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Cornberg M, Sandmann L, Jaroszewicz J, Kennedy P, Lampertico P, Lemoine M, Lens S, Testoni B, Lai-Hung Wong G, Russo FP. EASL Clinical Practice Guidelines on the management of hepatitis B virus infection. J Hepatol 2025:S0168-8278(25)00174-6. [PMID: 40348683 DOI: 10.1016/j.jhep.2025.03.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2025] [Accepted: 03/20/2025] [Indexed: 05/14/2025]
Abstract
The updated EASL Clinical Practice Guidelines on the management of hepatitis B virus (HBV) infection provide comprehensive, evidence-based recommendations for its management. Spanning ten thematic sections, the guidelines address diagnostics, treatment goals, treatment indications, therapeutic options, hepatocellular carcinoma surveillance, management of special populations, HBV reactivation prophylaxis, post-transplant care, HBV prevention strategies, and finally address open questions and future research directions. Chronic HBV remains a global health challenge, with over 250 million individuals affected and significant mortality due to cirrhosis and hepatocellular carcinoma. These guidelines emphasise the importance of early diagnosis, risk stratification based on viral and host factors, and tailored antiviral therapy. Attention is given to simplified algorithms, vaccination, and screening to support global HBV elimination targets. The guidelines also discuss emerging biomarkers and evolving definitions of functional and partial cure. Developed through literature review, expert consensus, and a Delphi process, the guidelines aim to equip healthcare providers across disciplines with practical tools to optimise HBV care and outcomes worldwide.
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Pak K, Sachar R, Saab S. Projected Mitigation of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B in the Gray Zone and the Immune-Tolerant Phase in the United States. Dig Dis Sci 2025; 70:1547-1554. [PMID: 39979574 DOI: 10.1007/s10620-025-08909-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2024] [Accepted: 02/02/2025] [Indexed: 02/22/2025]
Abstract
PURPOSE Based on current practice guidelines, there are a substantial number of individuals who do not meet criteria for chronic hepatitis B (CHB) treatment eligibility but may be at risk of developing HCC. We sought to determine the estimated number of untreated patients with CHB in the Gray Zone or immune-tolerant phase who would develop HCC. METHODS US epidemiologic data were obtained from the US Department of HHS. The literature was reviewed for studies that analyzed the distribution of phases of CHB patients including the Gray Zone and studies that determined the cumulative incidence of HCC over a set period unique to both the Gray Zone and the immune-tolerant phase populations. We modeled the projected number of patients in each group who would develop HCC in a period of 5 and 10 years. RESULTS There are about 880,000 to 1.89 million people living with CHB in the US. Based on our model, we estimated 1224-4146 patients and 6662-22,574 patients will likely develop HCC in 5 years and 10 years, respectively, if left untreated in the high viral load and normal liver enzyme Gray Zone. An estimated 356-1537 patients and 873-3774 patients will develop HCC in 5 years and 10 years, respectively, if left untreated in the immune-tolerant phase of CHB. Among patients who develop cirrhosis in the Gray Zone, approximately, 1615-5471 patients will develop HCC. CONCLUSION Current guidelines do not recommend hepatitis B antiviral therapy in patients in the Gray Zone and the immune-tolerant phase. Patients who fall into these categories are still at risk for HCC. By the numbers, the projected number of patients to develop HCC among these populations is in the order of thousands. Future guidelines should explore increasing treatment eligibility for potential mitigation of HCC burden in the US.
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Affiliation(s)
- Kevin Pak
- Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Ryan Sachar
- Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Sammy Saab
- Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
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Chen CH, Tai WC, Hu TH, Wang JH, Hung CH, Lu SN. Patterns of Hepatitis B Virus Viremia Change and Hepatitis B Surface Antigen Loss Rate in Patients Without Retreatment Within 2 Years After Entecavir or Tenofovir Cessation. Am J Gastroenterol 2025:00000434-990000000-01596. [PMID: 39996613 DOI: 10.14309/ajg.0000000000003372] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Accepted: 01/13/2025] [Indexed: 02/26/2025]
Abstract
INTRODUCTION This study investigated the patterns of hepatitis B virus (HBV) viremia change and hepatitis B surface antigen (HBsAg) loss rate without retreatment within 2 years after nucleos(t)ide analog (NA) cessation. METHODS We enrolled 481 patients who did not receive retreatment in the first 2 years after entecavir or tenofovir disoproxil fumarate cessation. RESULTS Group I was defined as persistent HBV DNA <2,000 IU/mL and normal alanine transaminase < 40 U/mL (inactive phase); Group II and Group III, as HBV DNA >2,000 IU/mL and ALT <40 U/L (Group II) or alanine transaminase 40-80 IU/mL (Group III); and Group IV, as HBV DNA >2,000 IU/mL and ALT>80 U/mL (active phase). Of the 242 Group I patients, 205 (84.7%) remained in the same group and 22 (9.1%) transitioned to active phase beyond the first 2 years. Of the 239 Group II, III, and IV patients, 33%, 28.8%, and 31.1% patients transitioned to inactive phase beyond the first 2 years, respectively. Of the 239 patients who achieved HBsAg <150 vs ≧150 IU/mL at the end of treatment, the transition to inactive phase and HBsAg loss rates at year 5 after NA cessation were 57.2% vs 16.1% ( P < 0.001) and 25.4% vs 4.7%, respectively ( P = 0.001). The 10-year HBsAg loss rate after NA cessation for patients in Group I who remained in inactive phase, and Groups II + III and Group IV patients who transitioned to inactive phase were 57.7%, 45.4%, and 55.1% ( P = 0.404), respectively. DISCUSSION Patients who remained or transitioned to the inactive phase had a high HBsAg loss rate without retreatment within 2 years after NA cessation.
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Affiliation(s)
- Chien-Hung Chen
- Department of Internal Medicine, Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
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Liu M, Zhao T, Zhang J, Bu B, Zhang R, Xia X, Geng J. Estimating the key outcomes and hepatocellular carcinoma risk in patients in immune-tolerant phase of chronic hepatitis B virus infection: A systematic review and meta-analysis. Rev Med Virol 2024; 34:e2570. [PMID: 38964866 DOI: 10.1002/rmv.2570] [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: 03/02/2024] [Revised: 06/10/2024] [Accepted: 06/26/2024] [Indexed: 07/06/2024]
Abstract
The question of whether patients in the immune-tolerant (IT) phase of chronic hepatitis B virus (HBV) infection should undergo antiviral therapy and determine the optimal regimen remains unclear. A comprehensive search of PubMed, Embase, MEDLINE, Cochrane Library, and Wanfang Data from inception to 5 December 2023, was conducted. Studies reporting on key outcomes such as HBV DNA undetectability, HBeAg loss or seroconversion, HBsAg loss or seroconversion, and hepatocellular carcinoma (HCC) incidence in patients in the IT phase of chronic HBV infection were included. In total, 23 studies were incorporated. Approximately 4% of patients in the IT phase achieved spontaneous HBeAg loss over 48 weeks of follow-up. Antiviral therapy demonstrated a favourable impact on HBV DNA negative conversion (Children: risk ratios [RR] = 6.83, 95% CI: 2.90-16.05; Adults: RR = 25.84, 95% CI: 6.47-103.31) and HBsAg loss rates (Children: RR = 9.49, 95% CI: 1.74-51.76; Adults: RR = 7.35, 95% CI: 1.41-38.27) for patients in the IT phase. Subgroup analysis revealed that in adult patients in the IT phase, interferon plus nucleos(t)ide analogues (NA)-treated patients exhibited a higher pooled rate of HBsAg loss or seroconversion than those treated with NA monotherapy (9% vs. 0%). Additionally, the pooled annual HCC incidence for patients in the IT phase was 3.03 cases per 1000 person-years (95% CI: 0.99-5.88). Adult patients in the IT phase had a significantly lower HCC incidence risk than HBeAg-positive indeterminate phase patients (RR = 0.46, 95% CI: 0.32-0.66), with no significant differences observed between IT and immune-active phases. Presently, there is insufficient evidence solely based on reducing the risk of HCC incidence, to recommend treating patients in the IT phase of chronic HBV infection. However, both adult and paediatric patients in the IT phase responded well to antiviral therapy, showing favourable rates of HBsAg loss or seroconversion.
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Affiliation(s)
- Min Liu
- Department of Infectious Disease and Hepatic Disease, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China
- Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan, China
| | - Taixue Zhao
- Medical School of Kunming University of Science and Technology, Kunming, Yunnan, China
| | - Jinyang Zhang
- Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan, China
| | - Bing Bu
- Department of Infectious Disease and Hepatic Disease, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China
| | - Ruyi Zhang
- Department of Infectious Disease and Hepatic Disease, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China
| | - Xueshan Xia
- Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan, China
- Kunming Medical University, Kunming, Yunnan, China
| | - Jiawei Geng
- Department of Infectious Disease and Hepatic Disease, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China
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Liu YC, Jeng WJ. Should Indications for Antiviral Therapy for Hepatitis B Be Broadened to Include Immune-Tolerant Patients, Inactive Carriers, or Patients in the “Gray Zone”? CURRENT HEPATOLOGY REPORTS 2024; 23:11-21. [DOI: 10.1007/s11901-024-00635-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 01/04/2024] [Indexed: 01/04/2025]
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Liu M, Zhao T, Zhang Y, Zhang AM, Geng J, Xia X. The incidence of hepatocellular carcinoma and clearance of hepatitis B surface for CHB patients in the indeterminate phase: a systematic review and meta-analysis. Front Cell Infect Microbiol 2023; 13:1226755. [PMID: 37771696 PMCID: PMC10523783 DOI: 10.3389/fcimb.2023.1226755] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Accepted: 08/21/2023] [Indexed: 09/30/2023] Open
Abstract
Background Nearly 30%-40% of patients with chronic hepatitis B do not fall into any of the traditional natural history classification and thus are classified as indeterminate. However, it is unclear whether patients in the indeterminate phase (IP) are at a higher risk for hepatocellular carcinoma (HCC) than those in the defined phases (DP) and would benefit from antiviral therapy. We performed a systematic review and meta-analysis of HCC incidence and HBsAg clearance among patients in the IP versus DP. Methods We defined the clinical phases as per the AASLD 2018 hepatitis B guidance. We searched PubMed, Embase, Medline, and Web of Science for relevant studies that reported HCC incidence or HBsAg clearance in IP versus DP patients published between January 2007 and March 2023. Annual HCC incidence and HBsAg clearance rates were pooled using a random/common-effects model. Results We analyzed data from 14 studies, comprising 7798 IP patients (222 patients developed HCC and 239 achieved HBsAg clearance) and 10,725 DP patients. The pooled annual HCC incidence was 2.54 cases per 1,000 person-years (95% CI, 1.14-4.39) and HBsAg clearance rate was 12.36 cases per 1,000 person-years (95% CI, 10.70-14.13) for the IP patients. IP patients were associated with significantly higher HCC incidence risk (RR = 1.64, 95% CI, 1.34-2.00) and slightly lower annual HBsAg clearance rate (RR = 0.83, 95% CI, 0.70-0.99) than the DP patients. In addition, HBeAg-negative IP patients (2.31%; 95% CI, 0.87-4.45) showed a significantly higher HCC incidence than those who were HBeAg positive (0.00%; 95% CI, 0.00-0.99) (p< 0.001). The Asia-Pacific region IP patients (4.30%; 95% CI, 2.07-7.27) were also associated with a higher HCC incidence versus Europe (0.05%; 95% CI, 0.00-1.39) (p< 0.001). However, there were no significant differences between different strategies (treated vs. untreated: 2.56%; 95% CI, 1.01-4.63 vs. 1.61%; 95% CI, 0.00-5.81, p = 0.09), and heterogeneity was substantial across the studies (I2 = 89%). Conclusion The systematic review and meta-analysis showed a high HCC incidence and low HBsAg clearance among patients in the IP, especially for HBeAg-negative patients and the Asian population. We emphasize that future multicenter prospective cohort studies or randomized trials are needed to verify if expanding antiviral therapy for patients in the IP is associated with reduced HCC risk or good treatment outcomes.
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Affiliation(s)
- Min Liu
- Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan, China
- Department of Infectious Disease and Hepatic Disease, The First People’s Hospital of Yunnan Province, Kunming, China
| | - Taixue Zhao
- Medical School of Kunming University of Science and Technology, Kunming, China
| | - Yuting Zhang
- Department of Infectious Disease and Hepatic Disease, The First People’s Hospital of Yunnan Province, Kunming, China
| | - A-Mei Zhang
- Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan, China
| | - Jiawei Geng
- Department of Infectious Disease and Hepatic Disease, The First People’s Hospital of Yunnan Province, Kunming, China
| | - Xueshan Xia
- Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, Yunnan, China
- Kunming Medical University, Kunming, China
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Abstract
Hepatitis B virus (HBV) infection is a major public health problem, with an estimated 296 million people chronically infected and 820 000 deaths worldwide in 2019. Diagnosis of HBV infection requires serological testing for HBsAg and for acute infection additional testing for IgM hepatitis B core antibody (IgM anti-HBc, for the window period when neither HBsAg nor anti-HBs is detected). Assessment of HBV replication status to guide treatment decisions involves testing for HBV DNA, whereas assessment of liver disease activity and staging is mainly based on aminotransferases, platelet count, and elastography. Universal infant immunisation, including birth dose vaccination is the most effective means to prevent chronic HBV infection. Two vaccines with improved immunogenicity have recently been approved for adults in the USA and EU, with availability expected to expand. Current therapies, pegylated interferon, and nucleos(t)ide analogues can prevent development of cirrhosis and hepatocellular carcinoma, but do not eradicate the virus and rarely clear HBsAg. Treatment is recommended for patients with cirrhosis or with high HBV DNA levels and active or advanced liver disease. New antiviral and immunomodulatory therapies aiming to achieve functional cure (ie, clearance of HBsAg) are in clinical development. Improved vaccination coverage, increased screening, diagnosis and linkage to care, development of curative therapies, and removal of stigma are important in achieving WHO's goal of eliminating HBV infection by 2030.
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Affiliation(s)
- Wen-Juei Jeng
- Department of Gastroenterology and Hepatology, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - George V Papatheodoridis
- Academic Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece
| | - Anna S F Lok
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA.
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Liu YC, Jeng WJ. Editorial: considerations for expanding treatment in grey zone chronic hepatitis B patients. Aliment Pharmacol Ther 2023; 57:577-578. [PMID: 36786455 DOI: 10.1111/apt.17340] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/15/2023]
Affiliation(s)
- Yen-Chun Liu
- College of Medicine, Chang Gung University, Taipei, Taiwan.,Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou medical center, Taoyuan, Taiwan
| | - Wen-Juei Jeng
- College of Medicine, Chang Gung University, Taipei, Taiwan.,Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou medical center, Taoyuan, Taiwan
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Lee HA, Kim SU, Seo YS, Ahn SH, Rim CH. Comparable outcomes between immune-tolerant and active phases in noncirrhotic chronic hepatitis B: a meta-analysis. Hepatol Commun 2023; 7:e0011. [PMID: 36691962 PMCID: PMC9851695 DOI: 10.1097/hc9.0000000000000011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2022] [Accepted: 10/10/2022] [Indexed: 01/25/2023] Open
Abstract
BACKGROUND Antiviral therapy is not indicated for patients with chronic hepatitis B (CHB) in the immune-tolerant (IT) phase. We compared the outcomes between the untreated IT phase and the treated immune-active (IA) phase in noncirrhotic HBeAg-positive CHB patients. METHODS We systematically searched 4 databases, including PubMed, Medline, Embase, and Cochrane, until August 2021. The pooled incidence rates of HCC and mortality in the IT and IA cohorts and phase change in the IT cohort were investigated. Studies that included patients with liver cirrhosis were excluded. RESULTS Thirteen studies involving 11,903 patients were included. The overall median of the median follow-up period was 62.4 months. The pooled 5-year and 10-year incidence rates of HCC were statistically similar between the IT and IA cohorts (1.1%, 95% CI: 0.4%-2.8% vs. 1.1%, 95% CI: 0.5%-2.3%, and 2.7%, 95% CI: 1.0%-7.3% vs. 3.6%, 95% CI: 2.4%-5.5%, respectively, all p>0.05). The pooled 5-year odds ratio of HCC between IT and IA cohorts was 1.05 (95% CI: 0.32-3.45; p=0.941). The pooled 5-year incidence rate of mortality was statistically similar between the IT and IA cohorts (1.9%, 95% CI: 1.1%-3.4% vs. 1.0%, 95% CI: 0.3%-2.9%, p=0.285). Finally, the pooled 5-year incidence rate of phase change in the IT cohort was 36.1% (95% CI: 29.5%-43.2%). CONCLUSION The pooled incidence rates of HCC and mortality were comparable between the untreated IT and the treated IA phases in noncirrhotic HBeAg-positive CHB patients.
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Affiliation(s)
- Han Ah Lee
- Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Yeon Seok Seo
- Departments of Internal Medicine, Korea University College of Medicine, Seoul, Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
| | - Chai Hong Rim
- Department of Radiation Oncology, Korea University College of Medicine, Seoul, Korea
- Department of Radiation Oncology, Korea University Ansan Hospital, Gyeonggi-do, Korea
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Huang DQ, Lee DH, Le MH, Le A, Yeo YH, Trinh HN, Chung M, Nguyen V, Johnson T, Zhang JQ, Wong C, Wong C, Li J, Cheung R, Nguyen MH. Liver Complications in Untreated Treatment-Ineligible versus Treated Treatment-Eligible Patients with Hepatitis B. Dig Dis 2023; 41:115-123. [PMID: 36070707 PMCID: PMC9909719 DOI: 10.1159/000526933] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Accepted: 08/15/2022] [Indexed: 02/02/2023]
Abstract
BACKGROUND A substantial number of patients who do not meet treatment criteria for chronic hepatitis B (CHB) later develop adverse outcomes such as cirrhosis and hepatocellular carcinoma (HCC). Our aim was to determine whether current practice guidelines adequately identify CHB patients who will benefit from antiviral therapy. METHODS We performed a retrospective cohort study comparing the incidence of adverse liver outcomes (cirrhosis and/or HCC) in untreated treatment-ineligible (at baseline and throughout follow-up) versus treated treatment-eligible patients according to standard American Association for the Study of Liver Diseases (AASLD) 2018 guidance (alanine aminotransferase [ALT] >70/50 U/L for men/women plus hepatitis B virus [HBV] DNA >20,000/2,000 IU/mL for HBeAg+/-) and with a sensitivity analyses using a lower threshold (ALT >40 U/L and HBV DNA >2,000 IU/mL). RESULTS We reviewed records of 5,840 patients from 5 clinics in California and identified 2,987 treatment-naive non-HCC CHB patients. Of those, 271 patients remained untreated treatment-ineligible, 514 patients were treatment-eligible and initiated treatment, with 5-year cumulative adverse liver incidences of 12.5% versus 7.2%, p = 0.074. On multivariable analysis adjusting for age, sex, diabetes, albumin, platelet count, and HBV DNA, compared to treated treatment-eligible patients, untreated treatment-ineligible patients had a significantly higher risk of adverse liver outcomes (adjusted hazard ratio: 2.38, 95% confidence interval 1.03-5.48, p = 0.04) in main analysis by AASLD 2018 criteria but not in sensitivity analysis using the lower treatment threshold (p = 0.09). CONCLUSION Patients never meeting standard AASLD 2018 criteria for antiviral therapy and never treated had twice the risk of developing cirrhosis and/or HCC when compared to eligible and treated patients.
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Affiliation(s)
- Daniel Q. Huang
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore,Division of Gastroenterology and Hepatology, National University Health System, Singapore, Singapore
| | - Dong Hyun Lee
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Good Gang-An Hospital, Busan, Republic of Korea,Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
| | - Michael H. Le
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
| | - An Le
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
| | - Yee Hui Yeo
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
| | - Huy N. Trinh
- San Jose Gastroenterology, San Jose, California, USA
| | - Mimi Chung
- Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Vy Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA
| | - Tiffani Johnson
- University of California, Berkeley, Berkeley, California, USA
| | | | | | | | - Jiayi Li
- Palo Alto Medical Foundation, Mountain View Division, Mountain View, California, USA
| | - Ramsey Cheung
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA,Department of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Healthcare, Palo Alto, California, USA
| | - Mindie H. Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California, USA,*Mindie H. Nguyen,
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Qian Z, Hu M, Wu H, Chen H, Liao G, Kang Z, Lin X, Peng J. The Efficacy of Antiviral Treatment for Chronic Hepatitis B Patients with Normal ALT Levels: A Systematic Review and Meta-analysis. HEPATITIS MONTHLY 2022; 22. [DOI: 10.5812/hepatmon-129836] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 10/03/2022] [Accepted: 10/06/2022] [Indexed: 01/04/2025]
Abstract
Context: When nucleos(t)ide analogues (NAs) were applied clinically to manage chronic hepatitis B virus infection, the prognosis of chronic hepatitis B (CHB) patients greatly improved. However, certain CHB patients with normal alanine aminotransferase (ALT) levels were not used to be considered as the population with the need for antiviral treatment. Objectives: This systematic review and meta-analysis collected and analyzed data from clinical trials to assess and compare the efficacy of antiviral treatment among patients with elevated and normal ALT levels. Methods: A systematic search was performed to gather studies published from 1990.01 to 2022.08 in PubMed and Web of Science databases. The quality of the literature was assessed, and 16 studies were included for further analysis. Basic information on included studies and study populations was collected. A meta-analysis was carried out to evaluate three major outcomes of viral response, hepatitis B envelope antigen (HBeAg) loss, and HBeAg seroconversion after NAs treatment based on data extracted from these studies. Odds ratios (ORs) with 95% confidence intervals (CIs) for all outcomes were calculated using fixed-effects models. Results: In the 16 relevant studies, 5,345 patients met the inclusion criteria, including 3,687 patients receiving NAs treatment. All patients were grouped into one with elevated ALT and another with normal ALT based on whether their pretreatment ALT levels > 1*upper limit of normal (ULN). For patients receiving lamivudine, the viral response showed no significant difference between the groups with elevated and normal ALT levels (pooled log OR: 0.51 [-0.23 - 1.26], P = 0.79); the pooled log OR for HBeAg loss was 1.19 (0.63 - 1.76, P = 0.03) and pooled log OR for HBeAg seroconversion was 2.19 (0.91 - 3.47, P = 0.40). For patients receiving first-line therapy with tenofovir disoproxil fumarate (TDF) and entecavir (ETV), the viral response showed no significant difference between the two groups: Pooled log OR (0.38 [-0.22 - 0.97], P = 0.10). The pooled log OR for HBeAg loss and HBeAg seroconversion was (-0.07 [-0.81 - 0.67], P = 0.68) and (0.40 [-0.84 - 1.63], P = 0.88), respectively. Conclusions: The efficacies of first-line therapy with TDF and ETV treatments were similar in groups with elevated and normal ALT levels for the outcomes of viral response and HBeAg loss. These findings may support further treatment of CHB patients with normal ALT levels.
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Sheng Q, Wang N, Zhang C, Fan Y, Li Y, Han C, Wang Z, Wei S, Dou X, Ding Y. HBeAg-negative Patients with Chronic Hepatitis B Virus Infection and Normal Alanine Aminotransferase: Wait or Treat? J Clin Transl Hepatol 2022; 10:972-978. [PMID: 36304490 PMCID: PMC9547271 DOI: 10.14218/jcth.2021.00443] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 12/25/2021] [Accepted: 02/27/2022] [Indexed: 12/04/2022] Open
Abstract
Alanine aminotransferase (ALT) is a common clinical indicator of liver inflammation. The current Chinese guidelines for the management of chronic hepatitis B (CHB) recommend antiviral treatment for patients with detectable hepatitis B virus (HBV) DNA and persistent ALT levels (ALTs) exceeding the upper limit of normal. However, it has been recently reported that patients with chronic HBV infection, especially HBeAg-negative patients with persistently normal ALTs, may have liver biopsy findings of significant inflammation and fibrosis. For HBeAg-negative patients with chronic HBV infection and normal ALTs, many controversial questions have been asked. To treat or not? When to initiate the treatment? Which drug is appropriate? In this review, we summarize the available data on the management of HBeAg-negative patients with chronic HBV infection and normal ALTs with the aim of improving the current clinical management.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Xiaoguang Dou
- Correspondence to: Xiaoguang Dou and Yang Ding, Department of Infectious Diseases, Shengjing Hospital of China Medical University, No. 39 HuaXiang Road, TieXi District,Shenyang, Liaoning 110022, China. ORCID: https://orcid.org/0000-0003-1856-7331 (XGD), https://orcid.org/0000-0002-7066-2865 (YD). Tel: +86-18940251121 (XGD), +86-13332434847 (YD), Fax: +86-24-25998744, E-mail: (XGD), (YD)
| | - Yang Ding
- Correspondence to: Xiaoguang Dou and Yang Ding, Department of Infectious Diseases, Shengjing Hospital of China Medical University, No. 39 HuaXiang Road, TieXi District,Shenyang, Liaoning 110022, China. ORCID: https://orcid.org/0000-0003-1856-7331 (XGD), https://orcid.org/0000-0002-7066-2865 (YD). Tel: +86-18940251121 (XGD), +86-13332434847 (YD), Fax: +86-24-25998744, E-mail: (XGD), (YD)
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13
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Bollerup S, Engsig F, Hallager S, Mocroft A, Roege BT, Christensen PB, Laursen AL, Krarup H, Clausen MR, Thielsen P, Madsen LG, Noerregaard L, Barfod TS, Balslev U, Tarp B, Hansen JB, Mygind LH, Gerstoft J, Weis N. Incidence of Hepatocellular Carcinoma and Decompensated Liver Cirrhosis and Prognostic Accuracy of the PAGE-B HCC Risk Score in a Low Endemic Hepatitis B Virus Infected Population. J Hepatocell Carcinoma 2022; 9:1093-1104. [PMID: 36281336 PMCID: PMC9587738 DOI: 10.2147/jhc.s372571] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Accepted: 08/22/2022] [Indexed: 11/21/2022] Open
Abstract
Purpose We aimed to determine incidence of hepatocellular carcinoma (HCC) and decompensated liver cirrhosis in persons with chronic hepatitis B virus (HBV) infection in Denmark stratified by disease phase, liver cirrhosis, and treatment status at baseline. Additionally, we aimed to assess the prognostic value of the PAGE-B HCC risk score in a mainly non-cirrhotic population. Patients and Methods In this register-based cohort study, we included all individuals over the age of 18, with chronic HBV infection first registered between 2002 and 2016 in at least one of three nationwide registers. The study population was followed until HCC, decompensated liver cirrhosis, death, emigration, or December 31, 2017, which ever came first. Results Among 6016 individuals included in the study, 10 individuals with and 23 without baseline liver cirrhosis developed HCC during a median follow up of 7.3 years (range 0.0-15.5). This corresponded to five-year cumulative incidences of 7.1% (95% confidence interval (CI) 2.0-12.3) and 0.2% (95% CI 0.1-0.4) in persons with and without baseline liver cirrhosis. The five-year cumulative incidence of decompensated liver cirrhosis was 0.7% (95% CI 0.5-1.0). Among 2038 evaluated for liver events stratified by disease phase, incidence of HCC was low in all who were non-cirrhotic and untreated for HBV at baseline. PAGE-B score was evaluated in 1529 persons. The 5-year cumulative incidence of HCC was 0, 0.8 (95% CI 0.5-1.8), and 8.7 (95% CI 1.0-16.4) in persons scoring <10, 10-17 and >17, respectively (c-statistic 0.91 (95% CI 0.84-0.98)). Conclusion We found low incidence of HCC and decompensated liver cirrhosis in persons with chronic HBV infection in Denmark. Moreover, the PAGE-B score showed good accuracy for five-year risk of developing HCC in the population with chronic HBV infection in Denmark.
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Affiliation(s)
- Signe Bollerup
- Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark
| | - Frederik Engsig
- Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark
| | - Sofie Hallager
- Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark
| | - Amanda Mocroft
- Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, UCL, London, England,Centre of Excellence for Health, Immunity and Infections (CHIP) and PERSIMUNE, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Birgit T Roege
- Department of Internal Medicine, Kolding Hospital, Kolding, Denmark
| | - Peer B Christensen
- Department of Infectious Diseases, Odense University Hospital, Odense, Denmark,Clinical Institute, University of Southern Denmark, Odense, Denmark
| | - Alex L Laursen
- Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark
| | - Henrik Krarup
- Department of Molecular Diagnostics, Aalborg University Hospital, Aalborg, Denmark,Department of Medical Gastroenterology, Aalborg University Hospital, Aalborg, Denmark
| | - Mette R Clausen
- Department of Medical Gastroenterology and Hepatology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Peter Thielsen
- Department of Gastroenterology, Herlev Hospital, Herlev, Denmark
| | - Lone G Madsen
- Department of Medical Gastroenterology, Zealand University Hospital, Koege, Denmark,Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Lars Noerregaard
- Department of Lung- and Infectious Diseases, North Zealand Hospital, Hilleroed, Denmark
| | - Toke S Barfod
- Department of Internal Medicine and Infectious Diseases, Zealand University Hospital, Roskilde, Denmark
| | - Ulla Balslev
- Department of Infectious Diseases, Herlev Hospital, Herlev, Denmark
| | - Britta Tarp
- Diagnostic Centre, University Research Clinic for Innovative Patient Pathways, Silkeborg Regional Hospital, Silkeborg, Denmark
| | - Jesper B Hansen
- Department of Medical Gastroenterology, Aalborg University Hospital, Aalborg, Denmark
| | - Lone H Mygind
- Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark
| | - Jan Gerstoft
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark,Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Nina Weis
- Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark,Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark,Correspondence: Nina Weis, Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark, Tel: +45 38623514, Email
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Natural History and Hepatocellular Carcinoma Risk in Untreated Chronic Hepatitis B Patients With Indeterminate Phase. Clin Gastroenterol Hepatol 2022; 20:1803-1812.e5. [PMID: 33465482 DOI: 10.1016/j.cgh.2021.01.019] [Citation(s) in RCA: 73] [Impact Index Per Article: 24.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Revised: 12/23/2020] [Accepted: 01/12/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Many patients with chronic hepatitis B (CHB) may not conform to any of the defined phases and hence are classified as indeterminate. We aimed to characterize the baseline prevalence of indeterminate patients and their natural history, phase transition, and hepatocellular carcinoma (HCC) risk. METHODS This was a retrospective cohort study of 3366 adult untreated noncirrhotic CHB patients seen at 5 US clinics and 7 Taiwanese townships who had at least 1 year of serial laboratory data before enrollment with a mean follow-up period of 12.5 years. Patients' clinical phases were determined at baseline and through serial data during follow-up evaluation, based on the American Association for the Study of Liver Diseases 2018 guidance. RESULTS At baseline, 1303 (38.7%) patients were in the indeterminate phase. By up to year 10 of follow-up evaluation, 686 patients (52.7%) remained indeterminate, while 283 patients (21.7%) became immune active. Compared with patients who remained inactive, patients who remained indeterminate had a higher 10-year cumulative HCC incidence (4.6% vs 0.5%; P < .0001) and adjusted hazard ratio for HCC of 14.1 (P = .03). Among patients who remained indeterminate, age 45 years and older (adjusted hazard ratio, 18.4; P = .005) was associated independently with HCC development. CONCLUSIONS Nearly 40% of patients had indeterminate CHB phase. Of these, half remained indeterminate and one-fifth transitioned to the immune active phase. HCC risk in persistently indeterminate CHB was 14 times higher than inactive CHB. Among persistently indeterminate CHB patients, age 45 years and older was associated with an 18 times higher risk for HCC development. Further studies are needed to evaluate the potential benefit of antiviral therapy for indeterminate patients, especially in the older subgroup.
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Jeng WJ, Lok AS. Should Treatment Indications for Chronic Hepatitis B Be Expanded? Clin Gastroenterol Hepatol 2021; 19:2006-2014. [PMID: 32434068 DOI: 10.1016/j.cgh.2020.04.091] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Revised: 03/20/2020] [Accepted: 04/24/2020] [Indexed: 12/22/2022]
Abstract
BACKGROUND & AIM Antiviral therapy has greatly improved the outcomes of patients with chronic hepatitis B virus (HBV) infection and active liver disease or advanced fibrosis/cirrhosis. However, current treatment does not eradicate HBV and long-term treatment is needed in most patients to maintain clinical benefit. Thus, professional society guidelines do not recommend treatment of all patients with chronic HBV infection. This review article will examine evidence for and against expansion of treatment to patients in whom treatment is not recommended based on current guidelines. RESULTS Available data support expanding treatment to immune tolerant patients and patients in the grey zones who have evidence of active/advanced liver disease based on liver biopsy or non-invasive tests and those who remain in the immune tolerant phase after age 40. Evidence supporting treatment expansion to confirmed inactive carriers and other immune tolerant patients is lacking. CONCLUSIONS HBV treatment indications can be more liberal when new therapies that can achieve HBsAg loss safely in a high percentage of patients after a finite course of treatment are available.
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Affiliation(s)
- Wen-Juei Jeng
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou branch, Taiwan; Chang Gung University College of Medicine, Taiwan
| | - Anna S Lok
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan.
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Marcellin P, Xie Q, Woon Paik S, Flisiak R, Piratvisuth T, Petersen J, Asselah T, Cornberg M, Ouzan D, Foster GR, Papatheodoridis G, Messinger D, Regep L, Bakalos G, Alshuth U, Lampertico P, Wedemeyer H. Final analysis of the international observational S-Collate study of peginterferon alfa-2a in patients with chronic hepatitis B. PLoS One 2020; 15:e0230893. [PMID: 32275726 PMCID: PMC7147799 DOI: 10.1371/journal.pone.0230893] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Accepted: 03/10/2020] [Indexed: 12/11/2022] Open
Abstract
Background and aims Sustained off-treatment immune control is achievable in a proportion of patients with chronic hepatitis B treated with peginterferon alfa-2a. We evaluated on-treatment predictors of hepatitis B surface antigen (HBsAg) clearance 3 years after peginterferon alfa-2a treatment and determined the incidence of hepatocellular carcinoma. Methods A prospective, international, multicenter, observational study in patients with chronic hepatitis B who have been prescribed peginterferon alfa-2a (40KD) in a real-world setting. The primary endpoint was HBsAg clearance after 3 years’ follow-up. Results The modified intention-to-treat population comprised 844 hepatitis B e antigen (HBeAg)-positive patients (540 [64%] completed 3 years’ follow-up), and 872 HBeAg-negative patients (614 [70%] completed 3 years’ follow-up). At 3 years’ follow-up, HBsAg clearance rates in HBeAg-positive and HBeAg-negative populations, respectively, were 2% (16/844) and 5% (41/872) in the modified intention-to-treat population and 5% [16/328] and 10% [41/394] in those with available data. In HBeAg-positive patients with data, Week 12 HBsAg levels <1500, 1500–20,000, and >20,000 IU/mL were associated with HBsAg clearance rates at 3 years’ follow-up of 11%, 1%, and 5%, respectively (Week 24 predictability was similar). In HBeAg-negative patients with available data, a ≥10% decline vs a <10% decline in HBsAg at Week 12 was associated with HBsAg clearance rates of 16% vs 4%. Hepatocellular carcinoma incidence was lower than REACH-B (Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B) model predictions. Conclusions Sustained off-treatment immune control is achieved with peginterferon alfa-2a in a real-world setting. HBsAg clearance 3 years after completion of peginterferon alfa-2a can be predicted on the basis of on-treatment HBsAg kinetics.
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Affiliation(s)
| | - Qing Xie
- Infectious Diseases, Ruijin Hospital, Shanghai, China
| | - Seung Woon Paik
- Gastroenterology and Hepatology, Sungkyunkwan University School of Medicine, Seoul, South Korea
| | - Robert Flisiak
- Infectious Disease and Hepatology, Medical University of Białystok, Białystok, Poland
| | - Teerha Piratvisuth
- Gastroenterology and Hepatology, Prince of Songkla University, Songkhla, Thailand
| | - Jörg Petersen
- Liver Unit, Asklepios Klinik St. Georg, Hamburg, Germany
| | - Tarik Asselah
- Hepatologie, Université Paris Diderot, Clichy, France
| | - Markus Cornberg
- Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
| | - Denis Ouzan
- Service d’Hepatologie, Institut Arnault Tzanck, Saint-Laurent-du-Var, France
| | - Graham R. Foster
- Liver Unit, Queen Mary University of London, London, United Kingdom
| | | | | | | | | | | | | | - Heiner Wedemeyer
- Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
- * E-mail:
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17
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Yeo YH, Ho HJ, Yang HI, Tseng TC, Hosaka T, Trinh HN, Kwak MS, Park YM, Fung JYY, Buti M, Rodríguez M, Treeprasertsuk S, Preda CM, Ungtrakul T, Charatcharoenwitthaya P, Li X, Li J, Zhang J, Le MH, Wei B, Zou B, Le A, Jeong D, Chien N, Kam L, Lee CC, Riveiro-Barciela M, Istratescu D, Sriprayoon T, Chong Y, Tanwandee T, Kobayashi M, Suzuki F, Yuen MF, Lee HS, Kao JH, Lok AS, Wu CY, Nguyen MH. Factors Associated With Rates of HBsAg Seroclearance in Adults With Chronic HBV Infection: A Systematic Review and Meta-analysis. Gastroenterology 2019; 156:635-646.e9. [PMID: 30342034 DOI: 10.1053/j.gastro.2018.10.027] [Citation(s) in RCA: 171] [Impact Index Per Article: 28.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2018] [Revised: 09/13/2018] [Accepted: 10/09/2018] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS Seroclearance of hepatitis B surface antigen (HBsAg) is a marker for clearance of chronic hepatitis B virus (HBV) infection, but reported annual incidence rates of HBsAg seroclearance vary. We performed a systematic review and meta-analysis to provide more precise estimates of HBsAg seroclearance rates among subgroups and populations. METHODS We searched PubMed, Embase, and the Cochrane library for cohort studies that reported HBsAg seroclearance in adults with chronic HBV infection with more than 1 year of follow-up and at least 1 repeat test for HBsAg. Annual and 5-, 10-, and 15-year cumulative incidence rates were pooled using a random effects model. RESULTS We analyzed 34 published studies (with 42,588 patients, 303,754 person-years of follow-up, and 3194 HBsAg seroclearance events), including additional and updated aggregated data from 19 studies. The pooled annual rate of HBsAg seroclearance was 1.02% (95% CI, 0.79-1.27). Cumulative incidence rates were 4.03% at 5 years (95% CI, 2.49-5.93), 8.16% at 10 years (95% CI, 5.24-11.72), and 17.99% at 15 years (95% CI, 6.18-23.24). There were no significant differences between the sexes. A higher proportion of patients who tested negative for HBeAg at baseline had seroclearance (1.33%; 95% CI, 0.76-2.05) than those who tested positive for HBeAg (0.40%; 95% CI, 0.25-0.59) (P < .01). Having HBsAg seroclearance was also associated with a lower baseline HBV DNA level (6.61 log10 IU/mL; 95% CI, 5.94-7.27) vs not having HBsAg seroclearance (7.71 log10 IU/mL; 95% CI, 7.41-8.02) (P < .01) and with a lower level of HBsAg at baseline (2.74 log10 IU/mL; 95% CI, 1.88-3.60) vs not having HBsAg seroclearance (3.90 log10 IU/mL, 95% CI, 3.73-4.06) (P < .01). HBsAg seroclearance was not associated with HBV genotype or treatment history. Heterogeneity was substantial across the studies (I2 = 97.49%). CONCLUSION In a systematic review and meta-analysis, we found a low rate of HBsAg seroclearance in untreated and treated patients (pooled annual rate, approximately 1%). Seroclearance occurred mainly in patients with less active disease. Patients with chronic HBV infection should therefore be counseled on the need for lifelong treatment, and curative therapies are needed.
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Affiliation(s)
- Yee Hui Yeo
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
| | - Hsiu J Ho
- Division of Translational Research, Taipei Veterans General Hospital, Taipei City, Taiwan
| | - Hwai-I Yang
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Tai-Chung Tseng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Tetsuya Hosaka
- Department of Hepatology, Toranomon Hospital, Takatsu-ku, Kawasaki, Japan
| | - Huy N Trinh
- San Jose Gastroenterology, San Jose, California
| | - Min-Sun Kwak
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
| | - Young Min Park
- Hepatology Center, Department of Internal Medicine and Biomedical Research Center, Bundang Jesaeng General Hospital, Seongnam-si, Gyeonggi-do, Republic of Korea
| | - James Yan Yue Fung
- Department of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China
| | - Maria Buti
- Liver Unit, Hospital Universitari Vall d'Hebron and Ciberehd del Instituto Carlos III, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Barcelona, Spain
| | - Manuel Rodríguez
- Liver Unit, Division of Gastroenterology and Hepatology, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain
| | - Sombat Treeprasertsuk
- Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
| | - Carmen Monica Preda
- Department of Gastroenterology, Clinic Fundeni Institute, Bucharest, Romania
| | - Teerapat Ungtrakul
- Faculty of Medicine and Public Health, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Thailand
| | | | - Xiangyong Li
- Department of Infectious Diseases, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Jiayi Li
- Palo Alto Medical Foundation, Mountain View Division, Palo Alto, California
| | - Jian Zhang
- Chinese Hospital, San Francisco, California; School of Nursing, University of California, San Francisco, California
| | - Michael Huan Le
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
| | - Bin Wei
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
| | - Biyao Zou
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
| | - An Le
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
| | - Donghak Jeong
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California
| | | | - Leslie Kam
- Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chiao-Chin Lee
- Department of Internal Medicine, Tri-Service General Hospital, Taipei, Taiwan
| | - Mar Riveiro-Barciela
- Liver Unit, Hospital Universitari Vall d'Hebron and Ciberehd del Instituto Carlos III, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Barcelona, Spain
| | - Doina Istratescu
- Department of Gastroenterology, Clinic Fundeni Institute, Bucharest, Romania
| | - Tassanee Sriprayoon
- Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Yutian Chong
- Department of Infectious Diseases, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China
| | - Tawesak Tanwandee
- Department of Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Mariko Kobayashi
- Research Institute for Hepatology, Toranomon Hospital, Takatsu-ku, Kawasaki, Japan
| | - Fumitaka Suzuki
- Department of Hepatology, Toranomon Hospital, Takatsu-ku, Kawasaki, Japan
| | - Man-Fung Yuen
- Department of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China
| | - Hyo-Suk Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
| | - Jia-Horng Kao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Anna S Lok
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan
| | - Chun-Ying Wu
- Division of Translational Research, Taipei Veterans General Hospital, Taipei City, Taiwan; College of Public Health, China Medical University, Taichung, Taiwan.
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, California.
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Risk factors of transmission and natural history of chronic hepatitis B infection in Iranian patients. GASTROENTEROLOGY AND HEPATOLOGY FROM BED TO BENCH 2019; 12:S149-S155. [PMID: 32099616 PMCID: PMC7011058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
AIM To investigate routes of transmission, demographic characteristics, and frequency of different phases of chronic hepatitis B (CHB) in 2000 Iranian patients. BACKGROUND Knowledge about the most frequent risk factors of CHB and its different phases is very important for optimal prevention and management policy making. METHODS In this cross-sectional study, 2000 HBsAg positive patients who were referred to Taleghani Hospital from 2011 through 2018 were enrolled. ELISA method was employed to detect serological markers of CHB. Taking into account the HBV DNA and ALT levels and HBeAg status, the patients were classified in four groups, according to AASLD 2017 guideline. RESULTS Male and female patients had nearly equal frequencies in our study and 82.5 % of them aged more than 20 years. A great number of our patients (95%) were HBeAg negative and the most frequent risk factors of HBV infection were positive periodontal and family history (40.3% and 24.9%, respectively). The majority of our patients were inactive carriers (63.35%), while s mall number of them were in the immune tolerant group (2.15 %). CONCLUSION Immune tolerance phase group had the minimum number of members in our study and most of them were above 20 years old. This can be due to the mass vaccination of neonates since 1993. Most of CHB patients were in inactive carrier group. Although it is recommended not to treat these patients, performing periodic liver function tests and disease severity assessment is warranted, especially in patients above 40 years old.
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Ashtari S, Sharifian A, Hatami B, Mohebbi SR, Nouri G, Bazdar M, Naderi N. Comparative study on guidelines in determining HBV phases in Iranian patients. GASTROENTEROLOGY AND HEPATOLOGY FROM BED TO BENCH 2019; 12:S145-S148. [PMID: 32099615 PMCID: PMC7011065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
AIM The aim of this study was to compare the different phases of chronic Hepatitis B virus (HBV) infection with different values for normal ALT. BACKGROUND For many years, the upper limit of 40 IU was considered normal for ALT for both sexes, but in recent years this value is challenged and some guidelines have lowered their limit. METHODS In this cross-sectional study, 2000 HBsAg positive patients who were referred to Taleghani Hospital, Tehran, Iran, from 2011 through 2018 were classified in four groups according to American Association of the study of the liver disease (AASLD), European Association of the study of the liver (EASL) /Asian-Pacific Association of the study of the liver (APASL) and American Collage of Gastroenterology (ACG) guidelines. The frequency of each group based on 3 different guidelines was compared. RESULTS In HBeAg positive patients (n=100), the percentage of immune tolerance phase was 43% according to AASLD cutoff for normal ALT (35 IU for men, 25 IU for women), while it was 68% and 28% with regard to EASL/APASL and ACG (30 IU for men, 19 IU for women) cutoffs respectively. In HBeAg negative patients (n=1900), 66.68% were inactive carriers according to AASLD, but the percentage changed to 82.89% and 52.42% considering EASL/APASL and ACG values, respectively. CONCLUSION Using ACG and to a lesser extent AASLD cutoff for ALT, many patients shift from immune tolerance and inactive carrier state into the immune active phase. Thus, more patients are candidates for treatment or intensive workup to determine the extent of liver damage.
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Affiliation(s)
- Sara Ashtari
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Afsaneh Sharifian
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Behzad Hatami
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Seyed Reza Mohebbi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Gholamreza Nouri
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Monireh Bazdar
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Nosratollah Naderi
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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20
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Bonacci M, Lens S, Mariño Z, Londoño MC, Rodríguez-Tajes S, Mas A, García-López M, Pérez-Del-Pulgar S, Sánchez-Tapias JM, Forns X. Anti-viral therapy can be delayed or avoided in a significant proportion of HBeAg-negative Caucasian patients in the Grey Zone. Aliment Pharmacol Ther 2018; 47:1397-1408. [PMID: 29577350 DOI: 10.1111/apt.14613] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2017] [Revised: 11/21/2017] [Accepted: 02/24/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND Grey Zone (GZ) is an ill-defined situation including patients falling between inactive carrier (IC) state and HBeAg-negative chronic hepatitis B (HBeAg-negative CHB). AIMS To assess the long-term outcomes of GZ patients compared to IC in the absence of treatment. METHODS Retrospective analysis of 287 IC and GZ HBeAg-negative patients. Patients were classified into 4 groups at baseline: HBV-DNA <2000 IU/mL and ALT <40 U/L (IC), HBV-DNA <2000 IU/mL and ALT 40-80 U/L (GZ-1), HBV-DNA 2000-20 000 IU/mL and ALT <40 U/L (GZ-2) or ALT 40-80 U/L (GZ-3). Data were also analysed using AASLD ALT criteria. RESULTS After a median follow-up of 8.2 (5-19) years, HBsAg loss occurred in about 15% ICs or GZ patients. Transition into IC state occurred in 40% of GZ patients. DNA fluctuations >2000 IU/mL correlated inversely with transition into IC and HBsAg loss. HBsAg levels were significantly lower in ICs than in GZ patients (338 IU/mL [20-3269] vs 5763 IU/mL [2172-17 754]; P < 0.05). Among the latter group, there was an increasing gradient of HBsAg levels from GZ-1 to GZ-3 patients (P < 0.05). HBeAg-negative CHB occurred in only 18 (6.3%) GZ patients. No patient developed cirrhosis nor advanced fibrosis. ALT/HBV-DNA fluctuations and HBeAg-negative CHB development were more frequent in genotype B/C patients, whereas HBsAg loss occurred only in genotype A/D patients. CONCLUSIONS Most Caucasian GZ patients present excellent long-term outcomes in the absence of treatment, with a high rate of HBsAg loss and low rate of progression to HBeAg-negative CHB. HBV-genotyping and HBsAg levels could help to predict outcomes and better classify GZ patients.
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Affiliation(s)
- M Bonacci
- Liver Unit, Hospital Clínic, CIBEREHD, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - S Lens
- Liver Unit, Hospital Clínic, CIBEREHD, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - Z Mariño
- Liver Unit, Hospital Clínic, CIBEREHD, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - M-C Londoño
- Liver Unit, Hospital Clínic, CIBEREHD, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - S Rodríguez-Tajes
- Liver Unit, Hospital Clínic, CIBEREHD, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - A Mas
- Liver Unit, Hospital Clínic, CIBEREHD, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - M García-López
- Liver Unit, Hospital Clínic, CIBEREHD, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - S Pérez-Del-Pulgar
- Liver Unit, Hospital Clínic, CIBEREHD, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - J M Sánchez-Tapias
- Liver Unit, Hospital Clínic, CIBEREHD, IDIBAPS, University of Barcelona, Barcelona, Spain
| | - X Forns
- Liver Unit, Hospital Clínic, CIBEREHD, IDIBAPS, University of Barcelona, Barcelona, Spain
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21
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Hou J, Wang G, Wang F, Cheng J, Ren H, Zhuang H, Sun J, Li L, Li J, Meng Q, Zhao J, Duan Z, Jia J, Tang H, Sheng J, Peng J, Lu F, Xie Q, Wei L, Chinese Society of Hepatology, Chinese Medical Association, Chinese Society of Infectious Diseases, Chinese Medical Association. Guideline of Prevention and Treatment for Chronic Hepatitis B (2015 Update). J Clin Transl Hepatol 2017; 5:297-318. [PMID: 29226097 PMCID: PMC5719188 DOI: 10.14218/jcth.2016.00019] [Citation(s) in RCA: 165] [Impact Index Per Article: 20.6] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/03/2016] [Revised: 01/14/2017] [Accepted: 01/16/2017] [Indexed: 02/05/2023] Open
Affiliation(s)
- Jinlin Hou
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
- *Correspondence to: Jinlin Hou, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, No. 1838 North Guangzhou avenue, Guangzhou 510515, China. E-mail: ; Lai Wei, Peking University People’s Hospital, Peking University Hepatology Institute, No. 11 Xizhimen South Street, Beijing 100044, China. E-mail:
| | - Guiqiang Wang
- Department of Infectious Diseases, Center for Liver Diseases, Peking University First Hospital, Beijing, China
| | - Fusheng Wang
- The Institute of Translational Hepatology, 302 Hospital of PLA, Peking University, Beijing, China
| | - Jun Cheng
- Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
| | - Hong Ren
- Institute for Viral Hepatitis, the Key Laboratory of Molecular Biology for Infectious Diseases, the second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Hui Zhuang
- Department of Microbiology of Peking University Health Science Center, Beijing, China
| | - Jian Sun
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Lanjuan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Jie Li
- Department of Microbiology of Peking University Health Science Center, Beijing, China
| | - Qinghua Meng
- Serious Illness Medicine Inpatient Area, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Jingmin Zhao
- Department of Pathology, 302 Hospital of PLA, Peking University, Beijing, China
| | - Zhongping Duan
- Artificial Liver Center, Beijing Youan Hospital, Capital Medical University, Beijing, China
| | - Jidong Jia
- Liver Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Hong Tang
- Center of Infectious Diseases, West China Hospital of Sichuan University, Division of Infectious Diseases, State Key Laboratory of Biotherapy, Sichuan University, Chengdu, China
| | - Jifang Sheng
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Jie Peng
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Fengmin Lu
- Department of Microbiology of Peking University Health Science Center, Beijing, China
| | - Qing Xie
- Department of Infectious Diseases, Shanghai Jiao Tong University School of Medicine Affiliated Ruijin Hospital, Shanghai, China
| | - Lai Wei
- Hepatology Institute, Peking University People’s Hospital, Beijing, China
- *Correspondence to: Jinlin Hou, Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, No. 1838 North Guangzhou avenue, Guangzhou 510515, China. E-mail: ; Lai Wei, Peking University People’s Hospital, Peking University Hepatology Institute, No. 11 Xizhimen South Street, Beijing 100044, China. E-mail:
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22
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Chen GF, Wang C, Lau G. Treatment of chronic hepatitis B infection-2017. Liver Int 2017; 37 Suppl 1:59-66. [PMID: 28052634 DOI: 10.1111/liv.13309] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2016] [Accepted: 11/01/2016] [Indexed: 12/14/2022]
Abstract
Since the registration of the first effective nucleoside analogue against the hepatitis B virus almost two decades ago, major progress has been made in the management of chronic hepatitis B infection. However, hepatitis B-related morbidity and mortality remain a major global health threat. This is partly due to the escalating costs and the decrease in compliance related to the need for prolonged therapy for most patients who cannot be "cured". New biomarkers such as quantitative hepatitis B surface antigen might help to determine if hepatitis B e antigen negative patients can be taken off nucleos(t)ide analogues. On the other hand, novel compounds that target the viral life cycle or modulate host immune response are in the pipeline. In the next few years, one should expect breakthrough advancement to be made leading to a "cure" for patients with chronic hepatitis B infection by inducing hepatitis surface antigen loss with or without the development of the hepatitis B surface antibody. In addition, attention and necessary actions should also be taken in patients with hepatitis B infection who are being treated with immunosuppressive therapy and direct anti-viral (DAAs) agents for hepatitis C infection to prevent hepatitis from hepatitis B reactivation.
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Affiliation(s)
- Guo-Feng Chen
- Beijing 302-Hong Kong Humanity and Health Hepatitis C Diagnosis and Treatment Center, Beijing, China.,Second Liver Cirrhosis Diagnosis and Treatment Center, 302 Hospital, Beijing, China
| | - Cheng Wang
- Beijing 302-Hong Kong Humanity and Health Hepatitis C Diagnosis and Treatment Center, Beijing, China.,Division of Gastroenterology and Hepatology, Humanity and Health Medical Centre, Hong Kong, SAR, China.,State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - George Lau
- Beijing 302-Hong Kong Humanity and Health Hepatitis C Diagnosis and Treatment Center, Beijing, China.,Division of Gastroenterology and Hepatology, Humanity and Health Medical Centre, Hong Kong, SAR, China.,Institute of Translational Hepatology, 302 Hospital, Beijing, China
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23
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Park YM, Lee SG. Clinical features of HBsAg seroclearance in hepatitis B virus carriers in South Korea: A retrospective longitudinal study. World J Gastroenterol 2016; 22:9836-9843. [PMID: 27956808 PMCID: PMC5124989 DOI: 10.3748/wjg.v22.i44.9836] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2016] [Revised: 08/26/2016] [Accepted: 09/28/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the characteristic features of hepatitis B surface antigen (HBsAg) seroclearance among Korean hepatitis B virus (HBV) carriers.
METHODS Carriers with HBsAg seroclearance were selected by analyzing longitudinal data collected from 2003 to 2015. The period of time from enrollment to the negative conversion of HBsAg (HBsAg-NC) was compared by stratifying various factors, including age, sex, hepatitis B e antigen (HBeAg), HBV DNA, sequential changes in the signal-to-cutoff ratio of HBsAg (HBsAg-SCR), as measured by qualitative HBsAg assay, and chronic liver disease on ultrasonography (US-CLD). Quantification of HBV DNA and HBsAg (HBsAg-QNT) in the serum was performed by commercial assay.
RESULTS Among the 1919 carriers, 90 (4.7%) exhibited HBsAg-NC at 6.2 ± 3.6 years after registration, with no differences observed among the different age groups. Among these carriers, the percentages of those with asymptomatic liver cirrhosis (LC) and hepatocellular carcinoma (HCC) at registration were 31% and 7.8%, respectively. The frequency of HBsAg-NC significantly differed according to the HBV DNA titer and US-CLD. HBeAg influenced HBsAg-NC in the 40-50 and 50-60 year age groups. HBsAg-SCR < 1000 was correlated with an HBsAg-QNT < 200 IU/mL. A gradual decrease in the HBsAg-SCR to < 1000 predicted HBsAg-NC. Six patients developed HCC after registration, including two before and four after HBsAg-NC. The rate at which the patients developed new HCC after HBsAg seroclearance was 4.8%. LC with excessive drinking and vertical infection were found to be risk factors for HCC in the HBsAg-NC group.
CONCLUSION HCC surveillance should be continued after HBsAg seroclearance. An HBsAg-SCR < 1000 and its decrease in sequential testing are worth noting as predictive markers of HBsAg loss.
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25
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Vlachogiannakos J, Papatheodoridis GV. HBV: Do I treat my immunotolerant patients? Liver Int 2016; 36 Suppl 1:93-9. [PMID: 26725904 DOI: 10.1111/liv.12996] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2015] [Accepted: 10/20/2015] [Indexed: 12/11/2022]
Abstract
Immunotolerant patients with chronic hepatitis B virus (HBV) infection are characterized by positive HBeAg, high viral replication, persistently normal ALT and no or minimal liver damage. Since the risk of the progression of liver disease and the chance of a sustained response with existing anti-HBV agents are low, current guidelines do not recommend treatment but close monitoring with serial alanine aminotransferase (ALT) and HBV DNA measurements instead. However, not treating all these patients is a concern because advanced histological lesions have been reported in certain cases who are usually older (>30-40 years old), and continued high HBV replication could increase the risk of hepatocellular carcinoma (HCC). Thus, the optimal management of immunotolerant patients is often individualised according to age, which is associated with histological severity and patient outcome. In particular, immunotolerant patients <30 years old can be monitored for ALT and HBV DNA, while treatment is often recommended in the few patients over 40. A liver biopsy and/or non-invasive assessment of fibrosis may be helpful to determine the therapeutic strategy in patients between 30 and 40 years old. Moreover, there are three specific subgroups of immunotolerant patients who often require treatment with oral anti-HBV agents: patients who will receive immunosuppressive treatment or chemotherapy, women with serum HBV DNA >10(6-7) IU/ml during the last trimester of pregnancy and certain healthcare professionals with high viraemia levels. More studies are needed to further clarify the natural history for the optimal timing of treatment in this setting.
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Affiliation(s)
- Jiannis Vlachogiannakos
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece
| | - George V Papatheodoridis
- Department of Gastroenterology, Medical School of National and Kapodistrian University of Athens, Laiko General Hospital, Athens, Greece
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26
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Sharifian A, Naderi N, Sanati A, Mohebi SR, Azimzadeh P, Golmohamadi A, Nori S, Khanyaghma M, Sheikhesmaeili F, Zali MR. The Early Results of a New Health Care Program Implementation in HBV Screening: an Iranian Experience. Middle East J Dig Dis 2015; 7:226-32. [PMID: 26609351 PMCID: PMC4655843] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
BACKGROUND According to the reports of World Health Organization (WHO) and Centers for Disease Control and Prevention, the prevalence of chronic hepatitis B infection in Iran has decreased from 2-7% in 2001 to 1.3-0.8% in children aged 2-14 years. In 2010 the Institute of Medicine recommended more comprehensive screening by primary care physicians (PCPs) for evaluation, vaccination, and management of infected patients for further decrease in the prevalence of chronic HBV infection. Thus, with contribution of the Health Department, we developed a practical flowchart for PCPs to start active screening of hepatitis B virus (HBV) in all visited patients and refer the positive cases for further evaluation and management to Taleghani Hospital. METHODS With collaboration of Health Department of Shahid Beheshti University of Medical Sciences), physicians of health centers were asked to screen all their patients for HBsAg. Positive cases were referred to Taleghani Hospital. They were first registered and educated about their disease, life style, and prevention methods. Their first degree families were screened for HBV infection too and were referred for vaccination if needed. According to the results of lab tests, appropriate management was done by a hepatologist. RESULTS Since implementation of this program, we have encountered a significant rise in patient detection (even in high risk groups). Many of them were not aware of their disease and most of those who were aware of their disease were not managed appropriately. Family screening and vaccination were inadequate and need more emphasis. CONCLUSION Although health system is active about screening of HBV infection in high risk populations, it is not perfect. It seems that health system needs to upgrade the screening and management programs of HBV infection.
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Affiliation(s)
- Afsaneh Sharifian
- 1 Associate Professor, Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Nostratollah Naderi
- 1 Associate Professor, Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Shahid Beheshti University of Medical Science, Tehran, Iran
, Corresponding Author: Nostratollah Naderi, MD Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Shahid Beheshti University of Medical Science, Tehran, Iran Tel: + 98 21 22432521 Fax:+ 98 21 22432517
| | - Azar Sanati
- 2 Researcher, Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Seyed Reza Mohebi
- 3 Assistant Professor, Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Pedram Azimzadeh
- 2 Researcher, Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Ali Golmohamadi
- 4 Researcher, Department of Health, Iran University of Medical Sciences, Tehran, Iran
| | - Simin Nori
- 4 Researcher, Department of Health, Iran University of Medical Sciences, Tehran, Iran
| | - Mahsa Khanyaghma
- 2 Researcher, Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Shahid Beheshti University of Medical Science, Tehran, Iran
| | - Farshad Sheikhesmaeili
- 5 Assistant Professor, Liver & Digestive Research Center, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Mohamad Reza Zali
- 6 Professor, Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Shahid Beheshti University of Medical Science, Tehran, Iran
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27
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Pan HY, Pan HY, Chen L, Yang DH, Huang HJ, Tong YX, Chen CR, Yan J. Ten-year follow-up of hepatitis B relapse after cessation of lamivudine or telbivudine treatment in chronic hepatitis B patients. Clin Microbiol Infect 2015; 21:1123.e1-9. [PMID: 26253290 DOI: 10.1016/j.cmi.2015.07.023] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2015] [Revised: 07/04/2015] [Accepted: 07/24/2015] [Indexed: 12/26/2022]
Abstract
The high rate of relapse after cessation of nucleos(t)ide analogues (NUCs) treatment in chronic hepatitis B (CHB) patients leads us to reassess the feasibility for off-therapy, but long-term follow-up data are scarce. We assessed the feasibility for off-therapy by a long-term observation of relapse in response to lamivudine (LAM) and telbivudine (LdT). Eighty-six NUC-naive CHB patients, treated with LAM (n = 46) or LdT (n = 40) who reached the guidelines recommended for off-therapy, were followed for up to 10 years. Hepatitis B virus (HBV), viral serology and biochemistries were periodically determined. COX model was used to predict the risk of relapse. A total of 52.3% of patients experienced relapse within a median of 115 months (range, 61-122 months). A total of 93.3% of relapses occurred within 48 months. Relapse rates in hepatitis B e antigen (HBeAg)-positive (n = 56) and HBeAg-negative (n = 30) patients were 39.3% and 76.7%, respectively (p < 0.01). HBeAg-positive patients who achieved an early viral response (EVR), defined as undetectable HBV DNA within 6 months, had a lower relapse rate compared to non-EVR patients (21.4% vs. 59.2%, p < 0.01). EVR patients who had both lower HBV DNA (<10(6) copies/mL) at baseline and lower hepatitis B surface antigen (HBsAg) at end of treatment had a relapse rate of 10.7%. The high relapse rates in CHB patients over this 10-year follow-up make LAM or LdT off therapy infeasible in most of the cases, except in the case of HBsAg loss and/or seroconversion. HBeAg-positive patients with EVR, lower HBV DNA and HBsAg had lower relapse rates and could be good candidates for off-therapy. Long-term monitoring, especially during the first 4 years, is critical for patients off-therapy.
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Affiliation(s)
- H-Y Pan
- Department of Infectious Diseases, Zhejiang Provincial People's Hospital, Zhejiang Chinese Medicinal University, China.
| | - H-Y Pan
- Department of Medicine, Pujiang People's Hospital, China
| | - L Chen
- Zhejiang Chinese Medicinal University, China
| | - D-H Yang
- Department of Infectious Diseases, Zhejiang Provincial People's Hospital, Zhejiang Chinese Medicinal University, China
| | - H-J Huang
- Department of Infectious Diseases, Zhejiang Provincial People's Hospital, Zhejiang Chinese Medicinal University, China
| | - Y-X Tong
- Department of Infectious Diseases, Zhejiang Provincial People's Hospital, Zhejiang Chinese Medicinal University, China
| | - C-R Chen
- Department of Internal Medicine, Hangzhou Xixi Hospital, Hangzhou, Zhejiang, China
| | - J Yan
- Department of Internal Medicine, Hangzhou Xixi Hospital, Hangzhou, Zhejiang, China
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