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Rodríguez M, Buti M, Esteban R, Lens S, Prieto M, Suárez E, García-Samaniego J. Consensus document of the Spanish Association for Study of the Liver on the treatment of hepatitis B virus infection (2020). GASTROENTEROLOGIA Y HEPATOLOGIA 2020; 43:559-587. [PMID: 32778356 DOI: 10.1016/j.gastrohep.2020.03.011] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/11/2020] [Accepted: 03/31/2020] [Indexed: 12/14/2022]
Abstract
Hepatitis B virus (HBV) infection remains a global public health problem. HBV vaccination is the most effective tool to reduce the incidence of HBV disease. Despite there has not been new clinical developments for the treatment of chronic hepatitis B in the last few years, changing epidemiology and current insights on natural history, diagnostic tools and therapy indications make necessary an update of the former version of the consensus document of the Spanish Association for Study of the Liver on the treatment of hepatitis B infection published in 2012. The current document updates the management of chronic hepatitis B. The treatment of choice is the long-term administration of a nucleos(t)ide analogue with high barrier to resistance (entecavir, tenofovir or tenofovir alafenamide). Pegylated interferon may be an option in patients with non-advanced liver disease, but its applicability is limited due to the low efficacy and poor tolerability. All patients must be monitored for the risk of progression to advanced liver disease and development of hepatocellular carcinoma.
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Affiliation(s)
- Manuel Rodríguez
- Sección de Hepatología, Servicio de Digestivo, Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Oviedo, España.
| | - María Buti
- Servicio de Hepatología-Medicina Interna, Hospital Universitario Valle Hebrón, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CiBERehd), Barcelona, España
| | - Rafael Esteban
- Servicio de Hepatología-Medicina Interna, Hospital Universitario Valle Hebrón, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CiBERehd), Barcelona, España
| | - Sabela Lens
- Servicio de Hepatología, Hospital Clínic, IDIBAPS, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CiBERehd), Universidad de Barcelona, Barcelona, España
| | - Martín Prieto
- Sección de Hepatología, Servicio de Medicina Digestiva, Hospital Universitari ì Politècnic La Fe, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CiBERehd), Valencia, España
| | - Emilio Suárez
- Unidad de Enfermedades Digestivas, Hospital Universitario Virgen de Valme, Sevilla, España
| | - Javier García-Samaniego
- Unidad de Hepatología, Hospital Universitario La Paz, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CiBERehd), Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid, España.
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Wang YH, Liao J, Zhang DM, Wu DB, Tao YC, Wang ML, Chen EQ, Tang H. Tenofovir monotherapy versus tenofovir plus entecavir combination therapy in HBeAg-positive chronic hepatitis patients with partial virological response to entecavir. J Med Virol 2020; 92:302-308. [PMID: 31609007 DOI: 10.1002/jmv.25608] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2019] [Revised: 09/24/2019] [Accepted: 10/08/2019] [Indexed: 02/05/2023]
Abstract
AIMS The aim of this retrospective study was to compare the efficacy and safety of tenofovir disoproxil fumarate (TDF) monotherapy and TDF + entecavir (ETV) combination therapy for chronic hepatitis B (CHB) patients with the partial virological response (PVR) to ETV. METHODS CHB patients with PVR to ETV were switched to TDF monotherapy or TDF + ETV combination therapy. The primary efficacy outcome was a virological response (VR), and the secondary efficacy outcomes were hepatitis B e antigen (HBeAg) seroconversion and alanine aminotransferase (ALT) normalization. The primary safety outcomes were changes in serum creatinine and serum phosphorus levels. RESULTS A total of 143 patients were investigated, including 63 patients in the TDF monotherapy group and 80 patients in the TDF + ETV combination therapy group. Baseline demographics and clinical characteristics were comparable between groups. The median age of patients was 44.5 years, and 76.2% of them were male. The VR rate in TDF + ETV group was higher than that of the TDF group at 48 weeks (88.8% vs 71.4%; P = .009). At 48 weeks, the HBeAg seroconversion rate of TDF + ETV group was higher than that of the TDF group (30% vs 15.9%; P = .049). There was no significant difference in the proportion of patients with elevated ALT in the TDF group and TDF + ETV group at 48 weeks (9.5% vs 7.5%; P = .665). After adjusting the treatment regimen, serum creatinine levels increased slightly and serum phosphorus level decreased slightly in both groups. CONCLUSIONS TDF + ETV combination therapy for 48 weeks had a higher VR rate than TDF monotherapy in CHB patients with PVR to ETV.
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Affiliation(s)
- Yong-Hong Wang
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Juan Liao
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Dong-Mei Zhang
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Dong-Bo Wu
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Ya-Chao Tao
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Meng-Lan Wang
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - En-Qiang Chen
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, Sichuan, China
| | - Hong Tang
- Center of Infectious Diseases, West China Hospital of Sichuan University, Chengdu, Sichuan, China
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Kim DY, Park JY. Step-down strategy in antiviral resistant chronic hepatitis B patients who achieved viral suppression with rescue combination therapy. Future Virol 2018. [DOI: 10.2217/fvl-2018-0078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
In the treatment of chronic hepatitis B (CHB) patients with drug resistance, rescue combination therapy leads to viral suppression in almost all patients. However, once it is achieved, lifelong maintenance especially, by using combination therapy is not always possible in a significant proportion of patients. At present, there is no consensus on whether it is possible to switch to monotherapy from combination therapy. However, there is robust evidence to support step-down therapy, which involves switching from combination therapy to monotherapy in antiviral resistant CHB patients who achieve complete viral response from combination therapy. We review the evidence in favor of switching to monotherapy in antiviral resistant CHB patients who achieve complete viral response by combination therapy.
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Affiliation(s)
- Dong Yun Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Yonsei Liver Center, Severance Hospital, Seoul, Korea
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Kim DY, Lee HW, Song JE, Kim BK, Kim SU, Kim DY, Ahn SH, Han KH, Park JY. Switching from tenofovir and nucleoside analogue therapy to tenofovir monotherapy in virologically suppressed chronic hepatitis B patients with antiviral resistance. J Med Virol 2018; 90:497-502. [PMID: 29077211 DOI: 10.1002/jmv.24986] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2017] [Accepted: 09/27/2017] [Indexed: 12/30/2022]
Abstract
It is unclear whether chronic hepatitis B (CHB) patients with antiviral resistance, who achieve a complete virologic response (CVR) with tenofovir disoproxil fumarate (TDF) and nucleoside analogue (NUC) combination therapy, maintain CVR if switched to TDF monotherapy. We investigated the persistence of CVR after cessation of NUC in virologically suppressed antiviral resistant CHB patients using TDF+NUC combination therapy. This study recruited 76 antiviral-resistant CHB patients showing CVR on TDF+entecavir (ETV) (n = 52), TDF+lamivudine (LAM; n = 14), and TDF+telbivudine (LdT; n = 10) combination therapy, who were switched to TDF monotherapy as step-down therapy. At baseline, 47 patients were male and the median age was 53.0 years (range: 30-78 years); 72.3% cases were hepatitis B e antigen-positive (HBeAg+) and 23.7% were of liver cirrhosis. The median duration of TDF+NUC combination therapy was 20.8 months (range: 3-46 months). At a median follow-up of 24.7 months (range: 12-48 months) after switching to TDF monotherapy, all 76 patients maintained CVR, regardless of the duration of combination therapy and the type of prior NUC and antiviral resistance. Renal dysfunction was not observed during the treatment period. The step-down strategy of switching from TDF+NUC combination therapy to TDF monotherapy in virologically suppressed CHB patients with antiviral resistance should be considered.
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Affiliation(s)
- Dong Yun Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea
| | - Hye Won Lee
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Severance Hospital, Seoul, South Korea
| | - Jeong Eun Song
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Severance Hospital, Seoul, South Korea
| | - Beom Kyung Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Severance Hospital, Seoul, South Korea
| | - Seung Up Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Severance Hospital, Seoul, South Korea
| | - Do Young Kim
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Severance Hospital, Seoul, South Korea
| | - Sang Hoon Ahn
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Severance Hospital, Seoul, South Korea
| | - Kwang-Hyub Han
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Severance Hospital, Seoul, South Korea
| | - Jun Yong Park
- Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
- Yonsei Liver Center, Severance Hospital, Seoul, South Korea
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Rodríguez M, Pascasio JM, Fraga E, Fuentes J, Prieto M, Sánchez-Antolín G, Calleja JL, Molina E, García-Buey ML, Blanco MÁ, Salmerón J, Bonet ML, Pons JA, González JM, Casado MÁ, Jorquera F, the TENOSIMP-B Research Group. Tenofovir vs lamivudine plus adefovir in chronic hepatitis B: TENOSIMP-B study. World J Gastroenterol 2017; 23:7459-7469. [PMID: 29151700 PMCID: PMC5685852 DOI: 10.3748/wjg.v23.i41.7459] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2017] [Revised: 05/22/2017] [Accepted: 06/19/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To demonstrate the non-inferiority (15% non-inferiority limit) of monotherapy with tenofovir disoproxil fumarate (TDF) vs the combination of lamivudine (LAM) plus adefovir dipivoxil (ADV) in the maintenance of virologic response in patients with chronic hepatitis B (CHB) and prior failure with LAM.
METHODS This study was a Phase IV prospective, randomized, open, controlled study with 2 parallel groups (TDF and LAM+ADV) of adult patients with hepatitis B e antigen (HBeAg)-negative CHB, prior failure with LAM, on treatment with LAM+ADV for at least 6 mo, without prior resistance to ADV and with an undetectable viral load at the start of the study, in 14 Spanish hospitals. The follow-up time for each patient was 48 wk after randomization, with quarterly visits in which the viral load, biochemical and serological parameters, adverse effects, adherence to treatment and consumption of hospital resources were analysed.
RESULTS Forty-six patients were evaluated [median age: 55.4 years (30.2-75.2); 84.8% male], including 22 patients with TDF and 24 with LAM+ADV. During study development, hepatitis B virus DNA (HBV-DNA) remained undetectable, all patients remained HBeAg negative, and hepatitis B surface antigen (HBsAg) positive. Alanine aminotransferase (ALT) values at the end of the study were similar in the 2 groups (25.1 ± 7.65, TDF vs 24.22 ± 8.38, LAM+ADV, P = 0.646). No significant changes were observed in creatinine or serum phosphorus values in either group. No significant differences between the 2 groups were noted in the identification of adverse effects (AEs) (53.8%, TDF vs 37.5%, LAM+ADV, P = 0.170), and none of the AEs which occurred were serious. Treatment adherence was 95.5% and 83.3% in the TDF and the LAM+ADV groups, respectively (P = 0.488). The costs associated with hospital resource consumption were significantly lower with the TDF treatment than the LAM+ADV treatment (€4943 ± 1059 vs €5811 ± 1538, respectively, P < 0.001).
CONCLUSION TDF monotherapy proved to be safe and not inferior to the LAM+ADV combination therapy in maintaining virologic response in patients with CHB and previous LAM failure. In addition, the use of TDF generated a significant savings in hospital costs.
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Affiliation(s)
- Manuel Rodríguez
- Division of Gastroenterology and Hepatology. Hospital Universitario Central de Asturias, Oviedo 33011, Spain
| | - Juan Manuel Pascasio
- Unit for the Clinical Management of Digestive Diseases, IBIS, Hospital Universitario Virgen del Rocío, Sevilla 41013, Spain and CIBERehd
| | - Enrique Fraga
- Liver Transplantation and Hepatology Unit, Gastroenterology Service, Hospital Universitario Reina Sofía, Córdoba 14004, Spain
| | - Javier Fuentes
- Digestive Medicine Service, Hospital Universitario Miguel Servet, Zaragoza 50009, Spain
| | - Martín Prieto
- Hepatology Unit, Digestive Medicine Service, Hospital Universitari i Politècnic La Fe, Valencia 46026, Spain and CIBERehd
| | | | - José Luis Calleja
- Liver Unit, Hospital Universitario Puerta de Hierro de Majadahonda, Universidad Autónoma de Madrid, Madrid 28049, Spain
| | - Esther Molina
- Digestive Medicine Service, Hospital Clínico de Santiago de Compostela, La Coruña 15706, Spain
| | | | - María Ángeles Blanco
- Digestive Medicine Service, Hospital General Universitario Gregorio Marañón, Madrid 28007, España
| | - Javier Salmerón
- Digestive Medicine Unit, Complejo Hospitalario de Granada, Granada 18014, Spain
| | - María Lucía Bonet
- Digestive Medicine Service, Hospital Universitario Son Espases, Palma de Mallorca 07120, Spain
| | - José Antonio Pons
- Hepatology Unit, IMIB Hospital Universitario Virgen de la Arrixaca, Murcia 30120, Spain
| | - José Manuel González
- Digestive Medicine Service, Hospital Clínico Universitario de Valladolid, Valladolid 47003, Spain
| | | | - Francisco Jorquera
- Division of Gastroenterology and Hepatology, Complejo Asistencial Universitario de León, León 24001, Spain CIBERehd and IBIOMED León
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Zhang L, Zhang FK. Recent advances in treatment of chronic hepatitis B with entecavir. Shijie Huaren Xiaohua Zazhi 2017; 25:7-16. [DOI: 10.11569/wcjd.v25.i1.7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Entecavir (ETV) is a potent hepatitis B virus inhibitor with a high barrier to resistance, and it has been recommended as one of the first-line drugs for treating chronic hepatitis B (CHB) by guidelines from several international and national societies. This paper reviews the recent advances in the treatment of CHB with ETV, in terms of treatment adherence, efficacy in the treatment of various kinds of patients with CHB, management of patients with partial virological response, viral resistance or treatment failure to ETV, treatment cessation, sequential or combination therapy with ETV and pegylated interferon, as well as the surveillance of hepatocellular carcinoma.
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