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Marrapu S, Kumar R. Chronic hepatitis B: Prevent, diagnose, and treat before the point of no return. World J Hepatol 2024; 16:1151-1157. [PMID: 39474571 PMCID: PMC11514616 DOI: 10.4254/wjh.v16.i10.1151] [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] [Received: 07/27/2024] [Revised: 09/26/2024] [Accepted: 10/10/2024] [Indexed: 10/21/2024] Open
Abstract
Hepatitis B remains a significant global health challenge, contributing to substantial morbidity and mortality. Approximately 254 million people worldwide live with Chronic hepatitis B (CHB), with the majority of cases occurring in sub-Saharan Africa and the Western Pacific regions. Alarmingly, only about 13.4% of the individuals infected with this disease have been diagnosed, and awareness of hepatitis B virus (HBV) infection status is as low as 1% in sub-Saharan Africa. In 2022, CHB led to 1.1 million deaths globally. The World Health Organization (WHO) has set a target of eliminating hepatitis B as a public health concern by 2030; however, this goal appears increasingly unattainable due to multiple challenges. These challenges include low vaccination coverage; a large number of undiagnosed cases; a low proportion of patients eligible for treatment under current guidelines; limited access to healthcare; and the costs associated with lifelong treatment. Treatment of HBV can yield significant clinical benefits within a long window of opportunity. However, the benefits of therapy are markedly diminished when the disease is detected at the advanced cirrhosis stage. This editorial aim to highlight the current challenges in hepatitis care and the necessary steps to achieve the WHO's hepatitis elimination goals for 2030.
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Affiliation(s)
- Sudheer Marrapu
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, India
| | - Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, India.
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Marrapu S, Kumar R. Chronic hepatitis B: Prevent, diagnose, and treat before the point of no return. World J Hepatol 2024; 16:1331-1337. [DOI: 10.4254/wjh.v16.i10.1331] [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] [Received: 07/27/2024] [Revised: 09/26/2024] [Accepted: 10/10/2024] [Indexed: 11/22/2024] Open
Abstract
Hepatitis B remains a significant global health challenge, contributing to substantial morbidity and mortality. Approximately 254 million people worldwide live with Chronic hepatitis B (CHB), with the majority of cases occurring in sub-Saharan Africa and the Western Pacific regions. Alarmingly, only about 13.4% of the individuals infected with this disease have been diagnosed, and awareness of hepatitis B virus (HBV) infection status is as low as 1% in sub-Saharan Africa. In 2022, CHB led to 1.1 million deaths globally. The World Health Organization (WHO) has set a target of eliminating hepatitis B as a public health concern by 2030; however, this goal appears increasingly unattainable due to multiple challenges. These challenges include low vaccination coverage; a large number of undiagnosed cases; a low proportion of patients eligible for treatment under current guidelines; limited access to healthcare; and the costs associated with lifelong treatment. Treatment of HBV can yield significant clinical benefits within a long window of opportunity. However, the benefits of therapy are markedly diminished when the disease is detected at the advanced cirrhosis stage. This editorial aim to highlight the current challenges in hepatitis care and the necessary steps to achieve the WHO's hepatitis elimination goals for 2030.
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Affiliation(s)
- Sudheer Marrapu
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, India
| | - Ramesh Kumar
- Department of Gastroenterology, All India Institute of Medical Sciences, Patna 801507, India
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Huang CH, Wu VCC, Wang CL, Wu CL, Huang YT, Chang SH. Silymarin Synergizes with Antiviral Therapy in Hepatitis B Virus-Related Liver Cirrhosis: A Propensity Score Matching Multi-Institutional Study. Int J Mol Sci 2024; 25:3088. [PMID: 38542062 PMCID: PMC10970014 DOI: 10.3390/ijms25063088] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 02/24/2024] [Accepted: 02/25/2024] [Indexed: 01/04/2025] Open
Abstract
Hepatitis B virus (HBV)-related liver cirrhosis (HBV-LC) presents a substantial mortality and hepatocellular carcinoma (HCC) risk. While antiviral therapy (AVT) is the standard, complete HBV clearance remains elusive and may not reduce the risk of death in patients with decompensated cirrhosis. Silymarin, a centuries-old herbal remedy, has shown promise against HBV infection and as an antifibrosis therapy. This study explores the potential of silymarin combined with AVT to reduce mortality and HCC incidence in patients with HBV-LC. This research, spanning from 2001 to 2019, entailed a multi-institutional retrospective cohort study which included 8447 HBV-LC patients all undergoing AVT. After applying inclusion and exclusion criteria, the study comprised two cohorts: a case cohort receiving silymarin alongside AVT for at least 30 days, and a control cohort on AVT alone. Propensity score matching, based on baseline parameters including HBV-DNA levels, comorbidity, and an important LC medication, namely, non-selective β-blockers, was employed to ensure balanced groups, resulting in 319 patients in each cohort for subsequent analyses. Overall mortality was the primary outcome, with HCC occurrence as a secondary outcome. Among 319 patients in both cohorts, the case cohort exhibited significant improvements in the international normalized ratio (INR), model for end-stage liver disease (MELD) score and the Charlson comorbidity index (CCI) one year after the index date. A competing risk survival analysis demonstrated superior one-year and two-year mortality outcomes in the case cohort. However, no significant impact on one-year and two-year HCC occurrence was observed in either cohort. The combination of silymarin and AVT in HBV-LC patients demonstrated a synergistic effect, leading to decreased overall mortality and an improved comorbidity index. While the incidence of HCC remained unchanged, our results suggested promising potential for further clinical trials investigating the synergistic role of silymarin in the treatment of HBV-LC.
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Affiliation(s)
- Chien-Hao Huang
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City 33305, Taiwan;
- School of Medicine, College of Medicine, Chang Gung University, Taoyuan City 33305, Taiwan (C.-L.W.)
| | - Victor Chien-Chia Wu
- School of Medicine, College of Medicine, Chang Gung University, Taoyuan City 33305, Taiwan (C.-L.W.)
- Department of Cardiology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan City 33305, Taiwan
| | - Chun-Li Wang
- School of Medicine, College of Medicine, Chang Gung University, Taoyuan City 33305, Taiwan (C.-L.W.)
- Department of Cardiology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan City 33305, Taiwan
| | - Chia-Ling Wu
- Center for Big Data Analytics and Statistics, Department of Medical Research and Development, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City 33305, Taiwan; (C.-L.W.)
| | - Yu-Tung Huang
- Center for Big Data Analytics and Statistics, Department of Medical Research and Development, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City 33305, Taiwan; (C.-L.W.)
| | - Shang-Hung Chang
- School of Medicine, College of Medicine, Chang Gung University, Taoyuan City 33305, Taiwan (C.-L.W.)
- Department of Cardiology, Chang-Gung Memorial Hospital, Linkou Medical Center, Taoyuan City 33305, Taiwan
- Center for Big Data Analytics and Statistics, Department of Medical Research and Development, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan City 33305, Taiwan; (C.-L.W.)
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Lee KC, Cheng JS, Chang ML, Chien RN, Liaw YF. Comparable outcomes of decompensated chronic hepatitis B patients treated with entecavir or tenofovir: an 8-year cohort study. Hepatol Int 2022; 16:799-806. [PMID: 35699864 DOI: 10.1007/s12072-022-10357-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Accepted: 05/07/2022] [Indexed: 11/30/2022]
Abstract
BACKGROUND/AIMS Whether the efficacies of entecavir (ETV) and tenofovir disoproxil fumarate (TDF) in treating liver-related outcomes of decompensated chronic hepatitis B (CHB) patients are comparable remained inconclusive. METHODS An 8-year cohort study of 736 decompensated CHB patients was conducted, and 65 TDF-treated patients were sex, age and model for end-stage liver disease (MELD) scores-1:4 matched with 260 ETV-treated patients through propensity score-matching method. RESULTS Of 736 patients, 574 (78%) were male, with a mean age of 54.3 years, 438 (59.5%) had cirrhosis, 147 (20%) were positive for HBeAg, and 84 (11.6%) and 652 (88.4%) were treated with TDF and ETV, respectively. The 652 ETV-treated patients were older, had higher baseline MELD score and rates of encephalopathy, but lower ALT levels than the 84 TDF-treated patients. No significant differences were observed in the cumulative incidences of liver-related mortality or liver transplantation (1-month, 18.45 vs. 14.01%, p = 0.368; 8-year, 39.74 vs. 34.24%, p = 0.298), and hepatocellular carcinoma development (5-year, 7.21 vs.13.17%, p = 0.994; 8-year, 11.60 vs.13.17%, p = 0.857) between the matched 260 ETV- and 65 TDF-treated patients, regardless of time points. Baseline MELD score (subdistribution hazard ratio (sHR): 1.063; 95% confidence interval (CI) of sHR: 1.016-1.112) and hepatic encephalopathy (sHR: 5.127; 95% CI sHR: 3.032-8.669) were independently associated with liver-related mortality or liver transplantation in the matched patients. CONCLUSIONS ETV and TDF had comparable efficacy in the short- and long-term liver-related outcomes of decompensated CHB patients, and baseline liver reserve was associated with the outcomes.
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Affiliation(s)
- Kuan-Chieh Lee
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, No. 5, Fu Hsing Street, Kuei Shan, Taoyuan, Taiwan.,Department of Medicine, College of Medicine, Chang Gung University, 199, Tung Hwa North Road, Taipei, 105, Taoyuan, Taiwan
| | - Jur-Shan Cheng
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, No. 5, Fu Hsing Street, Kuei Shan, Taoyuan, Taiwan.,Clinical Informatics and Medical Statistics Research Center, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Ming-Ling Chang
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, No. 5, Fu Hsing Street, Kuei Shan, Taoyuan, Taiwan. .,Department of Medicine, College of Medicine, Chang Gung University, 199, Tung Hwa North Road, Taipei, 105, Taoyuan, Taiwan.
| | - Rong-Nan Chien
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, No. 5, Fu Hsing Street, Kuei Shan, Taoyuan, Taiwan.,Department of Medicine, College of Medicine, Chang Gung University, 199, Tung Hwa North Road, Taipei, 105, Taoyuan, Taiwan
| | - Yun-Fan Liaw
- Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, No. 5, Fu Hsing Street, Kuei Shan, Taoyuan, Taiwan. .,Department of Medicine, College of Medicine, Chang Gung University, 199, Tung Hwa North Road, Taipei, 105, Taoyuan, Taiwan.
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Stella L, Santopaolo F, Gasbarrini A, Pompili M, Ponziani FR. Viral hepatitis and hepatocellular carcinoma: From molecular pathways to the role of clinical surveillance and antiviral treatment. World J Gastroenterol 2022; 28:2251-2281. [PMID: 35800182 PMCID: PMC9185215 DOI: 10.3748/wjg.v28.i21.2251] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Revised: 12/08/2021] [Accepted: 04/26/2022] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a global health challenge. Due to the high prevalence in low-income countries, hepatitis B virus (HBV) and hepatitis C virus infections remain the main risk factors for HCC occurrence, despite the increasing frequencies of non-viral etiologies. In addition, hepatitis D virus coinfection increases the oncogenic risk in patients with HBV infection. The molecular processes underlying HCC development are complex and various, either independent from liver disease etiology or etiology-related. The reciprocal interlinkage among non-viral and viral risk factors, the damaged cellular microenvironment, the dysregulation of the immune system and the alteration of gut-liver-axis are known to participate in liver cancer induction and progression. Oncogenic mechanisms and pathways change throughout the natural history of viral hepatitis with the worsening of liver fibrosis. The high risk of cancer incidence in chronic viral hepatitis infected patients compared to other liver disease etiologies makes it necessary to implement a proper surveillance, both through clinical-biochemical scores and periodic ultrasound assessment. This review aims to outline viral and microenvironmental factors contributing to HCC occurrence in patients with chronic viral hepatitis and to point out the importance of surveillance programs recommended by international guidelines to promote early diagnosis of HCC.
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Affiliation(s)
- Leonardo Stella
- Internal Medicine and Gastroenterology, Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome 00168, Italy
| | - Francesco Santopaolo
- Internal Medicine and Gastroenterology, Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome 00168, Italy
| | - Antonio Gasbarrini
- Internal Medicine and Gastroenterology, Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome 00168, Italy
| | - Maurizio Pompili
- Internal Medicine and Gastroenterology, Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome 00168, Italy
| | - Francesca Romana Ponziani
- Internal Medicine and Gastroenterology, Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome 00168, Italy
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The Korean Association for the Study of the Liver (KASL). KASL clinical practice guidelines for management of chronic hepatitis B. Clin Mol Hepatol 2022; 28:276-331. [PMID: 35430783 PMCID: PMC9013624 DOI: 10.3350/cmh.2022.0084] [Citation(s) in RCA: 69] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 04/01/2022] [Indexed: 01/10/2023] Open
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Kim TH, Um SH, Lee YS, Yim SY, Jung YK, Seo YS, Kim JH, An H, Yim HJ, Yeon JE, Byun KS. Determinants of re-compensation in patients with hepatitis B virus-related decompensated cirrhosis starting antiviral therapy. Aliment Pharmacol Ther 2022; 55:83-96. [PMID: 34662436 DOI: 10.1111/apt.16658] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2021] [Revised: 05/11/2021] [Accepted: 10/06/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Despite antiviral therapy, liver function often fails to recover in patients with hepatitis B virus (HBV)-related decompensated cirrhosis. AIM To establish a prognostic model to predict re-compensation in patients starting potent nucleos(t)ide analogue (NUC) therapy METHODS: We analysed 311 consecutive patients with HBV-related decompensated cirrhosis treated with entecavir or tenofovir. The primary outcome was re-compensation, defined as recovery to a Child-Pugh score of 5. The BC2AID score was developed from a cohort of 152 subjects based on competing risk models and validated in another cohort of 159 subjects. RESULTS Re-compensation occurred in 57.2% and 66.7% of the subjects in the derivation and validation cohorts, respectively. Six independent predictors for re-compensation were identified in the derivation cohort and these comprised the BC2AID score: bilirubin ≤5 mg/dL (adjusted sub-distribution hazard ratio [aSHR] 2.18), absence of severe complications (aSHR 2.78), alpha-fetoprotein (AFP) ≥50 ng/mL (aSHR 2.54), alanine aminotransferase ≥200 IU/L (aSHR 2.62), international normalised ratio ≤1.5 (aSHR 2.37) and ≤6 months from initial decompensation until initiation of NUCs (aSHR 4.79). In the validation cohort, the area under the receiver operating characteristic curve of the BC2AID score for re-compensation within 1 year of NUC therapy was significantly higher than that of the Child-Pugh, MELD, MELDNa and BE3A scores (0.813 vs 0.691, 0.638, 0.645 and 0.624, respectively; all P < 0.05). CONCLUSIONS Six clinical parameters, including AFP and the timing of antiviral therapy, were combined into a scoring system to accurately predict early re-compensation in patients with HBV-related decompensated cirrhosis.
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Affiliation(s)
- Tae Hyung Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Soon Ho Um
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Young-Sun Lee
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Sun Young Yim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Young Kul Jung
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Yeon Seok Seo
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Ji Hoon Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Hyunggin An
- Department of Biostatistics, Korea University College of Medicine, Seoul, Korea
| | - Hyung Joon Yim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Jong Eun Yeon
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Kwan Soo Byun
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
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Caligiuri A, Gentilini A, Pastore M, Gitto S, Marra F. Cellular and Molecular Mechanisms Underlying Liver Fibrosis Regression. Cells 2021; 10:cells10102759. [PMID: 34685739 PMCID: PMC8534788 DOI: 10.3390/cells10102759] [Citation(s) in RCA: 146] [Impact Index Per Article: 36.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Revised: 10/08/2021] [Accepted: 10/09/2021] [Indexed: 12/12/2022] Open
Abstract
Chronic liver injury of different etiologies may result in hepatic fibrosis, a scar formation process consisting in altered deposition of extracellular matrix. Progression of fibrosis can lead to impaired liver architecture and function, resulting in cirrhosis and organ failure. Although fibrosis was previous thought to be an irreversible process, recent evidence convincingly demonstrated resolution of fibrosis in different organs when the cause of injury is removed. In the liver, due to its high regenerative ability, the extent of fibrosis regression and reversion to normal architecture is higher than in other tissues, even in advanced disease. The mechanisms of liver fibrosis resolution can be recapitulated in the following main points: removal of injurious factors causing chronic hepatic damage, elimination, or inactivation of myofibroblasts (through various cell fates, including apoptosis, senescence, and reprogramming), inactivation of inflammatory response and induction of anti-inflammatory/restorative pathways, and degradation of extracellular matrix. In this review, we will discuss the major cellular and molecular mechanisms underlying the regression of fibrosis/cirrhosis and the potential therapeutic approaches aimed at reversing the fibrogenic process.
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Chen MH, Wu CS, Chen MH, Tsai CY, Lee FY, Huang YH. High Risk of Viral Reactivation in Hepatitis B Patients with Systemic Lupus Erythematosus. Int J Mol Sci 2021; 22:9116. [PMID: 34502025 PMCID: PMC8430791 DOI: 10.3390/ijms22179116] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Revised: 07/13/2021] [Accepted: 08/23/2021] [Indexed: 12/12/2022] Open
Abstract
HBV reactivation (HBVr) can occur in hepatitis B surface antigen (HBsAg)-positive and negative patients. Here, we determined the incidence of HBVr and its related hepatitis in patients with systemic lupus erythematosus (SLE). From 2000 to 2017, 3307 SLE cases were retrospectively reviewed for episodes of hepatitis. The incidence, long-term outcomes and risk factors associated with HBVr, including HBsAg reverse seroconversion (RS) were analyzed. Among them, 607 had available HBsAg status. Fifty-five (9.1%) patients were positive for HBsAg and 63 (11.4%) were HBsAg-negative/antibody to hepatitis B core antigen (anti-HBc)-positive (resolved hepatitis B infection, RHB). None of them received antiviral prophylaxis before immunosuppressive treatment. During a mean 15.4 years of follow-up, 30 (54.5%) HBsAg-positive patients developed HBVr and seven (23.3%) died of liver failure, whereas only two (3.2%) RHB cases experienced HBsAg reverse seroconversion (RS). Multivariate logistic regression analysis showed that age ≥ 40 years at diagnosis of SLE (HR 5.30, p < 0.001), receiving glucocorticoid-containing immunosuppressive therapy (HR 4.78, p = 0.003), and receiving glucocorticoid ≥ 10 mg prednisolone equivalents (HR 3.68, p = 0.003) were independent risk factors for HBVr in HBsAg-positive patients. Peak level of total bilirubin ≥ 5 mg/dL during HBVr was an independent factor of mortality (p = 0.002). In conclusion, the risk of HBVr was associated with glucocorticoid daily dose. Antiviral prophylaxis is mandatory for SLE patients diagnosed at age of ≥40 years who receive ≥ 10 mg daily dose of oral prednisone or equivalent.
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Affiliation(s)
- Ming-Han Chen
- Division of Allergy-Immunology-Rheumatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan;
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan;
| | - Chien-Sheng Wu
- Division of Allergy-Immunology-Rheumatology, Department of Medicine, Far Eastern Memorial Hospital, Taipei 220216, Taiwan;
| | - Ming-Huang Chen
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan;
| | - Chang-Youh Tsai
- Division of Allergy-Immunology-Rheumatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan;
- Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan;
| | - Fa-Yauh Lee
- Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan; (F.-Y.L.); (Y.-H.H.)
| | - Yi-Hsiang Huang
- Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan; (F.-Y.L.); (Y.-H.H.)
- Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan
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Poor Outcomes of Cirrhosis due to Nonalcoholic Steatohepatitis Compared With Hepatitis B After Decompensation With Ascites. Am J Gastroenterol 2021; 116:1437-1446. [PMID: 33834737 DOI: 10.14309/ajg.0000000000001176] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Accepted: 01/05/2021] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Decompensation with ascites portends a poor prognosis in cirrhosis. The aim of this study was to compare the outcomes of patients with nonalcoholic steatohepatitis (NASH) with hepatitis B virus (HBV) cirrhosis after decompensation with ascites. METHODS We conducted a retrospective study to evaluate the outcomes of patients with NASH and HBV cirrhosis who were admitted to hospital for first-onset ascites from January 1, 2004, to June 30, 2015. They were followed up until death, liver transplantation, or loss to follow up. RESULTS Patients with NASH had lower median (interquartile range) Model for End-Stage Liver Disease score (11 [9-14] vs 14 [11-17], P < 0.001). Over 60 months, patients with NASH cirrhosis had higher cumulative incidence of dilutional hyponatremia (P < 0.001) and refractory ascites (P = 0.028). They also had higher cumulative incidence of cirrhosis-related deaths and liver transplantation compared with HBV cirrhosis (65.7%; [95% confidence interval (CI) 53.6-75.4] vs 42.5% [95% CI 32.4-55.2], P = 0.008). Multivariable competing risk analysis showed that NASH (subdistribution hazard ratio [sHR] 1.88 [95% CI 1.14-3.11], P = 0.014), non-Chinese ethnicity (sHR 1.63 [95% CI 1.06-2.50], P = 0.027), history of hepatocellular carcinoma (sHR 1.76 [95% CI 1.05-2.95], P = 0.033), estimated glomerular filtration rate <60 mL/min/1.73 m2 (sHR 1.70 [95% CI 1.09-2.65], P = 0.020), and Model for End-Stage Liver Disease score ≥15 (sHR 3.26 [95% CI 2.11-5.05], P < 0.001) were independent predictors of poor transplant-free survival. DISCUSSION Patients with decompensated cirrhosis due to NASH had much poorer prognosis compared with HBV with more complications and greater healthcare resource utilization. Greater awareness is necessary for early diagnosis of NASH before decompensation.
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Recompensation of Decompensated Hepatitis B Cirrhosis: Current Status and Challenges. BIOMED RESEARCH INTERNATIONAL 2020; 2020:9609731. [PMID: 33029534 PMCID: PMC7527887 DOI: 10.1155/2020/9609731] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 09/07/2020] [Accepted: 09/15/2020] [Indexed: 02/07/2023]
Abstract
Liver-function decompensation or hepatocellular carcinoma (HCC) gradually appears after chronic hepatitis B progresses to cirrhosis. Effective antiviral treatment can significantly improve the long-term prognosis of decompensated patients, and some patients present recompensation of decompensated hepatitis B cirrhosis. At present, there are limited research data on the recompensation of decompensated hepatitis B cirrhosis. There is still controversy regarding the evaluation time, evaluation indicators, influencing factors, and long-term prognosis of recompensation.
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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] [MESH Headings] [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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Japan Society of Hepatology Guidelines for the Management of Hepatitis B Virus Infection: 2019 update. Hepatol Res 2020; 50:892-923. [PMID: 32343469 DOI: 10.1111/hepr.13504] [Citation(s) in RCA: 84] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Revised: 03/16/2020] [Accepted: 03/22/2020] [Indexed: 02/06/2023]
Abstract
The Drafting Committee for Hepatitis Management Guidelines established by the Japan Society of Hepatology published the first version of the Guidelines for the Management of Hepatitis B in 2013 (first English version in 2014), and has since been publishing updates to the Guidelines as new drugs become available, with the latest original Japanese version being Version 3.1. Herein, the Drafting Committee publishes the second English version that contains all the changes made since the first English version of the guidelines was published in 2014. This 2019 version covers: (i) the nucleos(t)ide analogs, tenofovir disoproxil fumarate and tenofovir alafenamide; (ii) updates to treatment recommendations and management of drug-resistant hepatitis B virus that reflect the new availability of these drugs; and (iii) new information about hepatitis B virus reactivation with each update. This latest update also contains information about treatment goals, indications for treatment and cessation of nucleos(t)ide analog therapy, most of which were covered by the first version.
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Chang ML, Cheng JS, Chien RN, Liaw YF. Hepatitis Flares Are Associated With Better Outcomes Than No Flare in Patients With Decompensated Cirrhosis and Chronic Hepatitis B Virus Infection. Clin Gastroenterol Hepatol 2020; 18:2064-2072.e2. [PMID: 31982607 DOI: 10.1016/j.cgh.2020.01.018] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2019] [Revised: 12/27/2019] [Accepted: 01/11/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Little is known about the effects of baseline hepatitis flares (level of alanine aminotransferase ≥5-fold above the upper limit of normal) on the outcomes of patients with chronic hepatitis B virus (HBV) infection with decompensated cirrhosis treated with nucleos(t)ide analogues. We aimed to investigate these effects. METHODS We performed a cohort study of 511 consecutive patients (78.1% men; 58.7% with flares at baseline) with chronic HBV infection and decompensated cirrhosis who were treated with nucleos(t)ide analogues as soon as decompensation was noted. Patients were enrolled from January 2002 to March 2018 at a tertiary care center in Taiwan and followed up for 16 years. RESULTS Patients with hepatitis flares had higher mean baseline levels of HBV DNA (6.44 ± 1.52 vs 6.08 ± 1.46 log10 IU/mL; P = .003), hepatitis B surface antigen, and total bilirubin; prolonged prothrombin time; higher platelet counts (108.0 ± 42.9 vs 83.6 ± 44.7 103/μL; P < .001); and a higher proportion were infected with HBV genotype B, compared with patients without flares. Patients with flares had lower ratios of neutrophils to lymphocytes than patients with flares (6.14 ± 9.18 vs 9.12 ± 1.36; P = .019); were less likely than patients without flares to be positive for hepatitis B e antigen, ascites, esophageal varices, or splenomegaly; and a lower proportion died or underwent liver transplantation (46.5% vs 73.2% of patients without flares; P < .001), even though the patients without flares had similar short-term (<3 mo) outcomes. Factors associated independently with baseline flares were esophageal varices (odds ratio [OR], 0.165; 95% CI, 0.067-0.406), ascites (OR, 0.415; 95% CI, 0.178-0.969), levels of total bilirubin (OR, 1.158; 95% CI, 1.041-1.269), prolonged prothrombin time (OR, 1.095; 95% CI, 1.033-1.168), and higher platelet counts (OR, 1.009; 95% CI, 1.00-1.018). After we used propensity score matching to match patients with and without baseline flares, factors associated with the cumulative incidence of death or liver transplantation were flares (hazard ratio [HR], 0.491; 95% CI, 0.317-0.76), ratio of neutrophils to lymphocytes (HR, 1.278; 95% CI, 1.027-1.591), and prolonged prothrombin time (HR, 1.223; 95% CI, 1.052-1.423). CONCLUSIONS In a 16-year study of patients with chronic HBV infection and decompensated cirrhosis treated with nucleos(t)ide analogues, a baseline flare of hepatitis was associated independently with better long-term (≥3 mo) outcomes than no flare.
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Affiliation(s)
- Ming-Ling Chang
- Liver Research Center, Division of Hepatology, Department of Gastroenterology and Hepatology, Taoyuan, Taiwan; Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
| | - Jur-Shan Cheng
- Clinical Informatics and Medical Statistics Research Center, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Department of Emergency Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Rong-Nan Chien
- Liver Research Center, Division of Hepatology, Department of Gastroenterology and Hepatology, Taoyuan, Taiwan; Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Yun-Fan Liaw
- Liver Research Center, Division of Hepatology, Department of Gastroenterology and Hepatology, Taoyuan, Taiwan; Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
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Mean Platelet Volume/Lymphocyte Ratio as a Prognostic Indicator for HBV-Related Decompensated Cirrhosis. Gastroenterol Res Pract 2020; 2020:4107219. [PMID: 32714387 PMCID: PMC7352138 DOI: 10.1155/2020/4107219] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2020] [Revised: 06/09/2020] [Accepted: 06/19/2020] [Indexed: 12/30/2022] Open
Abstract
Aim To evaluate the prognostic role of the mean platelet volume/lymphocyte ratio (MPVLR) for mortality in patients with hepatitis B virus-related decompensated cirrhosis (HBV-DeCi). Methods The medical records of 101 patients with HBV-DeCi were retrospectively reviewed, and their baseline clinical and laboratory characteristics were extracted. The predictive value of the MPVLR for death was estimated using receiver operating characteristic curve analysis and a multivariate logistic regression model. Results Patients with HBV-DeCi in the high-MPVLR group exhibited significantly increased 90-day mortality compared with that of the patients within the low-MPVLR group, and MPVLR was an independent predictor of 90-day mortality in patients with HBV-DeCi. Conclusions Increased MPVLR is associated with poor outcomes in patients with HBV-DeCi and might be a useful component of future prognostic scores.
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Sinn DH. [Natural History and Treatment Indications of Chronic Hepatitis B]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2020; 74:245-250. [PMID: 31765552 DOI: 10.4166/kjg.2019.74.5.245] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/12/2019] [Revised: 10/27/2019] [Accepted: 10/28/2019] [Indexed: 12/21/2022]
Abstract
HBV is the most common etiology of both liver cirrhosis and hepatocellular carcinoma in Korea. Despite much progress made, the currently available antiviral therapies cannot eradicate or eliminate this virus. Hence, the benefits and risks of antiviral therapy should be carefully evaluated on an individual basis and within the context of the clinical situation. The ultimate goals of treatment are to decrease the mortality from liver disease. The benefits of antiviral therapy come from prevention of progression of liver disease. Understanding the natural history of chronic HBV infection is a key step in the decision making process to treat patients with chronic HBV infection. Generally, chronic hepatitis B patients in the immune tolerant phase and immune inactive phase are not recommended to undergo antiviral treatment, except for those patients in special conditions (e.g., immunosuppression or anticancer chemotherapy). Chronic hepatitis B patients in the immune active phase are recommended for antiviral therapy. For patients with liver cirrhosis, treatment should be considered when serum HBV DNA is detectable regardless of the serum level of ALT.
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Affiliation(s)
- Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Fernández I, Pascasio JM, Colmenero J. Prophylaxis and treatment in liver transplantation. VII Consensus Document of the Spanish Society of Liver Transplantation. GASTROENTEROLOGIA Y HEPATOLOGIA 2020; 43:169-177. [PMID: 32094045 DOI: 10.1016/j.gastrohep.2019.11.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Revised: 11/05/2019] [Accepted: 11/20/2019] [Indexed: 12/26/2022]
Abstract
Whilst prophylaxis of hepatitis B is universally accepted after liver transplantation (LT), national recommendations for the prophylaxis and treatment of hepatitis B virus (HBV) infection after LT are lacking in Spain. The aim of the VII consensus meeting organised by the Spanish Society of Liver Transplantation (SETH) was to set recommendations on the prophylaxis and treatment of hepatitis B after LT. The scientific evidence and strength of recommendations was evaluated by using the "Grading of Recommendations Assessment, Development and Evaluation" (GRADE) system. This document describes the recommendations and their level of evidence for: the definition and risk factors for hepatitis B recurrence after LT, monitoring and prophylaxis of hepatitis B recurrence at different periods after LT, treatment of hepatitis B before and after LT, and the prophylaxis of HBV infection by the recipients of LT with hepatitis B core antigen positive donors.
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Affiliation(s)
- Inmaculada Fernández
- Sociedad Española de Trasplante Hepático, Unidad de Hepatología y Trasplante Hepático, Hospital 12 de Octubre, Madrid, España
| | - Juan Manuel Pascasio
- Sociedad Española de Trasplante Hepático, Unidad de Trasplante Hepático, Hospital Virgen del Rocío, Sevilla, España
| | - Jordi Colmenero
- Unidad de Trasplante Hepático, Hospital Clínic, IDIBAPS, CIBERehd, Univ. Barcelona, Barcelona, España.
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KASL clinical practice guidelines for management of chronic hepatitis B. Clin Mol Hepatol 2019; 25:93-159. [PMID: 31185710 PMCID: PMC6589848 DOI: 10.3350/cmh.2019.1002] [Citation(s) in RCA: 165] [Impact Index Per Article: 27.5] [Reference Citation Analysis] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Accepted: 03/25/2019] [Indexed: 02/06/2023] Open
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Abstract
Purpose of Review Acute HBV infection and acute exacerbations of chronic HBV infection can cause acute liver injury (ALI) or fulminant hepatitis (FH). At this stage, spontaneous survival is poor, less than 25%. The purpose of this review is to provide an overview of specific management of patients with HBV-ALI/FH. Recent Findings Acute HBVinfection and acute exacerbations of chronic HBVinfection can cause acute liver injury (ALI) or fulminant hepatitis (FH). Spontaneous survival at this stage is poor. It is urgent to distinguish between these two entities so that antiviral therapy can be initiated rapidly. Although the indications for antiviral therapy are clear for HBV reactivation, there is no true consensus regarding ALI/FH related to acute HBV infection. The global management of HBV-related FH does not differ from that implemented for other causes of FH, i.e. close cardiorespiratory and neurological monitoring, treatment with acetylcysteine, organ support in the event of organ failure (haemodynamic, renal, respiratory) and albumin dialysis. Liver transplantation remains the only alternative when certain criteria for a poor prognosis are met. A recurrence of HBV infection on the graft can be prevented post-transplant by the administration of HBIG and antiviral therapy for HBV, the modalities varying depending on the risk of recurrence.
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Affiliation(s)
- Philippe Ichai
- Centre Hépato-Biliaire, Liver Intensive Care Unit, AP-HP Hôpital Paul-Brousse, 12 Avenue Paul Vaillant Couturier, 94804 Villejuif, France
- INSERM, Unité 1193, Université ParisSud, Paris-Saclay, 94800 Villejuif, France
- DHU Hepatinov, 94800 Villejuif, France
| | - Didier Samuel
- Centre Hépato-Biliaire, Liver Intensive Care Unit, AP-HP Hôpital Paul-Brousse, 12 Avenue Paul Vaillant Couturier, 94804 Villejuif, France
- INSERM, Unité 1193, Université ParisSud, Paris-Saclay, 94800 Villejuif, France
- DHU Hepatinov, 94800 Villejuif, France
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Serum Cystatin C Predicts Mortality in HBV-Related Decompensated Cirrhosis. BIOMED RESEARCH INTERNATIONAL 2019; 2019:7272045. [PMID: 30949507 PMCID: PMC6425319 DOI: 10.1155/2019/7272045] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/05/2018] [Revised: 01/20/2019] [Accepted: 02/05/2019] [Indexed: 01/06/2023]
Abstract
Background Some studies have reported that renal dysfunction is associated with poor prognosis in cirrhotic patients. Serum cystatin C (CysC) is an accurate biomarker for early renal dysfunction. This study aimed to assess the prognostic value of serum CysC levels in patients with hepatitis B virus-related decompensated cirrhosis (HBV-DeCi). Methods This retrospective study included 75 subjects who had been diagnosed with HBV-DeCi. The association between serum CysC and prognosis was estimated by receiver operating characteristic curve analysis and a multivariable logistic regression model. Results Serum CysC levels were higher in nonsurvivors than in survivors and were positively correlated with model for end-stage liver disease (MELD) scores. In multivariate analysis, CysC and the MELD score were independent prognostic factors in all HBV-DeCi patients. However, only serum CysC was an independent factor predicting mortality in patients with normal creatinine levels. Conclusions These data suggest that high serum CysC levels can be considered an independent biomarker of 3-month mortality in patients with HBV-DeCi.
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Antiviral Therapy for AECHB and Severe Hepatitis B (Liver Failure). ACUTE EXACERBATION OF CHRONIC HEPATITIS B 2019. [PMCID: PMC7498919 DOI: 10.1007/978-94-024-1603-9_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
This chapter describes the principles of antiviral therapy, treatment strategies, medications and recommendations for AECHB, HBV-ACLF, HBV-related liver cirrhosis, HBV-related HCC, and liver transplantation.
Severe exacerbation of chronic hepatitis B is closely related to continuous HBV replication. Therefore, inhibiting HBV replication to reduce viral load may block disease progression and improve the quality of life of these patients. ETV or TDF has been recommend first-line drug for the treatment of AECHB. A hyperactive immune response due to continuous HBV replication is the main mechanism for development of severe hepatitis B. In addition to comprehensive treatment, early administration of potent nucleoside analogs can rapidly reduce HBV DNA concentration, relieve immune injury induced by HBV, and reduce liver inflammation and patient mortality. Antiviral agents have become important in the treatment of severe exacerbation of chronic hepatitis B. Long-term antiviral treatment with nucleoside analogs can delay or reverse the progress of liver cirrhosis. Virologic response, viral resistance and adverse drug reactions should be closely monitored during treatment. The treatment should be optimized for maximum effect based on each patient’s responses. Effective antiviral therapy can suppress HBV replication and reduce the incidence of HBV-related HCC. Patients with HBV-related HCC should receive individualized and optimal multidisciplinary comprehensive treatment. Anti-viral drugs with high efficacy, low resistance and low adverse drug reactions should be selected to improve the patient’s quality of life and prolong survival time. Methods to prevent HBV reinfection after liver transplantation include passive immunization (HBIG), antiviral treatment (nucleoside analogs) and active immunization (hepatitis B vaccine). Clinical trials involving sequential combination therapy with NUC and Peg-IFN have shown statistically significant decline in HBsAg levels on treatment and high rates of sustained post-treatment serologic response. Combination therapy with novel DAA and immunotherapeutic approach may hold promise to overcome both cccDNA persistence and immune escape, representing a critical step towards HBV cure.
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Is Low Level Viremia Acceptable During Antiviral Therapy of Patients With HBV Infection and Decompensated Cirrhosis? Clin Gastroenterol Hepatol 2018; 16:1876-1878. [PMID: 30213586 DOI: 10.1016/j.cgh.2018.09.010] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2018] [Revised: 09/04/2018] [Accepted: 09/05/2018] [Indexed: 02/07/2023]
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Jang JW, Choi JY, Kim YS, Yoo JJ, Woo HY, Choi SK, Jun CH, Lee CH, Sohn JH, Tak WY, Lee YR, Han KH. Effects of Virologic Response to Treatment on Short- and Long-term Outcomes of Patients With Chronic Hepatitis B Virus Infection and Decompensated Cirrhosis. Clin Gastroenterol Hepatol 2018; 16:1954-1963.e3. [PMID: 29753085 DOI: 10.1016/j.cgh.2018.04.063] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2017] [Revised: 03/23/2018] [Accepted: 04/20/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Little is known about the effects of antiviral therapy on short- and long-term survival of patients with hepatitis B virus (HBV)-related decompensated cirrhosis. We aimed to determine whether a maintained virologic response (MVR, defined as persistent undetectable HBV DNA during therapy) associates with short-term (6 mo) and long-term (6-120 mo) survival of patients with decompensated cirrhosis. METHODS We performed a 10-year observation analysis using data from the Epidemiology and Natural History of Liver Cirrhosis study of patients with decompensated liver cirrhosis in Korea. Of the entire cohort (1595 patients enrolled at onset of decompensation since 2005), our analysis comprised 295 patients who immediately began treatment with entecavir (n = 179) or lamivudine (n = 116) after decompensation. We collected laboratory test results, data on hepatocellular carcinoma (HCC) development, and Child-Turcotte-Pugh and model for end-stage liver disease (MELD) scores. The mean follow-up time was 62.3 ± 36.5 months. The primary end point was time of liver transplant-free survival. RESULTS The median survival time was 7.7 years; 60.1% of patients survived for 5 years and 45.7% survived for 10 years without liver transplantation. An MVR was observed in 116 patients (39.3%); these patients had significantly longer times of transplant-free survival than patients without MVR. Survival times associated with the occurrence of HCC; survival of patients without HCC was excellent if they survived the first 6 months after initiation of antiviral therapy, whereas the survival rates of patients with HCC decreased persistently over time. A baseline MELD score above 20 and multiple complications were associated with short-term mortality. MVR was the factor most strongly associated with long-term transplant-free survival. Significantly higher proportions of patients who received entecavir survived 10 years compared with patients who received lamivudine, but no difference was observed among patients with MVRs. Patients with MVRs had significant improvement in hepatic function over time, but nonsignificant reductions in risk of HCC or HCC-related mortality. CONCLUSIONS In a 10-year observation study of patients in Korea with HBV-related decompensated cirrhosis, we found baseline MELD score and MVR to entecavir or lamivudine to associate with short- and long-term transplant-free survival. The benefits of an MVR are maintained for up to 10 years even after decompensation, but patients are still at risk for HCC.
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Affiliation(s)
- Jeong Won Jang
- Department of Internal Medicine, The Catholic University of Korea, College of Medicine, Seoul, Republic of Korea; Liver Cirrhosis Clinical Research Center
| | - Jong Young Choi
- Department of Internal Medicine, The Catholic University of Korea, College of Medicine, Seoul, Republic of Korea; Liver Cirrhosis Clinical Research Center.
| | - Young Seok Kim
- Liver Cirrhosis Clinical Research Center; Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
| | - Jeong-Ju Yoo
- Liver Cirrhosis Clinical Research Center; Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Korea
| | - Hyun Young Woo
- Liver Cirrhosis Clinical Research Center; Department of Internal Medicine, Pusan National University Hospital, Busan, Korea
| | - Sung Kyu Choi
- Liver Cirrhosis Clinical Research Center; Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Chung Hwan Jun
- Liver Cirrhosis Clinical Research Center; Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
| | - Chang Hyeong Lee
- Liver Cirrhosis Clinical Research Center; Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, Korea
| | - Joo Hyun Sohn
- Liver Cirrhosis Clinical Research Center; Department of Internal Medicine, Hanyang University Guri Hospital, Guri, Korea
| | - Won Young Tak
- Liver Cirrhosis Clinical Research Center; Department of Internal Medicine, School of Medicine, Kyungpook National University Hospital, Daegu, Korea
| | - Yu Rim Lee
- Liver Cirrhosis Clinical Research Center; Department of Internal Medicine, School of Medicine, Kyungpook National University Hospital, Daegu, Korea
| | - Kwang-Hyub Han
- Liver Cirrhosis Clinical Research Center; Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
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Ju YC, Jun DW, Choi J, Saeed WK, Lee HY, Oh HW. Long term outcome of antiviral therapy in patients with hepatitis B associated decompensated cirrhosis. World J Gastroenterol 2018; 24:4606-4614. [PMID: 30386110 PMCID: PMC6209577 DOI: 10.3748/wjg.v24.i40.4606] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2018] [Revised: 09/06/2018] [Accepted: 10/05/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate survival rate and incidence of hepatocellular carcinoma (HCC) in patients with decompensated cirrhosis in the antiviral era.
METHODS We used the Korean Health Insurance Review and Assessment. Korea’s health insurance system is a public single-payer system. The study population consisted of 286871 patients who were prescribed hepatitis B antiviral therapy for the first time between 2007 and 2014 in accordance with the insurance guidelines. Overall, 48365 antiviral treatment-naïve patients treated between 2008 and 2009 were included, and each had a follow-up period ≥ 5 years. Data were analyzed for the 1st decompensated chronic hepatitis B (CHB) and treatment-naïve patients (n = 7166).
RESULTS The mean patient age was 43.5 years. The annual mortality rates were 2.4%-19.1%, and 5-year cumulative mortality rate was 32.6% in 1st decompensated CHB treatment-naïve subjects. But the annual mortality rates sharply decreased to 3.4% (2.4%-4.9%, 2-5 year) after one year of antiviral treatment. Incidence of HCC at first year was 14.3%, the annual incidence of HCC decreased to 2.5% (1.8%-3.7%, 2-5 year) after one year. 5-year cumulative incidence of HCC was 24.1%. Recurrence rate of decompensated event was 46.9% at first year, but the annual incidence of second decompensation events in decompensated CHB treatment-naïve patients was 3.4% (2.1%-5.4%, 2-5 year) after one year antiviral treatment. 5-year cumulative recurrence rate of decompensated events was 60.6%. Meanwhile, 5-year cumulative mortality rate was 3.1%, and 5-year cumulative incidence of HCC was 11.5% in compensated CHB treatment-naïve patients.
CONCLUSION Long term outcome of decompensated cirrhosis treated with antiviral agent improved much, and incidence of hepatocellular carcinoma and mortality sharply decreased after one year treatment.
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Affiliation(s)
- Young-Cheol Ju
- Department of Translational Medicine, Graduate school of Biomedical Science and Engineering, Hanyang University, Seoul 04763, South Korea
| | - Dae-Won Jun
- Department of Translational Medicine, Graduate school of Biomedical Science and Engineering, Hanyang University, Seoul 04763, South Korea
- Department of Internal Medicine, School of Medicine, Hanyang University, Seoul 04763, South Korea
| | - Jun Choi
- Department of Industrial Management Engineering, Korea University, Seoul 02841, South Korea
| | - Waqar Khalid Saeed
- Department of Internal Medicine, School of Medicine, Hanyang University, Seoul 04763, South Korea
| | - Hyo-Young Lee
- Department of Internal Medicine, School of Medicine, Hanyang University, Seoul 04763, South Korea
| | - Hyun-Woo Oh
- Department of Internal Medicine, School of Medicine, Hanyang University, Seoul 04763, South Korea
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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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Kim TH, Ku DH, Um SH, Lee HA, Park SW, Chang JM, Yim SY, Suh SJ, Jung YK, Seo YS, Kim JH, Yim HJ, Yeon JE, Byun KS, Ahn H. How can we improve the performance of Model for End-Stage Liver Disease sodium score in patients with hepatitis B virus-related decompensated liver cirrhosis commencing antiviral treatment? J Gastroenterol Hepatol 2018; 33:1641-1648. [PMID: 29462844 DOI: 10.1111/jgh.14128] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/17/2017] [Revised: 01/25/2018] [Accepted: 02/13/2018] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND AIM We aimed to develop a more efficient prognostic model to predict 1-year mortality in patients with hepatitis B virus-related decompensated cirrhosis beginning antiviral treatment. METHODS Using Cox regression analysis, survival analyses were performed on 554 patients with decompensated cirrhosis who were followed up from the start of nucleos(t)ide analogue antiviral treatment. RESULTS At baseline, ascites and hepatic encephalopathy were found in 78.0% and 18.1% of patients, respectively. Eighty-six events (77 deaths and 9 emergency liver transplants) occurred within the first year of treatment. Severity of ascites, presence of hepatic encephalopathy, and the Model for End-Stage Liver Disease (MELD)-sodium (MELDNa) score were independent risk factors for 1-year mortality. The new prognostic model (the revised MELDNa) constructed by adding ascites and encephalopathy to the MELDNa score significantly improved the area under the receiver operating characteristics curve for predicting 1-year events at baseline compared with the Child-Turcotte-Pugh system, MELD and MELDNa models, and Fontana index (0.905 vs 0.867, 0.843, 0.871, and 0.815, respectively; P < 0.05). Furthermore, repetitive application of revised MELDNa at 0, 1, 2, 3, and 6 months of treatment could predict 81.4% (70/86) of 1-year events, which was significantly (P < 0.05) higher than the sensitivity of the Child-Turcotte-Pugh system (68.6%), MELD (70.9%) and MELDNa (68.6%) scores, and Fontana index (64.0%), achieving similar specificities of ~96%. CONCLUSIONS Ascites and encephalopathy should be considered together with the MELDNa score when predicting short-term mortality and planning liver transplant in patients with decompensated hepatitis B virus-related cirrhosis starting antiviral treatment.
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Affiliation(s)
- Tae Hyung Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Dae Hoe Ku
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Soon Ho Um
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Han Ah Lee
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Seung Woon Park
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Jung Mi Chang
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Sun Young Yim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Sang Jun Suh
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Young Kul Jung
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Yeon Seok Seo
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Ji Hoon Kim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Hyung Joon Yim
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Jong Eun Yeon
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Kwan Soo Byun
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Hyonggin Ahn
- Department of Medical Statistics, Korea University College of Medicine, Seoul, Korea
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Wang B, Agarwal K, Joshi D. Management of chronic hepatitis B before and after liver transplantation. Frontline Gastroenterol 2018; 9:79-84. [PMID: 29484165 PMCID: PMC5824762 DOI: 10.1136/flgastro-2016-100768] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2016] [Revised: 01/19/2017] [Accepted: 01/22/2017] [Indexed: 02/04/2023] Open
Abstract
Chronic hepatitis B infection is a global public health problem associated with significant morbidity and mortality. Persistent infection may evolve to liver cirrhosis and hepatocellular carcinoma, and hepatitis B-related liver disease is a common indication for liver transplantation. Patients with advanced liver disease should be treated with antiviral therapy which may result in clinical improvement. The management of patients after liver transplant then focuses on preventing hepatitis B recurrence in the graft. With the introduction of prophylactic treatment, patient and graft survival has improved significantly. In this review, we will discuss the management of patients with hepatitis B-related cirrhosis, both compensated and decompensated. We also review the management of hepatitis B after liver transplantation.
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Affiliation(s)
- B Wang
- Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, UK
| | - K Agarwal
- Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, UK
| | - D Joshi
- Institute of Liver Studies, King's College Hospital NHS Foundation Trust, London, UK
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Genda T, Ichida T, Sakisaka S, Tanaka E, Mochida S, Ueno Y, Inui A, Egawa H, Umeshita K, Furukawa H, Kawasaki S, Inomata Y. Survival in patients with Child-Pugh class C cirrhosis: Analysis of the liver transplant registry in Japan. Hepatol Res 2017; 47:1155-1164. [PMID: 27995739 DOI: 10.1111/hepr.12855] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2016] [Revised: 12/06/2016] [Accepted: 12/18/2016] [Indexed: 12/30/2022]
Abstract
AIM To clarify the survival and prognostic factors in patients with Child-Turcotte-Pugh class C (CTP-C) cirrhosis. METHODS From all candidates for deceased donor liver transplantation in Japan between 2007 and 2015, 1014 adult patients with CTP-C cirrhosis were retrospectively enrolled in this study. The hazard ratio (HR) of factors associated with mortality was estimated by the Cox proportional hazard model. The survival probabilities were evaluated by Kaplan-Meier analysis and the log-rank test. RESULTS Median survival time of the entire cohort was 475 days. Univariate analysis identified age, CTP, Model for End-Stage Liver Disease (MELD) score, and primary biliary cholangitis (PBC) as significant variables associated with mortality and hepatitis B virus (HBV) infection as a close-to-significant variable. Multivariate analysis revealed that age-adjusted mortality risk increased by 59% and 12% per 1 score step up in CTP and MELD scores, respectively. The HRs for HBV infection and PBC were significant after adjustment for age and CTP score, and they showed a 26% lower risk and an 83% higher risk than hepatitis C virus (HCV) infection, respectively. After adjustment for age and MELD score, the HR was also significant for HBV infection, but lost statistical significance for PBC. The survival curves were well stratified by both CTP or MELD score and revealed significant difference in both HBV infection and PBC as compared to HCV infection. CONCLUSIONS In patients with CTP-C cirrhosis, CTP and MELD scores could well stratify the patients' survival, and HBV infection and PBC as etiologies have an impact on survival.
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Affiliation(s)
- Takuya Genda
- Department of Gastroenterology and Hepatology, Juntendo University Shizuoka Hospital, Izunokuni, Japan
| | - Takafumi Ichida
- Department of Hepatology, East Shonan General Hospital, Kanagawa, Japan
| | - Shotaro Sakisaka
- Department of Gastroenterology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan
| | - Eiji Tanaka
- Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan
| | - Satoshi Mochida
- Department of Gastroenterology and Hepatology, Saitama Medical University, Saitama, Japan
| | - Yoshiyuki Ueno
- Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan
| | - Ayano Inui
- Division of Hepatology and Gastroenterology, Department of Pediatrics, Eastern Yokohama Hospital, Yokohama, Japan
| | - Hiroto Egawa
- Department of Surgery, Institute of Gastroenterology, Tokyo Women's Medical University, Tokyo, Japan
| | - Koji Umeshita
- Department of Surgery, Osaka University Graduate School of Medicine, Suita, Japan
| | - Hiroyuki Furukawa
- Department of Gastroentrologic and General Surgery, Asahikawa Medical University, Asahikawa, Japan
| | - Seiji Kawasaki
- Department of Hepatobiliary-Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan
| | - Yukihiro Inomata
- Department of Transplantation and Pediatric Surgery, Postgraduate School of Medical Science, Kumamoto University, Kumamoto, Japan
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Disease Reversibility in Patients With Post-Hepatitis C Cirrhosis: Is the Point of No Return the Same Before and After Liver Transplantation? A Review. Transplantation 2017; 101:916-923. [PMID: 28060241 DOI: 10.1097/tp.0000000000001633] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Liver fibrosis can regress in patients with chronic hepatitis in whom the underlying cause of liver damage is adequately treated. Studies documenting this benefit have been mostly performed in the setting of viral hepatitis, particularly hepatitis C virus, where sustained viral response has been unequivocally shown to result in histological and clinical improvement. With the advent of the new IFN-free regimens, highly effective and safe even in those historically considered "difficult to treat and cure patients," additional benefits have been documented in patients treated at advanced stages of disease, including improvement in liver function with hepatic "recompensation," reduction of portal hypertension, and eventually avoidance of liver transplantation. Disease reversibility has been also demonstrated in the posttransplant setting and appears to be similar to what is observed in the nontransplant patient.
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Gwak GY. [Renewed 2015 Clinical Practice Guidelines for Management of Hepatitis C by Korean Association for the Study of the Liver; What Has Been Changed? - Treatment of Patients with Decompensated Cirrhosis]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2017; 67:137-41. [PMID: 26996183 DOI: 10.4166/kjg.2016.67.3.137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/03/2022]
Abstract
HCV-related decompensated liver cirrhosis is a life-threatening illness with an average 5-year survival rate of 50%. Because these patients have higher risk of morbidity and mortality including development of hepatocellular carcinoma, the benefits of eradicating the virus may be greater than in those with less-advanced disease. Recently, direct-acting antiviral agents (DAAs) are replacing interferon-based regimens that have serious adverse events and low tolerability in the treatment of HCV infection. Many clinical trials using combination of several DAAs with or without ribavirin are now actively on-going in HCV-related decompensated cirrhosis, and encouraging data are beginning to appear. In this review, recent advances in the treatment of HCV-related decompensated cirrhosis are introduced with special focus on new DAAs.
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Affiliation(s)
- Geum Youn Gwak
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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Abstract
Great strides have been made in hepatitis B virus (HBV)-related fibrosis and cirrhosis. Available evidence indicates that HBV viral suppression causes regression of advanced fibrosis and even cirrhosis, and therefore should be attempted in all patients with advanced fibrosis and cirrhosis. The preferred agents in patients with cirrhosis are entecavir and tenofovir, primarily because the risk of breakthrough is low. HBV viral suppression leads to improved clinical outcomes even in patients with cirrhosis and complications. The risk of hepatocellular carcinoma is reduced, but not eliminated. Thus, patients with HBV cirrhosis should continue to have routine screening for hepatocellular carcinoma, even after viral suppression.
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Affiliation(s)
- Don C Rockey
- Department of Internal Medicine, The Medical University of South Carolina, 96 Jonathan Lucas Street, 803 CSB, Charleston, SC 29425, USA.
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Abstract
The goal in patients with immune active hepatitis B virus (HBV) infection is to significantly suppress viral replication and prevent progression of fibrosis to cirrhosis and liver decompensation and decrease the incidence of hepatocellular carcinoma. This is achievable by the highly active antivirals, entecavir and tenofovir, which are considered first-line therapy in most patients with immune active hepatitis C virus and after liver transplantation to prevent HBV recurrence. Patients with decompensated cirrhosis should be referred for liver transplantation and treated with first-line antivirals as early as possible, with the goal of achieving complete viral suppression in the shortest time possible.
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Affiliation(s)
| | - Tarek I Hassanein
- Southern California Research Center, Coronado, CA 92118, USA; University of California, San Diego School of Medicine, San Diego, CA, USA.
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van der Meer AJ, Berenguer M. Reversion of disease manifestations after HCV eradication. J Hepatol 2016; 65:S95-S108. [PMID: 27641991 DOI: 10.1016/j.jhep.2016.07.039] [Citation(s) in RCA: 132] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2016] [Revised: 07/29/2016] [Accepted: 07/29/2016] [Indexed: 12/13/2022]
Abstract
Chronic infection with the hepatitis C virus (HCV) may lead to hepatic fibrosis and eventually cirrhosis, at which stage, patients have a substantial risk of liver failure, hepatocellular carcinoma (HCC) and liver-related death. Moreover, HCV infection is associated with several extrahepatic manifestations which impact the quality of life and increase the non-liver-related mortality rate. For patients with compensated liver disease, interferon (IFN)-based antiviral therapy has been a treatment option for over two decades. Long-term follow-up studies indicated that among those with sustained virological response (SVR) the extend of hepatic fibrosis can regress and that their risk of cirrhosis-related complications (including HCC) is reduced, also in case of cirrhosis. Recent population-based studies extended these observations for solid extrahepatic outcomes, such as end-stage renal failure and cardiovascular events. Most importantly, SVR has been associated with prolonged overall survival. These results highlight the importance of the development of new direct-acting antivirals (DAAs), by which almost all patients are able to eradicate HCV in a comfortable manner. Based on the excellent first experiences with the DAAs, physicians gained confidence to use these drugs among patients with decompensated cirrhosis on a more regular basis as well. This was not possible with interferon therapy. Also in this high risk population the DAAs show high SVR rates with improvements in biochemical parameters of liver function shortly after therapy, especially in case of SVR. In fact, some patients could actually be removed from the liver transplantation waiting list due to clinical improvement following DAA therapy. How these short-term results translate into a prolonged (long-term) survival has yet to be determined, as well as which patients with decompensated liver disease are likely or not to benefit from viral eradication. Here we review the current data regarding the beneficial clinical outcome with antiviral therapy as well the remaining uncertainties in this field, both for patients with compensated liver disease and patients with decompensated liver disease.
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Affiliation(s)
- Adriaan J van der Meer
- Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
| | - Marina Berenguer
- Hepatology and Liver Transplant Unit and Ciberehd, La Fe Univ. Hospital and Univ. Valencia, Spain
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Rational Basis for Optimizing Short and Long-term Hepatitis B Virus Prophylaxis Post Liver Transplantation: Role of Hepatitis B Immune Globulin. Transplantation 2016; 99:1321-34. [PMID: 26038873 PMCID: PMC4539198 DOI: 10.1097/tp.0000000000000777] [Citation(s) in RCA: 40] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Antiviral therapy using newer nucleos(t)ide analogues with lower resistance rates, such as entecavir or tenofovir, suppress hepatitis B virus (HBV) replication, improve liver function in patients with compensated or decompensated cirrhosis, and delay or obviate the need for liver transplantation in some patients. After liver transplantation, the combination of long-term antiviral and low-dose hepatitis B Immune globulin (HBIG) can effectively prevent HBV recurrence in greater than 90% of transplant recipients. Some forms of HBV prophylaxis need to be continued indefinitely after transplantation but, in patients with a low-risk of HBV recurrence (i.e., HBV DNA levels undetectable before transplantation), it is possible to discontinue HBIG and maintain only long-term nucleos(t)ide analogue(s) therapy. A more cautious approach is necessary for those patients with high pretransplant HBV DNA levels, those with limited antiviral options if HBV recurrence occurs (i.e., HIV or hepatitis D virus coinfection, preexisting drug resistance), those with a high risk of hepatocellular carcinoma recurrence, and those at risk of noncompliance with antiviral therapy. In this group, HBIG-free prophylaxis cannot be recommended. The combination of long-term antiviral and low-dose Hepatitis B Immune globulin (HBIG) can effectively prevent HBV recurrence in > 90% of liver transplant recipients. In patients with low HBV DNA levels, nucleos(t)ide analogue(s) treatment without HBIG is possible.
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36
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The Korean Association for the Study of the Liver (KASL). KASL clinical practice guidelines: management of chronic hepatitis B. Clin Mol Hepatol 2016; 22:18-75. [PMID: 27044762 PMCID: PMC4825166 DOI: 10.3350/cmh.2016.22.1.18] [Citation(s) in RCA: 150] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2016] [Accepted: 02/22/2016] [Indexed: 01/10/2023] Open
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Mareddy AS, Rangaswamy D, Vankalakunti M, Attur RP, Nagaraju SP, Koti N. Immune mediated crescentic MPGN secondary to HBV infection: A rare presentation for a common infection. Australas Med J 2016; 9:12-6. [PMID: 26913086 DOI: 10.4066/amj.2015.2568] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Hepatitis B virus (HBV) infection presenting as crescentic glomerulonephritis in the absence of cryoglobulinemia is an extremely rare phenomenon. We report a case of a 44-year-old male with HBV infection, who underwent kidney biopsy for rapidly progressive renal failure and nephrotic range proteinuria. Histopathological evaluation of the kidney biopsy was consistent with immune complex mediated crescentic membranoproliferative glomerulonephritis (MPGN). The patient achieved complete renal and virological remission with steroids, plasmapheresis and antiviral therapy. This case report summarises the importance of early initiation of immunosuppression and plasmapheresis under antiviral coverage for improved clinical outcomes.
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Affiliation(s)
| | - Dharshan Rangaswamy
- Department of Nephrology, Kasturba Medical College, Manipal University, Mangalore, India
| | | | - Ravindra Prabhu Attur
- Department of Nephrology, Kasturba Medical College, Manipal University, Mangalore, India
| | | | - Neeraja Koti
- Department of Medicine, Kasturba Medical College, Manipal University, Mangalore, India
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Jang JW, Choi JY, Kim YS, Woo HY, Choi SK, Lee CH, Kim TY, Sohn JH, Tak WY, Han KH. Long-term effect of antiviral therapy on disease course after decompensation in patients with hepatitis B virus-related cirrhosis. Hepatology 2015; 61:1809-1820. [PMID: 25627342 DOI: 10.1002/hep.27723] [Citation(s) in RCA: 107] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2014] [Accepted: 01/22/2015] [Indexed: 12/20/2022]
Abstract
UNLABELLED The effect of viral suppression on long-term disease outcome after decompensation in patients with hepatitis B virus (HBV)-related cirrhosis has not been established. The aim of this study was to determine the long-term effect of antiviral therapy (AVT) in patients with HBV-related decompensated cirrhosis. This was a multicenter, prospective, inception cohort study of 707 patients who presented with first-onset decompensated complications, including 284 untreated and 423 antiviral-treated patients (58 previously treated, 253 with early treatment, and 112 with delayed treatment). The primary endpoint was 5-year liver transplantation (LT)-free survival. Secondary endpoints included virological response (VR) and serological response and improvement in liver function. Despite baseline high HBV activity and worse liver function, antiviral-treated patients had significantly better transplant-free survival than untreated patients (5-year survival rates of 59.7% vs. 46.0%, respectively), with more apparent benefits from antivirals in Child-Turcotte-Pugh class B/C and high-viremia groups. The rate of VR and hepatitis B e antigen seroconversion at 5 years in antiviral-treated patients was 14.2% and 49.1%, respectively. A significant improvement in liver function was observed in treated versus untreated patients, with 33.9% of treated patients delisted for LT. Patients with early treatment had better clinical outcomes than those with delayed treatment. Survival was dependent on antiviral response, being significantly better in responders than in nonresponders or untreated cases. The initial benefit of AVT was negated over time in nonresponders. Antiviral treatment and maintained VR remained independently predictive of survival. The study results were corroborated by propensity score-matching analysis. CONCLUSION AVT significantly modifies the natural history of decompensated cirrhosis, improving liver function and increasing survival. The results underscore the importance of promptly administering potent antiviral drugs to patients under consideration for LT.
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Affiliation(s)
- Jeong Won Jang
- Department of Internal Medicine, The Catholic University of Korea, College of Medicine, Seoul, Korea
- Liver Cirrhosis Clinical Research Center, Seoul, Korea
| | - Jong Young Choi
- Department of Internal Medicine, The Catholic University of Korea, College of Medicine, Seoul, Korea
- Liver Cirrhosis Clinical Research Center, Seoul, Korea
| | - Young Seok Kim
- Department of Internal Medicine, Soonchunhyang University College of Medicine, Bucheon, Korea
- Liver Cirrhosis Clinical Research Center, Seoul, Korea
| | - Hyun Young Woo
- Department of Internal Medicine, Pusan National University Hospital, Busan, Korea
- Liver Cirrhosis Clinical Research Center, Seoul, Korea
| | - Sung Kyu Choi
- Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea
- Liver Cirrhosis Clinical Research Center, Seoul, Korea
| | - Chang Hyeong Lee
- Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, Korea
- Liver Cirrhosis Clinical Research Center, Seoul, Korea
| | - Tae Yeob Kim
- Department of Internal Medicine, Hanyang University Guri Hospital, Guri, Korea
- Liver Cirrhosis Clinical Research Center, Seoul, Korea
| | - Joo Hyun Sohn
- Department of Internal Medicine, Hanyang University Guri Hospital, Guri, Korea
- Liver Cirrhosis Clinical Research Center, Seoul, Korea
| | - Won Young Tak
- Department of Internal Medicine, Kyungpook National University Hospital, Daegu, Korea
- Liver Cirrhosis Clinical Research Center, Seoul, Korea
| | - Kwang-Hyub Han
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Liver Cirrhosis Clinical Research Center, Seoul, Korea
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Forns X, Charlton M, Denning J, McHutchison JG, Symonds WT, Brainard D, Brandt-Sarif T, Chang P, Kivett V, Castells L, Prieto M, Fontana RJ, Baumert TF, Coilly A, Londoño MC, Habersetzer F. Sofosbuvir compassionate use program for patients with severe recurrent hepatitis C after liver transplantation. Hepatology 2015; 61:1485-94. [PMID: 25557906 DOI: 10.1002/hep.27681] [Citation(s) in RCA: 177] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/10/2014] [Accepted: 12/23/2014] [Indexed: 12/13/2022]
Abstract
UNLABELLED Recurrent hepatitis C virus (HCV) infection after liver transplantation (LT) is associated with accelerated progression of liver disease, frequently leading to graft loss and early death. Existing treatment options for severe recurrent HCV infection are limited by suboptimal efficacy, poor tolerability, and numerous drug interactions. We provided sofosbuvir (SOF) and ribavirin (RBV) on a compassionate-use basis to patients with severe recurrent hepatitis C, including those with fibrosing cholestatic hepatitis (FCH) and decompensated cirrhosis who had a life expectancy of 1 year or less. All patients were to receive 24-48 weeks of SOF plus RBV. Investigators could add pegylated interferon to the regimen at their discretion. Data from the first 104 patients who completed or prematurely discontinued treatment by January 1, 2014 are presented. Of the 104 patients analyzed, 52 had an early severe recurrence (diagnosed <12 months after LT) and 52 had cirrhosis (diagnosed >12 months after LT). Twelve patients who underwent retransplantation were excluded from our efficacy analysis. Of the 92 patients assessed, 54 (59%) achieved sustained virological response (SVR) at 12 weeks after the end of treatment, with a higher rate (73%; 35 of 48) in patients with early severe recurrence. Of the 103 patients assessed for clinical outcome, 59 (57%) reported clinical improvement at the last study visit, 23 (22%) were unchanged, 3 (3%) had a worsened clinical status, and 13 (13%) died. Overall, 123 serious adverse events (SAEs) occurred in 49 patients (47%). SAEs associated with hepatic decompensation were the most frequent, with 26 SAEs occurring in 19 patients (18%). CONCLUSION SOF and RBV provide high rates of SVR in patients with severe recurrent HCV, including patients with early severe recurrence, FCH, and cirrhosis.
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Affiliation(s)
- Xavier Forns
- Liver Unit, IDIBAPS, CIBEREHD, Hospital Clinic, University of Barcelona, Barcelona, Spain
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Cholongitas E, Tziomalos K, Pipili C. Management of patients with hepatitis B in special populations. World J Gastroenterol 2015; 21:1738-1748. [PMID: 25684938 PMCID: PMC4323449 DOI: 10.3748/wjg.v21.i6.1738] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2014] [Revised: 10/27/2014] [Accepted: 11/18/2014] [Indexed: 02/06/2023] Open
Abstract
The development of effective nucleos(t)ide analogs (NAs) against hepatitis B virus (HBV) has improved the outcome of patients with chronic hepatitis B (CHB). This review updates issues related to the management of CHB patients included in special populations. Entecavir (ETV) and tenofovir (TDF) represent the currently recommended first-line NAs in patients with HBV decompensated cirrhosis. The combination of HBV immunoglobulin (usually for a finite duration) and NA is considered the standard of care for prophylaxis against HBV recurrence after liver transplantation. TDF is the best choice for hemodialysis patients and in patients with chronic kidney disease with nucleoside resistance. ETV and telbivudine are the preferred options in naïve renal transplant recipients and with low viremia levels, respectively. All hepatitis B surface antigen (HBsAg)-positive candidates should be treated with NAs before renal transplantation to achieve undetectable HBV DNA at the time of transplantation. Conventional interferon or NAs can also be used in children, on the basis of well-established therapeutic indication. Pregnant women at high risk of perinatal transmission could be treated with lamivudine, telbivudine or TDF in the last trimester of pregnancy. HBsAg-positive patients under immunosuppression should receive NA pre-emptively (regardless of HBV DNA levels) up to 12 mo after its cessation. In HBsAg negative, anti-HBc positive patients under immunosuppression, further studies are needed to form a final conclusion; however, it seems that anti-HBV prophylaxis is justified in such patients with hematological diseases and/or for those receiving rituximab-containing regimens, regardless of their anti-HBs or serum HBV DNA status.
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42
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Roche B, Samuel D. Prevention of hepatitis B virus reinfection in liver transplant recipients. Intervirology 2014; 57:196-201. [PMID: 25034488 DOI: 10.1159/000360944] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023] Open
Abstract
Antiviral therapy using newer nucleos(t)ide analogues with lower resistance rates such as entecavir or tenofovir could suppress hepatitis B virus (HBV) replication, improve liver function, delay or obviate the need for liver transplantation in some patients, and reduce the risk of HBV recurrence. The combination of long-term antiviral and low-dose hepatitis B immune globulin (HBIG) can effectively prevent HBV recurrence in more than 90% of transplant recipients. Some form of HBV prophylaxis needs be continued indefinitely after transplantation. However, in patients with a low risk of HBV recurrence (i.e. HBV DNA levels undetectable before transplantation), it is possible to discontinue HBIG and maintain long-term antiviral therapy. A more cautious approach to prophylaxis regimen is necessary for those patients with high pretransplant HBV DNA levels, those with limited antiviral options if HBV recurrence occurs (i.e. HIV or HDV coinfection, preexisting drug resistance), those with a high risk of hepatocellular carcinoma recurrence, and those with a risk of noncompliance to antiviral therapy.
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Affiliation(s)
- Bruno Roche
- Assistance Publique-Hôpitaux de Paris, Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France
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Woo HY, Choi JY, Yoon SK, Suh DJ, Paik SW, Han KH, Um SH, Kim BI, Lee HJ, Cho M, Lee CK, Kim DJ, Hwang JS. Rescue therapy with adefovir in decompensated liver cirrhosis patients with lamivudine-resistant hepatitis B virus. Clin Mol Hepatol 2014; 20:168-76. [PMID: 25032183 PMCID: PMC4099332 DOI: 10.3350/cmh.2014.20.2.168] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2014] [Revised: 05/30/2014] [Accepted: 06/05/2014] [Indexed: 12/14/2022] Open
Abstract
Background/Aims Adefovir dipivoxil (ADV) is a nucleotide analogue that is effective against lamivudine-resistant hepatitis B virus (HBV). The aim of this study was to determine the long-term clinical outcomes after ADV rescue therapy in decompensated patients infected with lamivudine-resistant HBV. Methods In total, 128 patients with a decompensated state and lamivudine-resistant HBV were treated with ADV at a dosage of 10 mg/day for a median of 33 months in this multicenter cohort study. Results Following ADV treatment, 86 (72.3%) of 119 patients experienced a decrease in Child-Pugh score of at least 2 points, and the overall end-stage liver disease score decreased from 16±5 to 14±10 (mean ± SD, P<0.001) during the follow-up period. With ADV treatment, 67 patients (56.3%) had undetectable serum HBV DNA (detection limit, 0.5 pg/mL). Virologic breakthrough occurred in 38 patients (36.1%) and 9 patients had a suboptimal ADV response. The overall survival rate was 89.9% (107/119), and a suboptimal response to ADV treatment was associated with both no improvement in Child-Pugh score (≥2 points; P=0.001) and high mortality following ADV rescue therapy (P=0.012). Conclusions Three years of ADV treatment was effective and safe in decompensated patients with lamivudine-resistant HBV.
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Affiliation(s)
- Hyun Young Woo
- Department of Internal Medicine, Pusan National University College of Medicine, Pusan, Korea
| | - Jong Young Choi
- Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea
| | - Seung Kew Yoon
- Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea
| | - Dong Jin Suh
- Department of Internal Medicine, University of Ulsan College of Medicine, Seoul, Korea
| | - Seung Woon Paik
- Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Kwang Hyub Han
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Soon Ho Um
- Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Byung Ik Kim
- Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Heon Ju Lee
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Korea
| | - Mong Cho
- Department of Internal Medicine, Pusan National University College of Medicine, Pusan, Korea
| | - Chun Kyon Lee
- Department of Internal Medicine, National Health Insurance Corporation Ilsan Hospital, Goyang, Korea
| | - Dong Joon Kim
- Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Korea
| | - Jae Seok Hwang
- Department of Internal Medicine, Keimyung University College of Medicine, Daegu, Korea
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Zeng T, Xu H, Liu JY, Lei Y, Zhong S, Zhou Z. Entecavir plus adefovir combination therapy versus lamivudine add-on adefovir for lamivudine-resistant chronic hepatitis B: A meta-analysis. J Clin Pharmacol 2014; 54:959-67. [PMID: 24964070 DOI: 10.1002/jcph.351] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2014] [Accepted: 06/20/2014] [Indexed: 12/24/2022]
Abstract
To determine whether adefovir (ADV) in combination with entecavir (ETV) is more effective than with lamivudine (LAM) in patients with lamivudine-resistant chronic HBV infection, electronic databases were searched through May 10th, 2013 to obtain relevant trials which met the inclusion criteria. Meta-analysis was performed on randomized controlled trials (RCTs) and non-randomized studies. Four trials containing a total of 323 patients were included. Serum HBV DNA reductions after 3 and 6 months of treatment in the ETV + ADV group were greater than that of LAM + ADV group (mean difference (MD) = 0.90, 95% confidence interval (CI): 0.74-1.07, P < 0.00001; MD = 0.81, 95% CI: 0.57-1.06, P < 0.00001). The rate of 6 months HBV DNA undetectability with ETV and ADV was higher than that of LAM and ADV (relative risk (RR) = 1.63, 95% CI: 1.14-2.34, P < 0.007). There were higher rates of serum ALT normalization than those in LAM + ADV group after 6 months of treatment (RR = 1.40, 95% CI: 1.11-1.77, P < 0.005). The ETV + ADV group had lower viral breakthrough and genotypic mutation rates than LAM + ADV group after 12 months of treatment (RR = 0.24, 95% CI: 0.10-0.58, P = 0.002). The combination of ETV plus ADV is a more effective rescue therapy than LAM add-on ADV in patients with LAM-resistant HBV.
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Affiliation(s)
- Teng Zeng
- Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Chung GE, Lee JH, Kim YJ. Does antiviral therapy reduce complications of cirrhosis? World J Gastroenterol 2014; 20:7306-7311. [PMID: 24966601 PMCID: PMC4064076 DOI: 10.3748/wjg.v20.i23.7306] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Revised: 01/02/2014] [Accepted: 04/03/2014] [Indexed: 02/06/2023] Open
Abstract
Chronic hepatitis B infection is associated with the development of cirrhosis, hepatocellular carcinoma, and finally liver-related mortality. Each year, approximately, 2%-5% of patients with hepatitis B virus (HBV)-related compensated cirrhosis develop decompensation, with additional clinical manifestations, such as ascites, jaundice, hepatic encephalopathy, and gastrointestinal bleeding. The outcome of decompensated HBV-related cirrhosis is poor, with a 5-year survival of 14%-35% compared to 84% in patients with compensated cirrhosis. Because the risk of disease progression is closely linked to a patient’s serum HBV DNA level, antiviral therapy may suppress viral replication, stabilize liver function and improve survival. This article briefly reviews the role that antiviral therapy plays in cirrhosis complications, particularly, in decompensation and acute-on-chronic liver failure.
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Skupsky J, Hu KQ. Current hepatitis B treatment guidelines and future research directions. Front Med 2014; 8:145-157. [PMID: 24871443 DOI: 10.1007/s11684-014-0335-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2014] [Accepted: 03/12/2014] [Indexed: 12/18/2022]
Abstract
Hepatitis B virus (HBV) infection causes a tremendous clinical burden across the world with more than half a million people dying annually from HBV related disease. Significant advances have been made in HBV treatment in the past decade and several guidelines have been published by professional societies and expert panels. Although these recommendations have been valuable to help optimize HBV treatment, there is discordance in treatment criteria and many patients infected with HBV may fall outside of these recommendations. This paper systematically reviews the natural history of the disease and compares and contrasts the recommendations for initiation of treatment from the various societies. There is also discussion of special groups that require particular consideration and some of the open research questions and future research directions within the field.
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Affiliation(s)
- Jonathan Skupsky
- Division of Gastroenterology and Hepatology, University of California, Irvine, School of Medicine, Orange, CA, 92868, USA
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Pipili C, Cholongitas E. Μanagement of patients with hepatitis B and C before and after liver and kidney transplantation. World J Hepatol 2014; 6:315-25. [PMID: 24868325 PMCID: PMC4033289 DOI: 10.4254/wjh.v6.i5.315] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2013] [Revised: 03/10/2014] [Accepted: 04/16/2014] [Indexed: 02/06/2023] Open
Abstract
New nucleos(t)ide analogues (NAs) with high genetic barrier to hepatitis B virus (HBV) resistance (such as entecavir, tenofovir) have improved the prognosis of patients with HBV decompensated cirrhosis and have prevented HBV recurrence after liver transplantation (LT). NAs are considered the most proper approach for HBV infection in patients under renal replacement therapy but their doses should be adjusted according to the patient's creatinine clearance. In addition, physicians should be aware of the potential nephrotoxicity. However, patients with chronic hepatitis C and decompensated cirrhosis can receive only one therapeutic option before LT, as well as for Hepatitis C virus (HCV) recurrence after LT, which is the combination of subcutaneous Peg-IFN and ribavirin. Generally, therapy for HCV after renal transplantation should be avoided. Although the optimal antiviral therapy for HCV infection has not been established, attention has turned to a new, oral direct acting antiviral treatment which marks a promising strategy in prognosis and in amelioration of these diseases.
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Affiliation(s)
- Chrysoula Pipili
- Chrysoula Pipili, Department of Nephrology, Laiki Merimna, 17343 Athens, Greece
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Keskin O, Ormeci AC, Baran B, Kabaçam G, Tüzün A, Karatayli E, Akyüz F, Karatayli S, Bozdayi AM, Onel D, Badur S, Idilman R, Kaymakoglu S, Yurdaydin C. Efficacy of tenofovir in adefovir-experienced patients compared with treatment-naive patients with chronic hepatitis B. Antivir Ther 2014; 19:543-50. [PMID: 24517926 DOI: 10.3851/imp2732] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/19/2013] [Indexed: 10/25/2022]
Abstract
BACKGROUND Tenofovir (TDF) has similar antiviral efficacy in both treatment-naive and lamivudine-resistant chronic hepatitis B (CHB) patients. Data on TDF use in patients with adefovir (ADV) resistance is inconsistent. The aim of our study was to assess antiviral efficacy of TDF against nucleoside analogue-naive (NN) and ADV-resistant (ADV-R) CHB and suboptimal responders to ADV (ADV-S). METHODS A database of 135 CHB patients treated with TDF was analysed. A total of 37 patients with incomplete data were excluded and analysis was performed in 98 (44 NN, 30 ADV-R and 24 ADV-S). Patients with primary ADV-R mutations had either A181T/V or N236T mutations or both. HBV DNA was measured at 3-month intervals until month 24. Primary outcome measures were comparison of the decline of HBV DNA between the three treatment groups. RESULTS NN patients had higher baseline HBV DNA compared with ADV-R and ADV-S patients (6.08 log10 IU/ml versus 5.53 and 4.88, respectively; P=0.002). By exponential regression analysis, HBV DNA decline kinetics differed between the three groups. HBV DNA decline was faster in NN patients compared to ADV-R and ADV-S CHB patients (P=0.002 and P=0.004, respectively). Undetectable HBV DNA was achieved in 77.2%, 60% and 75% of NN, ADV-R and ADV-S CHB patients, respectively, at month 12 (P= not significant). CONCLUSIONS HBV DNA decline is slower in ADV-experienced patients compared with treatment-naive patients. The clinical significance of this slow response may be important in patients with critical liver reserve and high viral load. Optimal combination treatment (TDF+ entecavir) could be considered in these patients.
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Affiliation(s)
- Onur Keskin
- Department of Gastroenterology, University of Ankara Medical School, Ankara, Turkey
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Abaalkhail F, Elsiesy H, AlOmair A, Alghamdi MY, Alalwan A, AlMasri N, Al-Hamoudi W. SASLT practice guidelines for the management of hepatitis B virus. Saudi J Gastroenterol 2014; 20:5-25. [PMID: 24496154 PMCID: PMC3952421 DOI: 10.4103/1319-3767.126311] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Affiliation(s)
- Faisal Abaalkhail
- Department of Liver and Small Bowel Transplantation, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Hussien Elsiesy
- Adult Transplant Hepatology, Organ Transplant Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
| | - Ahmed AlOmair
- Department of Medicine, Gastroenterology Unit, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Mohammed Y. Alghamdi
- Department of Gastroenterology, King Fahad Military Medical Complex, Dharan, Saudi Arabia
| | - Abduljaleel Alalwan
- Hepatobiliary Sciences and Liver Transplantation, King Abdulaziz Medical City, National Guard Health Affairs, Riyadh, Saudi Arabia
| | - Nasser AlMasri
- Department of Gastroenterology, Prince Sultan Medical Military City, Riyadh, Saudi Arabia
| | - Waleed Al-Hamoudi
- Adult Transplant Hepatology, Organ Transplant Center, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
- Gastroenterology Unit, College of Medicine, King Saud University, Riyadh, Saudi Arabia
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Drafting Committee for Hepatitis Management Guidelines and the Japan Society of Hepatology. JSH Guidelines for the Management of Hepatitis B Virus Infection. Hepatol Res 2014; 44 Suppl S1:1-58. [PMID: 24397839 DOI: 10.1111/hepr.12269] [Citation(s) in RCA: 133] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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