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Lin CY, Sun WC, Lu CM, Chen WC, Tsay FW, Tsai TJ, Kuo FY, Tsai WL. Entecavir vs. tenofovir disoproxil fumarate in the treatment of chronic hepatitis B patients with severe acute exacerbation. Eur J Gastroenterol Hepatol 2024; 36:1113-1118. [PMID: 38973530 DOI: 10.1097/meg.0000000000002709] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 07/09/2024]
Abstract
BACKGROUND The efficacy of different nucleos(t)ide analogs in the treatment of chronic hepatitis B virus (CHB) with severe acute exacerbation (SAE) remained unclear. Thus, this study aimed to compare the short-term efficacy of tenofovir disoproxil fumarate (TDF) and entecavir (ETV) in patients having CHB with SAE. METHODS We analyzed consecutive patients with treatment-naive CHB receiving TDF (n = 36) or ETV (n = 65) for SAE. The primary endpoint was overall mortality or receipt of liver transplantation (LT) by 24 weeks. The secondary endpoints are the comparison of ETV vs. TDF influences on renal function and virological and biochemical responses at 4, 12, 24, and 48 weeks. RESULTS The baseline characteristics were comparable between the two groups. By 24 weeks, 8 (22%) patients in the TDF group and 10 (15%) patients in the ETV group had either died (n = 15) or received LT (n = 3) ( P = 0.367). Cox-regression multivariate analysis revealed age ( P = 0.003), baseline international normalized ratio of prothrombin time ( P = 0.024), and early presence of hepatic encephalopathy ( P = 0.003) as independent factors associated with mortality or LT. The two groups of patients achieved comparable biochemical and virological responses at 48 weeks. No significant difference was found in the estimated glomerular filtration rate (eGFR) between the TDF and the ETV groups. However, a significant reduction in the eGFR at 48 weeks, as compared with the baseline, was found in each group. CONCLUSION TDF and ETV achieved similar short-term clinical outcomes and treatment responses in CHB patients with SAE.
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Affiliation(s)
- Chih-Yang Lin
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung
- School of Medicine, National Yang Ming Chiao Tung University, Taipei
| | - Wei-Chih Sun
- School of Medicine, National Yang Ming Chiao Tung University, Taipei
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital
| | - Chia-Ming Lu
- School of Medicine, National Yang Ming Chiao Tung University, Taipei
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital
| | - Wen-Chi Chen
- School of Medicine, National Yang Ming Chiao Tung University, Taipei
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital
| | - Feng-Woei Tsay
- School of Medicine, National Yang Ming Chiao Tung University, Taipei
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital
| | - Tzun-Jiun Tsai
- School of Medicine, National Yang Ming Chiao Tung University, Taipei
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital
| | - Feng-Yu Kuo
- Division of Cardiology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung
- School of Medicine, National Yang Ming Chiao Tung University, Taipei
| | - Wei-Lun Tsai
- School of Medicine, National Yang Ming Chiao Tung University, Taipei
- Division of General Internal Medicine, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
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Zeng F, Jiang W, Chang X, Yang F, Luo X, Liu R, Lei Y, Li J, Pan C, Huang X, Sun H, Lan Y. Sarcopenia is associated with short- and long-term mortality in patients with acute-on-chronic liver failure. J Cachexia Sarcopenia Muscle 2024; 15:1473-1482. [PMID: 38965993 PMCID: PMC11294047 DOI: 10.1002/jcsm.13501] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 03/21/2024] [Accepted: 04/08/2024] [Indexed: 07/06/2024] Open
Abstract
BACKGROUND While sarcopenia is recognized as a predictor of mortality in cirrhosis, its influence on acute-on-chronic liver failure (ACLF) remains uncertain. Despite multiple studies examining the impact of sarcopenia on short-term mortality in patients with ACLF, the sample size of these studies was limited, and their outcomes were inconsistent. Therefore, this study aimed to explore the impact of sarcopenia on both short- and long-term mortality in patients with ACLF. METHODS This retrospective cohort study included 414 patients with ACLF that were treated between January 2016 and September 2022. Sarcopenia was diagnosed based on the measurement of the skeletal muscle index at the third lumbar vertebra (L3-SMI). Subsequently, the patients were divided into sarcopenia and non-sarcopenia groups. We analysed the basic clinical data of the two groups. Multivariate Cox proportional analysis was used to analyse short-term (28 days) and long-term (1 year and overall) mortality rates. RESULTS A total of 414 patients were included, with a mean age of 52.88 ± 13.41 years. Among them, 318 (76.8%) were male, and 239 (57.7%) had sarcopenia. A total of 280 (67.6%) patients died during the study period. Among them, 153 patients died within 28 days (37%) and 209 patients died within 1 year (50.5%). We found that the 28-day, 1-year and overall mortality rates in the sarcopenia group were significantly higher than those in the non-sarcopenia group (37% vs. 22.3%, P < 0.01; 50.5% vs. 34.9%, P < 0.01; and 67.6% vs. 53.1%, P < 0.01, respectively). Multivariate Cox regression analysis revealed that sarcopenia was significantly associated with increased mortality. The hazard ratios for sarcopenia were 2.05 (95% confidence interval [CI] 1.41-3.00, P < 0.01) for 28-day mortality, 1.81 (95% CI 1.29-2.54, P < 0.01) for 1-year mortality and 1.82 (95% CI 1.30-2.55, P < 0.01) for overall mortality. In addition, muscle density and international normalized ratio were associated with short- and long-term mortality. CONCLUSIONS Sarcopenia is associated with both short- and long-term mortality in patients with ACLF. Therefore, regular monitoring for sarcopenia is important for these patients.
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Affiliation(s)
- Fan Zeng
- Department of Intensive Care UnitSichuan Academy of Medical Sciences and Sichuan Provincial People's HospitalChengduChina
| | - Wei Jiang
- Department of Intensive Care UnitSichuan Academy of Medical Sciences and Sichuan Provincial People's HospitalChengduChina
- Clinical Medicine School of Chengdu University of Traditional Chinese MedicineChengduChina
| | - Xiujun Chang
- Department of Intensive Care UnitSichuan Academy of Medical Sciences and Sichuan Provincial People's HospitalChengduChina
- Clinical Medicine School of Chengdu University of Traditional Chinese MedicineChengduChina
| | - Fuxun Yang
- Department of Intensive Care UnitSichuan Academy of Medical Sciences and Sichuan Provincial People's HospitalChengduChina
| | - Xiaoxiu Luo
- Department of Intensive Care UnitSichuan Academy of Medical Sciences and Sichuan Provincial People's HospitalChengduChina
| | - Rongan Liu
- Department of Intensive Care UnitSichuan Academy of Medical Sciences and Sichuan Provincial People's HospitalChengduChina
| | - Yu Lei
- Department of Intensive Care UnitSichuan Academy of Medical Sciences and Sichuan Provincial People's HospitalChengduChina
| | - Jiajia Li
- Department of Intensive Care UnitSichuan Academy of Medical Sciences and Sichuan Provincial People's HospitalChengduChina
| | - Chun Pan
- Department of Intensive Care UnitSichuan Academy of Medical Sciences and Sichuan Provincial People's HospitalChengduChina
| | - Xiaobo Huang
- Department of Intensive Care UnitSichuan Academy of Medical Sciences and Sichuan Provincial People's HospitalChengduChina
| | - Huaiqiang Sun
- Huaxi MR Research Center (HMRRC), Department of RadiologyWest China Hospital of Sichuan UniversityChengduChina
| | - Yunping Lan
- Department of Intensive Care UnitSichuan Academy of Medical Sciences and Sichuan Provincial People's HospitalChengduChina
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Song R, Wang X, Li Z, Wu H, Tan J, Tan J, Li H, Zeng T, Ren H, Chen Z. ALTA: a simple nutritional prognostic score for patients with hepatitis B virus-related acute-on-chronic liver failure. Front Nutr 2024; 11:1370025. [PMID: 38655546 PMCID: PMC11035766 DOI: 10.3389/fnut.2024.1370025] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2024] [Accepted: 03/27/2024] [Indexed: 04/26/2024] Open
Abstract
Background Malnutrition, despite being a common complication, is often neglected in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). The objective of this study was to develop a simplified nutritional prognostic score to accurately predict mortality in HBV-ACLF patients. Methods In this multicenter retrospective study, clinical data from 530 HBV-ACLF patients were used to create a new prognostic score, which was then validated in two external cohorts (n = 229 and 248). Results Four independent factors were significantly associated with 28-day mortality in HBV-ACLF patients, forming a novel prognostic score (ALTA score = 0.187 × age-0.849 × lymphocyte count-2.033 × total cholesterol-0.148 × albumin-0.971). Notably, the AUROC of ALTA score for 28/90-day mortality (0.950/0.967) were significantly higher than those of three other ACLF prognostic scores (COSSH-ACLF II, 0.864/0.734; MELD, 0.525/0.488; MELD-Na, 0.546/0.517; all P < 0.001), and three known nutritional scores (CONUT, 0.739/0.861; OPNI, 0.279/0.157; NRS-2002, 0.322/0.286; all P < 0.001). The prediction error rates of ALTA score for 28-day mortality were significantly lower than COSSH-ACLF II (7.3%), MELD (14.4%), MELD-Na (12.7%), CONUT (9.0%), OPNI (30.6%), and NRS2002 (34.1%) scores. Further classifying ALTA score into two strata, the hazard ratios of mortality at 28/90 days were notably increased in the high-risk groups compared to the low-risk group (15.959 and 5.740). These results were then validated in two external cohorts. Conclusion ALTA, as a simplified nutritional prognostic score for HBV-ACLF, demonstrates superiority over the COSSH-ACLF II and other scores in predicting short-term mortality among HBV-ACLF patients. Therefore, it may be used to guide clinical management, particularly in primary care settings.
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Affiliation(s)
- Rui Song
- Key Laboratory of Molecular Biology for Infectious Diseases, Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chinese Ministry of Education, Chongqing, China
| | - Xiaohao Wang
- Key Laboratory of Molecular Biology for Infectious Diseases, Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chinese Ministry of Education, Chongqing, China
| | - Zhao Li
- Department of Gastroenterology, The Seventh People’s Hospital of Chongqing, Chongqing, China
| | - Hongyu Wu
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Jiahe Tan
- Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Junyi Tan
- Department of Infectious Diseases, The Ninth People’s Hospital of Chongqing, Chongqing, China
| | - Hanlu Li
- Department of Infectious Diseases, The Ninth People’s Hospital of Chongqing, Chongqing, China
| | - Teng Zeng
- Department of Infectious Diseases, The Fifth People’s Hospital of Chongqing, Chongqing, China
| | - Hong Ren
- Key Laboratory of Molecular Biology for Infectious Diseases, Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chinese Ministry of Education, Chongqing, China
| | - Zhiwei Chen
- Key Laboratory of Molecular Biology for Infectious Diseases, Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, Chinese Ministry of Education, Chongqing, China
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Wang N, He S, Zheng Y, Wang L. Efficacy and safety of tenofovir disoproxil fumarate versus entecavir in the treatment of acute-on-chronic liver failure with hepatitis B: a systematic review and meta-analysis. BMC Gastroenterol 2023; 23:388. [PMID: 37957546 PMCID: PMC10642028 DOI: 10.1186/s12876-023-03024-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Accepted: 10/31/2023] [Indexed: 11/15/2023] Open
Abstract
BACKGROUND Oral nucleoside (acid) analogues (NAs) are recommended for patients with acute-on-chronic liver failure (ACLF) associated with hepatitis B virus (HBV-ACLF). The efficacy and safety of tenofovir (TDF) and entecavir (ETV) in these patients remain unclear. METHODS A comprehensive literature search in PubMed, Web of Science, The Cochrane Library, and Embase database was conducted to select studies published before December 2022 on TDF or ETV for HBV-ACLF. The primary outcomes were survival rates at 4, 12, and 48 weeks. Secondary outcomes were virologic and biochemical responses, serum antigen conversion, liver function score, and safety. RESULTS Four prospective and one retrospective cohort studies were selected. The overall analysis showed comparable survival rates at 4, 12, and 48 weeks for all patients receiving TDF or ETV (4-week: RR = 1.17, 95% CI: 0.90-1.51, p = 0.24; 12-week: RR = 1.00, 95% CI: 0.88-1.13, p = 0.94; 48-week: RR = 0.96, 95% CI: 0.58-1.57, p = 0.86). Child-Turcotte-Pugh (CTP) score and model for end-stage liver disease (MELD) score at 12 weeks were comparable in both groups but lower than baseline (CTP: SMD = -0.75, 95% CI:-2.81-1.30, p = 0.47; MELD: SMD = -1.10, 95% CI:-2.29-0.08, p = 0.07). At 48 weeks, estimated glomerular filtration rate (eGFR) levels were found to decrease to different degrees from baseline in both the TDF and ETV groups, and the decrease was greater in the TDF group than in the ETV group. No significant differences were found in biochemical, virologic response, and serum antigen conversion between the two groups during the observation period. CONCLUSION TDF treatment of HBV-ACLF is similar to ETV in improving survival, liver function, and virologic response but the effects on renal function in two groups in the long term remain unclear. More and larger long-term clinical trials are required to confirm these findings.
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Affiliation(s)
- Neng Wang
- Center of Infectious Disease, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China
| | - Sike He
- West China School of Medicine, Sichuan University, Chengdu, Sichuan, People's Republic of China
| | - Yu Zheng
- Center of Infectious Disease, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China
| | - Lichun Wang
- Center of Infectious Disease, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China.
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Shingina A, Mukhtar N, Wakim-Fleming J, Alqahtani S, Wong RJ, Limketkai BN, Larson AM, Grant L. Acute Liver Failure Guidelines. Am J Gastroenterol 2023; 118:1128-1153. [PMID: 37377263 DOI: 10.14309/ajg.0000000000002340] [Citation(s) in RCA: 64] [Impact Index Per Article: 32.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Accepted: 04/04/2023] [Indexed: 06/29/2023]
Abstract
Acute liver failure (ALF) is a rare, acute, potentially reversible condition resulting in severe liver impairment and rapid clinical deterioration in patients without preexisting liver disease. Due to the rarity of this condition, published studies are limited by the use of retrospective or prospective cohorts and lack of randomized controlled trials. Current guidelines represent the suggested approach to the identification, treatment, and management of ALF and represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence was reviewed using the Grading of Recommendations, Assessment, Development and Evaluation process to develop recommendations. When no robust evidence was available, expert opinions were summarized using Key Concepts. Considering the variety of clinical presentations of ALF, individualization of care should be applied in specific clinical scenarios.
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Affiliation(s)
- Alexandra Shingina
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Nizar Mukhtar
- Department of Gastroenterology, Kaiser Permanente, San Francisco, California, USA
| | - Jamilé Wakim-Fleming
- Department of Gastroenterology, Hepatology & Nutrition, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, Cleveland Ohio, USA
| | - Saleh Alqahtani
- Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, Maryland, USA
- Liver Transplantation Unit, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia
| | - Robert J Wong
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California, Gastroenterology Section, Veterans Affairs Palo Alto Healthcare System, Palo Alto, California, USA
| | | | - Anne M Larson
- Division of Gastroenterology and Hepatology, University of Washington, Seattle, Washington, USA
| | - Lafaine Grant
- Division of Digestive and Liver Diseases, UT Southwestern Medical Center, Dallas, Texas, USA
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Gama JFG, Cardoso LMDF, Lagrota-Candido JM, Alves LA. Animal models applied to acute-on-chronic liver failure: Are new models required to understand the human condition? World J Clin Cases 2022; 10:2685-2697. [DOI: 10.12998/wjcc.v10.i9.2685] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The liver is a multifaceted organ; its location and detoxifying function expose this organ to countless injuries. Acute-on-chronic failure liver (ACLF) is a severe syndrome that affects the liver due to acute decompensation in patients with chronic liver disease. An infection environment, ascites, increased liver enzymes and prothrombin time, encephalopathy and fast-evolving multiorgan failure, leading to death, usually accompany this. The pathophysiology remains poorly understand. In this context, animal models become a very useful tool in this regard, as understanding; the disease may be helpful in developing novel therapeutic methodologies for ACLF. However, although animal models display several similarities to the human condition, they do not represent all ACLF manifestations, resulting in significant challenges. An initial liver cirrhosis framework followed by the induction of an acute decompensation by administering lipopolysaccharide and D-GaIN, potentiating liver damage supports the methodologies applied to induce experimental ACLF. The entire methodology has been described mostly for rats. Nevertheless, a quick PubMed database search indicates about 30 studies concerning ACFL models and over 1000 regarding acute liver failure models. These findings demonstrate the clear need to establish easily reproducible ACFL models to elucidate questions about this quickly established and often fatal syndrome.
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Affiliation(s)
- Jaciara Fernanda Gomes Gama
- Laboratory of Cellular Communication, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21045900, Rio de Janeiro, Brazil
| | - Liana Monteiro da Fonseca Cardoso
- Laboratory of Cellular Communication, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21045900, Rio de Janeiro, Brazil
| | - Jussara Machado Lagrota-Candido
- Laboratory of Immunopathology, Department of Immunobiology, Fluminense Federal University, Niteroi 24210-200, Rio de Janeiro, Brazil
| | - Luiz Anastacio Alves
- Laboratory of Cellular Communication, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21045900, Rio de Janeiro, Brazil
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Gama JFG, Cardoso LMDF, Lagrota-Candido JM, Alves LA. Animal models applied to acute-on-chronic liver failure: Are new models required to understand the human condition? World J Clin Cases 2022; 10:2687-2699. [PMID: 35434112 PMCID: PMC8968822 DOI: 10.12998/wjcc.v10.i9.2687] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Revised: 12/20/2021] [Accepted: 02/13/2022] [Indexed: 02/06/2023] Open
Abstract
The liver is a multifaceted organ; its location and detoxifying function expose this organ to countless injuries. Acute-on-chronic failure liver (ACLF) is a severe syndrome that affects the liver due to acute decompensation in patients with chronic liver disease. An infection environment, ascites, increased liver enzymes and prothrombin time, encephalopathy and fast-evolving multiorgan failure, leading to death, usually accompany this. The pathophysiology remains poorly understand. In this context, animal models become a very useful tool in this regard, as understanding; the disease may be helpful in developing novel therapeutic methodologies for ACLF. However, although animal models display several similarities to the human condition, they do not represent all ACLF manifestations, resulting in significant challenges. An initial liver cirrhosis framework followed by the induction of an acute decompensation by administering lipopolysaccharide and D-GaIN, potentiating liver damage supports the methodologies applied to induce experimental ACLF. The entire methodology has been described mostly for rats. Nevertheless, a quick PubMed database search indicates about 30 studies concerning ACFL models and over 1000 regarding acute liver failure models. These findings demonstrate the clear need to establish easily reproducible ACFL models to elucidate questions about this quickly established and often fatal syndrome.
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Affiliation(s)
- Jaciara Fernanda Gomes Gama
- Laboratory of Cellular Communication, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21045900, Rio de Janeiro, Brazil
| | - Liana Monteiro da Fonseca Cardoso
- Laboratory of Cellular Communication, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21045900, Rio de Janeiro, Brazil
| | - Jussara Machado Lagrota-Candido
- Laboratory of Immunopathology, Department of Immunobiology, Fluminense Federal University, Niteroi 24210-200, Rio de Janeiro, Brazil
| | - Luiz Anastacio Alves
- Laboratory of Cellular Communication, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro 21045900, Rio de Janeiro, Brazil
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Sun Y, Li Z, Liao G, Xia M, Xu X, Cai S, Peng J. aMAP Score as a Predictor for Long-Term Outcomes in Patients with HBV-Related Acute-on-Chronic Liver Failure. Int J Gen Med 2022; 15:407-415. [PMID: 35046702 PMCID: PMC8759991 DOI: 10.2147/ijgm.s343457] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2021] [Accepted: 12/13/2021] [Indexed: 11/23/2022] Open
Abstract
Background and Aim Methods Results Conclusion
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Affiliation(s)
- Yunqing Sun
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China
| | - Zhuohong Li
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China
| | - Guichan Liao
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China
| | - Muye Xia
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China
| | - Xuwen Xu
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China
| | - Shaohang Cai
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China
| | - Jie Peng
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong Province, People’s Republic of China
- Correspondence: Jie Peng; Shaohang Cai Email ;
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Hossain SMS, Mahtab MA, Das DC, Noor-E-Alam SM, Mamun AA, Khan MSI, Akbar SMF, Rahman MZ, Rahman S. Comparative role of tenofovir versus entecavir for treating patients with hepatitis B virus-related acute on chronic liver failure. J Family Med Prim Care 2021; 10:2642-2645. [PMID: 34568149 PMCID: PMC8415666 DOI: 10.4103/jfmpc.jfmpc_2299_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 02/16/2021] [Accepted: 04/10/2021] [Indexed: 11/04/2022] Open
Abstract
INTRODUCTION The aim of the study was to compare the safety and efficacy of tenofovir versus entecavir for treatment of naive acute on chronic liver failure (ACLF) due to hepatitis B virus (HBV) (ACLF-B). METHODS Thirty-two patients aged 14-65 years were enrolled in the study. Diagnosis of ACLF was confirmed by clinical condition, biochemical analysis, and virological data. The causes of both chronic liver damages and acute insult in all patients were HBV. They were expressing HBV DNA in the sera, positive for IgM anti-HBc, had increased levels of serum bilirubin, compromised prothrombin time; and more than 50% patients had encephalopathy. The standard dose of tenofovir and entecavir was given. RESULTS The antiviral effects of tenofovir and entecavir were evident as most patients became negative for HBV DNA in the sera after 90 days of therapy. Also, the levels of serum bilirubin, CTP (Child-Turcotte-Pugh) and MELD (model for end-stage liver disease) score exhibited significant improvement due to antiviral therapy. Although the improvement of liver functions, and liver damages were detected in patients receiving both tenofovir and entecavir, the survival of the patients was significantly higher in those receiving tenofovir compared to entecavir-treated patients. CONCLUSION This prospective study with limited number patients provides a challenge to assess the real potential of tenofovir over entecavir as therapeutic option for ACLF-B by conducting a multicenter clinical trial enrolling patient of different races and background.
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Affiliation(s)
| | - Mamun A. Mahtab
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Dulal C. Das
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Sheikh M. Noor-E-Alam
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Ayub A. Mamun
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - Md. Sakirul I. Khan
- Department of Anatomy and Embryology, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Sheikh M. F. Akbar
- Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan
| | - Md Zakiur Rahman
- Department of Primary Care and Microbiology, Brahminbaria Medical College, Brahminbaria, Bangladesh
| | - Salimur Rahman
- Department of Hepatology, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
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Li J, Hu C, Chen Y, Zhang R, Fu S, Zhou M, Gao Z, Fu M, Yan T, Yang Y, Li J, Liu J, Chen T, Zhao Y, He Y. Short-term and long-term safety and efficacy of tenofovir alafenamide, tenofovir disoproxil fumarate and entecavir treatment of acute-on-chronic liver failure associated with hepatitis B. BMC Infect Dis 2021; 21:567. [PMID: 34126939 PMCID: PMC8201741 DOI: 10.1186/s12879-021-06237-x] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Accepted: 05/24/2021] [Indexed: 12/27/2022] Open
Abstract
Background & Aims There is limited evidence on the efficacy and safety of nucleos(t) ide analogues (NAs) in the treatment of HBV-ACLF. Our objective was to evaluate the outcomes among TAF, TDF and ETV, three first-line antivirals against chronic hepatitis B, in patients with HBV-ACLF. Methods Patients with HBV-related ACLF were recruited and received daily TAF (25 mg/d), TDF (300 mg/d) and ETV (0.5 mg/d). They were prospectively followed-up. The primary endpoint was overall survival at week 12 and week 48, the secondary endpoints were virological response and biochemical response. Results Forty gender and age matched eligible subjects were recruited and divided into three groups: TAF group, TDF group and ETV group. By week 48, 8 (80%) patients in TAF group, 6 (60%) patients in TDF group and 17 (85%) patients in ETV group survived without liver transplantation (P = 0.251). After 4 weeks of NAs treatment, all three groups showed paralleling reduction of HBV DNA levels. All three groups presented similar biochemical responses at week 4, patients treated with TAF showed a priority in total bilirubin reduction, albumin and cholesterol maintenance. Additionally, although there was no significant difference in changes of serum urea, serum creatinine, serum cystatin C and estimated GFR among the three groups by treatment week 4, TDF showed unfavorable renal safety even in short -term treatment. The treatment using NAs was well-tolerated and there was no serious drug-related adverse event reported. Conclusions TAF, TDF and ETV are of similar efficacy and safety in short-term and long-term treatment of HBV-ACLF. Trial registration This study is ongoing and is registered with ClinicalTrials.gov, NCT03640728 (05/02/2019).
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Affiliation(s)
- Juan Li
- Department of Infectious Diseases, First Affiliated Teaching Hospital, School of Medicine, Xi'an Jiaotong University, Yanta Road (w), No. 277, Xi'an City, 710061, Shaanxi Province, China
| | - Chunhua Hu
- Department of Infectious Diseases, First Affiliated Teaching Hospital, School of Medicine, Xi'an Jiaotong University, Yanta Road (w), No. 277, Xi'an City, 710061, Shaanxi Province, China
| | - Yi Chen
- Institution of Hepatology, First Affiliated Teaching Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi province, China
| | - Rou Zhang
- Department of Infectious Diseases, First Affiliated Teaching Hospital, School of Medicine, Xi'an Jiaotong University, Yanta Road (w), No. 277, Xi'an City, 710061, Shaanxi Province, China
| | - Shan Fu
- Institution of Hepatology, First Affiliated Teaching Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi province, China
| | - Mimi Zhou
- Institution of Hepatology, First Affiliated Teaching Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi province, China
| | - Zhijie Gao
- Department of Infectious Diseases, First Affiliated Teaching Hospital, School of Medicine, Xi'an Jiaotong University, Yanta Road (w), No. 277, Xi'an City, 710061, Shaanxi Province, China
| | - Mengjun Fu
- Department of Infectious Diseases, First Affiliated Teaching Hospital, School of Medicine, Xi'an Jiaotong University, Yanta Road (w), No. 277, Xi'an City, 710061, Shaanxi Province, China
| | - Taotao Yan
- Department of Infectious Diseases, First Affiliated Teaching Hospital, School of Medicine, Xi'an Jiaotong University, Yanta Road (w), No. 277, Xi'an City, 710061, Shaanxi Province, China
| | - Yuan Yang
- Department of Infectious Diseases, First Affiliated Teaching Hospital, School of Medicine, Xi'an Jiaotong University, Yanta Road (w), No. 277, Xi'an City, 710061, Shaanxi Province, China
| | - Jianzhou Li
- Department of Infectious Diseases, First Affiliated Teaching Hospital, School of Medicine, Xi'an Jiaotong University, Yanta Road (w), No. 277, Xi'an City, 710061, Shaanxi Province, China
| | - Jinfeng Liu
- Department of Infectious Diseases, First Affiliated Teaching Hospital, School of Medicine, Xi'an Jiaotong University, Yanta Road (w), No. 277, Xi'an City, 710061, Shaanxi Province, China
| | - Tianyan Chen
- Department of Infectious Diseases, First Affiliated Teaching Hospital, School of Medicine, Xi'an Jiaotong University, Yanta Road (w), No. 277, Xi'an City, 710061, Shaanxi Province, China.,Shaanxi Clinical Research Center of Infectious Diseases, Xi'an, 710061, Shaanxi province, China
| | - Yingren Zhao
- Department of Infectious Diseases, First Affiliated Teaching Hospital, School of Medicine, Xi'an Jiaotong University, Yanta Road (w), No. 277, Xi'an City, 710061, Shaanxi Province, China. .,Institution of Hepatology, First Affiliated Teaching Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi province, China. .,Shaanxi Clinical Research Center of Infectious Diseases, Xi'an, 710061, Shaanxi province, China.
| | - Yingli He
- Department of Infectious Diseases, First Affiliated Teaching Hospital, School of Medicine, Xi'an Jiaotong University, Yanta Road (w), No. 277, Xi'an City, 710061, Shaanxi Province, China. .,Shaanxi Clinical Research Center of Infectious Diseases, Xi'an, 710061, Shaanxi province, China.
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11
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A novel prognostic model to predict outcome of artificial liver support system treatment. Sci Rep 2021; 11:7510. [PMID: 33820919 PMCID: PMC8021558 DOI: 10.1038/s41598-021-87055-8] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Accepted: 03/17/2021] [Indexed: 02/05/2023] Open
Abstract
The prognosis of Artificial liver support system (ALSS) for hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is hard to be expected, which results in multiple operations of ALSS and excessive consumption of plasma, increase in clinical cost. A total of 375 HBV-ACLF patients receiving ALSS treatment were randomly divided a train set and an independent test set. Logistic regression analysis was conducted and a decision tree was built based on 3-month survival as outcome. The ratio of total bilirubin before and after the first time of ALSS treatment was the most significant prognostic factor, we named it RPTB. Further, a decision tree based on the multivariate logistic regression model using CTP score and the RPTB was built, dividing patients into 3 main groups such as favorable prognosis group, moderate prognosis group and poor prognosis group. A clearly-presented and easily-understood decision tree was built with a good predictive value of prognosis in HBV-related ACLF patients after first-time ALSS treatment. It will help maximal the therapeutic value of ALSS treatment and may play an important role in organ allocation for liver transplantation in the future.
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12
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Li Q, Wang J, Lu M, Qiu Y, Lu H. Acute-on-Chronic Liver Failure From Chronic-Hepatitis-B, Who Is the Behind Scenes. Front Microbiol 2020; 11:583423. [PMID: 33365018 PMCID: PMC7750191 DOI: 10.3389/fmicb.2020.583423] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Accepted: 11/13/2020] [Indexed: 12/12/2022] Open
Abstract
Acute-on-chronic liver failure (ACLF) is an acute syndrome accompanied with decompensation of cirrhosis, organ failure with high 28-day mortality rate. Systemic inflammation is the main feature of ACLF, and poor outcome is closely related with exacerbated systemic inflammatory responses. It is well known that severe systemic inflammation is an important event in chronic hepatitis B (CHB)-ACLF, which eventually leads to liver injury. However, the initial CHB-ACLF events are unclear; moreover, the effect of these events on host immunity as well as that of immune imbalance on CHB-ACLF progression are unknown. Here, we investigate the initial events of ACLF progression, discuss possible mechanisms underlying ACLF progression, and provide a new model for ACLF prediction and treatment. We review the characteristics of ACLF, and consider its plausible immune predictors and alternative treatment strategies.
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Affiliation(s)
- Qian Li
- Department of Infectious Diseases, Shanghai Public Health Clinical Center, Shanghai, China
| | - Jun Wang
- Center of Clinical Laboratory, The Fifth People's Hospital of Wuxi, Jiangnan University, Wuxi, China
| | - Mengji Lu
- Institute of Virology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany
| | - Yuanwang Qiu
- Department of Hepatology, The Fifth People's Hospital of Wuxi, Jiangnan University, Wuxi, China
| | - Hongzhou Lu
- Department of Infectious Diseases, Shanghai Public Health Clinical Center, Shanghai, China
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13
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Cullaro G, Sharma R, Trebicka J, Cárdenas A, Verna EC. Precipitants of Acute-on-Chronic Liver Failure: An Opportunity for Preventative Measures to Improve Outcomes. Liver Transpl 2020; 26:283-293. [PMID: 31714011 PMCID: PMC8046290 DOI: 10.1002/lt.25678] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2019] [Accepted: 10/12/2019] [Indexed: 02/06/2023]
Abstract
Acute-on-chronic liver failure (ACLF) is a feared complication that can develop at any stage of chronic liver disease. The incidence of ACLF is increasing, leading to a significant burden to both the affected individual and health care systems. To date, our understanding of ACLF suggests that it may be initiated by precipitants such as systemic infection, alcohol use, or viral hepatitis. The prevalence of these vary significantly by geography and underlying liver disease, and these precipitants have a varying impact on patient prognosis. Herein, we present a review of our current understanding of the precipitants of ACLF, including gaps in current data and opportunities for meaningful intervention and areas of future research.
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Affiliation(s)
- Giuseppe Cullaro
- Division of Gastroenterology and Hepatology, Department of Medicine, University of California, San Francisco, CA
| | - Rajani Sharma
- Center for Liver Disease and Transplantation, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY
| | - Jonel Trebicka
- Department of Internal Medicine I, Goethe University of Frankfurt, Frankfurt, Germany,European Foundation for the Study of Chronic Liver Failure, Barcelona, Spain,Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark,Institute for Bioengineering of Catalonia, Barcelona, Spain
| | - Andrés Cárdenas
- GI/Liver Unit, Institut de Malaties Digestives, Hospital Clinic, University of Barcelona, Barcelona, Spain
| | - Elizabeth C. Verna
- Center for Liver Disease and Transplantation, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY
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Abstract
Purpose of Review Acute HBV infection and acute exacerbations of chronic HBV infection can cause acute liver injury (ALI) or fulminant hepatitis (FH). At this stage, spontaneous survival is poor, less than 25%. The purpose of this review is to provide an overview of specific management of patients with HBV-ALI/FH. Recent Findings Acute HBVinfection and acute exacerbations of chronic HBVinfection can cause acute liver injury (ALI) or fulminant hepatitis (FH). Spontaneous survival at this stage is poor. It is urgent to distinguish between these two entities so that antiviral therapy can be initiated rapidly. Although the indications for antiviral therapy are clear for HBV reactivation, there is no true consensus regarding ALI/FH related to acute HBV infection. The global management of HBV-related FH does not differ from that implemented for other causes of FH, i.e. close cardiorespiratory and neurological monitoring, treatment with acetylcysteine, organ support in the event of organ failure (haemodynamic, renal, respiratory) and albumin dialysis. Liver transplantation remains the only alternative when certain criteria for a poor prognosis are met. A recurrence of HBV infection on the graft can be prevented post-transplant by the administration of HBIG and antiviral therapy for HBV, the modalities varying depending on the risk of recurrence.
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Affiliation(s)
- Philippe Ichai
- Centre Hépato-Biliaire, Liver Intensive Care Unit, AP-HP Hôpital Paul-Brousse, 12 Avenue Paul Vaillant Couturier, 94804 Villejuif, France
- INSERM, Unité 1193, Université ParisSud, Paris-Saclay, 94800 Villejuif, France
- DHU Hepatinov, 94800 Villejuif, France
| | - Didier Samuel
- Centre Hépato-Biliaire, Liver Intensive Care Unit, AP-HP Hôpital Paul-Brousse, 12 Avenue Paul Vaillant Couturier, 94804 Villejuif, France
- INSERM, Unité 1193, Université ParisSud, Paris-Saclay, 94800 Villejuif, France
- DHU Hepatinov, 94800 Villejuif, France
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15
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Tenofovir Versus Entecavir for the Treatment of Acute-on-Chronic Liver Failure due to Reactivation of Chronic Hepatitis B With Genotypes B and C. J Clin Gastroenterol 2019; 53:e171-e177. [PMID: 29659382 DOI: 10.1097/mcg.0000000000001038] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
BACKGROUND AND AIMS Acute-on-chronic liver failure (ACLF) can be triggered by reactivation of chronic hepatitis B (CHB). Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are now the most potent antiviral agents for CHB. This study aimed to compare the short-term safety and efficacy of TDF with ETV in the treatment of ACLF due to reactivation of CHB [hepatitis B virus (HBV)-ACLF]. PATIENTS AND METHODS In total, 67 consecutive patients with HBV-ACLF were divided into TDF group (n=32) receiving daily TDF (300 mg/d) and ETV group (n=35) receiving daily ETV (0.5 mg/d). They were prospectively followed-up and the primary endpoint was overall survival at 3 months. RESULTS At 2 weeks, the TDF group had significantly higher HBV-DNA reduction (P=0.003), lower HBV-DNA level (P=0.001), higher rate of HBV-DNA undetectbility (P=0.007), lower Child-Turcotte-Pugh (CTP; P=0.003), and model for end-stage liver disease (P=0.002) scores than the ETV group. At 3 months, HBV-DNA was undetectable in all survived patients; CTP (P=0.970) and model for end-stage liver disease (P=0.192) scores were comparable between the 2 groups, but markedly lower than at baseline (P<0.01); the TDF group had significantly higher cumulative survival rate than the ETV group (P=0.025). The white blood cell count (hazard ratio, 2.726; 95% confidence interval, 2.691-7.897; P=0.000), and HBV-DNA reduction (hazard ratio, 0.266; 95% confidence interval, 0.033-0.629; P=0.013) at 2 weeks were independent predictors for mortality. Both drugs were well tolerated. CONCLUSIONS The short-term efficacy of TDF was superior to ETV for the treatment of HBV-ACLF. The white blood cell count and HBV-DNA reduction at 2 weeks were independent predictors for mortality at 3 months.
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16
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Prognosis, Prevention and Research Prospects of Progression to Severe Hepatitis B (Liver Failure). ACUTE EXACERBATION OF CHRONIC HEPATITIS B 2019. [PMCID: PMC7498886 DOI: 10.1007/978-94-024-1603-9_6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
This chapter describes the factors involved in the disease prognosis, parameters of outcome evaluations, principles and techniques for progression prevention. In last section, the future perspectives in both basic and clinical investigations towards unmet medical needs in AECHB and HBV ACLF are discussed.
Factors affecting the prognosis of patients with severe hepatitis B include those related to the virus (including viral load, HBeAg expression, and gene mutation), patient age, co-morbidity, TBil, INR, serum Cr, and the host genetic background. Indicators associated with patient prognosis include TBil, total cholesterol, albumin and prealbumin, hepatic encephalopathy, kidney damage, alpha-fetoprotein and vitamin D binding protein, blood sodium level, virus HBeAg expression and genotype, and blood glucose. In addition to TBil, INR, hepatic encephalopathy, Cr level and AFP as indicators for prognosis of severe hepatitis, some other parameters such as clinical signs, symptoms, serum levels of total cholesterol and albumin and natrium, and coagulation factors are all valuable in assessment. The roles of cell apoptosis, liver regeneration and immunological parameters in assessing patient prognosis are under study. Prognostic evaluating systems include MELD score, MELD-Na score, iMELD score, KCI and CTP score. Prevention of severe hepatitis B should be started in asymptomatic patients. Close observation, sufficient rest, adequate nutrition, meticulous nursing and psychological care, preventing and removing exacerbating factors, treating concomitant diseases, reasonable antiviral and comprehensive therapies are helpful to prevent CHB patients from developing to severe hepatitis. For patients who already have severe hepatitis B, the prevention and management of complications is important for lowering mortality rate. New research directions in acute-on-chronic liver failure include: (1) Additional well controlled studies using present or new liver systems are warranted. Other approaches include the use of granulocyte colony stimulating factor to treat infections as well as the potential of use of stem cells to restore immune integrity and enhance liver regeneration. (2) Using new cell lines and animal models to understand the molecular biology of HBV, the immune response and to develop novel therapies. (3) Development of new anti-HBV strategies, e.g. silencing or remove cccDNA, enhancing immunologic clearance of HBV infection, inhibiting virus entry or HBc expression and using CRISP to disrupt cccDNA.
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17
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Zhao RH, Shi Y, Zhao H, Wu W, Sheng JF. Acute-on-chronic liver failure in chronic hepatitis B: an update. Expert Rev Gastroenterol Hepatol 2018; 12:341-350. [PMID: 29334786 DOI: 10.1080/17474124.2018.1426459] [Citation(s) in RCA: 80] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Acute-on-chronic liver failure is a common pattern of end-stage liver disease in clinical practice and occurs frequently in patients with chronic hepatitis B or HBV-related cirrhosis. New progress in recent years leads to a better understanding of this disease. Areas covered: This review updates the current comprehensive knowledge about HBV-ACLF from epidemiological studies, experimental studies, and clinical studies and provide new insights into the definition, diagnostic criteria, epidemiology, nature history, pathogenesis, treatment and prognostication of HBV-ACLF. Expert commentary: Patients with chronic hepatitis B or HBV-related cirrhosis are at risk of developing acute-on-chronic liver failure, with multi-organ failure and high short-term mortality. The precipitating events can be intra-hepatic or extra-hepatic and the underlying chronic liver injury can be cirrhotic or non-cirrhotic. Host and viral factors contribute to the susceptibility of developing HBV-ACLF. Systemic inflammation is the driver of HBV-ACLF, which can be attributed to non-sterile and sterile factors. Liver transplantation is the definitive treatment for HBV-ACLF. Cell therapy is a promising alternative to LT, but requires validation and still has concern of long-term safety. Other medical therapies, such as nucleoside analogue, artificial liver supporting and glucocorticoid may improve survival in a specific subgroup. New scoring systems improve the accuracy of prognostication in HBV-ACLF, which is critical for early identification of candidates for LT.
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Affiliation(s)
- Rui-Hong Zhao
- a Department of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine , Zhejiang University , Hangzhou , China
| | - Yu Shi
- a Department of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine , Zhejiang University , Hangzhou , China
| | - Hong Zhao
- a Department of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine , Zhejiang University , Hangzhou , China
| | - Wei Wu
- a Department of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine , Zhejiang University , Hangzhou , China
| | - Ji-Fang Sheng
- a Department of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine , Zhejiang University , Hangzhou , China
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18
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Wu J, Yin F, Zhou X. Efficacy of nucleoside analogues for hepatitis B virus-related liver failure: A network meta-analysis. ACTA PHARMACEUTICA (ZAGREB, CROATIA) 2018; 68:19-30. [PMID: 29453915 DOI: 10.2478/acph-2018-0010] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 12/04/2017] [Indexed: 01/30/2023]
Abstract
The purpose of this study was to compare the efficacy of nucleoside analogues (NAs) in the treatment of HBV-related liver failure. The data of patients with HBV-related liver failure treated with nucleoside analogues were used to conduct a network meta-analysis. A total of 1660 patients from 12 articles about the efficacy of lamivudine, entecavir, telbivudine and tenofovir for HBV-related liver failure treatment were recruited in the study. The highest two- and three-month survival rate was recorded for patients using tenofovir. The end-stage liver disease (MELD) score and mortality in patients undergoing tenofovir treatment were the lowest. Patients treated with telbivudine had the highest one-month survival rate. Patients receiving enticavir therapy showed the lowest HBV DNA level. Our results indicate that tenofovir may be the best therapy for the treatment of HBV-related liver failure compared to other nucleoside analogues (including lamivudine, entecavir and telbivudine) and non-NAs treatment.
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Affiliation(s)
- Jian Wu
- 1Digestion Internal Medicine Department, Xijing Hospital The First Affiliated Hospital of the Fourth Military Medical University Xi'an Shaanxi 710000, China
| | - Fang Yin
- 1Digestion Internal Medicine Department, Xijing Hospital The First Affiliated Hospital of the Fourth Military Medical University Xi'an Shaanxi 710000, China
| | - Xinmin Zhou
- 1Digestion Internal Medicine Department, Xijing Hospital The First Affiliated Hospital of the Fourth Military Medical University Xi'an Shaanxi 710000, China
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19
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Lin SD, Ren Y, Liu LL. Identification and management of patients with severe exacerbation of chronic hepatitis B. Shijie Huaren Xiaohua Zazhi 2017; 25:2747-2753. [DOI: 10.11569/wcjd.v25.i31.2747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Some patients with chronic hepatitis B (CHB) have a high risk to progress to acute-on-chronic liver failure (ACLF). Early identification and intervention of this group of patients are important to improve their prognosis. In China, the progression from CHB to ACLF has been termed severe acute exacerbation (SAE) of CHB. However, due to the fact that it is difficult to predict the outcomes of patients with CHB, it is reasonable to include these patients who have a high tendency to progress to ACLF as patients with SAE of CHB. It remains unclear how to identify this progression in patients with SAE of CHB. Therefore, it is needed to establish uniform criteria to identify patients with SAE. In this review, we discuss the identification and management of patients with SAE of CHB.
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Affiliation(s)
- Shi-De Lin
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical College, Zunyi 563003, Guizhou Province, China
| | - Yi Ren
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical College, Zunyi 563003, Guizhou Province, China
| | - Lu-Lu Liu
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical College, Zunyi 563003, Guizhou Province, China
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20
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Gao S, Joshi SS, Osiowy C, Chen Y, Coffin CS, Duan ZP. Chronic hepatitis B carriers with acute on chronic liver failure show increased HBV surface gene mutations, including immune escape variants. Virol J 2017; 14:203. [PMID: 29065883 PMCID: PMC5655973 DOI: 10.1186/s12985-017-0870-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2017] [Accepted: 10/13/2017] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND The pathogenesis of acute-on-chronic liver failure (ACLF) in chronic hepatitis B (CHB) is not well understood. The aim of this study was to investigate whether there is an association between HBV polymerase (P)/overlapping surface (S) gene and basal core promoter (BCP)/precore (PC) variants and development of ACLF in CHB. METHODS Two CHB patient cohorts were compared: (i) ACLF (N = 12) (11/12 M, median age 52 yrs., 5/9 genotype C, 6/12 HBeAg+), (ii) 27 treatment native CHB carriers (15/27 M, median age 44 yrs., 9 genotype B, 10 genotype C, 1 genotype A, 5 genotype D, 2 genotype E). Clonal sequencing of PCR-amplified HBV P/S and BCP/PC gene fragments was done and HBV diversity, frequency of immune escape (IE) and drug resistance (DR) mutations and mutations in BCP/PC gene (G1896A and A1762T/G1764A), were compared between each group. RESULTS Our data showed the incidence of IE and clusters of mutations in the HBV S region was significantly greater in ACLF patients vs. treatment naïve CHB patients (p < 0.05). Additionally, a significantly higher frequency of G1896A and A1762T/G1764A mutations were found in HBeAg negative than in ACLF patients (p < 0.0001). CONCLUSION In our study, ACLF was not associated with a specific genomic mutation. However, higher frequency of IE mutations along with various mutations clustering in the HBV S region could contribute to or be an outcome of ACLF in CHB infection. (words 226).
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Affiliation(s)
- Shan Gao
- Artificial Liver Center, Beijing Youan Hospital, Capital Medical University, 8 Xitoutiao, Youwai Street, Beijing, 100069, China
- Calgary Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, Cumming School of Medicine, University of Calgary 6D21, Teaching, Research and Wellness Building, 3280 Hospital Drive N.W, Calgary, AB, T2N 4Z6, Canada
- Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Shivali S Joshi
- Calgary Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, Cumming School of Medicine, University of Calgary 6D21, Teaching, Research and Wellness Building, 3280 Hospital Drive N.W, Calgary, AB, T2N 4Z6, Canada
- Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada
| | - Carla Osiowy
- Bloodborne Pathogens and Hepatitis Laboratory of the National Microbiology Laboratory, Winnipeg, MB, Canada
| | - Y Chen
- Artificial Liver Center, Beijing Youan Hospital, Capital Medical University, 8 Xitoutiao, Youwai Street, Beijing, 100069, China
| | - Carla S Coffin
- Calgary Liver Unit, Division of Gastroenterology and Hepatology, Department of Medicine, Cumming School of Medicine, University of Calgary 6D21, Teaching, Research and Wellness Building, 3280 Hospital Drive N.W, Calgary, AB, T2N 4Z6, Canada.
- Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
| | - Z-P Duan
- Artificial Liver Center, Beijing Youan Hospital, Capital Medical University, 8 Xitoutiao, Youwai Street, Beijing, 100069, China.
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Efficacy and Safety of Lamivudine Versus Entecavir for Treating Chronic Hepatitis B Virus-related Acute Exacerbation and Acute-on-Chronic Liver Failure: A Systematic Review and Meta-Analysis. J Clin Gastroenterol 2017; 51:539-547. [PMID: 28067752 DOI: 10.1097/mcg.0000000000000675] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Oral nucleos(t)ide analogs are recommended for patients with chronic hepatitis B virus (HBV)-related acute exacerbation (AE) and acute-on-chronic liver failure (ACLF). The efficacy and safety of administering entecavir (ETV) and lamivudine (LAM) to such patients remain unclear. METHODS A comprehensive literature search was performed to select studies published before December 2015 on therapy involving ETV or LAM for chronic HBV-related AE with or without ACLF. The main outcomes were short-term (within 4 mo) and long-term (beyond 4 mo) mortality. The secondary outcomes were virological and biochemical responses, ACLF recurrence, and safety. RESULTS Three prospective and 8 retrospective cohort studies involving 1491 patients were selected. An overall analysis revealed comparable short-term and long-term mortality rates among all patients who received ETV or LAM [short term: risk ratio (RR)=0.99; 95% confidence interval (CI), 0.78-1.27; long term: RR=0.82; 95% CI, 0.45-1.52]. However, in patients with ACLF, ETV yielded a more favorable long-term outcome than did LAM (RR=0.60; 95% CI, 0.45-0.80). Furthermore, ETV resulted in more efficient virological and biochemical responses than did LAM regarding the HBV DNA undetectable rate (RR=1.34; 95% CI, 1.09-1.63), HBV DNA reduction rate (weighted mean difference=-0.41; 95% CI, -0.69 to -0.13), and serum alanine aminotransferase normalization rate (RR=1.13; 95% CI, 1.05-1.21). CONCLUSIONS ETV and LAM treatments exerted similar effects on the mortality rate of patients with chronic HBV-related AE with or without ACLF. However, ETV yielded a more favorable long-term outcome than did LAM in patients with ACLF; ETV was associated with greater clinical improvements. Additional larger, long-term randomized controlled trials are required to confirm these conclusions.
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Sun FK, Gao S, Fan YC, Shi CH, Zhang ZH, Wang LY, Li F, Li XY, Ji XF, Zhao J, Wang K. High promoter methylation levels of glutathione-S-transferase M3 predict poor prognosis of acute-on-chronic hepatitis B liver failure. Hepatol Res 2017; 47:566-573. [PMID: 27442719 DOI: 10.1111/hepr.12777] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2016] [Revised: 07/15/2016] [Accepted: 07/17/2016] [Indexed: 12/11/2022]
Abstract
AIM This study aimed to evaluate the prognostic value of glutathione-S-transferase M3 (GSTM3) gene promoter methylation in patients with acute-on-chronic hepatitis B liver failure (ACHBLF). METHODS A total of 119 patients with ACHBLF, 60 patients with chronic hepatitis B and 30 healthy controls were enrolled. We used a quantitative methylation detection technique, MethyLight, to examine the methylation levels of GSTM3 in peripheral blood mononuclear cells. RESULTS The GSTM3 methylation level was significantly higher in patients with ACHBLF than those in patients with chronic hepatitis B and healthy controls (both P < 0.05). In patients with ACHBLF, GSTM3 methylation level percentage of methylated reference (PMR) positively correlated with total bilirubin, international normalized ratio, and Model for End-stage Liver Disease (MELD) score, and negatively correlated with prothrombin activity and albumin (all P < 0.05). The PMR for GSTM3 of non-survivors was significantly increased compared to that of survivors (P < 0.05). Multivariate analysis indicated that GSTM3 methylation level was one of the independent prognostic factors for 3-month mortality of ACHBLF (P = 0.000). The area under the receiver-operator characteristic curve of PMR for GSTM3 in predicting 3-month mortality of ACHBLF was not statistically different from that of MELD score (0.798 vs. 0.716, P = 0.152). However, the area under the curve of PMR for GSTM3 was significantly higher than that of MELD score in predicting 1-month mortality (0.887 vs. 0.737, P = 0.020). CONCLUSION Promoter methylation levels of GSTM3 in peripheral blood mononuclear cells closely correlated with disease severity and could be used to predict prognosis of patients with ACHBLF.
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Affiliation(s)
- Feng-Kai Sun
- Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China
| | - Shuai Gao
- Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China
| | - Yu-Chen Fan
- Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China
- Institute of Hepatology, Shandong University, Jinan, China
| | - Chang-He Shi
- Department of Hepatology, Qingdao Infectious Disease Hospital, Qingdao, China
| | - Zhao-Hua Zhang
- Department of Hepatology, Jinan Infectious Disease Hospital, Shandong University, Jinan, China
| | - Li-Yuan Wang
- Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China
| | - Feng Li
- Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China
| | - Xin-You Li
- Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China
| | - Xiang-Fen Ji
- Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China
| | - Jing Zhao
- Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China
| | - Kai Wang
- Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China
- Institute of Hepatology, Shandong University, Jinan, China
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Hu T, Yao L, Hu A, Jiang S, Ying H, Deng Q, Hu Y, Zhou W, Xiong T. Nucleos(t)ide analogs improve long-term prognosis in patients with chronic hepatitis B-associated liver failure. Hepatol Res 2017; 47:347-358. [PMID: 27283374 DOI: 10.1111/hepr.12755] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/25/2016] [Revised: 05/20/2016] [Accepted: 05/29/2016] [Indexed: 12/12/2022]
Abstract
AIM Chronic hepatitis B-associated liver failure (CHB-LF) is associated with high mortality. Antiviral therapy with nucleoside and nucleotide analogs (NUCs) has been reported to improve the short-term prognosis of patients with CHB-LF. However, the long-term effects of the therapy remain unclear. We undertook a cohort study to investigate the long-term effect of NUC-based antiviral therapy in patients with CHB-LF. METHODS A total of 976 patients with CHB-LF were enrolled between January 2001 and December 2009 at the Liver Disease Center of Ningbo No. 2 Hospital (Ningbo, China). The patients were divided into the NUC treatment group (n = 412) and control group (n = 564). The propensity score matching method was used to match the patients between the two groups to equilibrate the covariates. Survival analysis was carried out using the matched samples. The Cox proportional hazard model was used for the analysis of prognostic factors. RESULTS After propensity matching, 262 pairs were successfully matched. No statistically significant difference was observed in the baseline characteristics of the matching pairs (P > 0.05). The long-term survival rate and survival duration of the NUC treatment group were higher than that of the control group (P < 0.05). Gender, age, Model for End-stage Liver Disease values, cholinesterase levels, white blood cell counts, hepatic encephalopathy, concomitant infection, and treatment with NUCs were found to be the independent factors associated with long-term prognosis. CONCLUSION Antiviral therapy with NUCs may reduce the mortality rate and improve the long-term prognosis of patients with CHB-LF.
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Affiliation(s)
- Ting Hu
- Liver Diseases Center, Ningbo No. 2 Hospital, Ningbo University School of Medicine, Ningbo, China
| | - Lipeng Yao
- Ningbo College of Health Science, Ningbo, China
| | - Airong Hu
- Liver Diseases Center, Ningbo No. 2 Hospital, Ningbo University School of Medicine, Ningbo, China
| | - Suwen Jiang
- Liver Diseases Center, Ningbo No. 2 Hospital, Ningbo University School of Medicine, Ningbo, China
| | - Hao Ying
- Liver Diseases Center, Ningbo No. 2 Hospital, Ningbo University School of Medicine, Ningbo, China
| | - Qinzhi Deng
- Liver Diseases Center, Ningbo No. 2 Hospital, Ningbo University School of Medicine, Ningbo, China
| | - Yaoren Hu
- Liver Diseases Center, Ningbo No. 2 Hospital, Ningbo University School of Medicine, Ningbo, China
| | - Wenhong Zhou
- Liver Diseases Center, Ningbo No. 2 Hospital, Ningbo University School of Medicine, Ningbo, China
| | - Tao Xiong
- Liver Diseases Center, Ningbo No. 2 Hospital, Ningbo University School of Medicine, Ningbo, China
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Lamivudine improves short-term outcome in hepatitis B virus-related acute-on-chronic liver failure patients with a high model for end-stage liver disease score. Eur J Gastroenterol Hepatol 2017; 29:1-9. [PMID: 27749778 DOI: 10.1097/meg.0000000000000750] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
AIM Hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) has significant morbidity and mortality. There is no standard approach for the management of HBV-related ACLF with nucleos(t)ide analogs. Our objective was to compare the short-term mortality between entecavir (ETV) and lamivudine (LAM) in patients with HBV-related ACLF. METHODS We recruited 311 inpatients with HBV-related ACLF from December 2002 to January 2015. The patients were treated with ETV (n=143) or LAM (n=168). The primary endpoint was mortality rate at week 8. Virological and biochemical responses were also studied. RESULTS By week 8, 53 (37.06%) patients in the ETV group and 57 (33.93%) patients in the LAM group died, and the two groups had similar mortality (P=0.414). Multivariate analysis showed that age, total bilirubin, international normalized ratio, and model for end-stage liver disease (MELD) score were independent factors for mortality at week 8. The best cut-off value of the MELD score was 24.5 for 8-week mortality. Twenty-nine of the 170 (17.06%) patients with MELD score less than 24.5 died at week 8, and the ETV and LAM groups had similar mortality (P=0.743). Eighty-one of the 141 (57.45%) patients with MELD score of at least 24.5 died at week 8 and the LAM group had lower mortality than the ETV group (P=0.018 at week 4; P=0.039 at week 8). Both groups showed similar virological and biochemical responses at 4 weeks. CONCLUSION LAM reduces the 8-week mortality rate significantly in patients with HBV-related ACLF who had MELD score of at least 24.5.
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Abstract
The goal in patients with immune active hepatitis B virus (HBV) infection is to significantly suppress viral replication and prevent progression of fibrosis to cirrhosis and liver decompensation and decrease the incidence of hepatocellular carcinoma. This is achievable by the highly active antivirals, entecavir and tenofovir, which are considered first-line therapy in most patients with immune active hepatitis C virus and after liver transplantation to prevent HBV recurrence. Patients with decompensated cirrhosis should be referred for liver transplantation and treated with first-line antivirals as early as possible, with the goal of achieving complete viral suppression in the shortest time possible.
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Affiliation(s)
| | - Tarek I Hassanein
- Southern California Research Center, Coronado, CA 92118, USA; University of California, San Diego School of Medicine, San Diego, CA, USA.
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26
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Shen Y, Wang X, Zhang S, Qin G, Liu Y, Lu Y, Liang F, Zhuang X. A comprehensive validation of HBV-related acute-on-chronic liver failure models to assist decision-making in targeted therapeutics. Sci Rep 2016; 6:33389. [PMID: 27633520 PMCID: PMC5025883 DOI: 10.1038/srep33389] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2016] [Accepted: 08/25/2016] [Indexed: 12/13/2022] Open
Abstract
This research utilized an external longitudinal dataset of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) to compare and validate various predictive models that support the current recommendations to select the most effective predictive risk models to estimate short- and long-term mortality and facilitate decision-making about preferable therapeutics for HBV-ACLF patients. Twelve ACLF prognostic models were developed after a systematic literature search using the longitudinal data of 232 HBV-ACLF patients on the waiting list for liver transplantation (LT). Four statistical measures, the constant (A) and slope (B) of the fitted line, the area under the curve (C) and the net benefit (D), were calculated to assess and compare the calibration, discrimination and clinical usefulness of the 12 predictive models. According to the model calibration and discrimination, the logistic regression models (LRM2) and the United Kingdom model of end-stage liver disease(UKELD) were selected as the best predictive models for both 3-month and 5-year outcomes. The decision curve summarizes the benefits of intervention relative to the costs of unnecessary treatment. After the comprehensive validation and comparison of the currently used models, LRM2 was confirmed as a markedly effective prognostic model for LT-free HBV-ACLF patients for assisting targeted and standardized therapeutic decisions.
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Affiliation(s)
- Yi Shen
- Department of Epidemiology and Medical Statistics, Nantong University, Nantong, China
| | - Xulin Wang
- Department of Epidemiology and Medical Statistics, Nantong University, Nantong, China
| | - Sheng Zhang
- Department of Epidemiology and Medical Statistics, Nantong University, Nantong, China
| | - Gang Qin
- Center for Liver Diseases, Nantong Third People's Hospital, Nantong University, Nantong, China
| | - Yanmei Liu
- Department of Epidemiology and Medical Statistics, Nantong University, Nantong, China
| | - Yihua Lu
- Department of Epidemiology and Medical Statistics, Nantong University, Nantong, China
| | - Feng Liang
- Qidong Third People's Hospital, Nantong, China
| | - Xun Zhuang
- Department of Epidemiology and Medical Statistics, Nantong University, Nantong, China
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Yang J, Sun H, Liu Q. The Comparative Efficacy and Safety of Entecavir and Lamivudine in Patients with HBV-Associated Acute-on-Chronic Liver Failure: A Systematic Review and Meta-Analysis. Gastroenterol Res Pract 2016; 2016:5802674. [PMID: 27148364 PMCID: PMC4842383 DOI: 10.1155/2016/5802674] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2016] [Revised: 02/20/2016] [Accepted: 03/17/2016] [Indexed: 02/06/2023] Open
Abstract
Background. Currently, both of entecavir and lamivudine are effective for patients with HBV-associated acute-on-chronic liver failure (ACLF). However, there is no consensus on the efficacy of entecavir versus lamivudine for patients with HBV-associated ACLF. The aim of the study was to compare the efficacy and safety of entecavir with that of lamivudine for HBV-associated ACLF patients. Methods. Publications on entecavir versus lamivudine in HBV-associated ACLF patients were comprehensively identified. Odds ratio and mean difference were used to measure the effect. Results. Ten studies, totaling 1254 patients, were eligible. No significant differences between the two drugs presented in the 1-, 2-, 3-, or 6-month survival rates. However, after 12 months of treatment, patients prescribed entecavir had a statistically higher survival rate (p = 0.008) and lower total bilirubin (p < 0.0001) and alanine aminotransferase (p = 0.04) levels compared to patients prescribed lamivudine. More patients achieved HBV negative levels when taking entecavir as measured at 1-, 3-, and 12-month time points and had a lower rate of HBV recurrence. Conclusion. While entecavir and lamivudine are both relatively safe and well tolerated, entecavir was more efficacious in terms of survival rate and clinical improvement in long-term treatment. Further prospective randomized controlled trials are needed to validate these results.
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Affiliation(s)
- Jiao Yang
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Chongqing 400010, China
| | - Hang Sun
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Chongqing 400010, China
| | - Qi Liu
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, 76 Linjiang Road, Chongqing 400010, China
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Acute-on-Chronic Liver Failure (ACLF) in Coastal Eastern India: "A Single-Center Experience". J Clin Exp Hepatol 2016; 6:26-32. [PMID: 27194893 PMCID: PMC4862011 DOI: 10.1016/j.jceh.2015.08.002] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2014] [Accepted: 08/10/2015] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND AND OBJECTIVES Acute-On-Chronic liver failure (ACLF) is an emerging entity. The present study was undertaken to analyze the clinical profile and natural course of ACLF patients. PATIENTS AND METHODS ACLF was defined as per Asia Pacific Association for the Study of Liver consensus criteria 2009. Patients fulfilling these criteria with some deviations were included and prospectively evaluated for clinical profile, etiologies of acute decompensation (AD) and underlying chronic liver disease, and short-term natural course [3 months]. RESULTS Out of 123 patients with ACLF (mean age: 45.83 ± 12.05 years; male:female 109:14), 45.53% cases had prior history of AD, and 54.47% presented for the first time as ACLF. Etiologies of cirrhosis were alcohol, cryptogenic, and chronic hepatitis B virus infection in 65.04%, 23.57%, and 11.38% cases, respectively. Recent history of alcohol intake (within 4 weeks) [42.27%] followed by bacterial infections [36.58%] were the common etiologic precipitants for AD. Only 87 (70.73%) out of 123 cases could be followed up for a duration of 3 months; 62 (71.26%) cases died by 3 months. Most deaths occurred in the alcoholics compared to nonalcoholics [(43/53) 81.13% vs. (19/34) 55.88%; P = 0.01]. No significant difference in mortality rate was observed between ACLF cases with history of prior AD compared to newly diagnosed ACLF cases [30/40 (75%) vs. 32/47 (68.09%); P = 0.477]. The prognostic markers [MELD, MELD-Na, CTP] were not significantly different between survivors and nonsurvivors. CONCLUSION ACLF patients in our population had high short-term mortality rates with majority of deaths in alcoholics. Alcohol intake and bacterial infections were mainly responsible for AD in our study.
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Key Words
- ACLF, acute-on-chronic liver failure
- AD, acute decompensation
- ALD, alcoholic liver disease
- ALT, alanine transaminase
- APASL, Asian Pacific Association for the Study of the Liver
- CLD, chronic liver disease
- CTP, Child-Turcotte-Pugh
- EASL-AASLD, European Association for the Study of the Liver-American Association for the Study of Liver Diseases
- HBV, hepatitis B virus
- HE, hepatic encephalopathy
- HEV, hepatitis E virus
- HRS, hepatorenal syndrome
- INR, International Normalized Ratio
- MELD, Model for End-Stage Liver Disease
- MELD-Na, Model for End-Stage Liver Disease Sodium
- PT, prothrombin time
- SD, standard deviation
- SIRS, systemic inflammatory response syndrome
- ascites
- encephalopathy
- hepatic decompensation
- renal failure
- sepsis
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Zhang J, Gao S, Duan Z, Hu KQ. Overview on acute-on-chronic liver failure. Front Med 2016; 10:1-17. [PMID: 26976617 DOI: 10.1007/s11684-016-0439-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2015] [Accepted: 01/28/2016] [Indexed: 12/11/2022]
Abstract
Liver failure (LF) is defined as severe dysfunction in hepatic synthesis, detoxification, and metabolism induced by various etiologies. Clinical presentation of LF typically includes severe jaundice, coagulation disorder, hepatic encephalopathy, and ascites. LF can be classified into acute LF, acute-on-chronic LF (ACLF), and chronic LF. ACLF has been demonstrated as a distinct syndrome with unique clinical presentation and outcomes. The severity, curability, and reversibility of ACLF have attracted considerable attention. Remarkable developments in ACLF-related conception, diagnostic criteria, pathogenesis, and therapy have been achieved. However, this disease, especially its diagnostic criteria, remains controversial. In this paper, we systemically reviewed the current understanding of ACLF from its definition, etiology, pathophysiology, pathology, and clinical presentation to management by thoroughly comparing important findings between east and west countries, as well as those from other regions. We also discussed the controversies, challenges, and needs for future studies to promote the standardization and optimization of the diagnosis and treatment for ACLF.
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Affiliation(s)
- Jing Zhang
- Department of Hepatitis C and Drug Induced Liver Injury, Beijing YouAn Hospital, Capital Medical University, Beijing, 100069, China
- Collaborative Innovation Center of Infectious Diseases, Beijing, 100069, China
| | - Shan Gao
- Beijing Artificial Liver Treatment & Training Center, Beijing YouAn Hospital, Capital Medical University, Beijing, 100069, China
- Collaborative Innovation Center of Infectious Diseases, Beijing, 100069, China
| | - Zhongping Duan
- Beijing Artificial Liver Treatment & Training Center, Beijing YouAn Hospital, Capital Medical University, Beijing, 100069, China.
- Collaborative Innovation Center of Infectious Diseases, Beijing, 100069, China.
| | - Ke-Qin Hu
- Division of Gastroenterology and Hepatology, University of California, Irvine, Medical Center, Orange, CA, 92868, USA.
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30
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Lok ASF, McMahon BJ, Brown RS, Wong JB, Ahmed AT, Farah W, Almasri J, Alahdab F, Benkhadra K, Mouchli MA, Singh S, Mohamed EA, Abu Dabrh AM, Prokop LJ, Wang Z, Murad MH, Mohammed K. Antiviral therapy for chronic hepatitis B viral infection in adults: A systematic review and meta-analysis. Hepatology 2016; 63:284-306. [PMID: 26566246 DOI: 10.1002/hep.28280] [Citation(s) in RCA: 412] [Impact Index Per Article: 45.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2015] [Accepted: 09/23/2015] [Indexed: 01/10/2023]
Abstract
UNLABELLED Chronic hepatitis B viral (HBV) infection remains a significant global health problem. Evidence-based guidelines are needed to help providers determine when treatment should be initiated, which medication is most appropriate, and when treatment can safely be stopped. The American Association for the Study of Liver Diseases HBV guideline methodology and writing committees developed a protocol a priori for this systematic review. We searched multiple databases for randomized controlled trials and controlled observational studies that enrolled adults ≥18 years old diagnosed with chronic HBV infection who received antiviral therapy. Data extraction was done by pairs of independent reviewers. We included 73 studies, of which 59 (15 randomized controlled trials and 44 observational studies) reported clinical outcomes. Moderate-quality evidence supported the effectiveness of antiviral therapy in patients with immune active chronic HBV infection in reducing the risk of cirrhosis, decompensated liver disease, and hepatocellular carcinoma. In immune tolerant patients, moderate-quality evidence supports improved intermediate outcomes with antiviral therapy. Only very low-quality evidence informed the questions about discontinuing versus continuing antiviral therapy in hepatitis B e antigen-positive patients who seroconverted from hepatitis B e antigen to hepatitis B e antibody and about the safety of entecavir versus tenofovir. Noncomparative and indirect evidence was available for questions about stopping versus continuing antiviral therapy in hepatitis B e antigen-negative patients, monotherapy versus adding a second agent in patients with persistent viremia during treatment, and the effectiveness of antivirals in compensated cirrhosis with low-level viremia. CONCLUSION Most of the current literature focuses on the immune active phases of chronic HBV infection; decision-making in other commonly encountered and challenging clinical settings depends on indirect evidence.
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Affiliation(s)
- Anna S F Lok
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI
| | - Brian J McMahon
- Liver Diseases and Hepatitis Program, Alaska Native Tribal Health Consortium, Anchorage, AK
| | - Robert S Brown
- Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, NY
| | - John B Wong
- Division of Clinical Decision Making, Tufts Medical Center, Boston, MA
| | - Ahmed T Ahmed
- Evidence-Based Practice Research Program, Mayo Clinic, Rochester, MN.,Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN
| | - Wigdan Farah
- Evidence-Based Practice Research Program, Mayo Clinic, Rochester, MN.,Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN
| | - Jehad Almasri
- Evidence-Based Practice Research Program, Mayo Clinic, Rochester, MN.,Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN
| | - Fares Alahdab
- Evidence-Based Practice Research Program, Mayo Clinic, Rochester, MN.,Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN
| | - Khalid Benkhadra
- Evidence-Based Practice Research Program, Mayo Clinic, Rochester, MN.,Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN
| | | | - Siddharth Singh
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | - Essa A Mohamed
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN
| | | | | | - Zhen Wang
- Evidence-Based Practice Research Program, Mayo Clinic, Rochester, MN.,Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN
| | - Mohammad Hassan Murad
- Evidence-Based Practice Research Program, Mayo Clinic, Rochester, MN.,Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN.,Division of Preventive, Occupational and Aerospace Medicine, Mayo Clinic, Rochester, MN
| | - Khaled Mohammed
- Evidence-Based Practice Research Program, Mayo Clinic, Rochester, MN.,Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN.,Division of Preventive, Occupational and Aerospace Medicine, Mayo Clinic, Rochester, MN
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Chronic Hepatitis B with Spontaneous Severe Acute Exacerbation. Int J Mol Sci 2015; 16:28126-45. [PMID: 26703566 PMCID: PMC4691034 DOI: 10.3390/ijms161226087] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2015] [Revised: 11/03/2015] [Accepted: 11/09/2015] [Indexed: 02/08/2023] Open
Abstract
Chronic hepatitis B virus (HBV) infection is a major global health problem with an estimated 400 million HBV carriers worldwide. In the natural history of chronic hepatitis B (CHB), spontaneous acute exacerbation (AE) is not uncommon, with a cumulative incidence of 10%–30% every year. While exacerbations can be mild, some patients may develop hepatic decompensation and even die. The underlying pathogenesis is possibly related to the activation of cytotoxic T lymphocyte-mediated immune response against HBV. An upsurge of serum HBV DNA usually precedes the rise of alanine aminotransferase (ALT) and bilirubin. Whether antiviral treatment can benefit CHB with severe AE remains controversial, but early nucleos(t)ide analogues treatment seemed to be associated with an improved outcome. There has been no randomized study that compared the effects of different nucleos(t)ide analogues (NA) in the setting of CHB with severe AE. However, potent NAs with good resistance profiles are recommended. In this review, we summarized current knowledge regarding the natural history, pathogenetic mechanisms, and therapeutic options of CHB with severe AE.
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Blasco-Algora S, Masegosa-Ataz J, Gutiérrez-García ML, Alonso-López S, Fernández-Rodríguez CM. Acute-on-chronic liver failure: Pathogenesis, prognostic factors and management. World J Gastroenterol 2015; 21:12125-12140. [PMID: 26576097 PMCID: PMC4641130 DOI: 10.3748/wjg.v21.i42.12125] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2015] [Revised: 08/17/2015] [Accepted: 09/30/2015] [Indexed: 02/06/2023] Open
Abstract
Acute-on-chronic liver failure (ACLF) is increasingly recognized as a complex syndrome that is reversible in many cases. It is characterized by an acute deterioration of liver function in the background of a pre-existing chronic liver disease often associated with a high short-term mortality rate. Organ failure (OF) is always associated, and plays a key role in determining the course, and the outcome of the disease. The definition of ACLF remains controversial due to its overall ambiguity, with several disparate criteria among various associations dedicated to the study of liver diseases. Although the precise pathogenesis needs to be clarified, it appears that an altered host response to injury might be a contributing factor caused by immune dysfunction, ultimately leading to a pro-inflammatory status, and eventually to OF. The PIRO concept (Predisposition, Insult, Response and Organ Failure) has been proposed to better approach the underlying mechanisms. It is accepted that ACLF is a different and specific form of liver failure, where a precipitating event is always involved, even though it cannot always be ascertained. According to several studies, infections and active alcoholism often trigger ACLF. Viral hepatitis, gastrointestinal haemorrhage, or drug induced liver injury, which can also provoke the syndrome. This review mainly focuses on the physiopathology and prognostic aspects. We believe these features are essential to further understanding and providing the rationale for improveddisease management strategies.
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Chen EQ, Zeng F, Zhou LY, Tang H. Early warning and clinical outcome prediction of acute-on-chronic hepatitis B liver failure. World J Gastroenterol 2015; 21:11964-11973. [PMID: 26576085 PMCID: PMC4641118 DOI: 10.3748/wjg.v21.i42.11964] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2015] [Revised: 07/29/2015] [Accepted: 09/14/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) associated acute-on-chronic liver failure (ACLF) is an increasingly recognized fatal liver disease encompassing a severe acute exacerbation of liver function in patients with chronic hepatitis B (CHB). Despite the introduction of an artificial liver support system and antiviral therapy, the short-term prognosis of HBV-ACLF is still extremely poor unless emergency liver transplantation is performed. In such a situation, stopping or slowing the progression of CHB to ACLF at an early stage is the most effective way of reducing the morbidity and mortality of HBV-ACLF. It is well-known that the occurrence and progression of HBV-ACLF is associated with many factors, and the outcomes of HBV-ACLF patients can be significantly improved if timely and appropriate interventions are provided. In this review, we highlight recent developments in early warning and clinical outcome prediction in patients with HBV-ACLF and provide an outlook for future research in this field.
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Yue-Meng W, Yang LH, Yang JH, Xu Y, Yang J, Song GB. The effect of plasma exchange on entecavir-treated chronic hepatitis B patients with hepatic de-compensation and acute-on-chronic liver failure. Hepatol Int 2015; 10:462-9. [PMID: 26482576 DOI: 10.1007/s12072-015-9667-4] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2015] [Accepted: 08/30/2015] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND AIMS Various studies showed that entecavir (ETV) failed to improve the short-term survival in chronic hepatitis B (CHB) patients with severe acute exacerbation (SAE) and hepatic de-compensation or acute-on-chronic liver failure (ACLF). One study concluded that plasma exchange (PE) significantly decreased the short-term mortality of CHB patients with ACLF who were treated with lamivudine (LAM). Our study was designed to examine the effect of PE on CHB patients with ACLF who were treated with ETV. METHODS From August 2010 to January 2015, 38 (PE group) and 120 (control group) consecutive CHB-naïve patients with hepatic de-compensation and ACLF treated with PE plus ETV and ETV, respectively, were recruited. The primary endpoint was liver-related mortality at week 12. Biochemical and virological responses were also studied. RESULTS At baseline, the PE group had higher serum alanine aminotransferase (ALT) levels and model for end-stage liver disease (MELD) scores, and had lower albumin levels than the control group. The cumulative survival rate at week 4 and week 12 in the PE group and control group were, respectively, 37 and 18 %, and 29 and 14 % (p < 0.001, by log rank test). While the bilirubin levels in the PE group were more quickly lowered by PE therapy (p < 0.001), the decrease of ALT levels and virological response were similar in the two groups (p > 0.05). Univariate analysis showed that the control group had a higher liver-related mortality (p = 0.038) at week 12 than the PE group. Multivariate analysis showed that hepatic encephalopathy, ascites, PE treatment, and MELD scores were independent factors for liver-related mortality at week 12. CONCLUSIONS PE significantly improved the short-term survival of CHB patients with hepatic de-compensation and ACLF who were treated with ETV. Hepatic encephalopathy, ascites, PE treatment, and MELD scores were independent factors for liver-related mortality at week 12.
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Affiliation(s)
- Wan Yue-Meng
- Department of Hepatology Center, The Second Affiliated Hospital of Kunming Medical University, Kunming City, Yunnan Province, China
| | - Li-Hong Yang
- Department of Hepatology Center, The Second Affiliated Hospital of Kunming Medical University, Kunming City, Yunnan Province, China
| | - Jin-Hui Yang
- Department of Hepatology Center, The Second Affiliated Hospital of Kunming Medical University, Kunming City, Yunnan Province, China.
| | - Ying Xu
- Department of Hepatology Center, The Second Affiliated Hospital of Kunming Medical University, Kunming City, Yunnan Province, China
| | - Jing Yang
- Department of Hepatology Center, The Second Affiliated Hospital of Kunming Medical University, Kunming City, Yunnan Province, China
| | - Gui-Bo Song
- Department of Clinical Laboratory, The First Affiliated Hospital of Kunming Medical University, Kunming City, Yunnan Province, China
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Ha JM, Sohn W, Cho JY, Pyo JH, Choi K, Sinn DH, Gwak GY, Choi MS, Lee JH, Koh KC, Paik SW, Yoo BC, Paik YH. Static and dynamic prognostic factors for hepatitis-B-related acute-on-chronic liver failure. Clin Mol Hepatol 2015; 21:232-41. [PMID: 26523268 PMCID: PMC4612284 DOI: 10.3350/cmh.2015.21.3.232] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2015] [Revised: 08/21/2015] [Accepted: 08/21/2015] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND/AIMS Hepatitis-B-related acute-on-chronic liver failure has a poor prognosis. However, the advent of potent oral antiviral agents means that some patients can now recover with medical treatment. We aimed to identify the prognostic factors for hepatitis-B-related acute-on-chronic liver failure including the initial as well as the dynamically changing clinical parameters during admission. METHODS Sixty-seven patients were retrospectively enrolled from 2003 to 2012 at Samsung Medical Center. The patients were classified into three categories: Recovery group (n=23), Liver transplantation group (n=28), and Death group (n=16). The Liver transplantation and Death groups were combined into an Unfavorable prognosis group. We analyzed the prognostic factors including the Model for End-Stage Liver Disease (MELD) scores determined at 3-day intervals. RESULTS A multivariable analysis showed that the unfavorable prognostic factors were a high initial MELD score (≥28) (odds ratio [OR] =6.64, p=0.015), moderate-to-severe ascites at admission (OR=6.71, P=0.012), and the aggravation of hepatic encephalopathy during hospitalization (≥grade III) (OR=15.41, P=0.013). Compared with the baseline level, significant reductions in the MELD scores were observed on the 7th day after admission in the Recovery group (P=0.016). CONCLUSIONS Dynamic changes in clinical parameters during admission are useful prognostic factors for hepatitis-B-related acute-on-chronic liver failure.
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Affiliation(s)
- Jung Min Ha
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Won Sohn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Ju Yeon Cho
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jeung Hui Pyo
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kyu Choi
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Geum-Youn Gwak
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Moon Seok Choi
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Joon Hyeok Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kwang Chul Koh
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Seung Woon Paik
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Byung Chul Yoo
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yong-Han Paik
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Liu XY, Peng F, Pan YJ, Chen J. Advanced therapeutic strategies for HBV-related acute-on-chronic liver failure. Hepatobiliary Pancreat Dis Int 2015; 14:354-60. [PMID: 26256078 DOI: 10.1016/s1499-3872(15)60338-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Acute-on-chronic liver failure (ACLF) is increasingly recognized as a distinct clinical entity and is associated with a high short-term mortality. The most common cause of ACLF is chronic hepatitis B worldwide. Currently, there is no standardized approach for the management of ACLF and the efficacy and safety of therapeutic modalities are uncertain. DATA SOURCES PubMed and Web of Science were searched for English-language articles. The search criteria focused on clinical trials and observational studies on the treatment of patients with HBV-related ACLF. RESULTS Therapeutic approaches for ACLF in patients with chronic hepatitis B included nucleos(t)ide analogues, artificial liver support systems, immune regulatory therapy, stem cell therapy and liver transplantation. All of these therapeutic approaches have shown the potential to improve liver function and increase patients' survival rate, but most of the studies were not randomized or controlled. CONCLUSION Substantial challenges for the treatment of HBV-related ACLF remain and further basic research and randomized controlled clinical trials are needed.
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Affiliation(s)
- Xin-Yu Liu
- Liver Diseases Center, Second Xiangya Hospital, Central South University, Changsha 410011, China.
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Gao FY, Liu Y, Li XS, Ye XQ, Sun L, Geng MF, Wang R, Liu HM, Zhou XB, Gu LL, Liu YM, Wan G, Wang XB. Score model for predicting acute-on-chronic liver failure risk in chronic hepatitis B. World J Gastroenterol 2015; 21:8373-8381. [PMID: 26217089 PMCID: PMC4507107 DOI: 10.3748/wjg.v21.i27.8373] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2015] [Revised: 03/25/2015] [Accepted: 05/04/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To establish a clinical scoring model to predict risk of acute-on-chronic liver failure (ACLF) in chronic hepatitis B (CHB) patients.
METHODS: This was a retrospective study of 1457 patients hospitalized for CHB between October 2008 and October 2013 at the Beijing Ditan Hospital, Capital Medical University, China. The patients were divided into two groups: severe acute exacerbation (SAE) group (n = 382) and non-SAE group (n = 1075). The SAE group was classified as the high-risk group based on the higher incidence of ACLF in this group than in the non-SAE group (13.6% vs 0.4%). Two-thirds of SAE patients were randomly assigned to risk-model derivation and the other one-third to model validation. Univariate risk factors associated with the outcome were entered into a multivariate logistic regression model for screening independent risk factors. Each variable was assigned an integer value based on the regression coefficients, and the final score was the sum of these values in the derivation set. Model discrimination and calibration were assessed using area under the receiver operating characteristic curve and the Hosmer-Lemeshow test.
RESULTS: The risk prediction scoring model included the following four factors: age ≥ 40 years, total bilirubin ≥ 171 μmol/L, prothrombin activity 40%-60%, and hepatitis B virus DNA > 107 copies/mL. The sum risk score ranged from 0 to 7; 0-3 identified patients with lower risk of ACLF, whereas 4-7 identified patients with higher risk. The Kaplan-Meier analysis showed the cumulative risk for ACLF and ACLF-related death in the two risk groups (0-3 and 4-7 scores) of the primary cohort over 56 d, and log-rank test revealed a significant difference (2.0% vs 33.8% and 0.8% vs 9.4%, respectively; both P < 0.0001). In the derivation and validation data sets, the model had good discrimination (C index = 0.857, 95% confidence interval: 0.800-0.913 and C index = 0.889, 95% confidence interval: 0.820-0.957, respectively) and calibration demonstrated by the Hosmer-Lemeshow test (χ2 = 4.516, P = 0.808 and χ2 = 1.959, P = 0.923, respectively).
CONCLUSION: Using the scoring model, clinicians can easily identify patients (total score ≥ 4) at high risk of ACLF and ACLF-related death early during SAE.
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Initial combination anti-viral therapy with lamivudine and adefovir dipivoxil decreases short-term fatality rate of hepatitis-B-virus-related acute-on-chronic liver failure. Virol J 2015; 12:97. [PMID: 26104153 PMCID: PMC4501091 DOI: 10.1186/s12985-015-0323-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2014] [Accepted: 06/10/2015] [Indexed: 12/13/2022] Open
Abstract
Background Acute-on-chronic liver failure (ACLF) is a common serious hepatitis B virus (HBV)-related disease and has a poor prognosis. Until recently, initial combination antiviral treatment in ACLF patients was rarely reported. This study evaluated the effect of initial combination treatment with lamivudine and adefovir dipivoxil on the prognosis of HBV-related ACLF. Methods In this retrospective study, 131 eligible ACLF patients, including 61 treated with 100 mg lamivudine and 10 mg adefovir dipivoxil daily and 70 not treated with any nucleoside analogs (NAs), were selected and assigned into the NA and non-NA groups. All the patients received standard medicinal therapy. At weeks 0–4 and 12, serum markers for hepatic and renal functions were measured in all patients and accumulated fatality rates were calculated. Statistical analyses, including Student’s t test, χ2 test and unconditional logistic regression analysis, were performed using SPSS version 17.0 software. Results Clinical data indicated that improvement of hepatic function was better in the NA than in the non-NA group. The accumulated fatality rate in the NA group was lower than in the non-NA group at weeks 2–4 and 12, and these differences were significant. Univariate analysis showed that age, prothrombin activity, model of end-stage liver disease (MELD) score, and treatment without NAs were risk factors for short-term survival of ACLF. Further research by unconditional logistic regression analysis identified that older age, high MELD score and treatment without NAs were independent risk factors for short-term survival of ACLF. Conclusions Initial combination antiviral treatment is effective in decreasing short-term fatality of HBV-related ACLF.
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Seto WK. Hepatitis B virus reactivation during immunosuppressive therapy: Appropriate risk stratification. World J Hepatol 2015; 7:825-830. [PMID: 25937860 PMCID: PMC4411525 DOI: 10.4254/wjh.v7.i6.825] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2015] [Revised: 02/14/2015] [Accepted: 03/09/2015] [Indexed: 02/06/2023] Open
Abstract
Our understanding of hepatitis B virus (HBV) reactivation during immunosuppresive therapy has increased remarkably during recent years. HBV reactivation in hepatitis B surface antigen (HBsAg)-positive individuals has been well-described in certain immunosuppressive regimens, including therapies containing corticosteroids, anthracyclines, rituximab, antibody to tumor necrosis factor (anti-TNF) and hematopoietic stem cell transplantation (HSCT). HBV reactivation could also occur in HBsAg-negative, antibody to hepatitis B core antigen (anti-HBc) positive individuals during therapies containing rituximab, anti-TNF or HSCT.For HBsAg-positive patients, prophylactic antiviral therapy is proven to the effective in preventing HBV reactivation. Recent evidence also demonstrated entecavir to be more effective than lamivudine in this aspect. For HBsAg-negative, anti-HBc positive individuals, the risk of reactivations differs with the type of immunosuppression. For rituximab, a prospective study demonstrated the 2-year cumulative risk of reactivation to be 41.5%, but prospective data is still lacking for other immunosupressive regimes. The optimal management in preventing HBV reactivation would involve appropriate risk stratification for different immunosuppressive regimes in both HBsAg-positive and HBsAg-negative, anti-HBc positive individuals.
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The efficacy and safety of entecavir in patients with chronic hepatitis B- associated liver failure: a meta-analysis. Ann Hepatol 2015. [DOI: 10.1016/s1665-2681(19)30776-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/16/2023]
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Yi ZQ, Lu MH, Xu XW, Fu XY, Tan DM. A novel prognostic score for acute-on-chronic hepatitis B liver failure. ACTA ACUST UNITED AC 2015; 35:87-92. [PMID: 25673199 DOI: 10.1007/s11596-015-1394-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2014] [Revised: 12/31/2014] [Indexed: 12/20/2022]
Abstract
Patients with acute-on-chronic hepatitis B liver failure (HBV-ACLF) show high morbidity and mortality. Independent prognostic predictors of short-term HBV-ACLF mortality include the Child-Turcotte-Pugh (CTP) score, the model for end-stage liver disease (MELD) score, other MELD-based indices and the dynamic changes in these indices. The aims of this study were to evaluate the existing prognostic scores in a large cohort of HBV-ACLF patients and create a new predictive model. We retrospectively reviewed 392 HBV-ACLF patients from December 2008 to November 2011 and evaluated their 3-month survival. The predictive accuracy of CTP, MELD and MELD-based indices and the dynamic changes in the MELD-related scores (Δ scoring systems) upon admission and after two weeks of treatment were compared using the area under the receiver operating characteristic (ROC) curve method. Life-threatening factors and a series of bio-clinical parameters were studied by univariate and multivariate analyses. Among the existing scores, MELD had the best predictive ability. However, our new regression model provided an area under the curve of 0.930 ± 0.0161 (95% CI: 0.869 to 0.943), which was significantly larger than that obtained with the MELD score at admission and after two weeks of treatment as well as with the dynamic changes of the MELD score (0.819, 0.921, and 0.826, respectively) (Z=3.542, P=0.0004). In a large cohort of patients retrospectively reviewed for this study, our prognostic model was superior to the MELD score and is, therefore, a promising predictor of short-term survival in patients with HBV-ACLF.
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Affiliation(s)
- Zhao-Quan Yi
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, 410008, China
| | - Meng-Hou Lu
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, 410008, China
| | - Xu-Wen Xu
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, 410008, China
| | - Xiao-Yu Fu
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, 410008, China
| | - De-Ming Tan
- Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, 410008, China.
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Yasui S, Fujiwara K, Nakamura M, Miyamura T, Yonemitsu Y, Mikata R, Arai M, Kanda T, Imazeki F, Oda S, Yokosuka O. Virological efficacy of combination therapy with corticosteroid and nucleoside analogue for severe acute exacerbation of chronic hepatitis B. J Viral Hepat 2015; 22:94-102. [PMID: 24750410 DOI: 10.1111/jvh.12258] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2013] [Accepted: 02/09/2014] [Indexed: 12/19/2022]
Abstract
The short-term prognosis of patients with severe acute exacerbation of chronic hepatitis B (CHB) leading to acute liver failure is extremely poor. We have reported the efficacy of corticosteroid in combination with nucleoside analogue in the early stages, but virological efficacy has not been documented. Our aim was to elucidate the virological efficacy of this approach. Thirteen patients defined as severe acute exacerbation of CHB by our uniform criteria were prospectively examined for virological responses to treatment. Nucleoside analogue and sufficient dose of corticosteroids were introduced as soon as possible after the diagnosis of severe disease. Of the 13 patients, 7 (54%) survived, 5 (38%) died and 1 (8%) received liver transplantation. The decline of HBV DNA was significant between the first 2 weeks (P = 0.02) and 4 weeks (P < 0.01). Mean reduction in HBV DNA during the first 2 weeks was 1.7 ± 0.9 log copies per mL in overall patients, 2.1 ± 0.8 in survived patients and 1.2 ± 0.9 in dead/transplanted patients. The decline of HBV DNA was significant between the first 2 weeks (P = 0.03) and 4 weeks (P = 0.02) in survived patients, but not in dead/transplanted patients. Our study shows that corticosteroid treatment in combination with nucleotide analogue has sufficient virological effect against severe acute exacerbation of CHB, and a rapid decline of HBV DNA is conspicuous in survived patients.
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Affiliation(s)
- S Yasui
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
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Philips CA, Sarin SK. Potent antiviral therapy improves survival in acute on chronic liver failure due to hepatitis B virus reactivation. World J Gastroenterol 2014; 20:16037-16052. [PMID: 25473156 PMCID: PMC4239490 DOI: 10.3748/wjg.v20.i43.16037] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2014] [Revised: 07/02/2014] [Accepted: 07/29/2014] [Indexed: 02/06/2023] Open
Abstract
Acute on chronic liver failure (ACLF) is a disease entity with a high mortality rate. The acute event arises from drugs and toxins, viral infections, bacterial sepsis, interventions (both surgical and non-surgical) and vascular events on top of a known or occult chronic liver disease. ACLF secondary to reactivation of chronic hepatitis B virus is a distinct condition; the high mortality of which can be managed in the wake of new potent antiviral therapy. For example, lamivudine and entecavir use has shown definite short-term survival benefits, even though drug resistance is a concern in the former. The renoprotective effects of telbivudine have been shown in a few studies to be useful in the presence of renal dysfunction. Monotherapy with newer agents such as tenofovir and a combination of nucleos(t)ides is promising for improving survival in this special group of liver disease patients. This review describes the current status of potent antiviral therapy in patient with acute on chronic liver failure due to reactivation of chronic hepatitis B, thereby providing an algorithm in management of such patients.
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Zhang X, An Y, Jiang X, Xu M, Xu L, Chen S, Xi Y. Entecavir versus Lamivudine therapy for patients with chronic hepatitis B-associated liver failure: a meta-analysis. HEPATITIS MONTHLY 2014; 14:e19164. [PMID: 25598786 PMCID: PMC4286714 DOI: 10.5812/hepatmon.19164] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/28/2014] [Revised: 09/17/2014] [Accepted: 10/12/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND Nucleoside analogues are recommended as antiviral treatments for patients with hepatitis B virus (HBV)-associated liver failure. Clinical data comparing entecavir (ETV) and lamivudine (LAM) are inconsistent in this setting. OBJECTIVES To compare the efficacy and safety of ETV and LAM in patients with chronic hepatitis B (CHB)-associated liver failure. PATIENTS AND METHODS A literature search was performed on articles published until January 2014 on therapy with ETV and LAM for patients with CHB-associated liver failure. Risk ratio (RR) and mean difference (MD) were used to measure the effects. Survival rate was the primary efficacy measure, while total bilirubin (TBIL), prothrombin activity (PTA) changes and HBV DNA negative change rates were secondary efficacy measures. A quantitative meta-analysis was performed to compare the efficacy of the two drugs. Safety of ETV and LAM was observed. RESULTS Four randomized controlled trials and nine retrospective cohort studies comprising a total of 1549 patients were selected. Overall analysis revealed comparable survival rates between patients received ETV and those received LAM (4 weeks: RR = 1.03, 95%CI [0.89, 1.18], P = 0.73; 8 weeks: RR = 0.98, 95% CI [0.85, 1.14], P = 0.84; 12 weeks: RR = 0.98, 95% CI [0.90, 1.08], P = 0.70; 24 weeks: RR = 1.02, 95% CI [0.94, 1.10], P = 0.66). After 24 weeks of treatment, patients treated with ETV had a significantly lower TBIL levels (MD = -37.34, 95% CI [-63.57, -11.11], P = 0.005), higher PTA levels (MD = 11.10, 95% CI [2.47, 19.73], P = 0.01) and higher HBV DNA negative rates (RR = 2.76, 95% CI [1.69, 4.51], P < 0.0001) than those treated with LAM. In addition, no drug related adverse effects were observed in the two treatment groups. CONCLUSIONS ETV and LAM treatments had similar effects to improve 24 weeks survival rate of patients with CHB-associated liver failure, but ETV was associated with greater clinical improvement. Both drugs were tolerated well during the treatment. It is suggested to perform further studies to verify the results.
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Affiliation(s)
- Xiaoguo Zhang
- Division of Liver Disease, Jinan Infectious Disease Hospital, Shandong University, Jinan, China
| | - Yong An
- Division of Liver Disease, Qianfoshan Hospital, Shandong University, Jinan, China
| | - Xuemei Jiang
- Division of Liver Disease, Jinan Infectious Disease Hospital, Shandong University, Jinan, China
| | - Minling Xu
- Division of Liver Disease, Jinan Infectious Disease Hospital, Shandong University, Jinan, China
| | - Linlin Xu
- Division of Liver Disease, Jinan Infectious Disease Hospital, Shandong University, Jinan, China
| | - Shijun Chen
- Division of Liver Disease, Jinan Infectious Disease Hospital, Shandong University, Jinan, China
- Corresponding Author: Shijun Chen, Division of Liver Disease, Jinan Infectious Disease Hospital, Shandong University, Jinan, China. Tel: +86-13335153216, E-mail:
| | - Yaguang Xi
- Mitchell Cancer Institute, University of South Alabama, Mobile, USA
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Anti-viral therapy in hepatitis B virus reactivation with acute-on-chronic liver failure. Hepatol Int 2014; 9:373-7. [PMID: 25788180 DOI: 10.1007/s12072-014-9569-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2014] [Accepted: 08/01/2014] [Indexed: 12/14/2022]
Abstract
Hepatitis B virus (HBV) reactivation with hepatic decompensation leading to acute on chronic liver failure is not uncommon. It is associated with high mortality of up to 30-70%. Prognostic factors for mortality include high bilirubin level, more prolonged prothrombin time, low platelet count and presence of pre-existing cirrhosis. Several studies addressing the efficacy of different anti-viral therapies, namely lamivudine, entecavir and tenofovir, have been performed. Although the results were not highly consistent, it appeared that use of anti-viral agents was associated with decreasing chance of mortality, subsequent HBV reactivation, disease progression, and with excellent viral suppression. The beneficial effects were most prominently observed in patients with MELD score 20-30. However, even with anti-viral therapy, patients may still have irreversible liver decompensation requiring liver transplantation if other adverse parameters. including pre-existing cirrhosis, bilirubin >20 mg/dL (340 µmol/L), prothrombin time <40%, platelet count <120 × 10(9)/L. were present. Mortality rate in patients with MELD score >30 was >92% even with prompt anti-viral treatment. Liver transplantation should be considered urgently.
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Wu FL, Shi KQ, Chen YP, Braddock M, Zou H, Zheng MH. Scoring systems predict the prognosis of acute-on-chronic hepatitis B liver failure: an evidence-based review. Expert Rev Gastroenterol Hepatol 2014; 8:623-632. [PMID: 24762209 DOI: 10.1586/17474124.2014.906899] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Acute-on-chronic hepatitis B liver failure is a devastating condition that is associated with mortality rates of over 50% and is consequent to acute exacerbation of chronic hepatitis B in patients with previously diagnosed or undiagnosed chronic liver disease. Liver transplantation is the definitive treatment to lower mortality rate, but there is a great imbalance between donation and potential recipients. An early and accurate prognostic system based on the integration of laboratory indicators, clinical events and some mathematic logistic equations is needed to optimize treatment for patients. As parts of the scoring systems, the MELD was the most common and the donor-MELD was the most innovative for patients on the waiting list for liver transplantation. This review aims to highlight the various features and prognostic capabilities of these scoring systems.
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Affiliation(s)
- Fa-Ling Wu
- Department of Infection and Liver Diseases, Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
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Wang K, Wu ZB, Ye YN, Liu J, Zhang GL, Su YJ, He HL, Zheng YB, Gao ZL. Plasma Interleukin-10: A Likely Predictive Marker for Hepatitis B Virus-Related Acute-on-Chronic Liver Failure. HEPATITIS MONTHLY 2014; 14:e19370. [PMID: 25147572 PMCID: PMC4139694 DOI: 10.5812/hepatmon.19370] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/11/2014] [Revised: 05/27/2014] [Accepted: 06/22/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND The pathogenesis of HBV-related acute-on-chronic liver failure (HBV-ACLF) is mainly based on a heightened immune-inflammatory reaction; however, the intimate underlying mechanism remains unclear. OBJECTIVES The aim of the study was to explore potential key immune molecular targets that could serve as early predictive markers for HBV-ACLF. PATIENTS AND METHODS Twenty-seven patients with acute exacerbation of chronic hepatitis B (CHB) (defined by: alanine transaminase ≥ 20 ULN, total bilirubin ≥ 5 ULN, 40% < prothrombin time activity ≤ 60%) and without cirrhosis were divided into 18 cases which did not progress to HBV-ACLF (defined by: prothrombin time activity < 40% and development within four weeks of hepatic encephalopathy and/or ascites) and nine cases that developed HBV-ACLF. Nine healthy people defined the normal control group (NC). Interleukin-1β (IL-1β), IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, TNF-α and IFN-γ protein levels were assayed by Cytometric Bead Array (CBA) in blood plasma. The ELISA method was applied to confirm IL-10 detection using the CBA method. RESULTS IL-4, IL-12p70 and IFN-γ were undetectable; IL-1β, IL-6, IL-8, IL-10 and TNF-α levels were significantly higher than in NC. Moreover, cytokines reached the highest levels in acute exacerbation of CHB, with the exception of IL-2 and IL-8. When comparing the HBV-ACLF patients prior to and at the time of ACLF diagnosis, IL-10 was the only cytokine that exhibited a significant decrease (P = 0.008). IL-10 concentrations were positively correlated to ALT levels (r = 0.711, P < 0.001). CONCLUSIONS The assessment of plasma IL-10 levels in chronic hepatitis B acute exacerbation may provide an early predictive marker for progression to HBV-ACLF.
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Affiliation(s)
- Ke Wang
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zhe-bin Wu
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yi-nong Ye
- Department of Infectious Diseases, Foshan Hospital of Sun Yat-sen University, Foshan, China
| | - Jing Liu
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Geng-lin Zhang
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yu-jie Su
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Hong-liang He
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Yu-bao Zheng
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Zhi-liang Gao
- Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
- Corresponding Author: Zhi-liang Gao, Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-sen University, 600 # Tianhe Road, Guangzhou 510630, China. Tel: +86-2085252373, Fax: +86-2085252250, E-mail:
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Chung GE, Lee JH, Kim YJ. Does antiviral therapy reduce complications of cirrhosis? World J Gastroenterol 2014; 20:7306-7311. [PMID: 24966601 PMCID: PMC4064076 DOI: 10.3748/wjg.v20.i23.7306] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Revised: 01/02/2014] [Accepted: 04/03/2014] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis B infection is associated with the development of cirrhosis, hepatocellular carcinoma, and finally liver-related mortality. Each year, approximately, 2%-5% of patients with hepatitis B virus (HBV)-related compensated cirrhosis develop decompensation, with additional clinical manifestations, such as ascites, jaundice, hepatic encephalopathy, and gastrointestinal bleeding. The outcome of decompensated HBV-related cirrhosis is poor, with a 5-year survival of 14%-35% compared to 84% in patients with compensated cirrhosis. Because the risk of disease progression is closely linked to a patient’s serum HBV DNA level, antiviral therapy may suppress viral replication, stabilize liver function and improve survival. This article briefly reviews the role that antiviral therapy plays in cirrhosis complications, particularly, in decompensation and acute-on-chronic liver failure.
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Shouval D. The pros and cons of lamivudine vs. entecavir in decompensated or severe acute exacerbation of chronic hepatitis B. J Hepatol 2014; 60:1108-9. [PMID: 24636833 DOI: 10.1016/j.jhep.2014.03.004] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2014] [Accepted: 03/11/2014] [Indexed: 01/05/2023]
Affiliation(s)
- Daniel Shouval
- Liver Unit, Hadassah-Hebrew University Hospital, Jerusalem, Israel.
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Chen CH, Lin CL, Hu TH, Hung CH, Tseng PL, Wang JH, Chang JY, Lu SN, Chien RN, Lee CM. Entecavir vs. lamivudine in chronic hepatitis B patients with severe acute exacerbation and hepatic decompensation. J Hepatol 2014; 60:1127-34. [PMID: 24583247 DOI: 10.1016/j.jhep.2014.02.013] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2013] [Revised: 01/21/2014] [Accepted: 02/16/2014] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS We compared the mortality and treatment response between lamivudine (LAM) and entecavir (ETV) in chronic hepatitis B (CHB) patients with severe acute exacerbation and hepatic decompensation. METHODS From 2003 to 2010 (the LAM group) and 2008 to 2010 (the ETV group), 215 and 107 consecutive CHB naïve patients with severe acute exacerbation and hepatic decompensation treated with LAM and ETV respectively, were recruited. RESULTS At baseline, the LAM group had higher AST levels and end-stage liver disease (MELD) scores, and lower albumin levels than the ETV group. Univariate analysis showed that the LAM group had a higher rate of overall (p=0.02) and liver-related mortality (p=0.052) at week 24 than the ETV group, including in patients with acute-on-chronic liver failure. Multivariate analysis showed that MELD scores, ascites, and hepatic encephalopathy were independent factors for overall and liver-related mortality at week 24. ETV or LAM treatment was not an independent factor for mortality in all patients or patients with acute-on-chronic liver failure. The best cut-off value of MELD scores were 24 for 24-week liver-related mortality. The ETV group achieved better virological response (HBV DNA <300 copies/ml) than the LAM group at week 24 (p=0.043) and 48 (p=0.007). The T1753C/A mutation was also an independent predictor associated with overall and liver-related mortality at week 24. CONCLUSIONS The choice between ETV and LAM was not an independent factor for mortality in CHB patients with acute exacerbation and hepatic decompensation. Patients with ascites, hepatic encephalopathy, and MELD scores ⩾24 were associated with poor outcome and should be considered for liver transplantation.
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Affiliation(s)
- Chien-Hung Chen
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chih-Lang Lin
- Keelung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Tsung-Hui Hu
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Po-Lin Tseng
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Jing-Houng Wang
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Juan-Yu Chang
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Sheng-Nan Lu
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Rong-Nan Chien
- Keelung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chuan-Mo Lee
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
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