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1
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A prognostic score for patients with acute-on-chronic liver failure treated with plasma exchange-centered artificial liver support system. Sci Rep 2021; 11:1469. [PMID: 33446902 PMCID: PMC7809456 DOI: 10.1038/s41598-021-81019-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Accepted: 12/30/2020] [Indexed: 02/05/2023] Open
Abstract
Artificial liver support system (ALSS) therapy is widely used in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). We aimed to develop a predictive score to identify the subgroups who may benefit from plasma exchange (PE)-centered ALSS therapy. A total of 601 patients were retrospectively enrolled and randomly divided into a derivation cohort of 303 patients and a validation cohort of 298 patients for logistic regression analysis, respectively. Five baseline variables, including liver cirrhosis, total bilirubin, international normalized ratio of prothrombin time, infection and hepatic encephalopathy, were found independently associated with 3-month mortality. A predictive PALS model and the simplified PALS score were developed. The predicative value of PALS score (AUROC = 0.818) to 3-month prognosis was as capable as PALS model (AUROC = 0.839), R score (AUROC = 0.824) and Yue-Meng’ score (AUROC = 0.810) (all p > 0.05), and superior to CART model (AUROC = 0.760) and MELD score (AUROC = 0.765) (all p < 0.05). The PALS score had significant linear correlation with 3-month mortality (R2 = 0.970, p = 0.000). PALS score of 0–2 had both sensitivity and negative predictive value of > 90% for 3-month mortality, while PALS score of 6–9 had both specificity and positive predictive value of > 90%. Patients with PALS score of 3–5 who received 3–5 sessions of ALSS therapy had much lower 3-month mortality than those who received 1–2 sessions (32.8% vs. 59.2%, p < 0.05). The more severe patients with PALS score of 6–9 could still benefit from ≥ 6 sessions of ALSS therapy compared to ≤ 2 sessions (63.6% vs. 97.0%, p < 0.05). The PALS score could predict prognosis reliably and conveniently. It could identify the subgroups who could benefit from PE-centered ALSS therapy, and suggest the reasonable sessions. Trial registration: Chinese Clinical Trial Registry, ChiCTR2000032055. Registered 19th April 2020, http://www.chictr.org.cn/showproj.aspx?proj=52471.
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Yang F, Liu Y, Zeng B, Chu J, Hu H, Yang Y, Chen H, Tian C, Li Y, Lin S. Noninvasive assessment of liver fibrosis for predicting acute-on-chronic liver failure in patients with chronic hepatitis B. Hepatol Int 2021; 15:593-601. [PMID: 33389677 DOI: 10.1007/s12072-020-10106-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Accepted: 10/27/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND AIM The aim of this study was to evaluate the accuracy of serum markers of liver fibrosis for predicting progression to acute-on-chronic liver failure (ACLF) in patients with acute exacerbation (AE) and severe AE (SAE) of chronic hepatitis B virus (HBV) infection. METHODS The predictive accuracy of aminotransferase-to-platelet ratio index (APRI), Fibrosis-4, Lok index, and Forns index for progression to ACLF was evaluated via receiver operating characteristic (ROC) curve and area under the ROC (AUROC) in 441 and 130 patients with AE and SAE. RESULTS After admission, 24 (5.8%) and 25 (19.2%) patients with AE and SAE, respectively, progressed to ACLF. The Lok index was one of the independent risk factors associated with progression to ACLF in patients with AE and SAE. The AUROC of Lok index for diagnosing liver cirrhosis was 0.815 (0.774-0.851) in patients with AE and 0.715 (0.629-0.791) in patients with SAE. The AUROC of Lok index for predicting progression to ACLF in patients with AE and SAE was 0.756 (0.711-0.797) and 0.866 (0.795-0.919), respectively. In patients with AE and SAE, the cut-off values of the Lok index for predicting ACLF were higher and lower, respectively, than those for diagnosing liver cirrhosis. CONCLUSION The Lok index has predictive accuracy regarding progression to ACLF in patients with AE and SAE. Different thresholds of liver fibrosis are needed for determining progression to ACLF in patients with different severity of liver injury during acute exacerbation of chronic HBV infection.
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Affiliation(s)
- Fangwan Yang
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, 201 Dalian Street, Zunyi, 563003, Guizhou, China
| | - Yujuan Liu
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, 201 Dalian Street, Zunyi, 563003, Guizhou, China
| | - Baimei Zeng
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, 201 Dalian Street, Zunyi, 563003, Guizhou, China.,Department of Gastroenterology, The Third Hospital of Nanchang, Nanchang, 330009, Jiangxi, China
| | - Jun Chu
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, 201 Dalian Street, Zunyi, 563003, Guizhou, China
| | - Han Hu
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, 201 Dalian Street, Zunyi, 563003, Guizhou, China
| | - Yanqing Yang
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, 201 Dalian Street, Zunyi, 563003, Guizhou, China
| | - Huan Chen
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, 201 Dalian Street, Zunyi, 563003, Guizhou, China
| | - Caiyun Tian
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, 201 Dalian Street, Zunyi, 563003, Guizhou, China
| | - Ying Li
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, 201 Dalian Street, Zunyi, 563003, Guizhou, China
| | - Shide Lin
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, 201 Dalian Street, Zunyi, 563003, Guizhou, China.
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Fung J, Mak LY, Chan ACY, Chok KSH, Wong TCL, Cheung TT, Dai WC, Sin SL, She WH, Ma KW, Seto WK, Lai CL, Lo CM, Yuen MF. Model for End-Stage Liver Disease With Additional Criteria to Predict Short-Term Mortality in Severe Flares of Chronic Hepatitis B. Hepatology 2020; 72:818-828. [PMID: 31872444 DOI: 10.1002/hep.31086] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Accepted: 12/12/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND AND AIMS The prognosis in severe acute flares of chronic hepatitis B (AFOCHB) is often unclear. The current study aimed to establish the predictive value using the Model for End-Stage Liver Disease (MELD) score for short-term mortality for severe AFOCHB. APPROACH AND RESULTS Patients with severe AFOCHB with bilirubin > 50 µmol/L, alanine aminotransferase > 10× upper limit of normal, and international normalized ratio > 1.5 were included. All patients were commenced on entecavir and/or tenofovir. Laboratory results and MELD scores were pooled to calculate mortality at four time points (days 7, 14, 21, and 28). A total of 240 patients were included. Median hepatitis B virus DNA was 7.77 log IU/mL (range, 4.11-10.06), and 49 (20.4%) were hepatitis B e antigen-positive. The 7, 14, 21, and 28-day survival was 96.7%, 88.5%, 79.5%, and 72.8%, respectively. Using pooled results derived from 4,201 blood samples, the area under the receiver operating curve for the MELD score to predict day 7, 14, 21, and 28 mortality was 0.909, 0.892, 0.883, and 0.871, respectively. For MELD ≤ 28, mortality at day 28 was low (<25%) compared with > 50% mortality for MELD ≥ 32. For MELD = 28-32, higher day-28 mortality was observed for four criteria: age ≥52 years, alanine aminotransferase > 217 U/L, platelets < 127, and abnormal baseline imaging (all P < 0.001). In this MELD bracket, the 28-day mortality was 0%, 12.1%, 23.8%, 59.4%, and 78.8% for the presence of zero, one, two, three, and four criteria, respectively. CONCLUSIONS MELD score at any time points can accurately predict the short-term mortality. Patients with MELD ≥ 28 should be worked up for liver transplantation, and those with MELD = 28-32 with three to four at-risk criteria, or MELD ≥ 32 should be listed.
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Affiliation(s)
- James Fung
- Department of Medicine, The University of Hong Kong, Hong Kong SAR, China.,The Liver Transplant Center, Queen Mary Hospital, Hong Kong SAR, China.,State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong SAR, China
| | - Lung-Yi Mak
- Department of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Albert Chi-Yan Chan
- The Liver Transplant Center, Queen Mary Hospital, Hong Kong SAR, China.,State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong SAR, China.,Department of Surgery, The University of Hong Kong, Hong Kong SAR, China
| | - Kenneth Siu-Ho Chok
- The Liver Transplant Center, Queen Mary Hospital, Hong Kong SAR, China.,State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong SAR, China.,Department of Surgery, The University of Hong Kong, Hong Kong SAR, China
| | - Tiffany Cho-Lam Wong
- The Liver Transplant Center, Queen Mary Hospital, Hong Kong SAR, China.,Department of Surgery, The University of Hong Kong, Hong Kong SAR, China
| | - Tan-To Cheung
- The Liver Transplant Center, Queen Mary Hospital, Hong Kong SAR, China.,State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong SAR, China.,Department of Surgery, The University of Hong Kong, Hong Kong SAR, China
| | - Wing-Chiu Dai
- The Liver Transplant Center, Queen Mary Hospital, Hong Kong SAR, China.,Department of Surgery, The University of Hong Kong, Hong Kong SAR, China
| | - Sui-Ling Sin
- The Liver Transplant Center, Queen Mary Hospital, Hong Kong SAR, China.,Department of Surgery, The University of Hong Kong, Hong Kong SAR, China
| | - Wong-Hoi She
- The Liver Transplant Center, Queen Mary Hospital, Hong Kong SAR, China.,Department of Surgery, The University of Hong Kong, Hong Kong SAR, China
| | - Ka-Wing Ma
- The Liver Transplant Center, Queen Mary Hospital, Hong Kong SAR, China.,Department of Surgery, The University of Hong Kong, Hong Kong SAR, China
| | - Wai-Kay Seto
- Department of Medicine, The University of Hong Kong, Hong Kong SAR, China.,State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong SAR, China
| | - Ching-Lung Lai
- Department of Medicine, The University of Hong Kong, Hong Kong SAR, China.,State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong SAR, China
| | - Chung-Mau Lo
- The Liver Transplant Center, Queen Mary Hospital, Hong Kong SAR, China.,State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong SAR, China.,Department of Surgery, The University of Hong Kong, Hong Kong SAR, China
| | - Man-Fung Yuen
- Department of Medicine, The University of Hong Kong, Hong Kong SAR, China.,State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong SAR, China
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Brahmania M, Lombardero M, Hansen BE, Terrault NA, Lok AS, Perrillo RP, Belle SH, Di Bisceglie AM, Feld JJ, Lee WM, Fried MW, Janssen HLA. Association Between Severe Serum Alanine Aminotransferase Flares and Hepatitis B e Antigen Seroconversion and HBV DNA Decrease in Untreated Patients With Chronic HBV Infection. Clin Gastroenterol Hepatol 2019; 17:2541-2551.e2. [PMID: 30743006 PMCID: PMC6905460 DOI: 10.1016/j.cgh.2019.02.005] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2018] [Revised: 01/18/2019] [Accepted: 02/05/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The incidence and outcomes of alanine aminotransferase (ALT) flares during the natural history of chronic HBV infection has not been determined in a large, racially heterogeneous group of patients in North America. METHODS We collected data from the Hepatitis B Research Network-an observational cohort study of untreated adults with chronic HBV infection enrolled at 21 sites in the United States and Canada. Clinical and laboratory data were collected from 1587 participants (49.9% male, 73.7% Asian, 35.2% genotype B infection, mean age of 42.6 years) at enrollment, at weeks 12 and 24, and every 24 weeks thereafter for a planned 5 years of follow up (from January 2011 through May 2016). Participants were excluded if they had a history of hepatic decompensation, hepatocellular carcinoma, solid organ or bone marrow transplantation, chronic immune suppression, or antiviral therapy within 6 months before enrollment. Levels of ALT were measured in serum samples and flares were defined as at least 10 times the upper limit of normal (300 U/L in males and 200 U/L in females). RESULTS ALT flares occurred in 102 participants (6%), with 31 flares (30%) occurring at baseline. The 4-year cumulative incidence of ALT flares was 5.7%. The median peak level of ALT was 450 U/L (25th-75th percentile, 330 U/L to 747 U/L) with a maximum of 2578 U/L. In multivariable analysis, factors associated with the occurrence of an ALT flares were: male sex (odds ratio [OR], 3.02; P=.0007), higher baseline HBV DNA values (OR per log10, 1.41; P<.0001), at risk alcohol use (OR, 2.27 vs none or moderate; P=.02), and higher FIB-4 values (OR, 1.85 per log2; P<.0001). Older age was associated with lower odds of an ALT flare (OR, 0.63 per 10 years; P=.004). Rate of decrease in level of HBV DNA by 1 log10 or more (59 vs 23 per 100 person-years for HB e antigen (HBeAg)-positive vs HBeAg-negative patients; P=.003) and HBeAg loss (47 vs 15 per 100 person-years; P=.002) were higher in patients with an ALT flare than in patients without, but the rate of HBsAg loss was similar (4 vs 2 per 100 person-years; P=.26). No hepatic decompensation, liver transplants, or deaths were observed in participants with ALT flares. CONCLUSION In a large racially heterogeneous cohort of adults with chronic HBV infection, the cumulative incidence of severe ALT flares was low and associated with greater decreases in HBV DNA and loss of HBeAg, but not with loss of HBsAg.
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Affiliation(s)
- Mayur Brahmania
- Division of Gastroenterology, Toronto General Hospital, University Health Network, Toronto, Canada
| | - Manuel Lombardero
- Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Bettina E. Hansen
- Division of Gastroenterology, Toronto General Hospital, University Health Network, Toronto, Canada,IHPME, University of Toronto, Toronto, Canada
| | - Norah A. Terrault
- Division of Gastroenterology, University of California-San Francisco, San Francisco, California
| | - Anna S. Lok
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan
| | - Robert P. Perrillo
- Division of Gastroenterology, Baylor University Medical Center, Dallas, Texas
| | - Steven H. Belle
- Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania
| | | | - Jordan J. Feld
- Division of Gastroenterology, Toronto General Hospital, University Health Network, Toronto, Canada
| | - William M. Lee
- Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas
| | - Michael W. Fried
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, North Carolina
| | - Harry L. A. Janssen
- Division of Gastroenterology, Toronto General Hospital, University Health Network, Toronto, Canada
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5
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Yuan L, Zeng BM, Liu LL, Ren Y, Yang YQ, Chu J, Li Y, Yang FW, He YH, Lin SD. Risk factors for progression to acute-on-chronic liver failure during severe acute exacerbation of chronic hepatitis B virus infection. World J Gastroenterol 2019; 25:2327-2337. [PMID: 31148904 PMCID: PMC6529889 DOI: 10.3748/wjg.v25.i19.2327] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2019] [Revised: 03/29/2019] [Accepted: 04/20/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Acute exacerbation in patients with chronic hepatitis B virus (HBV) infection results in different severities of liver injury. The risk factors related to progression to hepatic decompensation (HD) and acute-on-chronic liver failure (ACLF) in patients with severe acute exacerbation (SAE) of chronic HBV infection remain unknown.
AIM To identify risk factors related to progression to HD and ACLF in compensated patients with SAE of chronic HBV infection.
METHODS The baseline characteristics of 164 patients with SAE of chronic HBV infection were retrospectively reviewed. Independent risk factors associated with progression to HD and ACLF were identified. The predictive values of our previously established prediction model in patients with acute exacerbation (AE model) and the model for end-stage liver disease (MELD) score in predicting the development of ACLF were evaluated.
RESULTS Among 164 patients with SAE, 83 (50.6%) had compensated liver cirrhosis (LC), 43 had progression to HD without ACLF, and 29 had progression to ACLF within 28 d after admission. Independent risk factors associated with progression to HD were LC and low alanine aminotransferase. Independent risk factors for progression to ACLF were LC, high MELD score, high aspartate aminotransferase (AST) levels, and low prothrombin activity (PTA). The area under the receiver operating characteristic of the AE model [0.844, 95% confidence interval (CI): 0.779-0.896] was significantly higher than that of MELD score (0.690, 95%CI: 0.613-0.760, P < 0.05) in predicting the development of ACLF.
CONCLUSION In patients with SAE of chronic HBV infection, LC is an independent risk factor for progression to both HD and ACLF. High MELD score, high AST, and low PTA are associated with progression to ACLF. The AE model is a better predictor of ACLF development in patients with SAE than MELD score.
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Affiliation(s)
- Ling Yuan
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou Province, China
| | - Bai-Mei Zeng
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou Province, China
| | - Lu-Lu Liu
- Department of Gastroenterology, Jiangsu Province Hospital, Pukou Branch, Nanjing 210000, Jiangsu Province, China
| | - Yi Ren
- Department of Respiratory Medicine, the Fifth People’s Hospital of Chongqing, Chongqing 400062, China
| | - Yan-Qing Yang
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou Province, China
| | - Jun Chu
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou Province, China
| | - Ying Li
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou Province, China
| | - Fang-Wan Yang
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou Province, China
| | - Yi-Huai He
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou Province, China
| | - Shi-De Lin
- Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou Province, China
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6
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Quaye O, Amuzu BG, Adadey SM, Tagoe EA. Effect of Hepatitis B Virus (HBV) Infection on Lipid Profile in Ghanaian Patients. Virology (Auckl) 2019; 10:1178122X19827606. [PMID: 30799916 PMCID: PMC6379792 DOI: 10.1177/1178122x19827606] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2018] [Accepted: 01/10/2019] [Indexed: 12/30/2022] Open
Abstract
Background: Worldwide, approximately 257 million people have chronic hepatitis B virus
(HBV) infection, with the highest infection rates recorded in Africa and
Asia. Although HBV infection has been associated with dyslipidemia, which
may lead to death via liver related complications, the effect of the virus
on the lipid profile of patients remain unclear. This study was designed to
evaluate the effect of chronic hepatitis B virus infection on lipid profile
of sero-positive individuals from Ghana. Methods: Blood samples were collected from chronic HBV infected patients who were
recruited from the Korle-Bu Teaching Hospital, Accra, and HBV sero-negative
healthy volunteers who were used as controls. Demographic and clinical data
were obtained using a structured questionnaire. Blood pressure and body mass
index were determined, and HBV profile markers and lipid profiles of the
patients were determined using a commercially available kit and a chemistry
analyzer, respectively. Results: Triglycerides, low density lipoproteins (LDL), high density lipoproteins
(HDL), very low density lipoproteins (VLDL), and total cholesterol were used
as indices of lipid metabolism disorder. Body mass index and diastolic blood
pressures were significantly elevated in patients compared to healthy
volunteers. Conclusion: The observed high total cholesterol and LDL, with a significantly lower HDL
levels compared to healthy controls suggest an increased cardiovascular
disease risk index in the patients. There is therefore the need to regularly
monitor HBV infected patients for signs of cardiovascular diseases.
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Affiliation(s)
- Osbourne Quaye
- Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Legon, Ghana.,West African Centre for Cell Biology of Infectious Pathogens, University of Ghana, Legon, Ghana
| | | | - Samuel Mawuli Adadey
- Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Legon, Ghana.,West African Centre for Cell Biology of Infectious Pathogens, University of Ghana, Legon, Ghana
| | - Emmanuel Ayitey Tagoe
- Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Legon, Ghana.,West African Centre for Cell Biology of Infectious Pathogens, University of Ghana, Legon, Ghana
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Abstract
Hepatitis B virus (HBV) is a hepatotropic virus that can establish a persistent and chronic infection in humans through immune anergy. Currently, 3.5% of the global population is chronically infected with HBV, although the incidence of HBV infections is decreasing owing to vaccination and, to a lesser extent, the use of antiviral therapy to reduce the viral load of chronically infected individuals. The course of chronic HBV infection typically comprises different clinical phases, each of which potentially lasts for decades. Well-defined and verified serum and liver biopsy diagnostic markers enable the assessment of disease severity, viral replication status, patient risk stratification and treatment decisions. Current therapy includes antiviral agents that directly act on viral replication and immunomodulators, such as interferon therapy. Antiviral agents for HBV include reverse transcriptase inhibitors, which are nucleoside or nucleotide analogues that can profoundly suppress HBV replication but require long-term maintenance therapy. Novel compounds are being actively investigated to achieve the goal of HBV surface antigen seroclearance (functional cure), a serological state that is associated with a higher remission rate (thus, no viral rebound) after treatment cessation and a lower rate of cirrhosis and hepatocellular carcinoma. This Primer addresses several aspects of HBV infection, including epidemiology, immune pathophysiology, diagnosis, prevention and management.
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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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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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10
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Ivanova L, Russev V. Chronic Liver Diseases and Parenterally Transmitted Hepatitis Viruses. EUR J INFLAMM 2016. [DOI: 10.1177/1721727x0700500101] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus (HDV) are the leading cause of chronic liver diseases. The aims of the present study are to determine the etiological relationship of HBV and HCV in patients with chronic liver disease in North-Eastern Bulgaria and prevalence of dual and triple infections. A total of 434 patients were investigated for HBsAg, 402 of whom were also tested for anti-HCV. The HBsAg positive subjects were tested for anti-HDV and 32 of them also for HbeAg/anti-Hbe. Separated commercial ELISA kits were used. HBsAg was detected in 132 (30.4%); 10.6% were co-infected with HDV. Anti-HCV was detected in 15.4%. Five of 132 HbsAg positive patients (3.78%) were simultaneously HBV and HCV positive. Two patients out of 132 (1.52%) were positive to HBV, HCV and HDV. Our data indicate that HBV infection was the main cause of chronic liver diseases in North-Eastern Bulgaria, and 10.6% of the patients suffered from severe disease because of co-infection with HDV. HCV plays the same role in 15.4% of the cases. Recently, we observed dually infected (HBV and HCV) and triple infected (HBV, HCV, HDV) patients suffering from severe chronic liver diseases.
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Affiliation(s)
- L. Ivanova
- Laboratory of Clinical Microbiology and Virology, University Hospital St. Marina, Varna, Bulgaria
| | - V. Russev
- Laboratory of Clinical Microbiology and Virology, University Hospital St. Marina, Varna, Bulgaria
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Sarin SK, Kumar M, Lau GK, Abbas Z, Chan HLY, Chen CJ, Chen DS, Chen HL, Chen PJ, Chien RN, Dokmeci AK, Gane E, Hou JL, Jafri W, Jia J, Kim JH, Lai CL, Lee HC, Lim SG, Liu CJ, Locarnini S, Al Mahtab M, Mohamed R, Omata M, Park J, Piratvisuth T, Sharma BC, Sollano J, Wang FS, Wei L, Yuen MF, Zheng SS, Kao JH. Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int 2016; 10:1-98. [PMID: 26563120 PMCID: PMC4722087 DOI: 10.1007/s12072-015-9675-4] [Citation(s) in RCA: 1884] [Impact Index Per Article: 209.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2015] [Accepted: 09/14/2015] [Indexed: 02/06/2023]
Abstract
Worldwide, some 240 million people have chronic hepatitis B virus (HBV), with the highest rates of infection in Africa and Asia. Our understanding of the natural history of HBV infection and the potential for therapy of the resultant disease is continuously improving. New data have become available since the previous APASL guidelines for management of HBV infection were published in 2012. The objective of this manuscript is to update the recommendations for the optimal management of chronic HBV infection. The 2015 guidelines were developed by a panel of Asian experts chosen by the APASL. The clinical practice guidelines are based on evidence from existing publications or, if evidence was unavailable, on the experts' personal experience and opinion after deliberations. Manuscripts and abstracts of important meetings published through January 2015 have been evaluated. This guideline covers the full spectrum of care of patients infected with hepatitis B, including new terminology, natural history, screening, vaccination, counseling, diagnosis, assessment of the stage of liver disease, the indications, timing, choice and duration of single or combination of antiviral drugs, screening for HCC, management in special situations like childhood, pregnancy, coinfections, renal impairment and pre- and post-liver transplant, and policy guidelines. However, areas of uncertainty still exist, and clinicians, patients, and public health authorities must therefore continue to make choices on the basis of the evolving evidence. The final clinical practice guidelines and recommendations are presented here, along with the relevant background information.
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Affiliation(s)
- S K Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
| | - M Kumar
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - G K Lau
- Division of Gastroenterology and Hepatology, Humanity and Health Medical Centre, Hong Kong SAR, China
- The Institute of Translational Hepatology, Beijing, China
| | - Z Abbas
- Department of Hepatogastroenterlogy, Sindh Institute of Urology and Transplantation, Karachi, Pakistan
| | - H L Y Chan
- Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - C J Chen
- Genomics Research Center, Academia Sinica, National Taiwan University, Taipei, Taiwan
| | - D S Chen
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - H L Chen
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - P J Chen
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - R N Chien
- Liver Research Unit, Chang Gung Memorial Hospital and University, Chilung, Taiwan
| | - A K Dokmeci
- Department of Gastroenterology, Ankara University School of Medicine, Ankara, Turkey
| | - Ed Gane
- New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand
| | - J L Hou
- Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Guangzhou, China
| | - W Jafri
- Department of Medicine, Aga Khan University, Karachi, Pakistan
| | - J Jia
- Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | | | - C L Lai
- Department of Medicine, University of Hong Kong, Hong Kong, China
| | - H C Lee
- Internal Medicine Asan Medical Center, Seoul, Korea
| | - S G Lim
- Division of Gastroenterology and Hepatology, National University Health System, Singapore, Singapore
| | - C J Liu
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - S Locarnini
- Research and Molecular Development, Victorian Infectious Diseases Reference Laboratory, Melbourne, Australia
| | - M Al Mahtab
- Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh
| | - R Mohamed
- Department of Medicine, Faculty of Medicine, University Malaya, Kuala Lumpur, Malaysia
| | - M Omata
- Yamanashi Hospitals (Central and Kita) Organization, 1-1-1 Fujimi, Kofu-shi, Yamanashi, 400-8506, Japan
| | - J Park
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - T Piratvisuth
- NKC Institute of Gastroenterology and Hepatology, Prince of Songkla University, Songkhla, Thailand
| | - B C Sharma
- Department of Gastroenterology, G.B. Pant Hospital, New Delhi, India
| | - J Sollano
- Department of Medicine, University of Santo Tomas, Manila, Philippines
| | - F S Wang
- Treatment and Research Center for Infectious Diseases, Beijing 302 Hospital, Beijing, China
| | - L Wei
- Peking University Hepatology Institute, Beijing, China
| | - M F Yuen
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Hong Kong, Pofulam, Hong Kong
| | - S S Zheng
- Department of Hepatobiliary and Pancreatic Surgery, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, Zhejiang Province, China
| | - J H Kao
- Graduate Institute of Clinical Medicine and Hepatitis Research Center, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
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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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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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Association between plasma fibrinogen levels and mortality in acute-on-chronic hepatitis B liver failure. DISEASE MARKERS 2015; 2015:468596. [PMID: 25960593 PMCID: PMC4415673 DOI: 10.1155/2015/468596] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/03/2015] [Revised: 03/17/2015] [Accepted: 03/27/2015] [Indexed: 12/30/2022]
Abstract
Acute-on-chronic liver failure (AoCLF) is the most common type of liver failure and is associated with high mortality. Fibrinogen is critical in maintaining primary and secondary hemostasis. Therefore, we prospectively analyzed the association between fibrinogen and outcomes in AoCLF patients. Plasma fibrinogen was measured in 169 AoCLF, 173 chronic hepatitis B (CHB), and 171 healthy patients using a coagulation method. The predictive ability of fibrinogen for 3-month mortality in AoCLF patients was assessed using receiver operating characteristic (ROC) curve and multivariable logistic regression analyses. Plasma fibrinogen was significantly lower in nonsurvivor AoCLF patients compared with survivor AoCLF, CHB, and control patients. The sensitivity, specificity, and area under the ROC curve of 1/fibrinogen predicting mortality in AoCLF patients were 66.7%, 72.5%, and 0.746 (95% confidence interval (CI): 0.672–0.820, P < 0.001), and the fibrinogen cutoff value was 0.90 g/L. On multivariate logistic regression analysis, low fibrinogen was an independent factor predicting mortality (odds ratio: 0.304; 95% CI: 0.094–0.983; P = 0.047). Nonsurvivor AoCLF patients had significantly decreased fibrinogen levels, suggesting that low plasma fibrinogen may be a useful predictor of poor prognosis in AoCLF patients.
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15
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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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Liang XS, Li CZ, Zhou Y, Yin W, Liu YY, Fan WH. Changes in circulating Foxp3 + regulatory T cells and interleukin-17-producing T helper cells during HBV-related acute-on-chronic liver failure. World J Gastroenterol 2014; 20:8558-8571. [PMID: 25024610 PMCID: PMC4093705 DOI: 10.3748/wjg.v20.i26.8558] [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: 10/15/2013] [Revised: 12/31/2013] [Accepted: 04/09/2014] [Indexed: 02/07/2023] Open
Abstract
AIM: To longitudinally investigate cytokine gene expression and protein levels in Th17 and Treg cells, to observe T-cell phenotypes during hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACHBLF) and to analyze changes in Th17 and Treg phenotypes during disease progression.
METHODS: We measured the expression of seven Th17/Treg differentiation-related genes and serum concentrations of the corresponding cytokines in 18 ACHBLF, 18 chronic hepatitis B (CHB) disease controls and 10 healthy controls (HCs) by real-time quantitative PCR and enzyme linked immunosorbent assay. Peripheral Th17 and Treg cell frequencies were analyzed by flow cytometry.
RESULTS: From the onset of ACHBLF, patients presented with a conductive Th17 differentiation cytokine environment accompanied by high Th17 frequency and high serum IL-17 levels, which were sustained throughout the disease course. The Treg-related cytokine IL-2 and Foxp3 were also up-regulated from disease onset, and Foxp3 gene expression showed a gradually increasing trend during ACHBLF. The circular phenotype of Treg and Th17 cells showed changes from the onset of ACHGLF. At disease onset, Th17 frequency increased significantly compared with both CHB and HCs, but Treg cell frequency decreased significantly compared with CHB. During the ACHBLF event, Th17 frequency remained higher compared with HCs, but decreased sharply from the peak point to the recovery point; Treg cell frequency increased gradually during the ACHBLF event. Treg and Th17 cell counts correlated with ACHBLF development; in all patients, serum IL-17 levels significantly correlated with patient serum ALT levels. In survivors, Th17 frequency at the onset point and the Treg to Th17 ratio at the peak point correlated with the patient’s model for end stage liver disease (MELD) plus sodium (MELD-Na) score. The Treg to Th17 ratio and the Th17 frequency at onset were significant predictors of patient survival. Low Treg/Th17 cell ratios at the onset predicted poor survival. Survivors exhibited an initial decrease in the circulating Treg/Th17 ratio from the onset to the peak time, and subsequently displayed a continuous increase.
CONCLUSION: Treg and Th17 cells showed changes in genes, protein levels and T cell phenotypes during ACHBLF events. An increased Treg/Th17 ratio was associated with the survival of ACHBLF patients.
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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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Early entecavir treatment for chronic hepatitis B with severe acute exacerbation. Antimicrob Agents Chemother 2014; 58:1918-21. [PMID: 24419351 DOI: 10.1128/aac.02400-13] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
A previous study found that lamivudine, if started early enough, may improve the chance of survival in chronic hepatitis B virus (HBV) with severe acute exacerbation (SAE). The aim of this study was to investigate the effect of early entecavir treatment before the bilirubin level exceeds 20 mg/dl for chronic HBV with SAE. Consecutive patients with chronic HBV with SAE and a serum bilirubin level of <20 mg/dl who received lamivudine or entecavir were enrolled. Short-term (4 months) survival was evaluated. One hundred fourteen patients received lamivudine, and 53 patients received entecavir. The baseline characteristics were similar for the two groups except that the entecavir group was older and had a lower alanine aminotransferase (ALT) level. Three patients (8.0%) in the entecavir group and 9 patients (7.9%) in the lamivudine group died (P=1.000). If only patients who started antiviral treatment before serum bilirubin level rose to more than 15 mg/dl were included, 3 patients (8.3%) in the entecavir group and 3 patients (3.0%) in the lamivudine group died (P=0.189). If only patients with an HBV DNA level higher than 10(5) copies/ml and a bilirubin level lower than 15 mg/dl were included, 5 out of 40 patients (12.5%) in the entecavir group died and 1 out of 59 patients (1.7%) in the lamivudine group died. Multivariate analysis found that entecavir treatment was associated with more mortality than lamivudine (P=0.035). Early entecavir treatment in patients with high viral load is associated with more short-term mortality than lamivudine for chronic HBV with severe acute exacerbation.
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Chen YC, Hsu CW, Chang MY, Yeh CT. On-treatment mortality predictors in chronic hepatitis B patients experiencing severe acute exacerbation: a prospective observational study. BMC Res Notes 2013; 6:349. [PMID: 24004574 PMCID: PMC3766709 DOI: 10.1186/1756-0500-6-349] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2013] [Accepted: 08/29/2013] [Indexed: 02/07/2023] Open
Abstract
Background Severe acute exacerbation in chronic hepatitis B could lead to mortality in some patients unless timely liver transplantation is performed. The baseline bilirubin level has been reported to be an important prognostic factor for mortality. Here we conducted a prospective observational study to examine the clinical performance of this predictor. Method Twenty-one consecutive chronic hepatitis B patients experiencing severe acute exacerbation were treated with either telbivudine or entecavir. The clinical characteristics at baseline and week-2 were documented and correlated with mortality. Results Of the 21 patients included, 9 had baseline bilirubin >10 mg/dL. Four of these 9 patients (44.4%) eventually died, whereas all other patients survived. During the initial 2-week period, the change of bilirubin was −1.2 mg/dl in the survivors, but was +8.05 mg/dl in the mortalities (P = 0.009). When this on-treatment factor was combined, 5 of the 21 patients had baseline bilirubin > 10 mg/dL plus an increase of bilirubin level at week-2. Of these 5 patients, 4 (80%) died. Thus, by combining the baseline and on-treatment bilirubin levels, a positive predictive value of 80% and a negative predictive value of 100% could be achieved. Other significant on-treatment mortality predictors (at week-2) included higher international normalized ratio of prothrombin time (2.75 vs. 1.3, P = 0.004), higher model for end-stage liver disease score (30 vs. 17, P = 0.006), lower alpha-fetoprotein level (36.3 vs. 459.6 ng/mL, P = 0.039), and more rapid deterioration of the estimated glomerular filtration rate (eGFR) (P = 0.008). Interestingly, during the course, deterioration of eGFR was statistically significant in entecavir-treated (P = 0.028), but not in telbivudine-treated patients. Additionally, the patients treated with telbivudine had significant increase in serum alpha-fetoprotein (27.9 to 191.9 ng/ml, P = 0.046) in the first 2 weeks, whereas the corresponding feature was not found in those treated with entecavir (P = 0.139). Conclusions In this prospective observational study, we discovered that the baseline and on-treatment bilirubin levels should be combined to achieve a better predictive value. Telbivudine might have a renoprotective effect in addition to its efficacy in viral suppression in patients with severe acute exacerbation.
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Affiliation(s)
- Yi-Cheng Chen
- Department of Gastroenterology-Hepatology, Liver Research Unit, Division of Hepatology, Taipei, Taiwan.
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Zhang L, Hao CQ, Liu JF, Wang M. Meta-analysis of the short-term effects of lamivudine treatment for severe chronic hepatitis B. Virol J 2013; 10:134. [PMID: 23627972 PMCID: PMC3655020 DOI: 10.1186/1743-422x-10-134] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2012] [Accepted: 04/11/2013] [Indexed: 01/14/2023] Open
Abstract
PURPOSE To evaluate the short-term effect of lamivudine (LMV) treatment for severe chronic hepatitis B. METHOD Patient data related to the safety and efficacy of using lamivudine (LMV) to treat hepatitis B virus (HBV)-induced liver failure or severe hepatitis were acquired from previous literature. These studies were retrieved from PubMed, Ovid, SpringerLink, Biosis Previews, Academic Search Premier, ProQuest Medical Library, Cochrane Library, China National Knowledge Infrastructure Full-text Database, VIP Chinese Scientific Journal Database, and Chinese Biomedicine. Relative risk and weighted mean difference were used to measure the effects. The major predictors observed included total bilirubin (TBIL), prothrombin activity (PTA), survival rate, and HBV-DNA negative change rate. Groups were further divided according to the clinical course and disease staging. RESULTS A total of 242 studies were retrieved from the databases. At weeks 4, 8, and 12 of the treatment course, the survival rates and PTA of the test group were distinctively higher than those of the control group. However, TBIL concentrations in the test group were lower than the control group. The HBV-DNA negative change rate was distinctively higher throughout the 12 weeks of LMV treatment. For patients who started LMV treatment in the middle stage, the mortality rate of the test group was lower. For patients who started LMV treatment during the advanced stage, no significant difference was observed between the test and control groups. CONCLUSION LMV decreased HBV-DNA levels in the serum, improved liver function in patients, and enhanced survival rate during the early and medium stages of severe chronic hepatitis B.
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Affiliation(s)
- Lin Zhang
- Department of Infectious Disease, Affiliated Sheng Jing Hospital of China Medical University, Sanhao Street of Heping District, Shenyang, Liaoning Province 110004, China.
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Hsu YC, Wu CY, Chang CY, Tai CM, Tseng CH, Perng DS, Mo LR, Lin JT. Pretreatment viral DNA stratifies mortality risk in patients receiving antiviral therapy for severe acute exacerbation of chronic hepatitis B. Antivir Ther 2012; 18:221-8. [PMID: 23128388 DOI: 10.3851/imp2435] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/31/2012] [Indexed: 12/12/2022]
Abstract
BACKGROUND Prognostic factors have not been elucidated for severe acute exacerbation of chronic hepatitis B treated with antiviral therapy. This study aimed to explore the role of baseline viral load in predicting mortality. METHODS This retrospective cohort study screened consecutive chronic hepatitis B patients (n=84) receiving antiviral therapy for severe acute exacerbation, defined as abrupt elevation of serum alanine aminotransferase >10× the upper limit of normal along with hyperbilirubinaemia. Survival pattern was evaluated by the Kaplan-Meier method and predictors for mortality determined by the Cox regression analysis. RESULTS A total of 66 patients were eligible and followed-up for a median of 23 months (range 0.1-75.0). Overall, 20 (30.3%) patients died during the study period, with the vast majority (n=17) succumbing rapidly within 3 months of severe acute exacerbation. The multivariate Cox model revealed that mortality was associated with baseline viral DNA level (HR 1.49 per log copies/ml, 95% CI 1.13, 1.96), international normalized ratio for prothrombin time (HR 2.68 per unit, 95% CI 1.81, 3.98), platelet count (HR 0.87 per 10(4) cells/μl, 95% CI 0.78, 0.98) and age (HR 1.10 per year, 95% CI 1.05, 1.15). A significant interaction existed between viral DNA and prolonged prothrombin time (P=0.005). Stratified analyses further demonstrated that pronounced coagulopathy heralded death irrespective of viral load, whereas serum level of viral DNA stratified mortality risk among those without marked coagulopathy. CONCLUSIONS Pretreatment viral DNA level stratifies risk of death in patients with severe acute exacerbation of chronic hepatitis B before the manifestation of overt liver failure.
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Affiliation(s)
- Yao-Chun Hsu
- Graduate Institute of Clinical Medicine, China Medical University, Taichung, Taiwan
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22
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Mori N, Suzuki F, Kawamura Y, Sezaki H, Hosaka T, Akuta N, Kobayashi M, Saito S, Suzuki Y, Arase Y, Ikeda K, Kobayashi M, Kumada H. Determinants of the clinical outcome of patients with severe acute exacerbation of chronic hepatitis B virus infection. J Gastroenterol 2012; 47:1022-9. [PMID: 22370817 DOI: 10.1007/s00535-012-0561-8] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2011] [Accepted: 02/07/2012] [Indexed: 02/04/2023]
Abstract
BACKGROUND Severe acute exacerbation of chronic hepatitis B can sometimes occur and lead to hepatic failure and death. The objective of this study was to elucidate the predictors of progression to hepatic decompensation during severe acute exacerbation. METHODS We prospectively analyzed 37 consecutive patients with acute exacerbation of chronic hepatitis B (accompanied by jaundice and coagulopathy) for clinical outcome and factors that influenced the development of severe acute exacerbation, including viral kinetics. RESULTS Fourteen (37.8%) patients progressed to severe acute exacerbation (accompanied by encephalopathy). Multivariate analysis identified serum bilirubin (>5 mg/dl, P = 0.002) as a significant determinant of progression to hepatic failure and prothrombin activity (<45%, P = 0.028) and as a determinant of liver-related death. The hepatitis B virus (HBV) DNA level before therapy was measured in 25 patients. HBV DNA levels increased or did not change from before commencement of treatment in all 11 patients who progressed to severe acute exacerbation. On the other hand, HBV DNA levels did not change or increased in 8 of 14 patients (57%) with acute exacerbation (P = 0.02). CONCLUSIONS Serum bilirubin and prothrombin activities were significant predictors of clinical outcome in patients with severe acute exacerbation of chronic hepatitis B. Viral kinetics until commencement of therapy can predict the severity of acute exacerbation of chronic hepatitis B.
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Affiliation(s)
- Nami Mori
- Department of Hepatology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo 105-8470, Japan
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Abstract
Acute-on-chronic liver failure (ACLF) in chronic hepatitis B (CHB) is most commonly caused by acute severe exacerbation of CHB. The pathophysiology of ACLF in CHB is still poorly understood. Despite the identification of important predisposing factors and prognostic markers, ACLF in CHB remains a disease associated with high mortality. The majority of studies using nucleoside analog therapy did not show any significant improvement in survival, although larger prospective studies are needed. Liver transplantation is the definitive treatment for ACLF in CHB. The challenge ahead would be prognosticating cases with favorable or unfavorable outcomes in order to streamline patients for early transplantation or for medical therapy.
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Affiliation(s)
- Wai-Kay Seto
- Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong
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Liu C, Wang YM, Fan K. Epidemiological and clinical features of hepatitis B virus related liver failure in China. World J Gastroenterol 2011; 17:3054-9. [PMID: 21799653 PMCID: PMC3132258 DOI: 10.3748/wjg.v17.i25.3054] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2010] [Revised: 06/20/2011] [Accepted: 06/27/2011] [Indexed: 02/06/2023] Open
Abstract
AIM: To examine the epidemiologic and clinical characteristics of hepatitis B virus (HBV) related liver failure in patients in China.
METHODS: This study was conducted with a retrospective design to examine 1066 patients with HBV-related liver failure in the southwest of China.
RESULTS: There were more male than female patients. Young and middle-aged people comprised most of the patients. Farmers and laborers comprised the largest proportion (63.09%). Han Chinese accounted for 98.12%, while minority ethnic groups only accounted for 0.88% of patients. A total of 43.47% patients had a family history of HBV-related liver failure and 56.66% patients had a history of drinking alcohol. A total of 42.59% patients with HBV-related liver failure had definite causes. With regard to the clinical manifestation of HBV-related liver failure, the symptoms were: hypodynamia, anorexia and abdominal distension. Total bilirubin (TBIL) and alanine aminotransferase (ALT) levels were altered in 46.23% of patients with evident damage of the liver. Univariate logistic regression analysis showed that the patients’ prognoses were correlated with ALT, aspartate aminotransferase, albumin, TBIL, prothrombin activity (PTA), and alpha-fetoprotein levels, and drinking alcohol, ascites, hepatorenal syndrome, infection and ≥ 2 complications. Multifactor logistic regression analysis showed that the activity of thrombinogen and the number of complications were related to the prognosis.
CONCLUSION: Alcohol influences the patients’ prognosis and condition. PTA and complications are independent factors that can be used for estimating the prognosis of HBV-related liver failure.
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Liu JF, Zhang L, Feng GH. Advances in treatment of HBV-related liver failure with nucleoside analogues. Shijie Huaren Xiaohua Zazhi 2011; 19:930-935. [DOI: 10.11569/wcjd.v19.i9.930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) infection is a common cause of liver failure in China. The mortality of fulminant hepatitis B is more than 70%. Adoption of antiviral therapy or not on the basis of comprehensive treatment has become a hot topic of recent research of treatment of fulminant hepatitis B, which causes liver failure in a way different from other reasons. HBV replication plays a critical role in initiating the development of fulminant hepatitis B. Reducing viral load to alleviate excessive immune response by antiviral therapy represents a new idea for the treatment of fulminant hepatitis B. The advent of nucleoside analogues makes it possible to conduct antiviral therapy against fulminant hepatitis B. This article summarizes recent advances in treatment of HBV-related liver failure with nucleoside analogues.
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Liaw YF, Brunetto MR, Hadziyannis S. The natural history of chronic HBV infection and geographical differences. Antivir Ther 2011; 15 Suppl 3:25-33. [PMID: 21041901 DOI: 10.3851/imp1621] [Citation(s) in RCA: 102] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Although chronic HBV infection is a global health issue, there are geographical differences in the mode of transmission, prevalence and HBV genotype distribution. Chronic HBV infection is a dynamic state of interactions between HBV, hepatocytes and immune cells of the host. Accordingly, the natural history of chronic HBV infection typically starts with an immune tolerant phase, followed by an immune clearance phase and finally an inactive phase. The duration of the immune tolerant phase is usually long in chronic HBV infection acquired perinatally or in early childhood, otherwise the duration is very short. During the inactive phase, spontaneous hepatitis B surface antigen (HBsAg) seroclearance might occur at an annual rate of 1-2%; however, HBV reactivation with hepatitis activity could occur over time in one-quarter to one-third of HBsAg-seropositive patients. This occurs more frequently in males and in patients infected with genotypes D, C and B. The effort of active HBV replication-triggered immune clearance is the driving force of liver injury and subsequent disease progression in patients with hepatitis B e antigen (HBeAg)-positive or HBeAg-negative hepatitis. Clinical studies have shown that chronic HBV infection in western countries is associated with a higher incidence of cirrhosis, but lower incidence of hepatocellular carcinoma, than in Asian countries. The geographical differences in age at the time of infection and predominant HBV genotype could account for the variance in the natural history of chronic HBV infection; however, some of these differences might actually result from comparisons between cohorts with different age, gender distribution or fibrosis stage.
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Affiliation(s)
- Yun-Fan Liaw
- Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan.
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Entecavir treatment in patients with severe acute exacerbation of chronic hepatitis B. J Hepatol 2011; 54:236-42. [PMID: 21030105 DOI: 10.1016/j.jhep.2010.06.043] [Citation(s) in RCA: 98] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2010] [Revised: 06/28/2010] [Accepted: 06/29/2010] [Indexed: 12/15/2022]
Abstract
BACKGROUND & AIMS Severe acute exacerbation of chronic hepatitis B is a unique clinical presentation with significant morbidity and mortality. Lamivudine was used in most previous studies, but the drug was limited by the development of resistance. Our objective is to study the safety and efficacy of entecavir in patients with severe acute exacerbation. METHODS Consecutive patients with severe acute exacerbation of chronic hepatitis B were recruited from 1998 to 2009. All patients had serum alanine aminotransferase and bilirubin increased beyond 10 and 3 times the upper limit of normal, respectively. The primary endpoint was overall mortality at week 48. Virological and biochemical responses were also studied. RESULTS Thirty-six patients and 117 patients were treated with entecavir and lamivudine, respectively. By week 48, 7 (19%) patients in the entecavir group and 5 (4%) patients in the lamivudine group died (adjusted hazard ratio 5.1, 95% confidence interval 1.5-17.2, p=0.010). Similarly, the entecavir group had higher liver-related mortality (adjusted hazard ratio 4.0, 95% confidence interval 1.0-15.7, p=0.044). Despite a lower prevalence of cirrhosis, more patients in the entecavir group developed prolonged jaundice, hepatic encephalopathy, and ascites. Entecavir resulted in more rapid and complete viral suppression, with 71% of patients achieving undetectable hepatitis B virus (HBV) DNA at week 48, compared to 40% in the lamivudine group (p=0.007). However, rapid HBV DNA reduction at week 4 was associated with prolonged jaundice. CONCLUSIONS Entecavir treatment is associated with increased short-term mortality in patients with severe acute exacerbation of chronic hepatitis B but achieves better virological response in the long run.
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Peng CY, Chen CB, Lai HC, Su WP, Chuang PH, Wu HDI, Jeng LB. Predictors for early HBeAg loss during lamivudine therapy in HBeAg-positive chronic hepatitis B patients with acute exacerbation. Hepatol Int 2010; 5:586-96. [PMID: 21442057 DOI: 10.1007/s12072-010-9227-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2010] [Accepted: 11/24/2010] [Indexed: 12/15/2022]
Abstract
PURPOSE To examine the rate of early HBeAg loss and predictors of HBeAg loss in HBeAg-positive chronic hepatitis B (CHB) patients with acute exacerbation (AE) treated with lamivudine. METHODS A total of 146 patients diagnosed with CHB and AEs were included in this retrospective study. Patients were divided into two groups: decompensated and compensated. RESULTS The mean treatment duration for the decompensated and compensated groups was 18.1 and 19.9 months, respectively. Decompensated patients were significantly older and had a higher prevalence of cirrhosis and genotype B infection than compensated patients. Compared to compensated patients, decompensated patients achieved a higher rate of HBeAg loss (25.8 vs. 14.3%; P = 0.0805) at 3 months of therapy, a higher rate of serum HBV DNA negativity (53.2 vs. 29.8%; P = 0.0042), and a lower rate of rtM204V/I mutation (3.2 vs. 16.7%; P = 0.0139) after 12 months of lamivudine therapy. The rates of HBeAg loss after 6 and 12 months of lamivudine therapy were similar between the two groups. Logistic regression analysis revealed that female gender and baseline ALT level ≥1,000 IU/L, but not decompensations, were significant predictors of HBeAg loss at 3 months; however, only female gender was a significant predictor of HBeAg loss after 6 and 12 months of lamivudine therapy. The early HBeAg losers showed a significantly higher sustained remission rate off lamivudine therapy. CONCLUSIONS Female gender and baseline serum ALT level ≥1,000 IU/L were independent predictors of early HBeAg loss during lamivudine therapy in HBeAg-positive CHB patients with AE. ELECTRONIC SUPPLEMENTARY MATERIAL The online version of this article (doi:10.1007/s12072-010-9227-x) contains supplementary material, which is available to authorized users.
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Hepatitis B virus DNA level predicts hepatic decompensation in patients with acute exacerbation of chronic hepatitis B. Clin Gastroenterol Hepatol 2010; 8:541-5. [PMID: 20298811 DOI: 10.1016/j.cgh.2010.02.023] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2010] [Accepted: 02/27/2010] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Acute exacerbations of chronic hepatitis B virus (HBV) infection can lead to hepatic decompensation. It is important to identify factors that predict the development of hepatic decompensation during exacerbation so that antiviral therapy can be initiated immediately. METHODS Acute exacerbation, defined by an abrupt increase in alanine aminotransferase (ALT) levels to >5-fold the upper limit of normal, occurred in 110 hepatitis B e antigen (HBeAg)-seropositive non-cirrhotic patients (138 episodes). The patients were monitored every 1 to 2 weeks for serum levels of ALT, bilirubin, albumin, and prothrombin. Sex, age, HBV genotype, ALT level, HBV viral load, and the causes (spontaneous or relapse from antiviral treatment) of exacerbation were included in multivariate logistic regression analyses. The receiver operating characteristic curve was used to identify the optimal cut-off value of serum HBV DNA level to identify patients at risk for decompensation. RESULTS Seven of the 138 episodes of acute exacerbation (5.1%) resulted in hepatic decompensation; serum HBV DNA level was the only significant risk factor (P = .003). The area under the receiver operating characteristic curve was 88.6% (P < .001). A serum HBV DNA cut-off value of 1.55 x 10(9) copies/mL predicted decompensation with a sensitivity of 85.7%, a specificity of 85.5%, a negative prediction value of 99.1%, and positive prediction value of 24.0%. CONCLUSIONS During acute exacerbation of HBeAg-positive chronic hepatitis B, a serum HBV DNA cut-off value of 1.55 x 10(9) copies/mL can be used to identify patients in need of immediate antiviral therapy.
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Chan AC, Fan ST, Lo CM, Liu CL, Chan SC, Ng KK, Yong BH, Chiu A, Lam BK. Liver transplantation for acute-on-chronic liver failure. Hepatol Int 2009; 3:571-81. [PMID: 19680733 PMCID: PMC2790588 DOI: 10.1007/s12072-009-9148-8] [Citation(s) in RCA: 101] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2009] [Revised: 07/23/2009] [Accepted: 08/03/2009] [Indexed: 12/13/2022]
Abstract
Purpose To evaluate the outcome of liver transplantation for acute-on-chronic liver failure. Patients and methods From November 1991 to December 2007, 517 patients underwent liver transplantation at Queen Mary Hospital, Hong Kong. Among them, 149 had acute-on-chronic liver failure as defined in the recent Asian Pacific Association for the Study of Liver Consensus Meeting. Their clinical data were reviewed and their survival outcomes were compared with those of patients who underwent liver transplantation for fulminant hepatic failure and for cirrhosis only in the same period. Results The patients with acute-on-chronic liver failure included 50 patients having acute exacerbation of chronic hepatitis B and 99 cirrhotic patients with acute deterioration. Their median model for end-stage liver disease scores were 35 and 37, respectively. Preoperative infection (35%), hepatorenal syndrome (38%), and respiratory failure (28.8%) were common. One hundred and three patients received living donor liver grafts and 46 patients received deceased donor liver grafts. The hospital mortality rate was 4.7%. The 5-year survival rates were 93.2% for patients with acute exacerbation of chronic hepatitis B and 90.5% for cirrhotic patients with acute deterioration. The results were similar to those of the patients with fulminant hepatic failure (n = 37) and the patients having cirrhosis only (n = 301). Conclusions Liver transplantation for acute-on-chronic liver failure is life-saving, and the survival rates it attains are similar to those attained by transplantation for other liver conditions.
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Affiliation(s)
- Albert C Chan
- Department of Surgery, Queen Mary Hospital, The University of Hong Kong, 102 Pok Fu Lam Road, Hong Kong, China
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Wong VWS, Chan HLY. Severe acute exacerbation of chronic hepatitis B: a unique presentation of a common disease. J Gastroenterol Hepatol 2009; 24:1179-86. [PMID: 19682192 DOI: 10.1111/j.1440-1746.2009.05924.x] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Severe acute exacerbation is a unique presentation of chronic hepatitis B characterized by very high alanine aminotransferase level accompanied by jaundice and hepatic decompensation. The underlying pathogenesis is likely related to excessive immune clearance, which may be related to the genotype of hepatitis B virus. The mortality is very high once hepatic encephalopathy develops, but some patients can recover to almost normal liver function in contrast to patients with end-stage liver cirrhosis. This condition should be differentiated from acute hepatitis B and other causes of acute hepatitis must be excluded. Conventional prognostic systems may not be applicable to severe acute exacerbation of chronic hepatitis B. In general, patients who have thrombocytopenia, hyperbilirubinemia and coagulopathy have a higher risk of mortality regardless of the serum alanine aminotransferase levels. There is no evidence that lamivudine treatment can reduce the short-term mortality of severe acute exacerbation. However, patients with severe acute exacerbation tend to have a higher rate of maintained virological response, higher rate of hepatitis B e antigen seroconversion and low rate of drug resistance on extended lamivudine treatment as compared to other chronic hepatitis B patients. Virological relapse and severe hepatitis reactivation is common after treatment cessation and therefore long-term antiviral treatment is recommended. Liver transplantation, particularly living donor liver transplantation, should be considered for patients who develop hepatic failure secondary to severe acute exacerbation.
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Affiliation(s)
- Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
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Matsumoto K, Miyake Y, Miyatake H, Takahara M, Imada T, Yagi S, Toyokawa T, Nakatsu M, Ando M, Hirohata M. A combination treatment of entecavir and early-phase corticosteroid in severe exacerbation of chronic hepatitis B. World J Gastroenterol 2009; 15:1650-2. [PMID: 19340912 PMCID: PMC2669952 DOI: 10.3748/wjg.15.1650] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Of patients with severe exacerbation of chronic hepatitis B accompanied by jaundice and coagulopathy, 20%-30% have a fatal outcome. In this report, we describe 2 cases of severe exacerbation of chronic hepatitis B with jaundice and coagulopathy who were successfully treated with a combination of entecavir and corticosteroid. In both cases, rapid reductions in serum hepatitis B virus (HBV)-DNA levels were observed, and corticosteroid was stopped after serum HBV-DNA levels became undetectable. Entecavir treatment was continued. Generally, entecavir treatment reduced serum HBV-DNA levels rapidly, although the improvement in liver function was delayed by a few weeks. During this time lag, liver cell injury continued and the disease progressed. Corticosteroid suppressed the excessive host immune response and was useful for stopping progressive deterioration. A combination of entecavir and early-phase corticosteroid may be a useful treatment in severe exacerbation of chronic hepatitis B.
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Abstract
Since the introduction of the hepatitis B vaccine and other preventive measures, the worldwide prevalence of hepatitis B infection has fallen. However, chronic infection remains a challenging global health problem, with more than 350 million people chronically infected and at risk of hepatic decompensation, cirrhosis, and hepatocellular carcinoma. An improved understanding of hepatitis B virology, immunology, and the natural course of chronic infection, has identified hepatitis B virus replication as the key driver of immune-mediated liver injury and disease progression. The approval of potent oral antiviral agents has revolutionised hepatitis B treatment since 1998. Conventional and pegylated interferon alfa and nucleoside and nucleotide analogues are widely authorised treatments, and monotherapy with these drugs greatly suppresses virus replication, reduces hepatitis activity, and halts disease progression. However, hepatitis B virus is rarely eliminated, and drug resistance is a major drawback during long term therapy. The development of new drugs and strategies is needed to improve treatment outcomes.
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Affiliation(s)
- Yun-Fan Liaw
- Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan
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35
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Tsai WL, Lo GH, Hsu PI, Lai KH, Lin CK, Chan HH, Chen WC, Cheng JS, Liu YC, Huang TS, Ger LP, Lin HH. Role of genotype and precore/basal core promoter mutations of hepatitis B virus in patients with chronic hepatitis B with acute exacerbation. Scand J Gastroenterol 2008; 43:196-201. [PMID: 18224565 DOI: 10.1080/00365520701745693] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE The results of long-term, follow-up studies show that the severity and frequency of acute exacerbation of chronic hepatitis B virus (HBV) are associated with the development of liver cirrhosis in chronic HBV infection. The aim of this study was to investigate the relationship between virological factors of HBV and the severity of acute exacerbation. MATERIAL AND METHODS Fifty-one chronic hepatitis B patients with symptomatic acute exacerbation without antiviral therapy were enrolled in the study. Genotype of HBV was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Precore (A1896) and basal core promoter (BCP) mutations (T1762 & A1764) were determined by PCR and direct sequencing. RESULTS Thirty-nine patients had genotype B, 11 patients had genotype C, and 1 patient had an unclassified genotype. Thirty-two patients had precore mutation and 24 patients had BCP mutation. After adjusting for age, gender, aspartate aminotransferase (ASAT) level, albumin level, and platelet count by multiple logistic regression test, precore mutation had a protective effect on the occurrence of hepatic decompensation (p=0.046), and genotype and BCP mutations were not associated with the occurrence of hepatic decompensation. CONCLUSIONS HBV precore mutation may confer less severe liver disease during acute exacerbation of chronic HBV. Genotype and BCP mutations did not have a significant association with the occurrence of hepatic decompensation.
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Affiliation(s)
- Wei-Lun Tsai
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
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Abstract
Appropriate treatment for chronic hepatitis B (CHB) to prevent disease progression and clinical complications requires an accurate knowledge of the natural history of this disorder. In patients who acquire the disease in early life, as is the situation in Asian CHB patients, complications of CHB continue to develop because of the prolonged insidious damage to the liver, even in the low viremic phase. Hepatitis B e antigen seroconversion with hepatitis B virus (HBV) DNA levels just below 10(5) copies/mL may not be an adequate treatment endpoint for Asian CHB patients. Furthermore, it has been shown that patients with mild elevation of alanine aminotransferase (ALT) levels are already at considerable risk of development of complications. More recent studies have shown that in order to move towards a better disease outcome, CHB patients should have HBV DNA levels at least less than 10(3) copies/mL, with ALT levels preferably in the range of less than 0.5 times the upper limit of the normal range. Therefore, prolonged, adequate suppression of viral replication should be the practical goal for the treatment of CHB disease in the Asian population.
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Affiliation(s)
- Man-Fung Yuen
- Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.
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Chiu A, Chan LMY, Fan ST. Molecular adsorbent recirculating system treatment for patients with liver failure: the Hong Kong experience. Liver Int 2006; 26:695-702. [PMID: 16842326 DOI: 10.1111/j.1478-3231.2006.01293.x] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
BACKGROUND The molecular adsorbent recirculating system (MARS) is an extracorporeal liver dialysis system that allows selective removal of bilirubin and other albumin-bound toxins. We reported here our experience with the use of this technique for management of liver failure at Queen Mary Hospital, Hong Kong. METHODS From December 2002 to 2004, a total of 74 MARS sessions were performed on 22 patients. The cause of liver failure included acute liver failure (n = 2), acute on chronic liver failure (n = 12), posthepatectomy liver failure (n = 4), and posttransplantation allograft failure (n = 4). RESULTS MARS treatment showed significant reduction in total bilirubin level, serum ammonia level and blood urea, and nitrogen (P < 0.001 for all three parameters). Five patients (22.7%) were able to bridge to transplantation and one patient (4.5%) made a spontaneous recovery. The 30-day mortality rate was 72.7%. CONCLUSIONS Our results indicated that MARS can effectively improve serum biochemistry and is suitable for temporarily supporting patients with liver failure where transplantation is not immediately available. There is, however, no clear evidence showing that MARS can increase survival, improve the chance of transplantation or assist liver regeneration. Future studies in the form of randomized-controlled trials are crucial to characterize the true potential of this treatment.
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Affiliation(s)
- Alexander Chiu
- Intensive Care Unit, Queen Mary Hospital, Hong Kong, China
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Ke WM, Li XJ, Yu LN, Lai J, Li XH, Gao ZL, Chen PJ. Etiological investigation of fatal liver failure during the course of chronic hepatitis B in southeast China. J Gastroenterol 2006; 41:347-51. [PMID: 16741614 DOI: 10.1007/s00535-005-1781-y] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2005] [Accepted: 11/17/2005] [Indexed: 02/04/2023]
Abstract
BACKGROUND The purpose of this study was to clarify the relationships between patients who had fatal liver failure during the course of chronic hepatitis B and those who were also superinfected with hepatitis A, C, D, or E virus, as well as their hepatitis B virus e system status, so that suitable measures could be adopted to decrease the mortality of patients with chronic hepatitis B. METHODS This study detected superinfections of hepatitis A, C, D, or E virus and the hepatitis B virus e system status in cases of fatal liver failure during the course of chronic hepatitis B by enzyme-lined immunosorbent assay. RESULTS The frequency of superinfections of hepatitis A, C, D, and E virus was 1.4% (4/282), 6.4% (18/282), 1.8% (5/282), and 28.4% (80/282), respectively, overall, 37.9% (107/282). Hepatitis E was prominent and steady in superinfection rates during the past 12 years. In 62.1% (175/282) of patients, the causes of fatal liver failure were not clear. The serological status frequency of HBeAg(+) and anti-HBe(-), HBeAg(-) and anti-HBe(-), and HBeAg(-) and anti-HBe(+) was 20.6% (22/107), 23.4% (25/107), and 56.1% (60/107), respectively, in the group with superinfections of hepatitis A, C, D, or E virus and 31.4% (55/175), 21.1% (37/175), and 47.4% (83/175), respectively, in the group in which causes were not clear. The serological status HBeAg(+) and anti-HBe(-) was more frequent in the group in which causes were not clear than in the group with superinfections of hepatitis A, C, D, or E virus (P < 0.05). Statistically, there were no differences (P > 0.05) between the serological status HBeAg(-), anti-HBe(-) and HBeAg(-), anti-HBe(+) between the two groups. CONCLUSIONS These results suggest that superinfection (107/282) is an important factor in fatal liver failure. The mortality of chronic hepatitis B can be decreased by strict food sanitation and the use of safe blood products. There were no significant relationships between hepatitis B e antigen seroconversion and fatal liver failure during the course of chronic hepatitis B.
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Affiliation(s)
- Wei-Min Ke
- Department of Infectious Diseases, The Third Affiliated Hospital, Sun Yat-Sen University, Shipai, Guangzhou 510630, P. R. China
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Gish RG. Current treatment and future directions in the management of chronic hepatitis B viral infection. Clin Liver Dis 2005; 9:541-65, v. [PMID: 16207563 DOI: 10.1016/j.cld.2005.08.005] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The World Health Organization places hepatitis B virus (HBV) in the top 10 causes of death worldwide. It is estimated that there are over 400 million carriers of HBV as well. At least 20% to 30% of hepatitis B surface antigen (HBsAg) carriers will die of complications of chronic liver disease, including cirrhosis and liver cancer. The serious consequences of end-stage liver disease and liver cancer occur in 30% of chronic carriers and confront patients and physicians throughout the world. Vaccination is the major form of treatment (prevention) that may eventually eliminate HBV worldwide. This article discusses the currently available treatments as well as evolving treatments for chronic HBV infection.
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Affiliation(s)
- Robert G Gish
- Department of Medicine, Division of Hepatology and Complex GI, Physicians Foundation, California Pacific Medical Center, 2340 Clay Street, Room 232, San Francisco, CA 94115, USA.
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Mondou E, Sorbel J, Anderson J, Mommeja-Marin H, Rigney A, Rousseau F. Posttreatment Exacerbation of Hepatitis B Virus (HBV) Infection in Long-Term HBV Trials of Emtricitabine. Clin Infect Dis 2005; 41:e45-7. [PMID: 16080074 DOI: 10.1086/432581] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2005] [Accepted: 05/04/2005] [Indexed: 11/03/2022] Open
Abstract
Posttreatment exacerbation of hepatitis B virus (HBV) infection in long-term HBV trials of emtricitabine occurred in 23% of patients. Development of antibody to hepatitis e antigen did not prevent hepatic flare. One patient with marked bridging fibrosis required liver transplantation. Patients with advanced liver disease are at risk for hepatic flare with decompensation if active treatment is withdrawn (e.g., when highly active antiretroviral treatment is modified).
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Affiliation(s)
- E Mondou
- Gilead Sciences, Durham, North Carolina 27707, USA
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Abstract
More than 400 million people worldwide are chronically infected by the hepatitis B virus. The virus is responsible for more than 300000 cases of liver cancer every year and for similar numbers of gastrointestinal haemorrhage and ascites. Major breakthroughs have been achieved in diagnosis and treatment of this virus. Hepatitis B vaccine reduces incidence of liver cancer. As with hepatitis C, advances have been made in molecular virology, especially for naturally occurring and treatment-induced mutant viruses. The clinical significance of low viral load and genotypes are also under investigation. Currently available monotherapies-interferon, lamivudine, and adefovir dipivoxil-very rarely eradicate the virus, but greatly reduce its replication, necroinflammatory histological activity, and progression of fibrosis. Lamivudine, and presumably other nucleoside analogues, can reverse cirrhosis of the liver.
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Affiliation(s)
- Ching Lung Lai
- Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, People's Republic of China.
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