donors for kidney transplantation are discussed.
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Affiliation(s)
- Purva Sharma
- Department of Medicine, Division of Nephrology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell; Glomerular Disease Center at Northwell Health, Hempstead, NY
| | - Rani Sawtell
- Department of Medicine, Division of Nephrology, Massachusetts General Hospital, Boston, MA
| | - Qiyu Wang
- Department of Medicine, Division of Nephrology, Massachusetts General Hospital, Boston, MA
| | - Meghan E Sise
- Department of Medicine, Division of Nephrology, Massachusetts General Hospital, Boston, MA.
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Fischer MG, Newman W, Hammer K, Rohrich M, Lo TS. Comparison of Renal Function Between Tenofovir Disoproxil Fumarate and Other Nucleos(t)ide Reverse Transcriptase Inhibitors in Patients With Hepatitis B Virus Infection. Fed Pract 2021; 38:363-367. [PMID: 34733088 DOI: 10.12788/fp.0169] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Background Nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs) have become a standard treatment for both HIV and hepatitis B virus (HBV) infections. Tenofovir disoproxil fumarate (TDF) has been associated with kidney injury and possible long-term damage in patients with HIV. Few studies have examined whether this holds true for patients treated for HBV. Methods Data were gathered from the Veterans Health Administration Corporate Data Warehouse between July 1, 2005 and July 31, 2015. Patients aged ≥ 18 years with HBV infection and prescribed a NRTI for > 1 month were included in the study and followed for 36 months. Patients with HIV infection were excluded, and patients treated with combination TDF/emtricitabine were analyzed separately from patients receiving only TDF. A linear mixed model was used to examine the effects of time and specific agent on renal function, which was measured with estimated glomerular filtration rate (eGFR) at various time intervals. Results There were 413 incidences of NRTI use in 308 subjects during the 10 years of the study with 39 cases of TDF use. There was a significant fixed effect of time, with eGFR reduction of 4.6 mL/min (P < .001) over the course of the study for the full cohort, but the effects of each medication were not significant. Conclusions This multicenter, retrospective study did not demonstrate an association between TDF use and a greater degree of kidney injury compared with other NRTIs in patients with HBV, but further studies are warranted.
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Affiliation(s)
- Matthew G Fischer
- At the time of the study, was Chief of Endocrinology and was a Pharmacy Resident; is Associate Chief of Staff/Research and Development; is Chief of Pharmacy; is Chief of Infectious Disease; all at Fargo Veterans Affairs Health Care System in North Dakota. Kimberly Hammer is Associate Professor, Internal Medicine Department, University of North Dakota School of Medicine and Health Sciences. Matthew Fischer is a Clinical Pharmacy Practitioner at Veterans Affairs Northern California Health Care System in Mather
| | - William Newman
- At the time of the study, was Chief of Endocrinology and was a Pharmacy Resident; is Associate Chief of Staff/Research and Development; is Chief of Pharmacy; is Chief of Infectious Disease; all at Fargo Veterans Affairs Health Care System in North Dakota. Kimberly Hammer is Associate Professor, Internal Medicine Department, University of North Dakota School of Medicine and Health Sciences. Matthew Fischer is a Clinical Pharmacy Practitioner at Veterans Affairs Northern California Health Care System in Mather
| | - Kimberly Hammer
- At the time of the study, was Chief of Endocrinology and was a Pharmacy Resident; is Associate Chief of Staff/Research and Development; is Chief of Pharmacy; is Chief of Infectious Disease; all at Fargo Veterans Affairs Health Care System in North Dakota. Kimberly Hammer is Associate Professor, Internal Medicine Department, University of North Dakota School of Medicine and Health Sciences. Matthew Fischer is a Clinical Pharmacy Practitioner at Veterans Affairs Northern California Health Care System in Mather
| | - Melissa Rohrich
- At the time of the study, was Chief of Endocrinology and was a Pharmacy Resident; is Associate Chief of Staff/Research and Development; is Chief of Pharmacy; is Chief of Infectious Disease; all at Fargo Veterans Affairs Health Care System in North Dakota. Kimberly Hammer is Associate Professor, Internal Medicine Department, University of North Dakota School of Medicine and Health Sciences. Matthew Fischer is a Clinical Pharmacy Practitioner at Veterans Affairs Northern California Health Care System in Mather
| | - Tze Shien Lo
- At the time of the study, was Chief of Endocrinology and was a Pharmacy Resident; is Associate Chief of Staff/Research and Development; is Chief of Pharmacy; is Chief of Infectious Disease; all at Fargo Veterans Affairs Health Care System in North Dakota. Kimberly Hammer is Associate Professor, Internal Medicine Department, University of North Dakota School of Medicine and Health Sciences. Matthew Fischer is a Clinical Pharmacy Practitioner at Veterans Affairs Northern California Health Care System in Mather
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Kulkarni AV, Duvvuru NR. Management of hepatitis B and C in special population. World J Gastroenterol 2021; 27:6861-6873. [PMID: 34790011 PMCID: PMC8567468 DOI: 10.3748/wjg.v27.i40.6861] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 05/30/2021] [Accepted: 09/14/2021] [Indexed: 02/06/2023] Open
Abstract
Chronic viral hepatitis is one of the leading causes of cirrhosis worldwide. Chronic hepatitis B is more common in the Asia-Pacific region due to the larger population and lower screening availability. Hepatitis C predominates in the west due to injection drug abuse. The discovery of (oral) direct-acting antiviral agents (DAAs) has changed the landscape of chronic hepatitis C (CHC) management. Nucleos(t)ide analogs (NUCs) have also changed the approach to the treatment of chronic hepatitis B (CHB). Oral NUCs and DAAs have excellent efficacy and patient acceptance as well as a lower risk of resistance. However, certain populations have no robust data and safety and efficacy of such oral drugs is still evolving. In this review, we provide an overview of the management of CHB and CHC in special populations, such as those with chronic kidney disease, pregnant women, healthcare workers, and those undergoing chemo- or immunosuppressive therapy.
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Affiliation(s)
- Anand V Kulkarni
- Department of Hepatology, Asian Institute of Gastroenterology, Hyderabad 500032, Telangana, India
| | - Nageshwar Reddy Duvvuru
- Department of Gastroenterology, Asian Institute of Gastroenterology, Hyderabad 500032, Telanagana, India
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Arora A, Kumar A, Prasad N, Duseja A, Acharya SK, Agarwal SK, Aggarwal R, Anand AC, Bhalla AK, Choudhary NS, Chawla YK, Dhiman RK, Dixit VK, Gopalakrishnan N, Gupta A, Hegde UN, Jasuja S, Jha V, Kher V, Kumar A, Madan K, Maiwall R, Mathur RP, Nayak SL, Pandey G, Pandey R, Puri P, Rai RR, Raju SB, Rana DS, Rao PN, Rathi M, Saraswat VA, Saxena S, Shalimar, Sharma P, Singh SP, Singal AK, Soin AS, Taneja S, Varughese S. INASL-ISN Joint Position Statements on Management of Patients with Simultaneous Liver and Kidney Disease. J Clin Exp Hepatol 2021; 11:354-386. [PMID: 33994718 PMCID: PMC8103529 DOI: 10.1016/j.jceh.2020.09.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Accepted: 09/27/2020] [Indexed: 01/10/2023] Open
Abstract
Renal dysfunction is very common among patients with chronic liver disease, and concomitant liver disease can occur among patients with chronic kidney disease. The spectrum of clinical presentation and underlying etiology is wide when concomitant kidney and liver disease occur in the same patient. Management of these patients with dual onslaught is challenging and requires a team approach of hepatologists and nephrologists. No recent guidelines exist on algorithmic approach toward diagnosis and management of these challenging patients. The Indian National Association for Study of Liver (INASL) in association with Indian Society of Nephrology (ISN) endeavored to develop joint guidelines on diagnosis and management of patients who have simultaneous liver and kidney disease. For generating these guidelines, an INASL-ISN Taskforce was constituted, which had members from both the societies. The taskforce first identified contentious issues on various aspects of simultaneous liver and kidney diseases, which were allotted to individual members of the taskforce who reviewed them in detail. A round-table meeting of the Taskforce was held on 20-21 October 2018 at New Delhi to discuss, debate, and finalize the consensus statements. The evidence and recommendations in these guidelines have been graded according to the Grading of Recommendations Assessment Development and Evaluation (GRADE) system with minor modifications. The strength of recommendations (strong and weak) thus reflects the quality (grade) of underlying evidence (I, II, III). We present here the INASL-ISN Joint Position Statements on Management of Patients with Simultaneous Liver and Kidney Disease.
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Affiliation(s)
- Anil Arora
- Institute of Liver, Gastroenterology, & Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110060, Delhi, India
| | - Ashish Kumar
- Institute of Liver, Gastroenterology, & Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110060, Delhi, India
| | - Narayan Prasad
- Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, 226014, Uttar Pradesh, India
| | - Ajay Duseja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh, 160012, India
| | - Subrat K. Acharya
- Kalinga Institute of Medical Sciences, KIIT, Bubaneswar, 751024, Odisha
| | - Sanjay K. Agarwal
- Department of Nephrology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, Delhi, India
| | - Rakesh Aggarwal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Raebareli Road, Lucknow, 226014, Uttar Pradesh, India
| | - Anil C. Anand
- Kalinga Institute of Medical Sciences, KIIT, Bubaneswar, 751024, Odisha
| | - Anil K. Bhalla
- Department of Nephrology, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110060, Delhi, India
| | - Narendra S. Choudhary
- Institute of Liver Transplantation and Regenerative Medicine, Medanta -The Medicity, CH Baktawar Singh Rd, Sector 38, Gurugram, 122001, Haryana, India
| | - Yogesh K. Chawla
- Kalinga Institute of Medical Sciences, KIIT, Bubaneswar, 751024, Odisha
| | - Radha K. Dhiman
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh, 160012, India
| | - Vinod K. Dixit
- Department of Gastroenterology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221005, Uttar Pradesh, India
| | | | - Ashwani Gupta
- Department of Nephrology, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110060, Delhi, India
| | - Umapati N. Hegde
- Department of Nephrology, Muljibhai Patel Urological Hospital, Dr VV Desai Road, Nadiad, 387001, Gujarat, India
| | - Sanjiv Jasuja
- Department of Nephrology, Indraprastha Apollo Hospital, Mathura Road, Sarita Vihar, New Delhi, 110076, India
| | - Vivek Jha
- The George Institute for Global Health, Elegance Tower, 311-312, Third Floor, Jasola Vihar, New Delhi, 110025, Delhi, India
| | - Vijay Kher
- Nephrology, Medanta Kidney & Urology Institute, Medanta -The Medicity, CH Baktawar Singh Rd, Sector 38, Gurugram, 122001, Haryana, India
| | - Ajay Kumar
- Institute for Digestive & Liver Diseases, BLK Hospital, Pusa Road, Radha Soami Satsang, Rajendra Place, New Delhi, 110005, Delhi, India
| | - Kaushal Madan
- Max Smart Super Specialty Hospital, Saket, New Delhi, 110017, Delhi, India
| | - Rakhi Maiwall
- Department of Hepatology, Institute of Liver & Biliary Sciences, D1, Vasant Kunj, New Delhi, 110070, Delhi, India
| | - Rajendra P. Mathur
- Department of Nephrology, Institute of Liver & Biliary Sciences, D1, Vasant Kunj, New Delhi, 110070, Delhi, India
| | - Suman L. Nayak
- Dharamshila Narayana Superspeciality Hospital, New Delhi, 110096, Delhi, India
| | - Gaurav Pandey
- Kalinga Institute of Medical Sciences, KIIT, Bubaneswar, 751024, Odisha
| | - Rajendra Pandey
- Department of Nephrology, Institute of Post Graduate Medical Education & Research, 244, Acharya Jagadish Chandra Bose Road, Bhowanipore, Kolkata, 700020, West Bengal, India
| | - Pankaj Puri
- Institute of Liver, Gastroenterology, & Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110060, Delhi, India
| | - Ramesh R. Rai
- Rai Specialty Center, H-6, Jan Path, Near DANA-PANI Restaurant, Kishan Nagar, Shyam Nagar, Jaipur, 302019, Rajasthan, India
| | - Sree B. Raju
- Department of Nephrology, Nizam's Institute of Medical Sciences, Panjagutta, Hyderabad, 500082, Telangana, India
| | - Devinder S. Rana
- Department of Nephrology, Sir Ganga Ram Hospital, New Delhi, 110060, Delhi, India
| | - Padaki N. Rao
- Department of Hepatology, Asian Institute of Gastroenterology, Somajiguda, Hyderabad, 500082, Telangana, India
| | - Manish Rathi
- Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India
| | - Vivek A. Saraswat
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, 226014, Uttar Pradesh, India
| | - Sanjiv Saxena
- Institute of Renal Sciences, PSRI Hospital, Press Enclave Marg, J Pocket, Phase II, Sheikh Sarai, New Delhi, 110017, Delhi, India
| | - Shalimar
- Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, Delhi, India
| | - Praveen Sharma
- Institute of Liver, Gastroenterology, & Pancreatico-Biliary Sciences, Sir Ganga Ram Hospital, Rajinder Nagar, New Delhi, 110060, Delhi, India
| | - Shivaram P. Singh
- Department of Gastroenterology, S.C.B. Medical College, Cuttack 753007, Odisha, India
| | - Ashwani K. Singal
- University of South Dakota Sanford School of Medicine and Avera Transplant Institute, Sioux Falls, SD 57105, USA
| | - Arvinder S. Soin
- Institute of Liver Transplantation and Regenerative Medicine, Medanta -The Medicity, CH Baktawar Singh Rd, Sector 38, Gurugram, 122001, Haryana, India
| | - Sunil Taneja
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh, 160012, India
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Yu HC, Lin KH, Tsay FW, Tsai TJ, Wu PC, Chen YH, Chen YH. Kinetics of hepatitis B surface antigen and estimated glomerular filtration rate in telbivudine-treated hepatitis B patients with different rescue strategies. PLoS One 2020; 15:e0237586. [PMID: 32785260 PMCID: PMC7423127 DOI: 10.1371/journal.pone.0237586] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Accepted: 07/29/2020] [Indexed: 01/09/2023] Open
Abstract
This study investigated the kinetics of estimated glomerular filtration rate (eGFR) and quantitative hepatitis B surface antigen (qHBsAg) in telbivudine (LdT)-treated chronic hepatitis B (CHB) patients whose treatment was subsequently adjusted with the adding on adefovir or by switching to tenofovir disoproxil fumarate (TDF) as rescue. Of 295 CHB patients initially treated with LdT, 102 of them who subsequently receiving either adding-on adefovir (group A, n = 58) or switching to TDF (group B, n = 44) for more than 24 months were enrolled. Serial eGFR and qHBsAg levels (3 to 6 monthly) in both LdT monotherapy and rescue therapy periods were analyzed retrospectively. Subsequent decline of qHBsAg especially in rescue therapy period were noted (p<0.001 and p = 0.068 in group A and B). However, patients in group B achieved a significant increase of eGFR (p = 0.010) in LdT monotherapy period but had a significant decline of eGFR (p<0.001) in rescue therapy period. In contrast, patients in group A maintained eGFR levels in both periods. Meanwhile, switch to TDF (hazard ratio: 3.036; 95% confidence interval: 1.040-8.861; p = 0.042) was the sole factor related to the decrease of eGFR>20% from baseline. Both rescue therapies achieved subsequent declines of qHBsAg over time but caused different changes in eGFR. LdT-based rescue therapy maintained eGFR but TDF switching therapy descended eGFR. Therefore, it is essential to monitor patient's renal function intensively when switching from LdT to TDF as a rescue strategy.
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Affiliation(s)
- Hsien-Chung Yu
- Health Management Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- Department of Nursing, Meiho University, Pingtung, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- Chung Shan Medical University, Taichung, Taiwan
- Institute of Health Care Management, Department of Business Management, National Sun Yat-Sen University, Kaohsiung, Taiwan
| | - Kung-Hung Lin
- Health Management Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- Department of Nursing, Meiho University, Pingtung, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Feng-Woei Tsay
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- Chung Shan Medical University, Taichung, Taiwan
| | - Tzung-Jiun Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- Chung Shan Medical University, Taichung, Taiwan
| | - Pin-Chieh Wu
- Health Management Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- Department of Nursing, Meiho University, Pingtung, Taiwan
- Department of Family Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Yu-Hsun Chen
- Health Management Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- Division of Colorectal Surgery, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Yan-Hua Chen
- Health Management Center, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- Department of Nursing, Meiho University, Pingtung, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- * E-mail:
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Zheng H, Liu H, Hao A, Zhang M, Wang D. Association between serum Cystatin C and renal injury in patients with chronic hepatitis B. Medicine (Baltimore) 2020; 99:e21551. [PMID: 32769895 PMCID: PMC7593051 DOI: 10.1097/md.0000000000021551] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
To explore the association between serum cystatin C (Cys-C) and renal damage in patients with chronic hepatitis B.We retrospectively analyzed the clinical data of 425 patients with chronic hepatitis B virus (HBV) infection. Liver stiffness measured by FibroScan was used to diagnosis liver fibrosis. Cys-C levels were detected via latex-enhanced immunoturbidimetric assay.A total of 425 patients were enrolled. Among them, 217 were patients with CHB with an eGFR > 90 mL/min/1.73 m and 208 with an eGFR ≤90 mL/min/1.73 m. Cys-C levels significantly differed in patients with eGFR > 90 mL/min/1.73 m compared with patients with eGFR ≤90 mL/min/1.73 m (0.81 ± 0.05 vs 1.05 ± 0.06 mg/L, P < .001). Moreover, the Cys-C levels were 0.82 ± 0.04 mg/L in patients without liver fibrosis, 0.98 ± 0.05 mg/L in patients with mild liver fibrosis, 1.05 ± 0.08 mg/L in patients with advanced liver fibrosis, and 1.12 ± 0.07 mg/L in patients with liver cirrhosis (P < .001). Multivariate analyses were conducted to explore the independent factors associated with a decreased eGFR. Multivariate analysis suggested that T2DM (P = .032), liver fibrosis (P = .013), and Cys-C level (P = .035) were the independent factors associated with the decreased eGFR in patients with CHB. While age (P = .020) and Cys-C level (P = .001) were the independent factors associated with the decreased eGFR in patients with CHB-related fibrosis.The fibrosis group had significantly higher Cys-C levels than those without fibrosis. Routine monitoring of Cys-C levels is of positive significance in preventing the development of renal impairment of CHB patients.
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Affiliation(s)
- Hui Zheng
- Department of Clinical Laboratory, Qingdao Fifth People's Hospital
| | - Haidong Liu
- Department of Gastroenterology, Qingdao Sixth People's Hospital
| | - Anhua Hao
- Hepatology Department, Qingdao Chengyang People's Hospital, Qingdao
| | - Min Zhang
- Department of Gastroenterology, Qingdao Sixth People's Hospital
| | - Dexin Wang
- Department of Hepatology, Qingdao Sixth People's Hospital, Qingdao, China
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Hajiani E, Parsi A, Seyedian SS, Rajaei E, Jolodarian P. Comparing the frequency of osteoporosis and osteopenia in chronic hepatitis B patients with and without Tenofovir treatment. CLINICAL EPIDEMIOLOGY AND GLOBAL HEALTH 2020. [DOI: 10.1016/j.cegh.2019.10.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022] Open
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10
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Chen CJ, Yu HC, Chang CW, Bair MJ, Lin CC, Lin YS, Cai ZS, Chen MJ. Efficacy of telbivudine and entecavir against virus reactivation in HBeAg-patients undergoing chemotherapy. Medicine (Baltimore) 2020; 99:e20330. [PMID: 32481407 DOI: 10.1097/md.0000000000020330] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/15/2023] Open
Abstract
The renal protective effect of telbivudine (LdT) was verified by a previous meta-analysis. It was left unclear, however if this effect offsets the associated risk of virological breakthrough in hepatitis B e-antigen-negative (HBeAg-) patients receiving chemotherapy (C/T).Records of 260 HBeAg-, non-cirrhotic cancer patients undergoing systemic C/T with prophylactic LdT or entecavir (ETV) were retrospectively investigated. The investigation was conducted 6 months after completion of C/T, patient death from cancer, or antiviral modification. Treatment duration, outcome, change of renal function, and reason for antiviral modification were analyzed. The primary endpoint was the occurrence of virological breakthrough during prophylaxis C/T and the change in renal function.Of the 126 HBeAg- patients treated with LdT, 3 (2.38%) experienced HBV virological breakthroughs, whereas none of the patients treated with ETV (P = .07) did. The estimated glomerular filtration rate for the patients treated with LdT was essentially unaltered, decreasing only slightly from 87.5 ± 23.1 to 87.3 ± 21.3 ml/minute/1.73 m (P = .55), while the rate for the ETV-treated patients was significantly lowered from 95.7 ± 32.2 to 85.5 ± 85.7 ml/minute/1.73 m (P = .0009).The absolute risk reduction ARR is 27.8% - 21.2% = 6.6%, comparing ETV with LdT for reduction of renal function impairment and the absolute risk increase for virological breakthrough during C/T, the absolute risk increase (ARI) is 2.38% - 0% = 2.38%. The overall likelihood of being helped over being harmed was 2.77. With careful selection of patients with the criteria of HBeAg-status and non-hematologic cancer, it is feasible that telbivudine raise lower probability of virological breakthroughs during prophylaxis treatment.
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Affiliation(s)
- Chih-Jen Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei City
- Department of Medicine, MacKay Medical College, New Taipei City
- Department of Nursing, MacKay Junior College of Medicine, Nursing, and Management
| | - Hsien-Chung Yu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung City
- Faculty of Medicine, School of Medicine, National Yang Ming University, Taipei
- Institute of Health Care Management, Department of Business Management, National Sun Yat-Sen University, Kaohsiung
| | - Chen-Wang Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei City
- Department of Medicine, MacKay Medical College, New Taipei City
- Department of Nursing, MacKay Junior College of Medicine, Nursing, and Management
| | - Ming-Jong Bair
- Department of Medicine, MacKay Medical College, New Taipei City
- Department of Nursing, MacKay Junior College of Medicine, Nursing, and Management
- Division of Gastroenterology, Department of Internal Medicine, Taitung MacKay Memorial Hospital, Taitung City, Taiwan
| | - Ching-Chung Lin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei City
- Department of Medicine, MacKay Medical College, New Taipei City
| | - Yang-Sheng Lin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei City
- Department of Medicine, MacKay Medical College, New Taipei City
- Department of Nursing, MacKay Junior College of Medicine, Nursing, and Management
| | - Zong-Sian Cai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei City
- Department of Medicine, MacKay Medical College, New Taipei City
- Department of Nursing, MacKay Junior College of Medicine, Nursing, and Management
| | - Ming-Jen Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei City
- Department of Medicine, MacKay Medical College, New Taipei City
- Department of Nursing, MacKay Junior College of Medicine, Nursing, and Management
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Telbivudine for renal transplant recipients with chronic hepatitis B infection: a randomized controlled trial with early termination. Clin Exp Nephrol 2020; 24:474-482. [PMID: 32219622 DOI: 10.1007/s10157-020-01850-7] [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: 04/06/2019] [Accepted: 01/05/2020] [Indexed: 10/24/2022]
Abstract
BACKGROUND The aim of this study was to analyze changes in renal function in HBsAg-positive renal transplant recipients receiving lamivudine who did or did not switch to telbivudine. METHODS In this prospective randomized clinical trial (RCT), HBsAg-positive renal transplant recipients who had received lamivudine prophylaxis for at least 6 months were 1:2 randomized to receive either lamivudine or telbivudine for another 24 months. Renal function was evaluated by creatinine level and estimated glomerular filtration rate (eGFR) at the time of randomization (baseline), 6, 12, 18, and 24 months respectively. RESULTS This RCT was prematurely terminated after recruiting only 17 patients due to a high incidence (61.5%; 8/13) of clinical myalgia in the telbivudine group. Cox's proportional hazards model revealed that there was no independent predictor of myalgia. Based on intention-to-treat and per protocol analyses using generalized estimating equations, the patients in the randomized telbivudine group had a significantly increased eGFR and the patients in the lamivudine group had a significantly decreased eGFR at the end of follow-up compared to the values at study enrollment. However, there was no significant difference between the lamivudine and telbivudine groups. CONCLUSIONS The renal protective effect of telbivudine for HBsAg positive renal transplant recipients was uncertain for high incidence of myalgia and only patients who were on telbivudine for 24 months had renal function maintenance.
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Chinese Herbal Medicine Ameliorated the Development of Chronic Kidney Disease in Patients with Chronic Hepatitis C: A Retrospective Population-Based Cohort Study. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2019; 2019:5319456. [PMID: 31871483 PMCID: PMC6906860 DOI: 10.1155/2019/5319456] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/22/2019] [Revised: 09/15/2019] [Accepted: 10/17/2019] [Indexed: 12/28/2022]
Abstract
Chronic kidney disease (CKD) is a serious complication affecting patients with chronic hepatitis. The effectiveness of CHM for the prevention of CKD in hepatitis patients remains unclear. Therefore, we conducted a retrospective cohort study to investigate the effectiveness of CHM in preventing the development of CKD in hepatitis patients. From a subdataset of the Taiwan National Health Insurance Research Database (NHIRD), we included 19,409 patients newly diagnosed with hepatitis B and hepatitis C between the years 2000 and 2010. After exclusion criteria and 1 : 1 propensity score matching process, we compared demographic factors, comorbidities, and correlated drugs between the CHM and non-CHM cohorts. Statistical analysis was applied to evaluate the differences in characteristic distributions and to compare the cumulative incidence of CKD between the CHM and non-CHM cohorts. This study showed that the patients suffering from hepatitis C with CHM treatment more than 90 days as an adjuvant therapy combined with western medical treatment modalities exhibited a decreased risk of developing CKD (hazard ratio (HR) = 0.40, 95% confidence interval (CI) = 0.21–0.76, p value <0.01). The Kaplan–Meier curve revealed a lower cumulative incidence rate of CKD (p value = 0.004) for the CHM cohort. For further reference, we herein offer the ten most frequently prescribed single herbs and herbal formulas; as such, Salviae miltiorrhizae and Jia-Wei-Xiao-Yao-San were the most commonly prescribed single herb and formula, respectively. This nationwide retrospective cohort study provides evidence that CHM is an effective adjuvant treatment to decrease the risk of developing CKD in hepatitis C patients.
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Suzuki K, Suda G, Yamamoto Y, Furuya K, Baba M, Kimura M, Maehara O, Shimazaki T, Yamamoto K, Shigesawa T, Nakamura A, Ohara M, Kawagishi N, Nakai M, Sho T, Natsuizaka M, Morikawa K, Ogawa K, Sakamoto N. Entecavir treatment of hepatitis B virus-infected patients with severe renal impairment and those on hemodialysis. Hepatol Res 2019; 49:1294-1304. [PMID: 31260579 DOI: 10.1111/hepr.13399] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2019] [Revised: 06/23/2019] [Accepted: 06/24/2019] [Indexed: 12/21/2022]
Abstract
AIM Entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF) are first-line nucleos(t)ide analogues for hepatitis B virus (HBV)-infected patients. However, consecutive TDF treatment causes renal dysfunction, and the safety and efficacy of TAF have not been established in severe renal dysfunction patients, including hemodialysis patients. The efficacy and safety of ETV in these populations has not been clarified. The study aimed to clarify this. METHODS In this retrospective multicenter study, between 2006 and 2018, a total of 567 HBV-infected patients treated with ETV monotherapy were screened. Patients were included if >20 years old, treated with ETV monotherapy for >1 year, and had proper clinical information. The efficacy of ETV and changes in renal function were evaluated according to renal function. RESULTS A total of 273 patients were included: 9.2% (25/273), 1.8% (5/273), and 3.7% (10/273) had chronic kidney disease (CKD) stage G3, CKD stage G4/5, and were on hemodialysis, respectively. Overall, 84.2%, 94.0%, and 96.2% of patients experienced serum HBV-DNA disappearance at 1, 2, and 3 years, respectively, after treatment initiation. In patients with CKD stage G3-5, estimated glomerular filtration rate tended to restore with time, which was in contrast to patients without renal dysfunction. The rate of disappearance in serum HBV-DNA, alanine transaminase normalization, and virological breakthrough was similar between patients with or without renal dysfunction. ETV showed high efficacy for all 10 hemodialysis patients without virological breakthrough. CONCLUSIONS Entecavir for HBV-infected patients with severe renal dysfunction, including hemodialysis patients, is highly effective and does not affect renal function.
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Affiliation(s)
- Kazuharu Suzuki
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University
| | - Goki Suda
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University
| | | | | | | | - Megumi Kimura
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University
| | - Osamu Maehara
- Department of Gastroenterology, Hakodate Municipal Hospital
| | - Tomoe Shimazaki
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University
| | - Koji Yamamoto
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University
| | - Taku Shigesawa
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University
| | - Akihisa Nakamura
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University
| | - Masatsugu Ohara
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University
| | - Naoki Kawagishi
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University
| | - Masato Nakai
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University
| | - Takuya Sho
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University
| | - Mitsuteru Natsuizaka
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University
| | - Kenichi Morikawa
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University
| | - Koji Ogawa
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University
| | - Naoya Sakamoto
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University
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Zheng C, Yan H, Zeng J, Cai S, Wu X. Comparison of pegylated interferon monotherapy and de novo pegylated interferon plus tenofovir combination therapy in patients with chronic hepatitis B. Infect Drug Resist 2019; 12:845-854. [PMID: 31114265 PMCID: PMC6489617 DOI: 10.2147/idr.s195144] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2018] [Accepted: 03/04/2019] [Indexed: 12/21/2022] Open
Abstract
Background and aim: We aimed to evaluate the effectiveness of pegylated interferon (Peg-IFN) monotherapy (IFN group) and combination therapy with tenofovir (TDF) and Peg-IFN (IFN+TDF group) in chronic hepatitis B (CHB) patients. Patients and methods: Data of 143 CHB patients were analyzed in this study. All patients enrolled received liver biopsy. Virologic responses were defined as hepatitis B virus (HBV) DNA <100 IU/mL, biochemical responses were defined as normalization of alanine aminotransferse (ALT) levels, and HBeAg serological response was defined as HBeAg loss or HBeAg seroconversion to HBeAb. HBsAg serological response was defined as HBsAg loss or HBsAg seroconversion to HBsAb. Results: We observed that a total of 16.7% (11/66) and 33.8% (26/77) patients in IFN and IFN+TDF group achieved complete viral suppression after 48 weeks treatment (P=0.02). Although HBeAg levels in CHB patients in the IFN+TDF group decreased more rapidly during the 48-week treatment, we did not observe significant differences in HBeAg serological loss or seroconversion rates between the two groups at 24 and 48 weeks. HBsAg loss was observed in 13.0% (10/77) of CHB patients in the IFN+TDF group at 48 weeks, compared with only 3% (2/66) patients in the IFN group (P=0.032). No significant difference was observed in HBsAg seroconversion rate between the two groups during 48-week treatment. The biochemical response rate was also significantly higher in the IFN+TDF group than that in the IFN group at week 48 (P=0.015). Multivariate logistic analysis showed that IFN+TDF treatment (OR=4.41, P=0.003), severe baseline hepatic inflammation (OR=4.16, P<0.001), and lower baseline serum HBV DNA levels (OR=0.98, P=0.03) were strong predictors for the virological response. Younger age (OR=0.89, P=0.01), higher baseline ALT level (OR=1.01, P=0.038), and lower baseline HBeAg level (OR=0.99, P=0.008) were independent predictors for HBeAg sero-response after 48 weeks treatment. While only severe liver fibrosis (OR=1.69, P=0.028) and lower baseline HBsAg level (OR=0.22, P=0.005) were independent factors associated with HBsAg sero-response after 48 weeks treatment. Conclusion: Peg-IFN combined with TDF may increase the virological response rate, biochemical response rate, and HBsAg loss rate in patients with CHB infection. The combination treatment is more suitable for those patients who are likely to respond to the treatment.
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Affiliation(s)
- Caixia Zheng
- Department of Infectious Diseases, First Affiliated Hospital of Xiamen University, Xiamen, Fujian Province, People's Republic of China
| | - Honghong Yan
- Intensive Care Unit, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong Province, People's Republic of China
| | - Jianyong Zeng
- Department of Infectious Diseases, First Affiliated Hospital of Xiamen University, Xiamen, Fujian Province, People's Republic of China
| | - Shaohang Cai
- Intensive Care Unit, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong Province, People's Republic of China.,Department of Infectious Diseases and Hepatology Unit, NanFang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People's Republic of China
| | - Xiaolu Wu
- Department of Infectious Diseases, First Affiliated Hospital of Xiamen University, Xiamen, Fujian Province, People's Republic of China
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Soi V, Daifi C, Yee J, Adams E. Pathophysiology and Treatment of Hepatitis B and C Infections in Patients With End-Stage Renal Disease. Adv Chronic Kidney Dis 2019; 26:41-50. [PMID: 30876616 DOI: 10.1053/j.ackd.2018.10.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2018] [Revised: 10/18/2018] [Accepted: 10/19/2018] [Indexed: 01/01/2023]
Abstract
An in-depth understanding of viral hepatitis is important to the care of patients with end-stage renal disease undergoing hemodialysis. Both hepatitis B and C viruses are acquired through hematogenous spread and can lead to horizontal transmission. Concurrent hepatic and renal injuries have ominous outcomes with significant morbidity. Hepatitis B incidence has decreased through practices including vaccination of nonimmune individuals and isolation of patients with the disease. The pathogenesis of hepatitis B leads to various symptoms and serologic changes with unique temporal associations dictating an acute or chronic presentation. Chronic hepatitis B develops when there is persistence of surface antigen for more than 6 months. Occult hepatitis B is an enigmatic form of the chronic disease where viral DNA is present despite the patient remaining seronegative. Nucleoside analogs are used as a treatment for individuals with hepatitis B who have comorbid CKD; however, the mainstay of infection control relies on immunization. Hepatitis C, an RNA virus, has increased in prevalence. Strict universal precautions with sound infection-control practices are important to prevent seroconversion. Recent therapeutic advances involving the development of direct-acting antiviral agents have broadened treatment options for patients with renal impairment and hepatitis C, offering the potential for a definitive cure. Controversy on the timeliness of treatment for transplant options has also risen with the advent of these newer therapies. We review the epidemiology, pathophysiology, and updates in treatment of these viral entities as they relate to the hemodialysis population.
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Arora A, Anand AC, Kumar A, Singh SP, Aggarwal R, Dhiman RK, Aggarwal S, Alam S, Bhaumik P, Dixit VK, Goel A, Goswami B, Kumar A, Kumar M, Madan K, Murugan N, Nagral A, Puri AS, Rao PN, Saraf N, Saraswat VA, Sehgal S, Sharma P, Shenoy KT, Wadhawan M. INASL Guidelines on Management of Hepatitis B Virus Infection in Patients receiving Chemotherapy, Biologicals, Immunosupressants, or Corticosteroids. J Clin Exp Hepatol 2018; 8:403-431. [PMID: 30568345 PMCID: PMC6286881 DOI: 10.1016/j.jceh.2018.06.010] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2018] [Accepted: 06/10/2018] [Indexed: 02/09/2023] Open
Abstract
Hepatitis B Virus (HBV) reactivation in patients receiving chemotherapy, biologicals, immunosupressants, or corticosteroids is emerging to be an important cause of morbidity and mortality in patients with current or prior exposure to HBV infection. These patients suffer a dual onslaught of illness: one from the primary disease for which they are receiving the culprit drug that led to HBV reactivation, and the other from HBV reactivation itself. The HBV reactivation not only leads to a compromised liver function, which may culminate into hepatic failure; it also adversely impacts the treatment outcome of the primary illness. Hence, identification of patients at risk of reactivation before starting these drugs, and starting treatment aimed at prevention of HBV reactivation is the best strategy of managing these patients. There are no Indian guidelines on management of HBV infection in patients receiving chemotherapy, biologicals, immunosupressants, or corticosteroids for the treatment of rheumatologic conditions, malignancies, inflammatory bowel disease, dermatologic conditions, or solid-organ or bone marrow transplantation. The Indian National Association for Study of the Liver (INASL) had set up a taskforce on HBV in 2016, with a mandate to develop consensus guidelines for management of various aspects of HBV infection, relevant to India. In 2017 the taskforce had published the first INASL guidelines on management of HBV infection in India. In the present guidelines, which are in continuation with the previous guidelines, the issues on management of HBV infection in patients receiving chemotherapy, biologicals, immunosupressants, or corticosteroids are addressed.
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Key Words
- ACLF, Acute-on-Chronic Liver Failure
- AFP, Alphafetoprotein
- ALT, Alanine Aminotransferase
- Anti-HBc, Antibodies to Hepatitis B Core Antigen
- Anti-HBs, Antibodies to Hepatitis B Surface Antigen
- CHB, Chronic Hepatitis B
- CHOP, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone
- CKD, Chronic Kidney Disease
- DILI, Drug-Induced Liver Injury
- DNA, Deoxyribonucleic Acid
- ETV, Entecavir
- GRADE, Grading of Recommendations, Assessment, Development and Evaluation
- HAV, Hepatitis A Virus
- HBIG, Hepatitis B Immune Globulin
- HBV DNA, Hepatitis B Virus Deoxyribonucleic Acid
- HBV, Hepatitis B Virus
- HBcAg, Hepatitis B Core Antigen
- HBeAg, Hepatitis B Envelope Antigen
- HBsAg, Hepatitis B Surface Antigen
- HDV, Hepatitis D Virus
- HEV, Hepatitis E Virus
- HLA, Human Leukocyte Antigen Class I
- INASL, Indian National Association for Study of the Liver
- LAM, Lamivudine
- NAs, Nucleos(t)ide Analogs
- NHL, Non-Hodgkin’s Lymphoma
- NK, Natural Killer
- PegIFN-α, Pegylated Interferon Alpha
- RA, Rheumatoid Arthritis
- SLE, Systemic Lupus Erythematosus
- TAF, Tenofovir Alafenamide
- TDF, Tenofovir Disoproxil Fumarate
- TLC, Total Leucocyte Count
- ULN, Upper Limit of Normal
- cancer
- cccDNA, Covalently Closed Circular Deoxyribonucleic Acid
- chemotherapy
- hepatitis B
- immunosupressants
- liver failure
- rcDNA, Relaxed-Circular Deoxyribonucleic Acid
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Affiliation(s)
- Anil Arora
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
| | | | - Ashish Kumar
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
| | - Shivaram P. Singh
- Department of Gastroenterology, S.C.B. Medical College, Cuttack, India
| | - Rakesh Aggarwal
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Radha K. Dhiman
- Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Shyam Aggarwal
- Department of Medical Oncology, Sir Ganga Ram Hospital, New Delhi, India
| | - Seema Alam
- Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Pradeep Bhaumik
- Department of Medicine, Agartala Govt. Medical College (AGMC), Agartala, India
| | - Vinod K. Dixit
- Department of Gastroenterology, Institute of Medical Sciences Banaras Hindu University, Varanasi, India
| | - Ashish Goel
- Department of Hepatology, Christian Medical College, Vellore, India
| | - Bhabadev Goswami
- Department of Gastoenterology, Gauhati Medical College, Guwahati, India
| | - Ashok Kumar
- Department of Rheumatology, Fortis Flt Lt Rajan Dhall Hospital, New Delhi, India
| | - Manoj Kumar
- Department of Hepatology and Liver Transplantation, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Kaushal Madan
- Gastroenterology & Hepatology, Max Smart Super Speciality Hospital, New Delhi, India
| | | | - Aabha Nagral
- Department of Gastroenterology, Jaslok and Apollo Hospitals, Mumbai, India
| | - Amarender S. Puri
- Department of Gastroenterology, G.B. Pant Hospital, New Delhi, India
| | - Padaki N. Rao
- Hepatology, Asian Institute Of Gastroenterology, Hyderabad, India
| | - Neeraj Saraf
- Hepatology, Medanta - The Medicity, Gurugram, India
| | - Vivek A. Saraswat
- Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Sanjeev Sehgal
- Institute of Liver Transplantation and Regenerative Medicine, Medanta - The Medicity, Gurugram, India
| | - Praveen Sharma
- Institute of Liver Gastroenterology & Pancreatico Biliary Sciences, Sir Ganga Ram Hospital, New Delhi, India
| | | | - Manav Wadhawan
- Hepatology & Liver Transplant (Medicine), Fortis Escorts Liver & Digestive Diseases Institute (FELDI), Fortis Escorts Hospital, Delhi, India
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Yan Z, Qiao B, Zhang H, Wang Y, Gou W. Effectiveness of telbivudine antiviral treatment in patients with hepatitis B virus-associated glomerulonephritis: A 104-week pilot study. Medicine (Baltimore) 2018; 97:e11716. [PMID: 30075577 PMCID: PMC6081091 DOI: 10.1097/md.0000000000011716] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
The aim of this study was to evaluate clinical efficacy of telbivudine in treatment of hepatitis B virus-associated glomerulonephritis (HBV-GN).A total of 43 HBV-GN patients combined with chronic hepatitis B were treated with telbivudine for 104 weeks. Serum levels of HBV DNA viral load, HBeAg, HBeAb, alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum creatinine (Cr), and 24-hour urinary protein were evaluated after telbivudine treatment of 12, 24, 52, 76, and 104 weeks. Estimated glomerular filtration rate (eGFR) was calculated at baseline, 24 weeks, 52 weeks, and 104 weeks of treatment, respectively. Complete remission (CR) was defined as urinary protein <0.3 g/day, with normal ALT, AST, Cr, and eGFR. Criteria for partial remission include: 24-hour urinary protein excretion decreased by >50% compared with baseline level, and ALT and AST decreased >50%.Proteinuria level gradually decreased in patients with HBV-GN after telbivudine treatment. The percentages of PR + CR were 90.7% and 95.3%, respectively, at 52 and 104 weeks. Compared to baseline, eGFR were significantly increased from 69.2 ± 23.1 mL/min/1.73 m to 116.2 ± 26.3 mL/min/1.73 m at 104 weeks of treatment. Multivariate analysis indicated that baseline HBV DNA viral load (odds ratio [OR] = 1.19, 95% confidence interval [CI] 1.11-2.19, P = .02) and baseline urinary protein (OR = 1.08, 95% CI 1.04-2.44, P = .03) were independent risk factors associated with CR after telbivudine treatment among patients with HBV-GN.Our study demonstrates that telbivudine can be used to treat HBV-GN and effectively improve eGFR in these patients.
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Affiliation(s)
- Zhaoping Yan
- Lab of Glycobiololgy, School of Medicine and Pharmacy, Ocean University of China
| | | | | | - Yanling Wang
- Department of Dermatology, No. 6 People's Hospital of Qingdao, Qingdao, Shandong, China
| | - Wei Gou
- The sixth Department of Hepatology
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18
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Lee GH, Inoue M, Chong RHH, Toh J, Wee SY, Loh KS, Lim SG. Pyrosequencing method for sensitive detection of HBV drug resistance mutations. J Med Virol 2018; 90:1071-1079. [PMID: 29488627 DOI: 10.1002/jmv.25066] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2017] [Accepted: 02/15/2018] [Indexed: 12/17/2022]
Abstract
Hepatitis B (HBV) drug resistance assay is important for guiding therapy after the development of virologic breakthrough for patients receiving nucleoside/-tide analog therapy. However, the existing genotyping tools are either costly or lack sensitivity to detect mixed genotypes, and an improved method of resistant mutation detection is needed. An assay protocol for clinical application using pyrosequencing method was developed, capable of detecting all known validated HBV polymerase gene mutations that impart resistance to lamivudine, adefovir, tenofovir, and entecavir. Sixty-eight serum samples with known HBV resistance genotypes, previously tested with either Sanger sequencing assay or commercial line probe assay, were used for validation. Where there were discrepancies between the two methods, clonal sequencing by Sanger's method was used for confirmation. The modified pyrosequencing method accurately identified all the cloned polymerase genotypes and was able to distinguish as little as 5% of the mutant populations. This assay can be performed on serum sample with HBV DNA as low as 13.5 IU/mL. The cost per test was less than existing commercial assay. HBV drug resistance pyrosequencing assay was accurate, more sensitive and cheaper compared with the existing methods. It can detect minor populations of drug-resistant clones earlier, before the drug resistant clones become dominant, allowing the opportunity for an earlier change of therapy.
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Affiliation(s)
- Guan-Huei Lee
- Department of Medicine, National University Health System, Singapore.,Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | | | | | - Jimmy Toh
- Experimental Therapeutics Centre, Singapore
| | | | - Kah-Sin Loh
- Department of Medicine, National University Health System, Singapore
| | - Seng-Gee Lim
- Department of Medicine, National University Health System, Singapore.,Yong Loo Lin School of Medicine, National University of Singapore, Singapore
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19
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Abstract
Renal involvement in hepatitis B occurs in various spectrums and its knowledge is important for clinicians in management of patients. The renal diseases most commonly associated with hepatitis B virus (HBV) infection include membranous nephropathy, membranoproliferative glomerulonephritis and Polyarteritis nodosa. The widespread use of hepatitis B vaccination has decreased the incidence of HBV-related renal diseases. The incidence of HBV infection in dialysis patients has significantly decreased over the past few decades because of screening of blood products for hepatitis B surface antigen (HBsAg) and hepatitis B core antibody, implementation of infection control measures and hepatitis B vaccination. The definition of acute kidney injury has been recently modified in cirrhotic population, helping in prognosis and prediction of mortality. The most common etiologies of acute kidney injury in this cirrhotic population, which account for 80% to 90% of all cases, include volume depletion, acute tubular necrosis and hepatorenal syndrome. Treatment with oral nucleoside/tide analogues (NA) brought a new paradigm in the management of HBsAg positive glomerulonephritis, kidney transplant recipients and dialysis patients, resulting in effective viral suppression, reduced hepatic complications and improved patient survival, without compromising renal allograft outcome. NAs are cleared by the kidneys and therefore their dosage has to be adjusted in all patients with impaired renal function. This article reviews the recent knowledge of the pathogenesis and treatment of HBV-related glomerulonephritis and discusses the management of hepatitis B in patients on dialysis, kidney transplant recipients and cirrhotics, which is continuously evolving.
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Affiliation(s)
- Apurva S Shah
- Department of Gastroenterology, Bombay Hospital and Medical Research Institute, Mumbai, Maharashtra, India
| | - Deepak N Amarapurkar
- Department of Gastroenterology, Bombay Hospital and Medical Research Institute, Mumbai, Maharashtra, India
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20
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Wilms T, Rischawy DF, Barz T, Esche E, Repke JU, Wagner A, Neubauer P, Cruz Bournazou MN. Dynamic Optimization of the PyNP/PNP Phosphorolytic Enzymatic Process Using MOSAICmodeling. CHEM-ING-TECH 2017. [DOI: 10.1002/cite.201700065] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- Terrance Wilms
- TU Berlin; Bioprocess Engineering; Ackerstraße 76 13355 Berlin Germany
| | | | - Tilman Barz
- AIT Austrian Institute of Technology GmbH; Donau-City-Straße 1 1220 Vienna Austria
| | - Erik Esche
- TU Berlin; Process Dynamics and Operations Group; Straße des 17. Juni 135 10623 Berlin Germany
| | - Jens-Uwe Repke
- TU Berlin; Process Dynamics and Operations Group; Straße des 17. Juni 135 10623 Berlin Germany
| | - Anke Wagner
- TU Berlin; Bioprocess Engineering; Ackerstraße 76 13355 Berlin Germany
- BioNukleo GmbH; Ackerstraße 76 13355 Berlin Germany
| | - Peter Neubauer
- TU Berlin; Bioprocess Engineering; Ackerstraße 76 13355 Berlin Germany
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21
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Lin TF, Hsu PI, Lin KH, Tsay FW, Tsai TJ, Chen YH, Yu HC. Factors Related to Significant Improvement of Estimated Glomerular Filtration Rates in Chronic Hepatitis B Patients Receiving Telbivudine Therapy. Gastroenterol Res Pract 2017; 2017:4192169. [PMID: 28757867 PMCID: PMC5516758 DOI: 10.1155/2017/4192169] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2017] [Revised: 06/04/2017] [Accepted: 06/12/2017] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND AND AIM The improvement of estimated glomerular filtration rates (eGFRs) in chronic hepatitis B (CHB) patients receiving telbivudine therapy is well known. The aim of this study was to clarify the kinetics of eGFRs and to identify the significant factors related to the improvement of eGFRs in telbivudine-treated CHB patients in a real-world setting. METHODS Serial eGFRs were calculated every 3 months using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. The patients were classified as CKD-1, -2, or -3 according to a baseline eGFR of ≥90, 60-89, or <60 mL/min/1.73 m2, respectively. A significant improvement of eGFR was defined as a more than 10% increase from the baseline. RESULTS A total of 129 patients were enrolled, of whom 36% had significantly improved eGFRs. According to a multivariate analysis, diabetes mellitus (DM) (p = 0.028) and CKD-3 (p = 0.043) were both significantly related to such improvement. The rates of significant improvement of eGFR were about 73% and 77% in patients with DM and CKD-3, respectively. CONCLUSIONS Telbivudine is an alternative drug of choice for the treatment of hepatitis B patients for whom renal safety is a concern, especially patients with DM and CKD-3.
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Affiliation(s)
- Te-Fu Lin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Ping-I Hsu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- National Yang-Ming University, Taipei, Taiwan
| | - Kung-Hung Lin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- National Yang-Ming University, Taipei, Taiwan
- Department of Nursing, Meiho University, Pingtung, Taiwan
| | - Feng-Woei Tsay
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- National Yang-Ming University, Taipei, Taiwan
| | - Tzung-Jiun Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- National Yang-Ming University, Taipei, Taiwan
| | - Yan-Hua Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- National Yang-Ming University, Taipei, Taiwan
- Department of Nursing, Meiho University, Pingtung, Taiwan
| | - Hsien-Chung Yu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- National Yang-Ming University, Taipei, Taiwan
- Department of Nursing, Meiho University, Pingtung, Taiwan
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22
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Sarmati L, Andreoni M, Antonelli G, Arcese W, Bruno R, Coppola N, Gaeta GB, Galli M, Girmenia C, Mikulska M, Pane F, Perno CF, Picardi M, Puoti M, Rambaldi A, Svicher V, Taliani G, Gentile G. Recommendations for screening, monitoring, prevention, prophylaxis and therapy of hepatitis B virus reactivation in patients with haematologic malignancies and patients who underwent haematologic stem cell transplantation-a position paper. Clin Microbiol Infect 2017; 23:935-940. [PMID: 28668466 DOI: 10.1016/j.cmi.2017.06.023] [Citation(s) in RCA: 60] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2017] [Revised: 06/15/2017] [Accepted: 06/17/2017] [Indexed: 12/18/2022]
Abstract
SCOPE Hepatitis B virus (HBV) infection reactivation is associated with high morbidity and mortality in patients with haematologic malignancy and/or haematopoietic stem cell transplantation (HSCT). However, information on this issue is limited. The scope of this position paper is to provide recommendations on HBV screening, monitoring, prophylaxis, treatment and vaccination in the patients described above. METHODS These recommendations were developed from one meeting of experts attended by different Italian scientific societies as well as from a systematic literature review (of articles published through December 31, 2016) on HBV infection in haematologic patients and in patients who underwent haematopoietic stem cell transplantation published in the same issue of the journal. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess each recommendation's quality. QUESTIONS ADDRESSED These recommendations provide the answers to the following questions: (a) HBV screening and monitoring: Who should be screened before chemotherapy? Which screening tests should be used? Should HBV-DNA detection be used to monitor HBV reactivation before starting antivirals? What is the best timeline to monitor HBV reactivation? (b) Prophylaxis in HBsAg-positive patients: Which antiviral drugs should be used to treat HBsAg-positive patients? How long should antiviral prophylaxis be provided to HBsAg-positive patients? (c) Prophylaxis in patients with resolved HBV infection: Which patients with resolved HBV infection should receive antiviral prophylaxis? Which antiviral drug should be used? How long should antiviral prophylaxis be provided? (d) HBV infection management strategy in autologous (auto-HSCT) and allogeneic HSCT (allo-HSCT): Which HSCT recipients should receive antiviral prophylaxis? Which antiviral drug should be used? How long should antiviral prophylaxis be provided? (e) Choice of antiviral drugs in the treatment of HBV reactivation: Should third-generation anti-HBV drugs be preferred to first- or second-generation antiviral drugs in the treatment of HBV reactivation with or without hepatitis flare in haematologic patients? (f) Immunization against HBV in patients with haematologic malignancies and/or patients who underwent HSCT: Should these patients be vaccinated? Which HBV vaccination schedule should be adopted? RECOMMENDATIONS Haematologic patients should be screened for hepatitis B surface antigen (HBsAg) plus anti-hepatitis B core protein (HBc), and HBV DNA before chemotherapy. HBV DNA levels should be monitored monthly in all HBV-positive patients who do not receive prophylaxis. HBsAg-positive haematologic patients and those undergoing HSCT should receive third-generation antiviral therapy as prophylaxis. Anti-HBc-positive lymphoma patients and those receiving HSCT should receive antiviral prophylaxis. All HBV-negative haematologic patients should be vaccinated for HBV. The acquisition of data from well-designed studies is desirable in the near future.
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Affiliation(s)
- L Sarmati
- Department of System Medicine, Clinical Infectious Diseases, Tor Vergata University, Rome, Italy.
| | - M Andreoni
- Department of System Medicine, Clinical Infectious Diseases, Tor Vergata University, Rome, Italy
| | - G Antonelli
- Department of Molecular Medicine, 'La Sapienza' University, Rome, Italy
| | - W Arcese
- Department of Hematology, Stem Cell Transplant Unit, Tor Vergata University, Rome, Italy
| | - R Bruno
- Department of Infectious Diseases, Hepatology Outpatients Unit, University of Pavia, IRCCS Policlinico San Matteo, Pavia, Italy
| | - N Coppola
- Department of Mental Health and Public Medicine, Section of Infectious Diseases, Second University of Naples, Naples, Italy
| | - G B Gaeta
- Infectious Diseases and Viral Hepatitis, Department of Mental and Physical Health and Preventive Medicine, Università della Campania, Naples, Italy
| | - M Galli
- Infectious Diseases Unit, University of Milan, L. Sacco Hospital, Milan, Italy
| | - C Girmenia
- Dipartimento di Ematologia, Oncologia, Anatomia Patologica e Medicina Rigenerativa, Azienda Policlinico Umberto I, La Sapienza University, Rome, Italy
| | - M Mikulska
- Division of Infectious Diseases, Department of Health Sciences, University of Genoa, Genoa, Italy; Division of Infectious Diseases, IRCCS San Martino University Hospital-IST, Genoa, Italy
| | - F Pane
- Department of Clinical Medicine and Surgery, Hematology, Federico II University, Naples, Italy
| | - C F Perno
- Department of Experimental Medicine and Surgery, Tor Vergata University, Rome, Italy
| | - M Picardi
- Department of Clinical Medicine and Surgery, Hematology, Federico II University, Naples, Italy
| | - M Puoti
- Infectious Diseases Department, Azienda Ospedaliera Ospedale Niguarda Ca' Granda, Milan, Italy
| | - A Rambaldi
- Dipartimento di Scienze Cliniche e di Comunità, Università degli Studi di Milano, Milan, Italy; Hematology and Bone Marrow Transplant Unit, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy
| | - V Svicher
- Department of Experimental Medicine and Surgery, Tor Vergata University, Rome, Italy
| | - G Taliani
- Clinic of Infectious and Tropical Medicine, Policlinico Umberto I, Rome, Italy
| | - G Gentile
- Department of Cellular Biotechnologies and Hematology, 'La Sapienza' University, Rome, Italy
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23
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Cannizzaro MV, Franceschini C, Esposito M, Bianchi L, Giunta A. Hepatitis B reactivation in psoriasis patients treated with anti-TNF agents: prevention and management. PSORIASIS-TARGETS AND THERAPY 2017; 7:35-40. [PMID: 29387606 PMCID: PMC5774605 DOI: 10.2147/ptt.s108209] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
The risk of hepatitis B virus (HBV) reactivation (HBVr) in chronic HBV carriers, in occult HBV patients or in acute HBV patients affected by psoriasis and treated with anti-tumor necrosis factor (TNF)-α agents is a clinical practice issue to face with, particularly if the treatment has a long-term maintenance finality. The aims of this review are to examine the current knowledge on HBVr incidence in chronic HBV carriers and potential occult carriers undergoing therapy with biologics for the treatment of psoriasis and psoriatic arthritis; analyze the prophylactic measure to prevent HBV reactivation and define how to manage HBVr in patients treated with biologics. We searched through PubMed, Google Scholar and Scopus databases and evaluated all published manuscripts concerning HBVr in psoriatic patients, both plaque-type and psoriatic arthritis, in treatment with any indicated anti-TNF-α. Although anti-TNFs are considered moderate immunosuppressive drugs, the incidence of HBVr in psoriatic patients is lower compared to patients affected by other immune-mediated diseases treated with TNF inhibitors. HBV prophylaxis should be probably reserved to anti-HBs+/anti-HBc+ patients with a viral load <2000 IU/mL and alterations in serum liver enzymes, in order to prevent HBVr.
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Affiliation(s)
| | | | - Maria Esposito
- Department of Dermatology, University of Rome Tor Vergata, Rome, Italy
| | - Luca Bianchi
- Department of Dermatology, University of Rome Tor Vergata, Rome, Italy
| | - Alessandro Giunta
- Department of Dermatology, University of Rome Tor Vergata, Rome, Italy
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Telbivudine attenuates gentamicin-induced kidney injury in rats. Int J Antimicrob Agents 2017; 49:595-602. [PMID: 28373116 DOI: 10.1016/j.ijantimicag.2017.01.015] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2016] [Revised: 12/26/2016] [Accepted: 01/06/2017] [Indexed: 01/10/2023]
Abstract
Nephrotoxicity has been associated with nucleos(t)ide analogues other than telbivudine (LdT). This study investigated the potential effects of LdT and lamivudine (LAM) on renal function in an experimental rat model of gentamicin-induced acute nephrotoxicity. A total of 28 healthy Wistar albino rats were randomly divided into four experimental groups: negative control; positive control (PC); LdT; and LAM. Nephrotoxicity was induced by gentamicin in the LdT, LAM and PC groups. LdT and LAM were administered to two groups for 6 weeks starting on the ninth day. Blood samples were collected weekly and cystatin C levels were measured by ELISA. Animals were sacrificed on the 50th day and the kidneys were removed for histological examination. Serum cystatin C levels differed significantly between the LdT and LAM groups (P <0.007) and between the LdT and PC groups (P <0.001). Renal function was significantly improved in the LdT group at the start of antiviral treatment on Day 8 and at the end of treatment on Day 50 (P = 0.001 and 0.007). Glomerular injury, acute tubular necrosis and total injury score were significantly reduced in the LdT group relative to the PC and LAM groups upon histopathological examination. LdT was associated with significant improvements in renal function as measured by biochemical and histopathological methods. The acute kidney injury model data should be supported by clinical studies to suggest that LdT treatment may have advantages for patients with underlying chronic kidney disease receiving chronic hepatitis B treatment.
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Kayaaslan B, Guner R. Adverse effects of oral antiviral therapy in chronic hepatitis B. World J Hepatol 2017; 9:227-241. [PMID: 28261380 PMCID: PMC5316843 DOI: 10.4254/wjh.v9.i5.227] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2016] [Revised: 11/29/2016] [Accepted: 12/07/2016] [Indexed: 02/06/2023] Open
Abstract
Oral nucleoside/nucleotide analogues (NAs) are currently the backbone of chronic hepatitis B (CHB) infection treatment. They are generally well-tolerated by patients and safe to use. To date, a significant number of patients have been treated with NAs. Safety data has accumulated over the years. The aim of this article is to review and update the adverse effects of oral NAs. NAs can cause class adverse effects (i.e., myopathy, neuropathy, lactic acidosis) and dissimilar adverse effects. All NAs carry a "Black Box" warning because of the potential risk for mitochondrial dysfunction. However, these adverse effects are rarely reported. The majority of cases are associated with lamivudine and telbivudine. Adefovir can lead to dose- and time-dependent nephrotoxicity, even at low doses. Tenofovir has significant renal and bone toxicity in patients with human immunodeficiency virus (HIV) infection. However, bone and renal toxicity in patients with CHB are not as prominent as in HIV infection. Entecavir and lamivudine are not generally associated with renal adverse events. Entecavir has been claimed to increase the risk of lactic acidosis in decompensated liver disease and high Model for End-Stage Liver Disease scores. However, current studies reported that entecavir could be safely used in decompensated cirrhosis. An increase in fetal adverse events has not been reported with lamivudine, telbivudine and tenofovir use in pregnant women, while there is no adequate data regarding entecavir and adefovir. Further long-term experience is required to highlight the adverse effects of NAs, especially in special patient populations, including pregnant women, elderly and patients with renal impairment.
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Affiliation(s)
- Bircan Kayaaslan
- Bircan Kayaaslan, Rahmet Guner, Department of Infectious Disease and Clinical Microbiology, Yildirim Beyazit University Faculty of Medicine, Ataturk Education and Research Hospital, 06800 Ankara, Turkey
| | - Rahmet Guner
- Bircan Kayaaslan, Rahmet Guner, Department of Infectious Disease and Clinical Microbiology, Yildirim Beyazit University Faculty of Medicine, Ataturk Education and Research Hospital, 06800 Ankara, Turkey
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Lin YS, Shih SC, Wang HY, Lin CC, Chang CW, Chen MJ. Comparison of telbivudine and entecavir on the change of off- treatment eGFR after 3 years of treatment in non-cirrhotic chronic hepatitis B patients. BMC Gastroenterol 2017; 17:22. [PMID: 28137301 PMCID: PMC5282840 DOI: 10.1186/s12876-017-0582-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2016] [Accepted: 01/27/2017] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND The change of estimated glomerular filtration rate (eGFR) with off-treatment nucleos(t)ide analogues (NA) in chronic hepatitis B patients (CHB) is unclear. This study is aimed to evaluate the off-treatment eGFR after 3 years of therapy with telbivudine (LdT) or entecavir (ETV) and to assess predictive factors for eGFR improvement. METHODS From January 2009 to December 2011, we identified NA-naïve patients who were at least 20 years of age diagnosed with compensated CHB. All patients received a 3-year NA treatment and 1 year off-treatment follow-up; the initial selection of patients for LdT or ETV treatment was at the physicians' discretion. An increase of more than 10% in eGFR from the baseline was identified as an improvement. The change of chronic kidney disease stages were recorded and compared with baseline at year 3 and year 4, respectively. RESULTS This study included two groups consisting of 46 patients each (each with3 years of treatment with LdT or ETV). In LdT-treated patients, the mean eGFR increased from 94.3 ± 28.3 to 104.0 ± 31.2 mL/min/1.73 m2 in year 3 (p = 0.01) and from 104.0 ± 31.2 to 104.0 ± 28.8 mL/min/1.73 m2 in year 4 (p = 0.99). However, in ETV-treated patients, the mean eGFR decreased from 93.1 ± 26.1 to 85.5 ± 25.1 mL/min/1.73 m2 in year 3 (p = 0.0009) and from 85.5 ± 25.1 to 87.7 ± 24.8 mL/min/1.73 m2 in year 4 (p = 0.2). After a multivariate analysis, the predictors for the off-treatment eGFR improvement were the LdT treatment (odds ratio [OR], 3.97 (1.37-11.5), p = 0.01) and pre-treated eGFR (OR, 0.98 (0.95-1.00), p = 0.04). CONCLUSIONS At year 4, 48.8 and 21.3% patients had an improved eGFR from baseline in LdT and ETV patients, respectively. Telbivudine may have a protective renal effect that can last for one year after treatment in non-cirrhotic CHB patients without a virological breakthrough.
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Affiliation(s)
- Yang-Sheng Lin
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei Campus, No. 92, Sec. 2, Chungshan North Road, 104, Taipei, Taiwan
- MacKay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan
- MacKay Medical College, New Taipei City, Taiwan
| | - Shou-Chuan Shih
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei Campus, No. 92, Sec. 2, Chungshan North Road, 104, Taipei, Taiwan
- MacKay Medical College, New Taipei City, Taiwan
| | - Horng-Yuan Wang
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei Campus, No. 92, Sec. 2, Chungshan North Road, 104, Taipei, Taiwan
- MacKay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan
- MacKay Medical College, New Taipei City, Taiwan
| | - Ching-Chung Lin
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei Campus, No. 92, Sec. 2, Chungshan North Road, 104, Taipei, Taiwan
- MacKay Medical College, New Taipei City, Taiwan
| | - Chen-Wang Chang
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei Campus, No. 92, Sec. 2, Chungshan North Road, 104, Taipei, Taiwan
- MacKay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan
- MacKay Medical College, New Taipei City, Taiwan
| | - Ming-Jen Chen
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei Campus, No. 92, Sec. 2, Chungshan North Road, 104, Taipei, Taiwan.
- MacKay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan.
- MacKay Medical College, New Taipei City, Taiwan.
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27
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Lovett GC, Nguyen T, Iser DM, Holmes JA, Chen R, Demediuk B, Shaw G, Bell SJ, Desmond PV, Thompson AJ. Efficacy and safety of tenofovir in chronic hepatitis B: Australian real world experience. World J Hepatol 2017; 9:48-56. [PMID: 28105258 PMCID: PMC5220271 DOI: 10.4254/wjh.v9.i1.48] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2016] [Revised: 07/21/2016] [Accepted: 09/22/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the long-term treatment outcomes of tenofovir therapy in patients in a real world Australian tertiary care setting.
METHODS We performed a retrospective analysis of treatment outcomes among treatment-naïve and treatment-experienced patients receiving a minimum 3 mo tenofovir therapy through St Vincent’s Hospital Melbourne, Australia. We included patients receiving tenofovir [tenofovir disoproxil fumarate (TDF)] monotherapy, as well as patients treated with TDF in combination with a second antiviral agent. Patients were excluded if they demonstrated human immune-deficiency virus/hepatitis C virus/hepatitis delta virus coinfection or were less than 18 years of age. We considered virological and biochemical response, as well as safety outcomes. Virological response was determined by measurement of hepatitis B virus (HBV) DNA using sensitive assays; biochemical response was determined via serum liver function tests; histological response was determined from liver biopsy and fibroscan; safety analysis focused on glomerular renal function and bone mineral density. The primary efficacy endpoint was complete virological suppression over time, defined by HBV DNA < 20 IU/mL. Secondary efficacy endpoints included rates of biochemical response, and HB e antigen (HBeAg)/HB surface antigen loss and seroconversion over time.
RESULTS Ninety-two patients were identified who fulfilled the enrolment criteria. Median follow-up was 26 mo (range 3-114). Mean age was 46 (24-78) years, 64 (70%) were male and 77 (84%) were of Asian origin. 55 (60%) patients were treatment-naïve and 62 patients (67%) were HBeAg-negative. Complete virological suppression was achieved by 45/65 (71%) patients at 12 mo, 37/46 (80%) at 24 mo and 25/28 (89%) at 36 mo. Partial virological response (HBV DNA 20-2000 IU/mL) was achieved by 89/92 (96.7%) of patients. Multivariate analysis showed a significant relationship between virological suppression at end of follow-up and baseline HBV DNA level (OR = 0.897, 95%CI: 0.833-0.967, P = 0.0046) and HBeAg positive status (OR = 0.373, 95%CI: 0.183-0.762, P = 0.0069). There was no difference in response comparing treatment-naïve and treatment-experienced patients. Three episodes of virological breakthrough occurred in the setting of non-compliance. Tenofovir therapy was well tolerated.
CONCLUSION Tenofovir is an efficacious, safe and well-tolerated treatment in an Australian real-world tertiary care setting. Our data are similar to the reported experience from registration trials.
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Uteng M, Mahl A, Beckmann N, Piaia A, Ledieu D, Dubost V, Tritto E, Wolf A, Moulin P, Li L, Chibout SD, Pognan F. Editor's Highlight: Comparative Renal Safety Assessment of the Hepatitis B Drugs, Adefovir, Tenofovir, Telbivudine and Entecavir in Rats. Toxicol Sci 2016; 155:283-297. [PMID: 27742868 DOI: 10.1093/toxsci/kfw208] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
The aim of this study was to determine the relative safety of 4 antiviral drugs (telbivudine, tenofovir, adefovir, and entecavir) against hepatitis B virus with respect to kidney function and toxicity in male Sprague Dawley rats. The antiviral drugs were administered once daily for 4 weeks by oral gavage at ∼10 and 25-40 times the human equivalent dose. Main assessments included markers of renal toxicity in urine, magnetic resonance imaging (MRI) of kidney function, histopathology, and electron microscopic examination. Administration of adefovir at 11 and 28 mg/kg for 4 weeks caused functional and morphological kidney alterations in a time- and dose-dependent manner, affecting mainly the proximal tubules and suggesting a mechanism of toxicity related to mitochondrial degeneration/depletion. Of note, the observed adefovir-induced reduction of kidney function was not detected by the standard method of glomerular filtration rate (GFR) measurements (clearance rate of the endogenous marker, creatinine), thereby emphasizing the superiority of MRI in terms of sensitive detection of GFR in rats. For the low dose of 300 mg/kg of tenofovir, minor kidney effects such as nuclear enlargement in the tubular epithelium, and hyaline droplets accumulation were detected, which was also observed for the low dose (11 mg/kg) of adefovir. No assessments could be done at the higher dose of 600/1000 mg/kg tenofovir due to gastrointestinal tract toxicity which prevented treatment of the animals for longer than 1 week. Entecavir at 1 and 3 mg/kg and telbivudine at 600 and 1600 mg/kg caused no toxicologically relevant effects on the kidney.
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Affiliation(s)
- Marianne Uteng
- Department of Discovery and Investigative Safety, Novartis Institutes for BioMedical Research, Basel, Switzerland;
| | - Andreas Mahl
- Department of Discovery and Investigative Safety, Novartis Institutes for BioMedical Research, Basel, Switzerland
| | - Nicolau Beckmann
- Department of Discovery and Investigative Safety, Novartis Institutes for BioMedical Research, Basel, Switzerland
| | - Alessandro Piaia
- Department of Discovery and Investigative Safety, Novartis Institutes for BioMedical Research, Basel, Switzerland
| | - David Ledieu
- Department of Discovery and Investigative Safety, Novartis Institutes for BioMedical Research, Basel, Switzerland
| | - Valerie Dubost
- Department of Discovery and Investigative Safety, Novartis Institutes for BioMedical Research, Basel, Switzerland
| | - Elaine Tritto
- Department of Discovery and Investigative Safety, Novartis Institutes for BioMedical Research, Basel, Switzerland
| | - Armin Wolf
- Department of Discovery and Investigative Safety, Novartis Institutes for BioMedical Research, Basel, Switzerland
| | - Pierre Moulin
- Department of Discovery and Investigative Safety, Novartis Institutes for BioMedical Research, Basel, Switzerland
| | - Li Li
- Novartis Institutes for BioMedical Research, East Hanover, New Jersey
| | - Salah-Dine Chibout
- Department of Discovery and Investigative Safety, Novartis Institutes for BioMedical Research, Basel, Switzerland
| | - Francois Pognan
- Department of Discovery and Investigative Safety, Novartis Institutes for BioMedical Research, Basel, Switzerland
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Treatment of Hepatitis B: A Concise Review. Clin Transl Gastroenterol 2016; 7:e190. [PMID: 27628420 PMCID: PMC5288592 DOI: 10.1038/ctg.2016.46] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2016] [Accepted: 07/26/2016] [Indexed: 02/07/2023] Open
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Law MF, Ho R, Cheung CKM, Tam LHP, Ma K, So KCY, Ip B, So J, Lai J, Ng J, Tam THC. Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies treated with anticancer therapy. World J Gastroenterol 2016; 22:6484-6500. [PMID: 27605883 PMCID: PMC4968128 DOI: 10.3748/wjg.v22.i28.6484] [Citation(s) in RCA: 65] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2016] [Revised: 05/24/2016] [Accepted: 06/15/2016] [Indexed: 02/06/2023] Open
Abstract
Hepatitis due to hepatitis B virus (HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximab-containing therapy for hematological malignancies and those receiving stem cell transplantation. All patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti-HBc). Patients found to be positive for HBsAg should be given prophylactic antiviral therapy to prevent HBV reactivation. For patients with resolved HBV infection, no standard strategy has yet been established to prevent HBV reactivation. There are usually two options. One is pre-emptive therapy guided by serial HBV DNA monitoring, whereby antiviral therapy is given as soon as HBV DNA becomes detectable. However, there is little evidence regarding the optimal interval and period of monitoring. An alternative approach is prophylactic antiviral therapy, especially for patients receiving high-risk therapy such as rituximab, newer generation of anti-CD20 monoclonal antibody, obinutuzumab or hematopoietic stem cell transplantation. This strategy may effectively prevent HBV reactivation and avoid the inconvenience of repeated HBV DNA monitoring. Entecavir or tenofovir are preferred over lamivudine as prophylactic therapy. Although there is no well-defined guideline on the optimal duration of prophylactic therapy, there is growing evidence to recommend continuing prophylactic antiviral therapy for at least 12 mo after cessation of chemotherapy, and even longer for those who receive rituximab or who had high serum HBV DNA levels before the start of immunosuppressive therapy. Many novel agents have recently become available for the treatment of hematological malignancies, and these agents may be associated with HBV reactivation. Although there is currently limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBsAg-positive patients receiving novel treatments, especially the Bruton tyrosine kinase inhibitors and the phosphatidylinositol 3-kinase inhibitors, which are B-cell receptor signaling modulators and reduce proliferation of malignant B-cells. Further studies are needed to clarify the risk of HBV reactivation with these agents and the best prophylactic strategy in the era of targeted therapy for hematological malignancies.
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Tsai MC, Chen CH, Tseng PL, Hung CH, Chiu KW, Chang KC, Yen YH, Lin MT, Hu TH. Does Nucleos(t)ide Analogues Treatment Affect Renal Function in Chronic Hepatitis B Patients Who Have Already Decreased eGFR? A Longitudinal Study. PLoS One 2016; 11:e0149761. [PMID: 26964034 PMCID: PMC4786133 DOI: 10.1371/journal.pone.0149761] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2015] [Accepted: 02/04/2016] [Indexed: 01/10/2023] Open
Abstract
This study aimed to assess the renal function in chronic hepatitis B (CHB) patients who received nucleos(t)ide analogues (NAs) therapy using estimated glomerular filtration rate (eGFR) titer. We performed a longitudinal observational study of 37 tenofovir-, 42 telbivudine-, and 62 entecavir-naïve CHB patients, who had impaired renal function (eGFR, 90-30 ml/min/1.73m2) without history of diabetes, hypertension, and chemotherapy. Calculation and evaluation of eGFR was performed with the Modification of Diet in Renal Disease, Chronic Kidney Disease Epidemiology Collaboration, and Cockcroft-Gault formula at pretreatment, at baseline, and after the 1st and 2nd year of treatment. The eGFR was significantly increased in patients given telbivudine or entecavir (p = 0.003 and p = 0.012, respectively), but the eGFR was decreased in patients given tenofovir (p = 0.001) after 2 years of treatment. Of all patients, eGFR was stable one year prior to treatment. If we analyzed the renal function by change of chronic kidney disease (CKD) category with a change of 25% of eGFR, the proportion of uncertain drop (drop in CKD category with <25% decrease in eGFR) and certain drop (drop in CKD category with ≧25% decrease in eGFR) in tenofovir group was smaller (5.4%) than those of telbivudine (12.9%) or entecavir (6.5%). Furthermore, telbivudine had the lowest stable rate (76.2%), the highest certain rise rate (9.5%), and certain drop rate (7.1%) compared to the other groups (p = 0.049). In conclusion, in NAs-naïve CHB patients with impaired renal function, telbivudine and entecavir resulted in a significant increase in eGFR while tenofovir resulted in a significant decrease after a 2-year treatment. Interestingly, TDF had the lowest proportion of patients reclassified to certain and uncertain drop groups; in contrast, LdT had a higher proportion in both raise and drop groups. The outcomes of this renal effect remain to be determined.
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Affiliation(s)
- Ming-Chao Tsai
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chien-Hung Chen
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Po-Lin Tseng
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chao-Hung Hung
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - King-Wah Chiu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Kuo-Chin Chang
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yi-Hao Yen
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Ming-Tsung Lin
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
- Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Tsung-Hui Hu
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan
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Cheung KS, Seto WK, Lai CL, Yuen MF. Prevention and management of hepatitis B virus reactivation in cancer patients. Hepatol Int 2016; 10:407-14. [PMID: 26739135 DOI: 10.1007/s12072-015-9692-3] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2015] [Accepted: 11/24/2015] [Indexed: 12/19/2022]
Abstract
Hepatitis B virus (HBV) reactivation during immunosuppressive therapy is common in patients with solid tumor or hematological malignancies. It is associated with significant morbidity and mortality due to hepatitis flare and/or hepatic decompensation. These consequences arising from HBV reactivation are, however, largely preventable. Routine screening for HBV serologic status is recommended for all cancer patients undergoing chemotherapy or biologics. By recognizing different serological patterns (which represent either overt or occult HBV infection) and the types of immunosuppressive therapies prescribed, a risk-adapted approach can be established. Prophylactic therapy with nucleos(t)ide analogues (prior to or concomitantly with the commencement of immunosuppressive therapies) is more effective than pre-emptive therapy (starting antiviral when HBV DNA level is rising) in high-risk individuals. Entecavir has been proven to be more effective than lamivudine according to recent studies. Close monitoring of serum HBV level is the preferred strategy in low-risk patients. However, the optimal interval of DNA monitoring and the duration of therapy remain unknown.
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Affiliation(s)
- Ka-Shing Cheung
- Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam Road, Hong Kong, China
| | - Wai-Kay Seto
- Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam Road, Hong Kong, China.,State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China
| | - Ching-Lung Lai
- Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam Road, Hong Kong, China.,State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China
| | - Man-Fung Yuen
- Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Pokfulam Road, Hong Kong, China. .,State Key Laboratory for Liver Research, The University of Hong Kong, Hong Kong, China.
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Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HLY, Chen CJ, Chen DS, Chen HL, Chen PJ, Chien RN, Dokmeci AK, Gane E, Hou JL, Jafri W, Jia J, Kim JH, Lai CL, Lee HC, Lim SG, Liu CJ, Locarnini S, Al Mahtab M, Mohamed R, Omata M, Park J, Piratvisuth T, Sharma BC, Sollano J, Wang FS, Wei L, Yuen MF, Zheng SS, Kao JH. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int 2016; 10:1-98. [PMID: 26563120 PMCID: PMC4722087 DOI: 10.1007/s12072-015-9675-4] [Citation(s) in RCA: 1918] [Impact Index Per Article: 213.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2015] [Accepted: 09/14/2015] [Indexed: 02/06/2023]
Abstract
Worldwide, some 240 million people have chronic hepatitis B virus (HBV), with the highest rates of infection in Africa and Asia. Our understanding of the natural history of HBV infection and the potential for therapy of the resultant disease is continuously improving. New data have become available since the previous APASL guidelines for management of HBV infection were published in 2012. The objective of this manuscript is to update the recommendations for the optimal management of chronic HBV infection. The 2015 guidelines were developed by a panel of Asian experts chosen by the APASL. The clinical practice guidelines are based on evidence from existing publications or, if evidence was unavailable, on the experts' personal experience and opinion after deliberations. Manuscripts and abstracts of important meetings published through January 2015 have been evaluated. This guideline covers the full spectrum of care of patients infected with hepatitis B, including new terminology, natural history, screening, vaccination, counseling, diagnosis, assessment of the stage of liver disease, the indications, timing, choice and duration of single or combination of antiviral drugs, screening for HCC, management in special situations like childhood, pregnancy, coinfections, renal impairment and pre- and post-liver transplant, and policy guidelines. However, areas of uncertainty still exist, and clinicians, patients, and public health authorities must therefore continue to make choices on the basis of the evolving evidence. The final clinical practice guidelines and recommendations are presented here, along with the relevant background information.
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Affiliation(s)
- S K Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
| | - M Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - G K Lau
- Division of Gastroenterology and Hepatology, Humanity and Health Medical Centre, Hong Kong SAR, China
- The Institute of Translational Hepatology, Beijing, China
| | - Z Abbas
- Department of Hepatogastroenterlogy, Sindh Institute of Urology and Transplantation, Karachi, Pakistan
| | - H L Y Chan
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - C J Chen
- Genomics Research Center, Academia Sinica, National Taiwan University, Taipei, Taiwan
| | - D S Chen
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - H L Chen
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - P J Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - R N Chien
- Liver Research Unit, Chang Gung Memorial Hospital and University, Chilung, Taiwan
| | - A K Dokmeci
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
| | - Ed Gane
- New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand
| | - J L Hou
- Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Guangzhou, China
| | - W Jafri
- Department of Medicine, Aga Khan University, Karachi, Pakistan
| | - J Jia
- Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | | | - C L Lai
- Department of Medicine, University of Hong Kong, Hong Kong, China
| | - H C Lee
- Internal Medicine Asan Medical Center, Seoul, Korea
| | - S G Lim
- Division of Gastroenterology and Hepatology, National University Health System, Singapore, Singapore
| | - C J Liu
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - S Locarnini
- Research and Molecular Development, Victorian Infectious Diseases Reference Laboratory, Melbourne, Australia
| | - M Al Mahtab
- Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - R Mohamed
- Department of Medicine, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia
| | - M Omata
- Yamanashi Hospitals (Central and Kita) Organization, 1-1-1 Fujimi, Kofu-shi, Yamanashi, 400-8506, Japan
| | - J Park
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - T Piratvisuth
- NKC Institute of Gastroenterology and Hepatology, Prince of Songkla University, Songkhla, Thailand
| | - B C Sharma
- Department of Gastroenterology, G.B. Pant Hospital, New Delhi, India
| | - J Sollano
- Department of Medicine, University of Santo Tomas, Manila, Philippines
| | - F S Wang
- Treatment and Research Center for Infectious Diseases, Beijing 302 Hospital, Beijing, China
| | - L Wei
- Peking University Hepatology Institute, Beijing, China
| | - M F Yuen
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Hong Kong, Pofulam, Hong Kong
| | - S S Zheng
- Department of Hepatobiliary and Pancreatic Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, Zhejiang Province, China
| | - J H Kao
- Graduate Institute of Clinical Medicine and Hepatitis Research Center, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
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Pipili C, Cholongitas E. Pharmaceutical management of hepatitis B and C in liver and kidney transplant recipients. World J Gastrointest Pharmacol Ther 2015; 6:105-10. [PMID: 26558143 PMCID: PMC4635149 DOI: 10.4292/wjgpt.v6.i4.105] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2015] [Revised: 07/05/2015] [Accepted: 07/29/2015] [Indexed: 02/06/2023] Open
Abstract
The combination of hepatitis B immune globulin with entecavir or tenofovir (at least for a certain period of time) seems to be the most reasonable prophylaxis against recurrent hepatitis B after liver transplantation. Entecavir represents an attractive option for treatment of naïve kidney transplant recipients, because of its high efficacy and the low rates of resistance. However antiviral treatment should be individualized in the view of kidney function and the previous resistance. To date, new captivating therapeutic strategies could make interferon-free regimens viable for treatment of hepatitis C virus positive liver transplant recipients. The recent combinations of sofosbuvir with simeprevir or daclatasvir or ledipasvir plus/minus ribavirin have boosted the on treatment and sustained virological response to rates approaching 100% within liver transplant recipients with recurrent chronic hepatitis C (CHC). Preliminary data showed that the second generation direct oral antivirals could result to high treatment rates of recurrent CHC in kidney transplant recipients as well. Ongoing studies will clarify the optimal treatment of recurrent CHC in kidney transplant recipients.
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Lee JG, Lee J, Lee JJ, Song SH, Ju MK, Choi GH, Kim MS, Choi JS, Kim SI, Joo DJ. Adefovir- or Lamivudine-Induced Renal Tubular Dysfunction after Liver Transplantation. Medicine (Baltimore) 2015; 94:e1569. [PMID: 26402818 PMCID: PMC4635758 DOI: 10.1097/md.0000000000001569] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
To reduce hepatitis B virus reinfection after liver transplantation (LT), patients often receive antihepatitis B immunoglobulin (HBIG) alone or combined with antiviral nucleoside/nucleotide analogs (NUCs); however, proximal renal tubular dysfunction (RTD) that was induced by NUCs in liver recipients was rarely reported. Here, we analyzed RTD and renal impairment (RI) following adefovir (ADV) and lamivudine (LAM) treatment in liver recipients. We retrospectively reviewed medical records of patients treated with HBIG alone (group 1, n = 42) or combined with ADV or LAM (group 2, n = 21) after LT. We compared RTD and RI incidence during the 12 months after LT. An RTD diagnosis required manifestation of at least 3 of the following features: hypophosphatemia, RI, hypouricemia, proteinuria, or glucosuria. No significant differences were observed regarding sex, age, donor type, model of end-stage liver score, and estimated glomerular filtration rate at pre-LT between the 2 groups. Hepatitis B virus recurrence within 12 months was 4.8% in both groups (P = 1.000); however, the RTD incidence was 0% in group 1 and 19.0% in group 2 (P = 0.010). RI occurrence did not differ between the groups. The only risk factor for RI was HBIG administration combined with both LAM and ADV (odds ratio 11.27, 95% confidence interval 1.13-112.07, P = 0.039, vs HBIG alone). RTD occurred more frequently in patients treated with HBIG combined with LAM or ADV compared with HBIG alone. Thus, LAM or ADV therapy can induce RTD after LT, and when administered, liver recipients should be monitored.
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Affiliation(s)
- Jae Geun Lee
- From the Yonsei University College of Medicine, Seoul (JGL, JL, SHS, MKJ, GHC, MSK, JSC, SIK, DJJ), Department of Surgery, CHA Bundang Medical Center, CHA University, Bundang (JJL); and The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea (JGL, MSK, SIK, DJJ)
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Mikolajczyk AE, Aronsohn AI. Current Management of Chronic Hepatitis B and C in Chronic Kidney Disease. Adv Chronic Kidney Dis 2015; 22:352-60. [PMID: 26311596 DOI: 10.1053/j.ackd.2015.06.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2015] [Revised: 06/18/2015] [Accepted: 06/22/2015] [Indexed: 12/15/2022]
Abstract
The landscape of therapeutic options for hepatitis B and C has changed drastically over the course of 2 decades. There are now novel, effective, well-tolerated, oral antiviral agents being used to successfully control chronic hepatitis B (HBV) infections and cure chronic hepatitis C (HCV) infections. However, patients with CKD were rarely included in the Phase II and III randomized trials for these medications. This paucity of data and the high prevalence of comorbidities associated with CKD pose distinct challenges to physicians treating chronic hepatitis B virus and hepatitis C virus infections in the setting of kidney insufficiency/failure. Thus, this review will attempt to summarize the current data regarding novel antiviral therapies for HBV and HCV in the CKD population.
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Cholongitas E, Vasiliadis T, Goulis I, Fouzas I, Antoniadis N, Papanikolaou V, Akriviadis E. Telbivudine is associated with improvement of renal function in patients transplanted for HBV liver disease. J Viral Hepat 2015; 22:574-80. [PMID: 25385239 DOI: 10.1111/jvh.12362] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2014] [Accepted: 10/14/2014] [Indexed: 12/13/2022]
Abstract
Recent studies showed that telbivudine in patients with hepatitis B virus (HBV) infection improved their glomerular filtration rate (GFR), but data regarding its impact on renal function in liver transplant (LT) recipients are very limited. We evaluated 17 consecutive recipients who received at baseline nucleos(t)ide analogue(s) (NAs) other than telbivudine for 12 months, and then they were switched to telbivudine prophylaxis for another 12 months. In each patient, laboratory data including evaluation of GFR (using MDRD and CKD-EPI) were prospectively recorded. The changes in GFR (ΔGFR) between baseline and after 12 months (1st period) and between telbivudine initiation and 24 months (2nd period) were evaluated. All patients remained serum HBsAg and HBV-DNA negative. GFR-MDRD at baseline, 12 months and 24 months were 72 ± 18, 67.8 ± 16 and 70.3 ± 12 mL/min, respectively, (P = 0.025 for comparison between 12 months and 24 months). ΔGFR at the 1st period was significantly lower, compared with ΔGFR at the 2nd period [mean ΔGFR-MDRD: -4.2 (range: -24-9) vs 2.5 (range: -7-22) mL/min, P = 0.013; mean ΔGFR-CKD-EPI: -4.2 (range: -19-10) vs 4.0 (range: -7-23) mL/min, P = 0.004], although the serum levels of calcineurin inhibitors were similar between the two periods. A second group of recipients (n = 17) who remained under the same nontelbivudine NA(s) for 24 months had a decline in the mean eGFR during the total follow-up period. In conclusion, we showed that telbivudine administration in LT recipients for HBV cirrhosis was effective and it was associated with significant improvement in renal function, but this remains to be confirmed in larger well-designed studies.
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Affiliation(s)
- E Cholongitas
- 4th Department of Internal Medicine, Medical School of Aristotle University, Hippokration General Hospital of Thessaloniki, Thessaloniki, Greece
| | - T Vasiliadis
- 1st Pr. Department of Internal Medicine, AHEPA General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - I Goulis
- 4th Department of Internal Medicine, Medical School of Aristotle University, Hippokration General Hospital of Thessaloniki, Thessaloniki, Greece
| | - I Fouzas
- Department of Transplant Surgery, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - N Antoniadis
- Department of Transplant Surgery, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - V Papanikolaou
- Department of Transplant Surgery, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - E Akriviadis
- 4th Department of Internal Medicine, Medical School of Aristotle University, Hippokration General Hospital of Thessaloniki, Thessaloniki, Greece
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The case of chronic hepatitis B treatment with tenofovir: an update for nephrologists. J Nephrol 2015; 28:393-402. [DOI: 10.1007/s40620-015-0214-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2015] [Accepted: 05/22/2015] [Indexed: 12/29/2022]
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Abstract
Hepatitis outbreaks in hemodialysis (HD) patients and staff were reported in the late 1960s, and a number of hepatotropic viruses transmitted by blood and other body fluids have been identified. Hepatitis B virus (HBV) was the first significant hepatotropic virus to be identified in HD centers. HBV infection has been effectively controlled by active vaccination, screening of blood donors, the use of erythropoietin and segregation of HBV carriers. Hepatitis delta virus is a defective virus that can only infect HBV-positive individuals. Hepatitis C virus (HCV) is the most significant cause of non-A, non-B hepatitis and is mainly transmitted by blood transfusion. The introduction in 1990 of routine screening of blood donors for HCV contributed significantly to the control of HCV transmission. An effective HCV vaccine remains an unsolved challenge; however, pegylation of interferon-alfa has made it possible to treat HCV-positive dialysis patients. Unexplained sporadic outbreaks of hepatitis by the mid-1990s prompted the discovery of hepatitis G virus, hepatitis GB virus C and the TT virus. The vigilant observation of guidelines on universal precaution and regular virologic testing are the cornerstones of the effective control of chronic hepatitis in the setting of HD. Major recent advances in the viral diagnosis technology and the development of new oral, direct-acting antiviral agents allow early diagnosis and better therapeutic response. The current update will review the recent developments, controversies and new treatment of viral hepatitis in HD patients.
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Affiliation(s)
- Bassam Bernieh
- Consultant and Chief of Nephrology, Tawam Hospital in Affiliation with Johns Hopkins Medicine, Clinical Professor of Medicine, COMHS, UAE University, Al Ain, UAE
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Wahle RC, Perez RM, Pereira PF, Oliveira EMG, Emori CT, Uehara SNDO, Silva ISDS, Silva AEB, Ferraz MLG. Hepatitis B virus reactivation after treatment for hepatitis C in hemodialysis patients with HBV/HCV coinfection. Braz J Infect Dis 2015; 19:533-7. [PMID: 25997784 PMCID: PMC9427496 DOI: 10.1016/j.bjid.2015.04.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2014] [Revised: 12/30/2014] [Accepted: 04/17/2015] [Indexed: 12/30/2022] Open
Abstract
In coinfected HBV/HCV patients, HBV replication is usually suppressed by HCV over the time. No study to date has evaluated the HBV viremia in long-term follow-up after HCV treatment in hemodialysis patients with HBV/HCV coinfection. This study aimed to assess the evolution of HBV viremia after HCV treatment in this special population. Ten hemodialysis patients with HBV/HCV coinfection with dominant HCV infection (HBV lower than 2000 IU/mL) and significant fibrosis were treated with interferon-alpha 3 MU 3×/week for 12 months and could be followed for at least 36 months after HCV treatment. Six cases of HBV reactivation (60%) during follow-up were observed and 5/6 had been successfully treated for HCV. Patients with HBV reactivation received anti-HBV therapy. Our preliminary findings indicate that treatment of hepatitis C in HBV/HCV coinfected hemodialysis patients may favor HBV reactivation. Thus, continued monitoring of HBV viremia must be recommended and prompt anti-HBV therapy should be implemented.
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Affiliation(s)
- Raul Carlos Wahle
- Discipline of Gastroenterology, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.
| | - Renata Mello Perez
- Department of Internal Medicine, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil
| | - Patrícia Fucuta Pereira
- Discipline of Gastroenterology, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil
| | | | - Christini Takemi Emori
- Discipline of Gastroenterology, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil
| | | | | | | | - Maria Lucia Gomes Ferraz
- Discipline of Gastroenterology, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil
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41
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Ridruejo E. Antiviral treatment for chronic hepatitis B in renal transplant patients. World J Hepatol 2015; 7:189-203. [PMID: 25729474 PMCID: PMC4342601 DOI: 10.4254/wjh.v7.i2.189] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2014] [Revised: 11/07/2014] [Accepted: 11/17/2014] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis B infection is frequent in renal transplant patients. It negatively impacts long term outcomes reducing graft and patient survival. Current guidelines clearly define who needs treatment, when to start, what is the first line therapy, how to monitor treatment response, when to stop, and how patients must be controlled for its safety. There is some data showing a favorable safety and efficacy profile of nucleos(t)ide analogue (NUC) treatment in the renal transplant setting. Entecavir, a drug without major signs of nephrotoxicity, appears to be the first option for NUC naïve patients and tenofovir remains the preferred choice for patients with previous resistance to lamivudine or any other NUC. Renal transplant recipients under antiHBV therapy should be monitored for its efficacy against HBV but also for its safety with a close renal monitoring. Studies including a large number of patients with long term treatment and follow up are still needed to better demonstrate the safety and efficacy of newer NUCs in this population.
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Affiliation(s)
- Ezequiel Ridruejo
- Ezequiel Ridruejo, Hepatology Section, Department of Medicine, Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno "CEMIC", Ciudad Autónoma de Buenos Aires, C1425ASG Buenos Aires, Argentina
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42
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Cholongitas E, Tziomalos K, Pipili C. Management of patients with hepatitis B in special populations. World J Gastroenterol 2015; 21:1738-1748. [PMID: 25684938 PMCID: PMC4323449 DOI: 10.3748/wjg.v21.i6.1738] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2014] [Revised: 10/27/2014] [Accepted: 11/18/2014] [Indexed: 02/06/2023] Open
Abstract
The development of effective nucleos(t)ide analogs (NAs) against hepatitis B virus (HBV) has improved the outcome of patients with chronic hepatitis B (CHB). This review updates issues related to the management of CHB patients included in special populations. Entecavir (ETV) and tenofovir (TDF) represent the currently recommended first-line NAs in patients with HBV decompensated cirrhosis. The combination of HBV immunoglobulin (usually for a finite duration) and NA is considered the standard of care for prophylaxis against HBV recurrence after liver transplantation. TDF is the best choice for hemodialysis patients and in patients with chronic kidney disease with nucleoside resistance. ETV and telbivudine are the preferred options in naïve renal transplant recipients and with low viremia levels, respectively. All hepatitis B surface antigen (HBsAg)-positive candidates should be treated with NAs before renal transplantation to achieve undetectable HBV DNA at the time of transplantation. Conventional interferon or NAs can also be used in children, on the basis of well-established therapeutic indication. Pregnant women at high risk of perinatal transmission could be treated with lamivudine, telbivudine or TDF in the last trimester of pregnancy. HBsAg-positive patients under immunosuppression should receive NA pre-emptively (regardless of HBV DNA levels) up to 12 mo after its cessation. In HBsAg negative, anti-HBc positive patients under immunosuppression, further studies are needed to form a final conclusion; however, it seems that anti-HBV prophylaxis is justified in such patients with hematological diseases and/or for those receiving rituximab-containing regimens, regardless of their anti-HBs or serum HBV DNA status.
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43
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Koklu S, Gulsen MT, Tuna Y, Koklu H, Yuksel O, Demir M, Guner R, Dogan Z, Kucukazman M, Poyrazoglu OK, Biyik M, Ozturk NA, Aydogan T, Coban S, Kocaman O, Sapmaz F, Gokturk SH, Karaca C, Demirezer A, Tanoglu A, Yildirim B, Altinbas A, Atak BM, Cosar AM, Alkan E. Differences in nephrotoxicity risk and renal effects among anti-viral therapies against hepatitis B. Aliment Pharmacol Ther 2015; 41:310-9. [PMID: 25982037 DOI: 10.1111/apt.13036] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2014] [Revised: 09/03/2014] [Accepted: 11/06/2014] [Indexed: 12/12/2022]
Abstract
BACKGROUND Results are conflicting with respect to the renal effects of anti-viral agents used for hepatitis B virus infection. AIM To compare short and long-term renal effects in real-life settings and to determine risk factors for renal impairment during treatment. METHODS 2221 treatment-naïve patients were enrolled. Among these, 895 (302 lamivudine, 27 telbivudine, 282 entecavir, 273 tenofovir and 11 adefovir initiated patients) had 'repeated measures' of creatinine (baseline, 1st, 6th, 12th and 24th month of treatment). Telbivudine and adefovir groups were excluded from further analysis because of the low number of patients. We calculated the glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease (MDRD) formula at each time point. Hypophosphataemia was also recorded. Risk factors for renal impairment were analysed. RESULTS Tenofovir caused a decline in GFR at each time point when compared to baseline levels. However, lamivudine and entecavir did not change GFR. GFR-shifting from ≥90 to 60-89 mL/min/1.73 m(2) was comparable among groups. The proportion of patients whose baseline creatinine increased more than 25% was comparable among all anti-virals. GFR showed a decline in patients who switched from entecavir to tenofovir. One patient with compensated cirrhosis needed to change from tenofovir because of renal safety. Seven and three patients developed transient hypophosphataemia in the tenofovir and lamivudine groups, respectively. CONCLUSIONS Although tenofovir caused a decline in GFR, differences between the anti-viral agents do not appear to be so impressive. In patients with and without renal risk factors at baseline, there is no impact of anti-virals, including tenofovir.
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Affiliation(s)
- S Koklu
- Department of Gastroenterology, Hacettepe University School of Medicine, Ankara, Turkey
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44
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Buti M, Morillas RM, Pérez J, Prieto M, Solà R, Palau A, Diago M, Bonet L, Gallego A, García-Samaniego J, Testillano M, Rodríguez M, Castellano G, Gutiérrez ML, Delgado M, Mas A, Romero-Gómez M, Calleja JL, González-Guirado A, Arenas JI, García-Buey L, Andrade R, Gila A. Entecavir has high efficacy and safety in white patients with chronic hepatitis B and comorbidities. Eur J Gastroenterol Hepatol 2015; 27:46-54. [PMID: 25341057 DOI: 10.1097/meg.0000000000000195] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
OBJECTIVES The aim of this study was to evaluate the efficacy and safety of entecavir monotherapy in nucleos(t)ide-naive chronic hepatitis B patients and to analyse the influence of the comorbidity burden on therapy outcome. METHODS We retrospectively analysed data from 237 nucleos(t)ide-naive chronic hepatitis B white patients treated with entecavir (0.5 mg/day) at 23 Spanish centres. For the efficacy and safety analyses, patients were grouped according to their baseline comorbidities. RESULTS The mean age of the cohort was 43 years (range: 19-82 years); 73% were male, 83% were white, and 33% were hepatitis B e antigen (HBeAg) positive. At baseline, the median hepatitis B virus DNA level was 6.20 log10 IU/ml. Of the patients, 18% had cirrhosis, 9.7% had diabetes, 16.3% had hypertension, and 15.7% had obesity; 13.4% of patients had more than one comorbid condition. Virological and biochemical responses at month 36 were obtained independently of the patients' baseline comorbid condition. Of 10 HBeAg-positive patients who discontinued treatment after HBeAg seroconversion, those who had not also cleared HBsAg (six) experienced virological recurrence in a median 5.6 months. There were no treatment discontinuations due to adverse events. Three patients were diagnosed with hepatocellular carcinoma at months 12, 30 and 54, and six experienced hepatic decompensation during follow-up. The median serum creatinine levels did not increase after 36 months of treatment, even in patients with comorbidities. CONCLUSION Entecavir is safe, well tolerated, and highly effective, even in patients with comorbid condition(s). Discontinuation of treatment in patients who have not been cleared of HBsAg may lead to virological recurrence.
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Affiliation(s)
- Maria Buti
- aCIBER on Liver and Digestive Diseases (CIBERehd), Hospital Vall d'Hebron bHospital del Mar, IMIM, Universitat Autònoma de Barcelona cHospital de la Santa Creu i Sant Pau dHospital Clínic, Barcelona eCIBERehd H. La Fe, Hospital General Universitario de Castellón, Castellón fHospital Son Espases, Palma de Mallorca gCIBERehd, Hospital Universitari Germans Trias i Pujol, Badalona hCIBERehd, Hospital Carlos III iHospital Universitario 12 de Octubre jHospital Puerta del Hierro kFundación Jiménez Díaz lCIBERehd, Hospital Universitario La Princesa, Madrid mHospital de Cruces, Bizkaia nHospital Virgen Macarena oCIBERehd, Hospital Universitario de Valme, Sevilla pHospital Central de Asturias, Oviedo qHospital Universitario Fundación Alcorcón, Alcorcón rHospital Universitario de La Coruña, A Coruña sHospital Universitario Donostia, Donostia tCIBERehd, Hospital Universitario y Politécnico La Fe uHospital General Universitario de Valencia, Valencia vCIBERehd, Hospital Virgen de la Victoria, Málaga wHospital Universitario San Cecilio, Granada, Spain
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45
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Chen TM, Lin CC. Letter: tenofovir is associated with higher probability of acute kidney injury compared with entecavir. Aliment Pharmacol Ther 2014; 40:406-7. [PMID: 25040928 DOI: 10.1111/apt.12854] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2014] [Accepted: 06/08/2014] [Indexed: 02/02/2023]
Affiliation(s)
- T-M Chen
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Tungs' Taichung MetroHarbor Hospital, Taichung, Taiwan
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46
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Chen EQ, Shi Y, Wu DB, Tang H. Liquid oral suspension adefovir dipivoxil (GS-02-526): an update on treatments for hepatitis B infection. Expert Rev Anti Infect Ther 2014; 12:919-928. [PMID: 24927815 DOI: 10.1586/14787210.2014.928588] [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] [Indexed: 02/05/2023]
Abstract
Though the global epidemiology of hepatitis B virus infection has declined due to effective immunization, chronic hepatitis B (CHB) remains a serious public health problem and there is still a need for more treatment options that are efficient, safe and simple for different kinds of CHB patients. Adefovir dipivoxil (ADV) liquid suspension (GS-02-526), as a new form of oral ADV, not only has competent antiviral efficacy, but is also more convenient for patients with swallowing difficulties or patients with impaired renal function requiring dosage adjustment. The clinical data evaluating the safety, tolerability and antiviral activity of liquid suspension of ADV as well as its tablet are summarized in this article. The availability of liquid oral suspension of ADV would allow more patients to receive timely and reasonable antiviral treatments.
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Affiliation(s)
- En-Qiang Chen
- Center of Infectious Diseases, West China Hospital of Sichuan University, No. 37 Guo Xue Xiang, Chengdu 610041, China
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Marengo A, Marietti M, Rizzetto M, Marzano A. Letter: renal effects of tenofovir in adefovir dipivoxil-experienced HBV patients. Aliment Pharmacol Ther 2014; 40:324. [PMID: 25040751 DOI: 10.1111/apt.12839] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2014] [Accepted: 05/26/2014] [Indexed: 12/08/2022]
Affiliation(s)
- A Marengo
- Gastro-Hepatology Unit, Città della Salute e della Scienza di Torino, San Giovanni Battista Hospital, University of Turin, Italy.
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Pipili C, Cholongitas E. Μanagement of patients with hepatitis B and C before and after liver and kidney transplantation. World J Hepatol 2014; 6:315-25. [PMID: 24868325 PMCID: PMC4033289 DOI: 10.4254/wjh.v6.i5.315] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2013] [Revised: 03/10/2014] [Accepted: 04/16/2014] [Indexed: 02/06/2023] Open
Abstract
New nucleos(t)ide analogues (NAs) with high genetic barrier to hepatitis B virus (HBV) resistance (such as entecavir, tenofovir) have improved the prognosis of patients with HBV decompensated cirrhosis and have prevented HBV recurrence after liver transplantation (LT). NAs are considered the most proper approach for HBV infection in patients under renal replacement therapy but their doses should be adjusted according to the patient's creatinine clearance. In addition, physicians should be aware of the potential nephrotoxicity. However, patients with chronic hepatitis C and decompensated cirrhosis can receive only one therapeutic option before LT, as well as for Hepatitis C virus (HCV) recurrence after LT, which is the combination of subcutaneous Peg-IFN and ribavirin. Generally, therapy for HCV after renal transplantation should be avoided. Although the optimal antiviral therapy for HCV infection has not been established, attention has turned to a new, oral direct acting antiviral treatment which marks a promising strategy in prognosis and in amelioration of these diseases.
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Affiliation(s)
- Chrysoula Pipili
- Chrysoula Pipili, Department of Nephrology, Laiki Merimna, 17343 Athens, Greece
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