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1
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Wei N, Zheng B, Cai H, Li N, Yang J, Liu M. Systematic review and meta-analysis: de novo combination of nucleos(t)ide analogs and pegylated interferon alpha versus pegylated interferon alpha monotherapy for the functional cure of chronic hepatitis B. Front Pharmacol 2024; 15:1403805. [PMID: 39035984 PMCID: PMC11259969 DOI: 10.3389/fphar.2024.1403805] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Accepted: 06/10/2024] [Indexed: 07/23/2024] Open
Abstract
Introduction: Chronic hepatitis B (CHB) is a worldwide infectious disease caused by hepatitis B virus (HBV). Optimizing antiviral treatment strategies could improve the functional cure (FC) rate of patients with CHB. This study aims to systematically review the FC rate of the de novo combination of nucleos(t)ide analogs (NAs) and pegylated interferon α (PEG-IFNα) versus that of PEG-IFNα monotherapy for CHB. Methods: Databases were searched until 31 December 2023. Selected studies included randomized controlled trials on the de novo combination of NAs and PEG-IFNα versus PEG-IFNα monotherapy for 48 weeks in patients with CHB to achieve FC, which was defined as hepatitis B surface antigen (HBsAg) loss and/or HBsAg seroconversion. Meta-analysis was conducted in accordance with the efficacy at the end of treatment and different time points during follow-up. Results: A total of 10 studies, encompassing 2,339 patients in total, were included. Subgroup analysis was conducted in accordance with whether first-line NAs were used. It found no statistically significant difference between HBsAg loss and HBsAg seroconversion at the end of treatment. Serum HBV DNA <500 copies/mL significantly differed between the two groups at the end of treatment and did not significantly differ during follow-up. Meanwhile, HBsAg loss and HBsAg seroconversion showed statistically significant differences at 24 weeks of follow-up. By contrast, no statistically significant difference was found in HBsAg loss at 48 weeks of follow-up. Discussion: Without distinguishing the eligible preponderant population, the efficacy of the de novo combination of NAs and PEG-IFNα in treating patients with CHB was not superior to that of PEG-IFNα monotherapy. Systematic Review Registration: PROSPERO, identifier CRD42022325239.
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Affiliation(s)
| | | | | | | | | | - Maobai Liu
- Department of Pharmacy, Fujian Medical Union Hospital, Fuzhou, China
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Yao Y, Zhang J, Li X, Zao X, Cao X, Chen G, Ye Y. Systematic review: Clinical outcomes of discontinuation of oral antivirals in hepatitis B-related liver cirrhosis. Front Public Health 2022; 10:1037527. [PMID: 36407996 PMCID: PMC9670108 DOI: 10.3389/fpubh.2022.1037527] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Accepted: 10/20/2022] [Indexed: 11/06/2022] Open
Abstract
Background Discontinuation of Nucleos(t)ide analogs (NAs) remains one of the most controversial topics in the management of hepatitis B-related liver cirrhosis. However, clinical outcomes after NAs discontinuation have not been studied. Aim The aim of this systematic review is to evaluate existing data on clinical outcomes of NAs withdrawal in chronic hepatitis B (CHB) patients with cirrhosis. Methods A literature search (until May 2022) was performed in order to identify all published studies including hepatitis B-related cirrhotic patients who discontinued NAs in virological remission with off-therapy follow-up >12 months. Results Nineteen studies with 1,287 hepatitis B-related cirrhotic patients were included. Most cirrhotic patients were compensated and achieved complete virological suppression when they stopped the antiviral therapy. The pooled proportions of virological relapse and clinical relapse after NAs discontinuation in cirrhotic patients were 55.23 (95% CI: 40.33-69.67) and 43.56% (95% CI: 26.13-61.85), respectively. HBsAg loss was observed in 56 of 500 (pooled proportion = 13.68%, 95% CI: 5.82-24.18) cirrhotic patients. And the pooled proportions of HCC development, hepatic decompensation and overall mortality were 8.76 (95% CI: 2.25-18.95), 3.63 (95% CI: 1.31-7.03), and 0.85% (95% CI: 0.35-1.57), respectively, after NAs discontinuation in cirrhotic patients. Conclusion In hepatitis B-related compensated cirrhosis, who have achieved complete virological suppression, discontinuation of oral antivirals still carries a high relapse rate, but the incidence of adverse events is generally low and controlled during follow-up of at least 12 months. Of attention is that discontinuation of NAs can achieve a high rate of HBsAg seroclearance. This study may be helpful in the management of NAs in cirrhotic patients. Systematic review registration http://www.crd.york.ac.uk/PROSPERO, identifier: CRD42020170103.
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Affiliation(s)
- Yuhao Yao
- Department of Gastroenterology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- First School of Clinical Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Jiaxin Zhang
- Department of Gastroenterology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Institute of Liver Diseases, Beijing University of Chinese Medicine, Beijing, China
| | - Xiaoke Li
- Department of Gastroenterology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Institute of Liver Diseases, Beijing University of Chinese Medicine, Beijing, China
| | - Xiaobin Zao
- Department of Gastroenterology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Institute of Liver Diseases, Beijing University of Chinese Medicine, Beijing, China
- Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Xu Cao
- Department of Gastroenterology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Guang Chen
- Department of Gastroenterology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Institute of Liver Diseases, Beijing University of Chinese Medicine, Beijing, China
| | - Yong'an Ye
- Department of Gastroenterology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Institute of Liver Diseases, Beijing University of Chinese Medicine, Beijing, China
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Tony SM, Shaaban MEA, Mohamed AIM, Abdelrahim MEA. Effect of entecavir and tenofovir disoproxil fumarate on hepatocellular carcinoma in subjects with chronic hepatitis B: a meta-analysis. BENI-SUEF UNIVERSITY JOURNAL OF BASIC AND APPLIED SCIENCES 2022. [DOI: 10.1186/s43088-022-00294-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Abstract
Background
A meta-analysis was made to assess the impact of entecavir comparison with tenofovir disoproxil fumarate as nucleos(t)ide analogue on hepatic cellular carcinoma (HCC). The study had subjects with chronic hepatitis B virus (HBV). Systemic research was done for all studies concerned with our topic till the date (March 2022). We included 19 studies in which 27,618 subjects participated. All subjects included were diagnosed with chronic HBV at the beginning of the study. A total of 15,734 subjects from the overall 27,618 were medicated with entecavir; however, 11,884 subjects were on tenofovir disoproxil fumarate. We calculated the odds ratio (OR) with confidence intervals (CIs) of 95% to evaluate the impact of entecavir and tenofovir disoproxil fumarate on HCC in subjects with chronic HBV by applying a dichotomous approach with a random or fixed-effect model.
Results
Chronic HBV subjects treated with entecavir showed a higher significant biochemical response than those treated with tenofovir disoproxil fumarate (OR 1.39; 95% CI 1.21–1.60, at p < 0.001). Also, no significant difference was detected with entecavir compared to tenofovir disoproxil fumarate concerning the occurrence of hepatic cells cancer (OR 1.26; 95% CI 0.96–1.67, p = 0.10), virological response (OR 0.89; 95% CI 0.63–1.25, p = 0.49), and seroconversion (OR 1.27; 95% CI 0.76–2.14, p = 0.37).
Conclusions
The use of entecavir resulted in a significantly higher biochemical response; nevertheless, it did not show any significant variation concerning the occurrence of hepatic cancer, virological response, or serological conversion compared to tenofovir disoproxil fumarate in chronic HBV subjects. So, results interpretation needs to be carried out carefully owing to the limited number of studies included in specific comparisons, e.g., serological conversion.
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Wang X, Liu X, Dang Z, Yu L, Jiang Y, Wang X, Yan Z. Nucleos(t)ide Analogues for Reducing Hepatocellular Carcinoma in Chronic Hepatitis B Patients: A Systematic Review and Meta-Analysis. Gut Liver 2021. [PMID: 31158948 DOI: 10.5009/gnl18546.] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Background/Aims Studies have shown that nucleos(t)ide analogue (NA) treatment can reduce the risk of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients, but it is unclear which NA is most effective. We performed a meta-analysis and systematic review comparing the efficacies of NAs in CHB patients. Methods We searched literature databases for randomized controlled trials (RCTs) and observational studies that analyzed the hepatic biochemical response, virological response, seroconversion rate, drug resistance rate, and HCC incidence rate in CHB patients treated with NAs. Meta-analyses were performed with RevMan and Stata/SE software. Results Twelve cohort studies and one RCT were selected, in which entecavir (ETV), lamivudine (LAM), telbivudine (LdT), and/or tenofovir disoproxil fumarate (TDF) were evaluated in CHB patients. The meta-analysis showed that ETV was superior to LAM with regard to the HCC incidence (p<0.001), biochemical response (p=0.001), virological response (p=0.02), and drug resistance (p<0.001), and ETV was superior to LdT with regard to the virological response (p<0.001) and drug resistance (p<0.001). We found no significant difference between ETV and TDF with regard to the HCC incidence (p=0.08), biochemical response (p=0.39), virological response (p=0.31), serological conversion (p=0.38), or drug resistance (p=0.95). NA-treated patients with pre-existing cirrhosis had a 5.49 times greater incidence of HCC than those without cirrhosis (p<0.001). Conclusions ETV or TDF should be used for long-term first-line monotherapy in CHB patients according to the current guidelines. Standardized protocols are needed for future studies of ETV and TDF to facilitate conclusive comparisons. Patients with cirrhosis are at significantly elevated risk for HCC, despite the benefits of NA treatment.
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Affiliation(s)
- Xinhui Wang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xiaoli Liu
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Zhibo Dang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Lihua Yu
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yuyong Jiang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xianbo Wang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Zhiyun Yan
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
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Wang X, Liu X, Dang Z, Yu L, Jiang Y, Wang X, Yan Z. Nucleos(t)ide Analogues for Reducing Hepatocellular Carcinoma in Chronic Hepatitis B Patients: A Systematic Review and Meta-Analysis. Gut Liver 2021; 14:232-247. [PMID: 31158948 PMCID: PMC7096226 DOI: 10.5009/gnl18546] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2018] [Revised: 03/12/2019] [Accepted: 04/05/2019] [Indexed: 01/10/2023] Open
Abstract
Background/Aims Studies have shown that nucleos(t)ide analogue (NA) treatment can reduce the risk of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients, but it is unclear which NA is most effective. We performed a meta-analysis and systematic review comparing the efficacies of NAs in CHB patients. Methods We searched literature databases for randomized controlled trials (RCTs) and observational studies that analyzed the hepatic biochemical response, virological response, seroconversion rate, drug resistance rate, and HCC incidence rate in CHB patients treated with NAs. Meta-analyses were performed with RevMan and Stata/SE software. Results Twelve cohort studies and one RCT were selected, in which entecavir (ETV), lamivudine (LAM), telbivudine (LdT), and/or tenofovir disoproxil fumarate (TDF) were evaluated in CHB patients. The meta-analysis showed that ETV was superior to LAM with regard to the HCC incidence (p<0.001), biochemical response (p=0.001), virological response (p=0.02), and drug resistance (p<0.001), and ETV was superior to LdT with regard to the virological response (p<0.001) and drug resistance (p<0.001). We found no significant difference between ETV and TDF with regard to the HCC incidence (p=0.08), biochemical response (p=0.39), virological response (p=0.31), serological conversion (p=0.38), or drug resistance (p=0.95). NA-treated patients with pre-existing cirrhosis had a 5.49 times greater incidence of HCC than those without cirrhosis (p<0.001). Conclusions ETV or TDF should be used for long-term first-line monotherapy in CHB patients according to the current guidelines. Standardized protocols are needed for future studies of ETV and TDF to facilitate conclusive comparisons. Patients with cirrhosis are at significantly elevated risk for HCC, despite the benefits of NA treatment.
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Affiliation(s)
- Xinhui Wang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xiaoli Liu
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Zhibo Dang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Lihua Yu
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Yuyong Jiang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Xianbo Wang
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Zhiyun Yan
- Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, China
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Su CW, Wu CY, Lin JT, Ho HJ, Wu JC. Nucleos(t)ide analogue continuous therapy associated with reduced adverse outcomes of chronic hepatitis B. J Chin Med Assoc 2020; 83:125-133. [PMID: 32015266 DOI: 10.1097/jcma.0000000000000247] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
BACKGROUND Nucleos(t)ide analogue (NA) therapy reduces the risk of disease progression in chronic hepatitis B virus-infected patients. However, the risk of liver decompensation, hepatic failure, and mortality after discontinuation of NA therapy remains unknown. METHODS Among 51,574 chronic hepatitis B patients who received NAs in the Taiwan National Health Insurance Research Database, we identified 8,631 patients who continued NA therapy (treatment cohort) and 8,631 propensity-score matched patients who stopped NA therapy after their initial 1.5 years treatment (off-therapy cohort) between October 1, 2003 and December 31, 2011. All study subjects were followed up from the index date, that is, the date 1.5 years after the first prescription of NA, until development of liver decompensation and hepatic failure, death or end of 18-month follow-up period. RESULTS Treatment cohort had significantly lower risks of liver decompensation (1.05%; 95% confidence interval [CI], 0.81%-1.30% vs 2.13%; 95% CI, 1.82%-2.45%; p < 0.001), hepatic failure (0.35%; 95% CI, 0.21%-0.49% vs 0.63%; 95% CI, 0.46%-0.80%; p = 0.008) and overall mortality (1.67%; 1.37%-1.98% vs 2.44%; 95% CI, 2.10%-2.77%; p < 0.001) during the 18-month follow-up period. After adjusting for potential confounders, NA continuous therapy was associated with reduced risks of liver decompensation (hazard ratio [HR]: 0.47; 95% CI, 0.36-0.62, p < 0.001), hepatic failure (HR: 0.53; 95% CI, 0.33-0.86, p = 0.01) and overall mortality (HR: 0.67; 95% CI, 0.53-0.84, p = 0.001). The number needed to reduce one less disease progression and mortality was 47. The protective effect of NA continuous therapy was found in nearly all subgroups. CONCLUSION NA continuous therapy is associated with reduced risks of liver decompensation, hepatic failure, and overall mortality.
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Affiliation(s)
- Chien-Wei Su
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
| | - Chun-Ying Wu
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
- Division of Translational Research, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Department of Public Health and Graduate Institute of Clinical Medical Sciences, China Medical University, Taichung, Taiwan, ROC
- National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan, ROC
- Department of Life Sciences and RongHsing Research Center for Translational Medicine, National Chung-Hsing University, Taichung, Taiwan, ROC
| | - Jaw-Town Lin
- School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan, ROC
- Division of Gastroenterology and Hepatology, Fu-Jen Catholic University Hospital, New Taipei City, Taiwan, ROC
- Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan, ROC
| | - Hsiu J Ho
- Division of Translational Research, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
| | - Jaw-Ching Wu
- Division of Translational Research, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan, ROC
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7
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Zhang J, Ma J, Wang H, Li J. Correlation between cortisol levels and concurrent infection for hepatitis B cirrhosis patients and countermeasure analysis. Exp Ther Med 2018; 15:2951-2955. [PMID: 29456701 PMCID: PMC5795706 DOI: 10.3892/etm.2018.5738] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2017] [Accepted: 12/13/2017] [Indexed: 11/29/2022] Open
Abstract
The study assessed the correlation between cortisol (COR) levels and concurrent infection for the patients with hepatitis B cirrhosis for corresponding countermeasure analysis. In total, 86 patients with hepatitis B cirrhosis (non-infection group) and 32 patients with hepatitis B cirrhosis complicated with infection (infection group) who were diagnosed and treated in the Beijing YouAn Hospital from March 2014 to March 2017 were selected. The fasting venous blood of all the patients was drawn to detect COR, cortisol binding globulin (CBG), blood routine indexes, C-reactive protein (CRP), procalcitonin (PCT), endotoxin and other indicators. The relative expression of CBG mRNA was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR). The differences and correlation of COR levels between the infection and non-infection groups were compared and analyzed. The concentrations of COR and CBG were decreased with the increase of Child-Pugh grade, and the difference was statistically significant (P<0.05). COR, CBG and free cortisol (FC) concentrations with the same Child-Pugh grade in the non-infection group were higher than those in the infection group (P<0.05). COR, CBG and FC concentrations of abdominal infection complicated with sepsis or abdominal infection complicated with pulmonary infection were lower than those of simple abdominal infection (P<0.05). The relative expression of CBG mRNA was detected by RT-qPCR, which also showed that: for Child-Pugh grade, grade A > grade B > grade C (P<0.05), non-infection group > infection group (P<0.05), abdominal infection + sepsis group and abdominal infection + pulmonary infection group were lower than the simple abdominal infection group (P<0.05). The values of white blood cells (WBC), neutrophils, CRP, PCT and endotoxin in the infection group were higher than those in the non-infection group, and the differences were statistically significant (P<0.05). COR, CGB and FC were negatively correlated with inflammatory indexes such as WBC, neutrophils, CRP, PCT and endotoxin. The r value of COR and FC in the non-infection group was 0.678, while that of OR and FC in the infection group was 0.787. COR was positively correlated with FC before and after infection. The results of the study show that the cortisol levels of patients with hepatitis B cirrhosis are significantly correlated with whether infected or not, levels of disease condition and infection types, and can be used as sensitive indicators of hepatitis B cirrhosis infection.
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Affiliation(s)
- Jian Zhang
- Department of Emergency, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, P.R. China
| | - Junwei Ma
- Department of Emergency, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, P.R. China
| | - Hongxin Wang
- Department of Emergency, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, P.R. China
| | - Junhong Li
- Department of Emergency, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, P.R. China
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Long-term outcomes of hepatitis B virus-related cirrhosis treated with nucleos(t)ide analogs. J Formos Med Assoc 2017; 116:512-521. [DOI: 10.1016/j.jfma.2016.08.006] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2016] [Revised: 08/19/2016] [Accepted: 08/22/2016] [Indexed: 02/07/2023] Open
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Wei L, Kao JH. Benefits of long-term therapy with nucleos(t)ide analogues in treatment-naïve patients with chronic hepatitis B. Curr Med Res Opin 2017; 33:495-504. [PMID: 27882776 DOI: 10.1080/03007995.2016.1264932] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
OBJECTIVE To assess the benefits of long-term nucleos(t)ide analogue (NA) therapy in reducing the severity and progression of liver disease in treatment-naïve patients with chronic hepatitis B (CHB). SCOPE As complications of CHB, such as hepatic decompensation and hepatocellular carcinoma (HCC), take a long time to develop in patients with less advanced disease, the long-term benefits of NA therapy in such patients are more difficult to prove than short- or medium-term benefits. Thus, the recent literature was reviewed to evaluate the impact of NA therapy on the long-term outcomes of treatment-naïve CHB patients. METHODS A literature search of the MEDLINE/PubMed database was undertaken to identify studies published since 2010 of the long-term use of NAs with high potency and low drug resistance profiles in treatment-naïve CHB patients. A total of 22 studies were identified, many of which were retrospective analyses or case-control studies, as well as three meta-analyses and one systematic review. RESULTS Analysis of the retrieved studies showed that long-term NA therapy in treatment-naïve CHB patients did prevent or delay the occurrence of complications, including hepatic decompensation, HCC, and liver-related death, in comparison with no treatment. However, it did not completely eliminate the risk of these complications, particularly in those with cirrhosis. Although long-term NA therapy improved the clinical status of patients with decompensated cirrhosis, the risk of cirrhotic complications including HCC, liver transplantation, and liver-related mortality remained significant in comparison with those with compensated cirrhosis. CONCLUSIONS Long-term administration is generally advised in all CHB patients treated with NAs because of the high rates of virological and clinical relapse after stopping therapy. The findings of this analysis lend support to the choice of highly potent agents with a low drug resistance profile to maximize viral suppression in CHB patients and halt or delay progression to end-stage liver disease.
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Affiliation(s)
- Lai Wei
- a Peking University People's Hospital, Peking Hepatology Institute , Beijing
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Tawada A, Kanda T, Imazeki F, Yokosuka O. Prevention of hepatitis B virus-associated liver diseases by antiviral therapy. Hepatol Int 2016; 10:574-593. [PMID: 27026375 DOI: 10.1007/s12072-016-9720-y] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2015] [Accepted: 02/28/2016] [Indexed: 02/06/2023]
Abstract
Hepatitis B virus (HBV) is a major cause of acute and chronic hepatitis, cirrhosis and hepatocellular carcinoma, particularly in Asia-Pacific countries. The major complications in HBV carriers are hepatocellular carcinoma (HCC), liver failure and esophageal varices following the progression to cirrhosis, while some develop HCC without cirrhosis. The progression to liver fibrosis and these other complications could be prevented by treatment with nucleos(t)ide analogues (NUCs); however, NUCs must be continuously administered for a long time. Peginterferon could lead to HBV surface antigen loss. It is difficult to use peginterferon in HBV-infected patients with decompensated cirrhosis. Acute liver failure due to HBV infection and acute exacerbation of chronic hepatitis B could be treated by NUCs. Universal vaccination programs against HBV could prevent new HBV infections globally. Here, we review the currently available treatments for HBV infection.
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Affiliation(s)
- Akinobu Tawada
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan
- Safety and Health Organization, Chiba University, Chiba, 263-8522, Japan
| | - Tatsuo Kanda
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan.
| | - Fumio Imazeki
- Safety and Health Organization, Chiba University, Chiba, 263-8522, Japan
| | - Osamu Yokosuka
- Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan
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Shim JJ. Long-term suppression of viral replication in chronic hepatitis B: outcomes and future directions. Gut Liver 2016; 9:265-6. [PMID: 25918259 PMCID: PMC4413963 DOI: 10.5009/gnl15105] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022] Open
Affiliation(s)
- Jae-Jun Shim
- Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Korea
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12
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Russo FP, Rodríguez-Castro K, Scribano L, Gottardo G, Vanin V, Farinati F. Role of antiviral therapy in the natural history of hepatitis B virus-related chronic liver disease. World J Hepatol 2015; 7:1097-1104. [PMID: 26052398 PMCID: PMC4450186 DOI: 10.4254/wjh.v7.i8.1097] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2014] [Revised: 01/22/2015] [Accepted: 02/09/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatitis B virus (HBV) infection is a dynamic state of interactions among HBV, hepatocytes, and the host immune system. Natural history studies of chronic hepatitis B (CHB) infection have shown an association between active viral replication and adverse clinical outcomes such as cirrhosis and hepatocellular carcinoma. The goal of therapy for CHB is to improve quality of life and survival by preventing progression of the disease to cirrhosis, decompensation, end-stage liver disease, hepatocellular carcinoma (HCC) and death. This goal can be achieved if HBV replication is suppressed in a sustained manner. The accompanying reduction in histological activity of CHB lessens the risk of cirrhosis and of HCC, particularly in non-cirrhotic patients. However, CHB infection cannot be completely eradicated, due to the persistence of covalently closed circular DNA in the nucleus of infected hepatocytes, which may explain HBV reactivation. Moreover, the integration of the HBV genome into the host genome may favour oncogenesis, development of HCC and may also contribute to HBV reactivation.
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Affiliation(s)
- Francesco Paolo Russo
- Francesco Paolo Russo, Kryssia Rodríguez-Castro, Gastroenterology/Multiviseral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, 35128 PD Padua, Italy
| | - Kryssia Rodríguez-Castro
- Francesco Paolo Russo, Kryssia Rodríguez-Castro, Gastroenterology/Multiviseral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, 35128 PD Padua, Italy
| | - Laura Scribano
- Francesco Paolo Russo, Kryssia Rodríguez-Castro, Gastroenterology/Multiviseral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, 35128 PD Padua, Italy
| | - Giorgia Gottardo
- Francesco Paolo Russo, Kryssia Rodríguez-Castro, Gastroenterology/Multiviseral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, 35128 PD Padua, Italy
| | - Veronica Vanin
- Francesco Paolo Russo, Kryssia Rodríguez-Castro, Gastroenterology/Multiviseral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, 35128 PD Padua, Italy
| | - Fabio Farinati
- Francesco Paolo Russo, Kryssia Rodríguez-Castro, Gastroenterology/Multiviseral Transplant Unit, Department of Surgery, Oncology and Gastroenterology, Padua University Hospital, 35128 PD Padua, Italy
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Chang ML, Jeng WJ, Liaw YF. Clinical events after cessation of lamivudine therapy in patients recovered from hepatitis B flare with hepatic decompensation. Clin Gastroenterol Hepatol 2015; 13:979-86. [PMID: 25445774 DOI: 10.1016/j.cgh.2014.10.023] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2014] [Revised: 10/14/2014] [Accepted: 10/15/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Before guidelines were issued, many patients with hepatitis B flare and hepatic decompensation had discontinued lamivudine therapy instead of indefinite therapy. We investigated their outcomes. METHODS We performed a retrospective cohort study of 263 consecutive patients with chronic hepatitis B (94 with cirrhosis) who recovered from a flare of hepatitis with hepatic decompensation and were followed after cessation of lamivudine therapy. Clinical events that occurred during the follow-up period were assessed by chart review and analysis of results from retrospective assays. RESULTS The mean duration of lamivudine therapy was 12.1 ± 8.6 months; data were collected from patients for 89.1 ± 38.7 months after therapy ended. In the first year off therapy, 29.9% of patients had clinical relapse, 16.2% had hepatitis flares, and 8.2% had hepatic decompensation. There was no significant difference in the incidence of hepatic decompensation between patients with and without cirrhosis. Hepatocellular carcinoma developed in 14 patients 20-109 months after cessation of therapy, with 5-year cumulative incidence of 5.2% in patients with cirrhosis. Three patients with cirrhosis died of hepatic decompensation 38-76 months after cessation of therapy (5-year cumulative mortality, 2.9%). Multivariate analyses showed that men were more likely than women to have recurrence of hepatic decompensation (hazard ratio [HR], 4.339; P = .014). Liver cirrhosis (HR, 2.766; P = .041) and age (HR, 1.054; P = .023) increased risk for hepatocellular carcinoma. CONCLUSIONS Cessation of lamivudine therapy after recovery from hepatitis B flare with decompensation was safe for most patients. However, 8.2% develop decompensation within 1 year and can be rescued by timely retreatment. With close monitoring, the stopping strategy could be a feasible alternative to indefinite therapy, especially in low resource settings.
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Affiliation(s)
- Ming-Ling Chang
- Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan
| | - Wen-Juei Jeng
- Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan
| | - Yun-Fan Liaw
- Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan.
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Abstract
INTRODUCTION Liver cancer is one of the most common cancers. Hepatocellular carcinoma (HCC) represents > 90% of primary liver cancers and is a major global health problem today. Chronic hepatitis B virus (HBV) infection is associated with more than half of HCCs. AREAS COVERED Long-term therapy with nucleos(t)ide analogues (NUCs) improves outcomes in HBV-infected patients by slowing the progression of liver disease. It is associated with improvements in histological and clinical outcomes, improved patient survival, reduced need for liver transplantation and improved liver function in patients with decompensated liver disease. This review highlights the results of previous studies conducted on HCC prevention with long-term NUC therapy. Studies include the use of all available drugs in different clinical scenarios, and the comparison between treated and untreated patients. EXPERT OPINION NUCs have been studied extensively in HCC prevention. A comprehensive review of the literature has shown that they can be safely and effectively used for this purpose. Despite some discrepancies between studies, most of the evidence favors using NUC therapy for HCC prevention.
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Affiliation(s)
- Ezequiel Ridruejo
- Centro de Educación Médica e Investigaciones Clínicas Norberto Quirno "CEMIC", Hepatology Section, Department of Medicine , Ciudad Autónoma de Buenos Aires , Argentina +54 11 4809 1980 ; +54 11 4809 1992 ;
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15
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Niederau C. Chronic hepatitis B in 2014: great therapeutic progress, large diagnostic deficit. World J Gastroenterol 2014; 20:11595-617. [PMID: 25206267 PMCID: PMC4155353 DOI: 10.3748/wjg.v20.i33.11595] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2013] [Revised: 01/03/2014] [Accepted: 04/27/2014] [Indexed: 02/06/2023] Open
Abstract
This review analyzes progress and limitations of diagnosis, screening, and therapy of patients with chronic hepatitis B infection. A literature review was carried out by framing the study questions. Vaccination in early childhood has been introduced in most countries and reduces the infection rate. Treatment of chronic hepatitis B can control viral replication in most patients today. It reduces risks for progression and may reverse liver fibrosis. The treatment effect on development of hepatocellular carcinoma is less pronounced when cirrhosis is already present. Despite the success of vaccination and therapy chronic hepatitis B remains a problem since many infected patients do not know of their disease. Although all guidelines recommend screening in high risk groups such as migrants, these suggestions have not been implemented. In addition, the performance of hepatocellular cancer surveillance under real-life conditions is poor. The majority of people with chronic hepatitis B live in resource-constrained settings where effective drugs are not available. Despite the success of vaccination and therapy chronic hepatitis B infection remains a major problem since many patients do not know of their disease. The problems in diagnosis and screening may be overcome by raising awareness, promoting partnerships, and mobilizing resources.
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16
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Wu CY, Lin JT, Ho HJ, Su CW, Lee TY, Wang SY, Wu C, Wu JC. Association of nucleos(t)ide analogue therapy with reduced risk of hepatocellular carcinoma in patients with chronic hepatitis B: a nationwide cohort study. Gastroenterology 2014; 147:143-151.e5. [PMID: 24704525 DOI: 10.1053/j.gastro.2014.03.048] [Citation(s) in RCA: 246] [Impact Index Per Article: 22.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2013] [Revised: 03/20/2014] [Accepted: 03/26/2014] [Indexed: 12/17/2022]
Abstract
BACKGROUND & AIMS Treatment for hepatitis B virus infection reduces the risk of hepatocellular carcinoma (HCC). However, the long-term protective effects for subgroups of patients with chronic hepatitis B are unclear. METHODS We conducted a retrospective nationwide cohort study using data from Taiwan's National Health Insurance Research Database (from January 1, 1997, through December 31, 2010). Cumulative incidences were calculated and multivariable analyses were carried out after adjusting for competing mortality. Propensity scores were used to match 21,595 patients with chronic hepatitis B who received nucleoside analogue therapy for at least 90 days (treated cohort) with 21,595 untreated patients with chronic hepatitis B (controls), who received hepatoprotectants for at least 90 days. Data were collected from the treated cohort for a mean period of 3.46 years and from controls for 5.24 years. RESULTS The treated cohort had a significantly lower 7-year incidence of HCC (7.32%; 95% confidence interval [CI], 6.77%-7.87%) than controls (22.7%; 95% CI, 22.1%-23.3%; P < .001). After adjusting for competing mortality and other confounders, nucleos(t)ide analogue treatment was associated with a reduced risk of HCC, with an adjusted hazard ratio of 0.37 (95% CI, 0.34-0.39; P < .001). Sensitivity analyses confirmed the association between nucleos(t)ide analogue treatment and reduced risk of HCC. Age, sex, cirrhosis, and diabetes mellitus modified this association. CONCLUSIONS Based on a retrospective, nationwide study in Taiwan, nucleoside analogue therapy use is associated with reduced risk of HCC in patients with chronic hepatitis B virus infection.
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Affiliation(s)
- Chun-Ying Wu
- Division of Gastroenterology, Taichung Veterans General Hospital, Taichung, Taiwan; Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Public Health and Graduate Institute of Clinical Medicine, China Medical University, Taichung, Taiwan; Department of Life Sciences, National Chung-Hsing University, Taichung, Taiwan
| | - Jaw-Town Lin
- School of Medicine, Fu Jen Catholic University, Taipei, Taiwan; Department of Internal Medicine, E-Da Hospital/I-Shou University, Kaohsiung, Taiwan; Institute of Population Health Sciences, National Health Research Institutes, Miaoli, Taiwan.
| | - Hsiu J Ho
- School of Medicine, Fu Jen Catholic University, Taipei, Taiwan
| | - Chien-Wei Su
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Institute of Clinical Medicine and Genomic Research Center, National Yang-Ming University, Taipei, Taiwan; Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Teng-Yu Lee
- Division of Gastroenterology, Taichung Veterans General Hospital, Taichung, Taiwan; Department of Public Health and Graduate Institute of Clinical Medicine, China Medical University, Taichung, Taiwan
| | - Shen-Yung Wang
- Institute of Clinical Medicine and Genomic Research Center, National Yang-Ming University, Taipei, Taiwan
| | - Chuhui Wu
- Institute of Clinical Medicine and Genomic Research Center, National Yang-Ming University, Taipei, Taiwan
| | - Jaw-Ching Wu
- Institute of Clinical Medicine and Genomic Research Center, National Yang-Ming University, Taipei, Taiwan; Translational Research Division, Medical Research Department, Taipei Veterans General Hospital, Taipei, Taiwan.
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17
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Durazzo M, Belci P, Collo A, Prandi V, Pistone E, Martorana M, Gambino R, Bo S. Gender specific medicine in liver diseases: A point of view. World J Gastroenterol 2014; 20:2127-2135. [PMID: 24605011 PMCID: PMC3942817 DOI: 10.3748/wjg.v20.i9.2127] [Citation(s) in RCA: 33] [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: 09/02/2013] [Revised: 11/01/2013] [Accepted: 12/06/2013] [Indexed: 02/06/2023] Open
Abstract
Gender medicine focuses on the patho-physiological, clinical, prevention and treatment differences in diseases that are equally represented in men and women. The purpose of gender medicine is to ensure that each individual man and woman receives the best treatment possible based on scientific evidence. The concept of “gender” includes not only the sexual characteristics of individuals but also physiological and psychological attributes of men and women, including risk factors, protective/aggravating effects of sexual hormones and variances linked to genetics and corporal structures that explain biological and physiological differences between men and women. It is very important to consider all the biological, physiological, functional, psychological, social and cultural characteristics to provide patients with individualized disease management. Herein, we critically analyze the literature regarding gender differences for diseases and acquired conditions of the most representative hepatic pathologies: primary biliary cirrhosis, autoimmune hepatitis, primary sclerosing cholangitis, non alcoholic fatty liver disease and alcoholic liver disease, and viral chronic hepatitis B and C. The last section addresses hemochromatosis, which is a prevalent iron overload disorder in the Caucasian population. This review aims to describe data from the literature concerning viral chronic hepatitis during pregnancy, management during pregnancy and delivery, and new effective drugs for the prevention of maternal infection transmission without significant adverse effects or complications.
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