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Maqsood Q, Sumrin A, Iqbal M, Younas S, Hussain N, Mahnoor M, Wajid A. Hepatitis C virus/Hepatitis B virus coinfection: Current prospectives. Antivir Ther 2023; 28:13596535231189643. [PMID: 37489502 DOI: 10.1177/13596535231189643] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/26/2023]
Abstract
In endemic areas, hepatitis C virus (HCV)/hepatitis B virus (HBV) coinfection is common, and patients with coinfection have a higher risk of developing liver disease such as hepatocellular carcinoma, liver fibrosis and cirrhosis. In such cases, HCV predominates, and HBV replication is suppressed by HCV. HCV core proteins and interferons that are activated by HCV are responsible for the suppression of HBV. Immunosuppression is also seen in patients with HCV and HBV coinfections. A decrease in HCV-neutralizing antibody response and circulation of Th1-like Tfh cells is observed in patients with HCV and HBV coinfection. Both viruses interacted in the liver, and treatment of HCV/HBV coinfection is genotype-based and complex due to the interaction of both viruses. In HCV-dominant cases, direct-acting antiviral drugs and peg interferon plus ribavirin are used for the treatment, with continuous monitoring of AST and ALT. HBV-dominant cases are less common and are treated with peg interferon and nucleoside nucleotide analogues with monitoring of AST and ALT. The SVR rate in HCV-HBV coinfection is higher than that in monoinfection when treated with direct-acting antiviral drugs. But there is a risk of reactivation of HBV during and after therapy. The rate of reactivation is lower in patients treated with direct-acting antiviral drugs as compared to those treated with peg interferon plus ribavirin. Biomarkers of HBV such as HBcrAg, HBV DNA and HBVpg RNA are not effective in the prediction of HBV reactivation; only the hepatitis B surface antigen titre can be used as a biomarker for HBV reactivation. HCV can also be reactive, but this is found in very rare cases in which HBV is present and is treated first.
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Affiliation(s)
- Quratulain Maqsood
- Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
| | - Aleena Sumrin
- Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
| | - Maryam Iqbal
- Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
| | - Saima Younas
- Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
| | - Nazim Hussain
- Centre for Applied Molecular Biology, University of the Punjab, Lahore, Pakistan
| | - Muhammada Mahnoor
- Department of Rehabilitation Science, The University of Lahore, Lahore, Pakistan
| | - Abdul Wajid
- Department of Biotechnology, Balochistan University of Information Technology, Engineering and Management Science, Quetta, Pakistan
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The Korean Association for the Study of the Liver (KASL). KASL clinical practice guidelines for management of chronic hepatitis B. Clin Mol Hepatol 2022; 28:276-331. [PMID: 35430783 PMCID: PMC9013624 DOI: 10.3350/cmh.2022.0084] [Citation(s) in RCA: 69] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Accepted: 04/01/2022] [Indexed: 01/10/2023] Open
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Zhou K, Terrault NA. Treatment of HCV, HDV, or HIV Coinfections. HEPATITIS B VIRUS AND LIVER DISEASE 2021:339-373. [DOI: 10.1007/978-981-16-3615-8_15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Shih YF, Liu CJ. Hepatitis C Virus and Hepatitis B Virus Co-Infection. Viruses 2020; 12:E741. [PMID: 32664198 PMCID: PMC7412310 DOI: 10.3390/v12070741] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2020] [Revised: 06/28/2020] [Accepted: 07/08/2020] [Indexed: 12/11/2022] Open
Abstract
Hepatitis C virus (HCV) and hepatitis B virus (HBV) co-infection can be encountered in either virus endemic countries. Co-infection can also be found in populations at risk of parenteral transmission. Previous studies demonstrated a high risk of liver disease progression in patients with HCV/HBV co-infection; thus, they should be treated aggressively. Previous evidence recommended therapy combining peginterferon (pegIFN) alfa and ribavirin for co-infected patients with positive HCV RNA. Recent trials further advise using direct-acting antivirals (DAAs) for the clearance of HCV in the co-infected patients. Reactivation of HBV has been observed in patients post-intervention, with higher risks and earlier onset in those having had HCV cured by DAA- versus pegIFN-based therapy. The mechanism of HBV reactivation is an interesting but unsolved puzzle. Our recent study revealed that in vitro HBV replication was suppressed by HCV co-infection; HBV suppression was attenuated when interferon signaling was blocked. In vivo, the HBV viremia, initially suppressed by the presence of HCV super-infection, rebounded following HCV clearance by DAA treatment and was accompanied by a reduced hepatic interferon response. In summary, major achievements in the treatment of HCV/HBV co-infection have been accomplished over the past 20 years. Future clinical trials should address measures to reduce or prevent HBV reactivation post HCV cure.
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Affiliation(s)
- Yi-Fen Shih
- Department of Physical Therapy and Assistive Technology, National Yang-Ming University, Taipei 112, Taiwan;
| | - Chun-Jen Liu
- Hepatitis Research Center, National Taiwan University Hospital, Taipei 100, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei 100, Taiwan
- Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei 100, Taiwan
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KASL clinical practice guidelines for management of chronic hepatitis B. Clin Mol Hepatol 2019; 25:93-159. [PMID: 31185710 PMCID: PMC6589848 DOI: 10.3350/cmh.2019.1002] [Citation(s) in RCA: 165] [Impact Index Per Article: 27.5] [Reference Citation Analysis] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Accepted: 03/25/2019] [Indexed: 02/06/2023] Open
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The Korean Association for the Study of the Liver (KASL). 2017 KASL clinical practice guidelines management of hepatitis C: Treatment of chronic hepatitis C. Clin Mol Hepatol 2018; 24:169-229. [PMID: 30092624 PMCID: PMC6166104 DOI: 10.3350/cmh.2018.1004] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2018] [Accepted: 03/06/2018] [Indexed: 12/11/2022] Open
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Jiang XW, Ye JZ, Li YT, Li LJ. Hepatitis B reactivation in patients receiving direct-acting antiviral therapy or interferon-based therapy for hepatitis C: A systematic review and meta-analysis. World J Gastroenterol 2018; 24:3181-3191. [PMID: 30065564 PMCID: PMC6064961 DOI: 10.3748/wjg.v24.i28.3181] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Revised: 06/02/2018] [Accepted: 06/22/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To assess the incidence of hepatitis B virus (HBV) reactivation in patients receiving direct-acting antiviral agent (DAA)-based therapy or interferon (IFN)-based therapy for hepatitis C and the effectiveness of preemptive anti-HBV therapy for preventing HBV reactivation. METHODS The PubMed, MEDLINE and EMBASE databases were searched, and 39 studies that reported HBV reactivation in HBV/hepatitis C virus coinfected patients receiving DAA-based therapy or IFN-based therapy were included. The primary outcome was the rate of HBV reactivation. The secondary outcomes included HBV reactivation-related hepatitis and the effectiveness of preemptive anti-HBV treatment with nucleos(t)ide analogues. The pooled effects were assessed using a random effects model. RESULTS The rate of HBV reactivation was 21.1% in hepatitis B surface antigen (HBsAg)-positive patients receiving DAA-based therapy and 11.9% in those receiving IFN-based therapy. The incidence of hepatitis was lower in HBsAg-positive patients with undetectable HBV DNA compared to patients with detectable HBV DNA receiving DAA therapy (RR = 0.20, 95%CI: 0.06-0.64, P = 0.007). The pooled HBV reactivation rate in patients with previous HBV infection was 0.6% for those receiving DAA-based therapy and 0 for those receiving IFN-based therapy, and none of the patients experienced a hepatitis flare related to HBV reactivation. Preemptive anti-HBV treatment significantly reduced the potential risk of HBV reactivation in HBsAg-positive patients undergoing DAA-based therapy (RR = 0.31, 95%CI: 0.1-0.96, P = 0.042). CONCLUSION The rate of HBV reactivation and hepatitis flare occurrence is higher in HBsAg-positive patients receiving DAA-based therapy than in those receiving IFN-based therapy, but these events occur less frequently in patients with previous HBV infection. Preemptive anti-HBV treatment is effective in preventing HBV reactivation.
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Affiliation(s)
- Xian-Wan Jiang
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, Zhejiang Province, China
| | - Jian-Zhong Ye
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, Zhejiang Province, China
| | - Ya-Ting Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, Zhejiang Province, China
| | - Lan-Juan Li
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, Zhejiang Province, China
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Terrault NA, Lok ASF, McMahon BJ, Chang KM, Hwang JP, Jonas MM, Brown RS, Bzowej NH, Wong JB. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology 2018; 67:1560-1599. [PMID: 29405329 PMCID: PMC5975958 DOI: 10.1002/hep.29800] [Citation(s) in RCA: 2788] [Impact Index Per Article: 398.3] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Accepted: 01/11/2018] [Indexed: 12/11/2022]
Affiliation(s)
- Norah A Terrault
- Division of Gastroenterology/Hepatology, University of California San Francisco, San Francisco, CA
| | - Anna S F Lok
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI
| | - Brian J McMahon
- Liver Diseases and Hepatitis Program, Alaska NativeTribal Health Consortium, Anchorage, AK
| | - Kyong-Mi Chang
- Division of Gastroenterology, Corporal Michael J. Crescenz VA Medical Center & University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Jessica P Hwang
- Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Maureen M Jonas
- Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA
| | - Robert S Brown
- Division of Gastroenterology and Hepatology, Weill Cornell Medical College, New York, NY
| | | | - John B Wong
- Division of Clinical Decision Making, Tufts Medical Center, Tufts University School of Medicine, Boston, MA
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Coffin CS, Terrault NA. Treatment of HCV, HDV, or HIV Coinfection. HEPATITIS B VIRUS AND LIVER DISEASE 2018:239-262. [DOI: 10.1007/978-981-10-4843-2_13] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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10
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Chen G, Wang C, Chen J, Ji D, Wang Y, Wu V, Karlberg J, Lau G. Hepatitis B reactivation in hepatitis B and C coinfected patients treated with antiviral agents: A systematic review and meta-analysis. Hepatology 2017; 66:13-26. [PMID: 28195337 DOI: 10.1002/hep.29109] [Citation(s) in RCA: 116] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2016] [Revised: 01/27/2017] [Accepted: 02/06/2017] [Indexed: 12/12/2022]
Abstract
UNLABELLED There is an increased awareness of hepatitis B (HBV) reactivation in chronic hepatitis C (CHC) patients coinfected with HBV treated with pan-oral direct-acting antiviral agents (DAAs). We performed a systematic review and meta-analysis to compare the rate of HBV reactivation in CHC patients coinfected with overt HBV (hepatitis B surface antigen [HBsAg] positive) and occult HBV (HBsAg negative with positive HBV DNA) infection separately, treated with interferon (IFN)-based therapy to those with pan-oral DAAs. The primary outcome was HBV reactivation, and the secondary outcomes included hepatitis due to HBV reactivation, sustained virologic response (SVR) for CHC, loss of HBV DNA and HBsAg seroclearance. Although the pooled incidence rate of HBV reactivation, among CHC patients with overt HBV (n = 779), was similar among those treated with IFN-based therapy (14.5%, P < 0.001) and DAAs (12.2%, P = 0.03; P = 0.91 for heterogeneity between subgroups), it was reported to occur much earlier in those treated with DAAs (4-12 weeks during treatment) than in those treated with IFN-based therapies (most at the end of treatment and some during follow-up). Also, studies with DAA-based therapies were more likely to report incidence of hepatitis due to HBV reactivation (12.2% in DAAs vs. 0% in IFN; P = 0.009 for heterogeneity between subgroups). HBV reactivation and hepatitis due to HBV reactivation also occurred, though less frequently in CHC patients with occult HBV infection. CHC SVR was not affected by HBV reactivation (P = 0.27). CONCLUSION HBV reactivation occurs earlier and is clinically more significant in CHC patients coinfected with overt and occult HBV who are treated with pan-oral DAAs compared with IFN-based therapy. It is therefore important to have all patients screened for evidence of overt or occult HBV infection and managed during pan-oral DAAs therapy. (Hepatology 2017;66:13-26).
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Affiliation(s)
- Guofeng 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.,Humanity and Health Research 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
| | - Jing Chen
- Beijing 302-Hong Kong Humanity and Health Hepatitis C Diagnosis and Treatment Center, Beijing, China.,Humanity and Health Research Centre, Hong Kong SAR, China
| | - Dong Ji
- 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
| | - Yudong Wang
- Beijing 302-Hong Kong Humanity and Health Hepatitis C Diagnosis and Treatment Center, Beijing, China.,Humanity and Health Research Centre, Hong Kong SAR, China
| | - Vanessa Wu
- Beijing 302-Hong Kong Humanity and Health Hepatitis C Diagnosis and Treatment Center, Beijing, China.,Humanity and Health Research Centre, Hong Kong SAR, China
| | - Johan Karlberg
- Humanity and Health Research Centre, Hong Kong SAR, China
| | - George Lau
- Beijing 302-Hong Kong Humanity and Health Hepatitis C Diagnosis and Treatment Center, Beijing, China.,Humanity and Health Research Centre, Hong Kong SAR, 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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11
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Yeh ML, Hsieh MY, Huang CI, Huang CF, Hsieh MH, Huang JF, Dai CY, Chuang WL, Yu ML. Long-term efficacy of Peg-Interferon/Ribavirin with and without Lamivudine therapy for HBeAg-positive hepatitis B and C dual infection. J Gastroenterol Hepatol 2016; 31:835-841. [PMID: 26478984 DOI: 10.1111/jgh.13203] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2015] [Revised: 09/21/2015] [Accepted: 10/11/2015] [Indexed: 12/23/2022]
Abstract
BACKGROUND The optimal therapeutic strategy for hepatitis B virus (HBV) e antigen (HBeAg)-seropositive and hepatitis C virus (HCV) dually infected patients remains unknown. We aimed to elucidate the effectiveness of peginterferon (Peg-IFN)/ribavirin (RBV) with and without lamivudine (LAM) combination therapy in the clinical settings. PATIENTS AND METHODS Nine patients seropositive for HBV surface antigen, HBeAg, antibodies to HCV and HCV RNA for >6 months were treated with Peg-IFN/RBV with (n = 5) and without (n = 4) a 12-month LAM add-on therapy at treatment week 12. The treatment duration of Peg-IFN/RBV was 24 weeks (HCV genotype 1 [HCV-1] with rapid virological response [RVR] or HCV-2) or 48 weeks (HCV-1 without RVR). Primary endpoints included HBeAg loss and HCV-sustained virological response (SVR). RESULTS All of the nine patients had undetectable HCV RNA at treatment weeks 4 and 12 and end-of-Peg-IFN/RBV therapy. However, SVR was achieved in 100% of patients treated with triple therapy, compared with only 50% in those with Peg-IFN/RBV therapy (P = 0.167). The 3-year durability of HCV SVR was 100%. HBeAg loss and HBV DNA <2000 IU/mL at 6 months post-LAM treatment were found in 100% and 40% of patients treated with triple therapy, compared with none of the four patients with Peg-IFN/RBV therapy achieved any HBV responses. Of the five patients with triple therapy, four had persistent HBeAg loss during 3-year follow-up period; one developed HBeAg seroreversion 15 months after treatment. CONCLUSION For HBeAg-positive HBV/HCV dually infected patients, Peg-IFN/RBV was effective for HCV eradication. Add-on LAM might promote HBeAg loss in the clinical setting.
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Affiliation(s)
- Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Yen Hsieh
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ching-I Huang
- Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Occupational Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Meng-Hsuan Hsieh
- Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Preventive Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Center for Lipid Science and Aging Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan
- Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Center for Lipid Science and Aging Research, Kaohsiung Medical University, Kaohsiung, Taiwan
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The Korean Association for the Study of the Liver (KASL). KASL clinical practice guidelines: management of chronic hepatitis B. Clin Mol Hepatol 2016; 22:18-75. [PMID: 27044762 PMCID: PMC4825166 DOI: 10.3350/cmh.2016.22.1.18] [Citation(s) in RCA: 150] [Impact Index Per Article: 16.7] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2016] [Accepted: 02/22/2016] [Indexed: 01/10/2023] Open
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The Korean Association for the Study of the Liver (KASL). KASL clinical practice guidelines: management of hepatitis C. Clin Mol Hepatol 2016; 22:76-139. [PMID: 27044763 PMCID: PMC4825161 DOI: 10.3350/cmh.2016.22.1.76] [Citation(s) in RCA: 63] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2016] [Accepted: 02/22/2016] [Indexed: 12/11/2022] Open
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Yeh ML, Hsieh MY, Huang CI, Huang CF, Hsieh MH, Liang PC, Lin YH, Hou NJ, Lin ZY, Chen SC, Huang JF, Dai CY, Chuang WL, Yu ML. Personalized Therapy of Chronic Hepatitis C and B Dually Infected Patients With Pegylated Interferon Plus Ribavirin: A Randomized Study. Medicine (Baltimore) 2015; 94:e1837. [PMID: 26496327 PMCID: PMC4620800 DOI: 10.1097/md.0000000000001837] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2015] [Revised: 09/19/2015] [Accepted: 09/23/2015] [Indexed: 12/18/2022] Open
Abstract
We aimed to investigate whether response-guided therapy (RGT) with peginterferon-alpha plus ribavirin by using hepatitis C virus (HCV) genotype, pretreatment HCV RNA levels, and rapid virological response (RVR, undetectable HCV RNA at treatment week 4) could be applied for active HCV/hepatitis B virus (HBV) dually infected patients, without compromised the treatment efficacy.A total of 203 patients, seropositive of HCV antibody, HCV RNA and HBV surface antigen (HBsAg), and seronegative for HBV e antigen for >6 months, were randomized to receive peginterferon-alpha/ribavirin by either genotype-guided therapy (GGT, n = 102: HCV genotype 1 [HCV-1], 48 weeks; HCV-2/3, 24 weeks) or RGT (n = 101: HCV-1, 48 or 24 weeks if patients with baseline VL <400,000 IU/mL and RVR; HCV-2/3, 24 or 16 weeks if patients with RVR). The primary endpoint was HCV-sustained virological response (SVR).The HCV SVR rate was comparable between the GGT (77.5%, 79/102) and RGT groups (70.3%, 71/101, P = 0.267), either among HCV-1/HBV (69.4% [43/62] vs 63.5% [40/63], P = 0.571) or among HCV-2/3/HBV (90.0% [36/40] vs 81.6% [31/38], P = 0.342) dually infected patients based on intention-to-treat analysis. In HCV-1/HBV dually infected patients, RVR (odds ratio [OR]: 6.05; 95% confidence intervals [CI]: 2.148-17.025, P = 0.001) and lower pretreatment blood glucose levels (OR: 0.97; CI: 0.944-0.989, P = 0.003) were independent predictors of HCV SVR. Although RVR (OR: 10.68; CI: 1.948-58.514, P = 0.006) was the only significant factor associated with HCV SVR in HCV-2/3/HBV dually infected patients. HBsAg loss at 1 year posttreatment was observed in 17 of 185 (9.2%) patients. The rates of discontinuation and adverse events were similar between the 2 groups.RGT with peginterferon-alpha/RBV may be considered for HBeAg-negative HBV/HCV dually infected patients.
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Affiliation(s)
- Ming-Lun Yeh
- From the Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital (M-LYeh, M-YH, C-FH, P-CL, Y-HL, Z-YL, S-CC, J-FH, C-YD, W-LC, M-LYu), Faculty of Internal Medicine, College of Medicine, and Graduate Institute of Clinical Medicine, and Center for Infectious Disease and Cancer Research, Kaohsiung Medical University (M-LYeh, C-FH, M-HH, Z-YL, S-CC, J-FH, C-YD, W-LC; M-LYu), Institute of Biomedical Sciences, National Sun Yat-Sen University (M-LYu), Department of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital (C-IH, N-JH), Department of Occupational Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University (C-FH), Department of Preventive Medicine, Kaohsiung Medical University Hospital (M-HH), Graduate Institute of Medicine, College of Medicine (M-LYeh, C-YD), Center for Infectious Disease and Cancer Research; and Center for Lipid Science and Aging Research, Kaohsiung Medical University, Kaohsiung, Taiwan (C-YD, W-LC, M-LYu)
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Liu CJ, Chen PJ, Chen DS, Tseng TC, Kao JH. Perspectives on dual hepatitis B and C infection in Taiwan. J Formos Med Assoc 2015; 115:298-305. [PMID: 26188762 DOI: 10.1016/j.jfma.2015.06.005] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2015] [Revised: 06/04/2015] [Accepted: 06/09/2015] [Indexed: 02/06/2023] Open
Abstract
Dual hepatitis C virus (HCV) and hepatitis B virus (HBV) infection is not rare in HBV or HCV endemic areas, and can be found in populations at risk of parenteral viral transmission. Clinical observatory studies suggest a higher risk of liver disease progression in patients with dual HCV/HBV infection than in HBV or HCV monoinfected patients. Recent trials confirmed that combination therapy of peginterferon alfa-2a or alfa-2b and ribavirin was effective and safe in dually infected patients with positive HCV RNA. Moreover, about 30% of the dually infected patients cleared hepatitis B surface antigen within 5 years after the start of peginterferon-based therapy. The optimal treatment strategies for dually infected patients with active hepatitis B, with decompensated cirrhosis, or in other clinical situations should be explored in further studies. Finally, the advent of new direct-acting antiviral-based anti-HCV therapy may lead to the development of strategies for the treatment of dually infected patients with active hepatitis C, particularly for those not tolerating or not eligible for peginterferon-based therapy. Notably, direct-acting antivirals would not have any activity against HBV infection; simultaneous or on-demand nucleos(t)ide analogs would be needed if clinically indicated.
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Affiliation(s)
- Chun-Jen Liu
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan.
| | - Pei-Jer Chen
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan
| | - Ding-Shinn Chen
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan
| | - Tai-Chung Tseng
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan
| | - Jia-Horng Kao
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan; Department of Internal Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan; Hepatitis Research Center, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan
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16
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Wahle RC, Perez RM, Pereira PF, Oliveira EMG, Emori CT, Uehara SNDO, Silva ISDS, Silva AEB, Ferraz MLG. Hepatitis B virus reactivation after treatment for hepatitis C in hemodialysis patients with HBV/HCV coinfection. Braz J Infect Dis 2015; 19:533-7. [PMID: 25997784 PMCID: PMC9427496 DOI: 10.1016/j.bjid.2015.04.003] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2014] [Revised: 12/30/2014] [Accepted: 04/17/2015] [Indexed: 12/30/2022] Open
Abstract
In coinfected HBV/HCV patients, HBV replication is usually suppressed by HCV over the time. No study to date has evaluated the HBV viremia in long-term follow-up after HCV treatment in hemodialysis patients with HBV/HCV coinfection. This study aimed to assess the evolution of HBV viremia after HCV treatment in this special population. Ten hemodialysis patients with HBV/HCV coinfection with dominant HCV infection (HBV lower than 2000 IU/mL) and significant fibrosis were treated with interferon-alpha 3 MU 3×/week for 12 months and could be followed for at least 36 months after HCV treatment. Six cases of HBV reactivation (60%) during follow-up were observed and 5/6 had been successfully treated for HCV. Patients with HBV reactivation received anti-HBV therapy. Our preliminary findings indicate that treatment of hepatitis C in HBV/HCV coinfected hemodialysis patients may favor HBV reactivation. Thus, continued monitoring of HBV viremia must be recommended and prompt anti-HBV therapy should be implemented.
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Affiliation(s)
- Raul Carlos Wahle
- Discipline of Gastroenterology, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.
| | - Renata Mello Perez
- Department of Internal Medicine, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, Brazil
| | - Patrícia Fucuta Pereira
- Discipline of Gastroenterology, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil
| | | | - Christini Takemi Emori
- Discipline of Gastroenterology, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil
| | | | | | | | - Maria Lucia Gomes Ferraz
- Discipline of Gastroenterology, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil
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17
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Konstantinou D, Deutsch M. The spectrum of HBV/HCV coinfection: epidemiology, clinical characteristics, viralinteractions and management. Ann Gastroenterol 2015; 28:221-228. [PMID: 25830779 PMCID: PMC4367211] [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] [Received: 09/01/2014] [Accepted: 10/22/2014] [Indexed: 11/06/2022] Open
Abstract
Monoinfection with either hepatitis B (HBV) or C virus (HCV) represents one of the major causes of chronic liver disease globally. However, in endemic areas a substantial number of patients are infected with both viruses mainly as a result of the common routes of transmission. Numerous studies have demonstrated that dually infected patients carry a greater risk of advanced liver disease, cirrhosis and hepatocellular carcinoma compared with monoinfected patients. The choice of treatment is based on the virological profile of each patient taking into account the dominant virus pattern. In predominant HCV, standard combination treatment with pegylated interferon and ribavirin has proven equally effective in HBV/HCV-coinfected patients as well as in HCV-monoinfected patients. Strikingly, approximately 60% of patients with inactive HBV infection before HCV treatment may present HBV reactivation while others experience hepatitis B surface antigen seroconversion after clearing HCV, demonstrating the complexity of the interaction between the two viruses during the follow up. The therapeutic strategies for the predominant HBV dually infected patients are more vague, although high genetic barrier nucleos(t)ide analogues play an indisputable role. Finally, the recently approved combination treatments for chronic hepatitis C containing direct-acting antivirals may definitely change the treatment protocols in the future although there is no experience with these drugs in dually infected patients until today.
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Affiliation(s)
- Dimitris Konstantinou
- 2nd Department of Internal Medicine, Athens University Medical School, Hippokration General Hospital of Athens, Greece,
Correspondence to: Dimitris Konstantinou, 2nd Department of Internal Medicine, Athens University Medical School, ‘‘Hippokration’’ General Hospital of Athens, 114 Vas. Sophias Ave., 115 27 Athens, Greece, Tel.: +30 210 7774742, Fax: +30 210 7706871, e-mail:
| | - Melanie Deutsch
- 2nd Department of Internal Medicine, Athens University Medical School, Hippokration General Hospital of Athens, Greece
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18
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KASL clinical practice guidelines: management of hepatitis C. Clin Mol Hepatol 2014; 20:89-136. [PMID: 25032178 PMCID: PMC4099340 DOI: 10.3350/cmh.2014.20.2.89] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2014] [Accepted: 05/20/2014] [Indexed: 12/16/2022] Open
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Liu CJ, Chen PJ. Updates on the treatment and outcomes of dual chronic hepatitis C and B virus infection. World J Gastroenterol 2014; 20:2955-2961. [PMID: 24659886 PMCID: PMC3961993 DOI: 10.3748/wjg.v20.i11.2955] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2013] [Revised: 10/25/2013] [Accepted: 01/15/2014] [Indexed: 02/06/2023] Open
Abstract
Dual hepatitis C virus (HCV)/hepatitis B virus (HBV) infection is found in HBV or HCV endemic areas, and in specific populations exhibiting a high risk of parenteral viral transmission. Clinical observations have revealed that HCV/HBV dually infected patients demonstrate a higher risk of liver disease progression compared with HBV or HCV monoinfected patients. The viral activity responsible for liver disease progression can be determined by examining the viral loads of HCV and HBV and by conducting liver biopsy examinations. Recent trials have confirmed that the combination therapy of peginterferon alpha-2a or 2b and ribavirin for dual hepatitis patients with HCV dominance appears to be as effective and safe as it is in patients with HCV monoinfections. Strikingly, approximately 60% of dually infected patients with inactive hepatitis B before treatment develop HBV reactivation after the clearance of the HCV. The clinical significance of this HBV reactivation and the strategy to prevent and treat this event should be determined. Furthermore, approximately 30% of dually infected patients lost hepatitis B surface antigen (HBsAg) within 5 years after the start of peginterferon-based therapy, and 40% of them harbored occult HBV infection. The underlying mechanisms of their accelerating HBsAg seroclearance and the development of occult HBV await further investigations. Moreover, the optimal treatment strategies for dually infected patients who are seropositive for the hepatitis B e antigen must be explored. Finally, the advent of new direct-acting antiviral-based anti-HCV therapy may change the optimal therapies for patients with dual hepatitis in the near future, which warrants further clinical trials.
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Liu CJ. Treatment of patients with dual hepatitis C virus and hepatitis B virus infection: resolved and unresolved issues. J Gastroenterol Hepatol 2014; 29:26-30. [PMID: 24199625 DOI: 10.1111/jgh.12421] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/18/2013] [Indexed: 12/13/2022]
Abstract
Dual hepatitis C virus (HCV)/hepatitis B virus (HBV) infection is not uncommon in HCV or HBV endemic areas and among subjects at risk of parenteral transmission. In patients dually infected with hepatitis C and B, the disease manifestations are usually more severe than those with either virus infection. In the past decade, the following issues have been resolved. In dually infected patients with active hepatitis C, combined pegylated interferon alfa plus ribavirin was effective, the treatment outcomes being similar to patients with HCV monoinfection. During long-term follow-up, the HCV response was sustained in around 97% of patients; and the long-term outcomes including the development of hepatocellular carcinoma and liver-related mortality were improved. However, several clinical issues remain to be resolved. First, host and viral factors influencing the long-term outcomes and treatment options in patients with dual HCV/HBV infection await further studies. Second, about 60% of dually infected patients with baseline undetectable serum HBV DNA levels develop HBV reactivation after the start of treatment. How to prevent and treat HBV reactivation should be clarified. Third, about 30% of dually infected patients lose hepatitis B surface antigen at 5 years after the end of combination therapy; the mechanisms need further investigations. Fourth, the optimal treatment strategies for dually infected patients with active hepatitis B or established cirrhosis should be explored in future clinical trials. Finally, the role of new direct-acting antiviral-based therapy for the treatment of patients with dual HCV/HBV infection also remains to be evaluated.
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Affiliation(s)
- Chun-Jen Liu
- Graduate Institute of Clinical Medicine, Department of Internal Medicine, and Hepatitis Research Center, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan
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