Clinical trial NCT00388674: Study of Entecavir in Patients With Chronic Hepatitis B Virus (HBV) Infection
Official title: Randomized, Observational Study of Entecavir to Assess Long-term Outcomes Associated With Nucleoside/Nucleotide Monotherapy for Patients With Chronic HBV Infection: The REALM Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Chronic Hepatitis B
Keywords: Chronic Hepatitis B Virus
Lead sponsor: Bristol-Myers Squibb
Sponsor class: INDUSTRY
First posted: 2006-10-17
Enrollment: 12522
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Chronic hepatitis B patients receiving nucleoside therapy

Brief summary: The purpose of this study is to prospectively assess the long-term outcomes (benefits and risks) associated with entecavir (ETV) therapy as compared to other antivirals approved for the treatment of chronic HBV infection. For the China substudy, patients randomized to entecavir will have safety and efficacy assessments performed during the first year of the study.


Eligibility criteria: Inclusion Criteria:

* Chronic HBV infection
* HBV nucleoside/tide-naive or -experienced
* Patients who, in opinion of investigator, are appropriate for initiating or modifying their HBV therapy and who are appropriate for a treatment regimen comprised of nucleoside/tide monotherapy with either ETV or another standard of care HBV nucleoside/tide analogue
* Age 16 and older or minimum age required in a given country

Exclusion Criteria:

* Women who are pregnant or breastfeeding
* Patients who, in the opinion of the investigator, are expected to have a liver transplant-free survival of less than one year
* Patients who, in the opinion of the investigator, are virologically controlled on their current treatment regimen and clinically responding to treatment, unless the regimen needs to be modified for medication intolerance
* Coinfection with HIV
* History of malignant neoplasm(s), including hepatocellular carcinoma (HCC) and carcinoma in situ (CIS), but excluding non-melanoma skin cancers
* Patients with chronic renal insufficiency, defined as a creatinine clearance \< 50 ml/min who do not have either of the following means of dose reducing ETV:

  i. an approved country-specific ETV label which includes the extended interval ETV dose modification method and/or ii. an approved country specific label for the ETV oral solution AND access to the oral solution
* History of dysplastic liver nodules
* Known history of allergy to nucleoside/tide analogues
* Prior or current treatment with entecavir
* An investigator proposed study regimen which will include only interferon-alfa
* An investigator proposed study regimen of combination (two or more) HBV nucleoside/tide analogues

Primary outcomes:
measure: Number of Participants With Adjudicated Overall Malignant Neoplasms
timeFrame: 10 years
measure: Number of Deaths
timeFrame: 10 years
measure: Number of Participants With Liver-related HBV Disease Progression
timeFrame: 10 years
Secondary outcomes:
measure: Number of Participants With Non-HCC Malignant Neoplasm
timeFrame: 10 years
measure: Number of Participants With HCC Malignant Neoplasm
timeFrame: 10 years
measure: Number of Participants With Liver-related Death
timeFrame: 10 years
Other outcomes:
Locations:
city: Coronado
country: United States
facility: Scti Research Foundation
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Comprehensive Transplant Center
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente Medical Center
state: California
city: Farmington
country: United States
facility: University Of Connecticut Health Center
state: Connecticut
city: Miami
country: United States
facility: University Of Miami Center For Liver Diseases
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Atlanta
country: United States
facility: Atlanta Gastroenterology Associates
state: Georgia
city: Chicago
country: United States
facility: Rush University Med Ctr
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: New Orleans
country: United States
facility: Tulane University Health Sciences Center
state: Louisiana
city: Flushing
country: United States
facility: Medical Procare, Pllc
state: New York
city: Flushing
country: United States
facility: Office Of Sing Chan Md
state: New York
city: New York
country: United States
facility: Beth Israel Medical Center
state: New York
city: New York
country: United States
facility: Va New York Harbor Healthcare System
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Oklahoma City
country: United States
facility: Integris Baptist Medical Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Phgi Associates, Ltd
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson Medical College
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Upmc Center For Liver Diseases
state: Pennsylvania
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Ciudad De Buenos Aires
country: Argentina
facility: Local Institution
state: Buenos Aires
city: El Palomar
country: Argentina
facility: Local Institution
state: Buenos Aires
city: San Salvador De Jujuy
country: Argentina
facility: Local Institution
state: Jujuy
city: Guaymallen
country: Argentina
facility: Local Institution
state: Mendoza
city: Salta
country: Argentina
facility: Local Institution
state: Provincia de Salta
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Buenos Aires
country: Argentina
facility: Local Institution
city: Neuquen
country: Argentina
facility: Local Institution
city: Rio Branco
country: Brazil
facility: Local Institution
state: AC
city: Manaus
country: Brazil
facility: Local Institution
state: Amazonas
city: Salvador
country: Brazil
facility: Local Institution
state: Bahia
city: Salvador
country: Brazil
facility: Local Institution
state: Bahia
city: Goiania
country: Brazil
facility: Local Institution
state: Goias
city: Cuiaba
country: Brazil
facility: Local Institution
state: Mato Grosso
city: Belo Horizonte
country: Brazil
facility: Local Institution
state: Minas Gerais
city: Belo Horizonte
country: Brazil
facility: Local Institution
state: Minas Gerais
city: Belo Horizonte
country: Brazil
facility: Local Institution
state: Minas Gerais
city: Ipatinga
country: Brazil
facility: Local Institution
state: Minas Gerais
city: Juiz De Fora
country: Brazil
facility: Local Institution
state: Minas Gerais
city: Curitiba
country: Brazil
facility: Local Institution
state: Parana
city: Belem
country: Brazil
facility: Local Institution
state: Para
city: Recife
country: Brazil
facility: Local Institution
state: Pernambuco
city: Rio De Janeiro / Rj
country: Brazil
facility: Local Institution
state: Rio de Janeiro
city: Porto Alegres/rs
country: Brazil
facility: Local Institution
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Local Institution
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Local Institution
state: Rio Grande Do Sul
city: Sao Jose
country: Brazil
facility: Local Institution
state: Santa Catarina
city: Campinas
country: Brazil
facility: Local Institution
state: Sao Paulo
city: Campinas
country: Brazil
facility: Local Institution
state: Sao Paulo
city: Marilia
country: Brazil
facility: Local Institution
state: Sao Paulo
city: Santo Andre - Sp
country: Brazil
facility: Local Institution
state: Sao Paulo
city: Sao Jose Do Rio Preto
country: Brazil
facility: Local Institution
state: Sao Paulo
city: Sorocaba
country: Brazil
facility: Local Institution
state: Sao Paulo
city: Sao Paulo
country: Brazil
facility: Local Institution
state: SP
city: Ribeirao Preto
country: Brazil
facility: Local Institution
city: Rio De Janeiro
country: Brazil
facility: Local Institution
city: Rio De Janeiro
country: Brazil
facility: Local Institution
city: Sao Paulo
country: Brazil
facility: Local Institution
city: Calgary
country: Canada
facility: Local Institution
state: Alberta
city: Edmonton
country: Canada
facility: Local Institution
state: Alberta
city: Vancouver
country: Canada
facility: Local Institution
state: British Columbia
city: Toronto
country: Canada
facility: Local Institution
state: Ontario
city: Montreal
country: Canada
facility: Local Institution
state: Quebec
city: Hefei
country: China
facility: Local Institution
state: Anhui
city: Beijing
country: China
facility: Local Institution
state: Beijing
city: Beijing
country: China
facility: Local Institution
state: Beijing
city: Beijing
country: China
facility: Local Institution
state: Beijing
city: Beijing
country: China
facility: Local Institution
state: Beijing
city: Beijing
country: China
facility: Local Institution
state: Beijing
city: Chongqing
country: China
facility: Local Institution
state: Chongqing
city: Chongqing
country: China
facility: Local Institution
state: Chongqing
city: Guangzhou
country: China
facility: Local Institution
state: Guangdong
city: Guangzhou
country: China
facility: Local Institution
state: Guangdong
city: Shenzhen
country: China
facility: Local Institution
state: Guangdong
city: Guiyang
country: China
facility: Local Institution
state: Guizhou
city: Haikou
country: China
facility: Local Institution
state: Hainan
city: Zhengzhou
country: China
facility: Local Institution
state: Henan
city: Zhengzhou
country: China
facility: Local Institution
state: Henan
city: Wuhan
country: China
facility: Local Institution
state: Hubei
city: Changsha
country: China
facility: Local Institution
state: Hunan
city: Changsha
country: China
facility: Local Institution
state: Hunan
city: Nanjing
country: China
facility: Local Institution
state: Jiangsu
city: Nanjing
country: China
facility: Local Institution
state: Jiangsu
city: Nanjing
country: China
facility: Local Institution
state: Jiangsu
city: Suzhou
country: China
facility: Local Institution
state: Jiangsu
city: Changchun
country: China
facility: Local Institution
state: Jilin
city: Dalian
country: China
facility: Local Institution
state: Liaoning
city: Shenyang
country: China
facility: Local Institution
state: Liaoning
city: Shenyang
country: China
facility: Local Institution
state: Liaoning
city: Taiyuan
country: China
facility: Local Institution
state: Shan1xi
city: Xi'an
country: China
facility: Local Institution
state: Shan3xi
city: Xi'an
country: China
facility: Local Institution
state: Shan3xi
city: Jinan
country: China
facility: Local Institution
state: Shandong
city: Shanghai
country: China
facility: Local Institution
state: Shanghai
city: Shanghai
country: China
facility: Local Institution
state: Shanghai
city: Shanghai
country: China
facility: Local Institution
state: Shanghai
city: Shanghai
country: China
facility: Local Institution
state: Shanghai
city: Shanghai
country: China
facility: Local Institution
state: Shanghai
city: Shanghai
country: China
facility: Local Institution
state: Shanghai
city: Chengdu
country: China
facility: Local Institution
state: Sichuan
city: Tianjin
country: China
facility: Local Institution
state: Tianjin
city: Tianjin
country: China
facility: Local Institution
state: Tianjin
city: Kunming
country: China
facility: Local Institution
state: Yunnan
city: Hangzhou
country: China
facility: Local Institution
state: Zhejiang
city: Hangzhou
country: China
facility: Local Institution
state: Zhejiang
city: Linhai
country: China
facility: Local Institution
state: Zhejiang
city: Ningbo
country: China
facility: Local Institution
state: Zhejiang
city: Guangzhou
country: China
facility: Local Institution
city: ShangHai
country: China
facility: Local Institution
city: Bogota
country: Colombia
facility: Local Institution
state: Cundinamarca
city: Bogota
country: Colombia
facility: Local Institution
city: Brno
country: Czechia
facility: Local Institution
city: Hradec Kralove
country: Czechia
facility: Local Institution
city: Ostrava
country: Czechia
facility: Local Institution
city: Prague 8
country: Czechia
facility: Local Institution
city: Usti Nad Labem
country: Czechia
facility: Local Institution
city: Creteil
country: France
facility: Local Institution
city: Grenoble Cedex 9
country: France
facility: Local Institution
city: Lille
country: France
facility: Local Institution
city: Limoges Cedex
country: France
facility: Local Institution
city: Lyon
country: France
facility: Local Institution
city: Paris Cedex 14
country: France
facility: Local Institution
city: Paris Cedex
country: France
facility: Local Institution
city: Paris
country: France
facility: Local Institution
city: Vandoeuvre Cedex
country: France
facility: Local Institution
city: Berlin
country: Germany
facility: Local Institution
city: Bonn
country: Germany
facility: Local Institution
city: Dusseldorf
country: Germany
facility: Local Institution
city: Hamburg
country: Germany
facility: Local Institution
city: Leipzig
country: Germany
facility: Local Institution
city: Tuebingen
country: Germany
facility: Local Institution
city: Wurzburg
country: Germany
facility: Local Institution
city: Athens
country: Greece
facility: Local Institution
state: Kolonaki
city: Alexandroupolis
country: Greece
facility: Local Institution
city: Athens
country: Greece
facility: Local Institution
city: Athens
country: Greece
facility: Local Institution
city: Hyderabad
country: India
facility: Local Institution
state: Andhra Pradesh
city: Hyderabad
country: India
facility: Local Institution
state: Andhra Pradesh
city: Hyderabad
country: India
facility: Local Institution
state: Andhra Pradesh
city: Hyderabad
country: India
facility: Local Institution
state: Andhra Pradesh
city: Visakhapatnam
country: India
facility: Local Institution
state: Andhra Pradesh
city: Secunderabad
country: India
facility: Local Institution
state: Andhra Pradsh
city: Ahemedabad
country: India
facility: Local Institution
state: Gujarat
city: Ahmedabad
country: India
facility: Local Institution
state: Gujarat
city: Gurgaon
country: India
facility: Local Institution
state: Haryana
city: Bangalore
country: India
facility: Local Institution
state: Karnataka
city: Bangalore
country: India
facility: Local Institution
state: Karnataka
city: Mangalore
country: India
facility: Local Institution
state: Karnataka
city: Kochi
country: India
facility: Local Institution
state: Kerala
city: Bhopal
country: India
facility: Local Institution
state: Madhya Pradesh
city: Nagpur
country: India
facility: Local Institution
state: Maharashtra
city: Nasik
country: India
facility: Local Institution
state: Maharashtra
city: Ludhiana
country: India
facility: Local Institution
state: Punjab
city: Jaipur
country: India
facility: Local Institution
state: Rajasthan
city: Madurai
country: India
facility: Local Institution
state: Tamil Nadu
city: Chennai
country: India
facility: Local Institution
state: Tamilnadu
city: Madurai
country: India
facility: Local Institution
state: Tamilnadu
city: Lucknow
country: India
facility: Local Institution
state: Uttar Pradesh
city: Coimbatore
country: India
facility: Local Institution
city: Hyderabad
country: India
facility: Local Institution
city: Indore
country: India
facility: Local Institution
city: Kolkata
country: India
facility: Local Institution
city: Ludhiana
country: India
facility: Local Institution
city: Mumbai
country: India
facility: Local Institution
city: New Delhi
country: India
facility: Local Institution
city: Bologna
country: Italy
facility: Local Institution
city: Napoli
country: Italy
facility: Local Institution
city: Rome
country: Italy
facility: Local Institution
city: Ansan-si
country: Korea, Republic of
facility: Local Institution
state: Gyeonggi-do
city: Uijeongbu-Si
country: Korea, Republic of
facility: Local Institution
state: Gyeonggi-do
city: Bucheon
country: Korea, Republic of
facility: Local Institution
city: Busan
country: Korea, Republic of
facility: Local Institution
city: Busan
country: Korea, Republic of
facility: Local Institution
city: Busan
country: Korea, Republic of
facility: Local Institution
city: Busan
country: Korea, Republic of
facility: Local Institution
city: Chuncheon
country: Korea, Republic of
facility: Local Institution
city: Chung-ju
country: Korea, Republic of
facility: Local Institution
city: Dae-jeon
country: Korea, Republic of
facility: Local Institution
city: Daegu
country: Korea, Republic of
facility: Local Institution
city: Daegu
country: Korea, Republic of
facility: Local Institution
city: Daejeon City
country: Korea, Republic of
facility: Local Institution
city: Gangneung-si
country: Korea, Republic of
facility: Local Institution
city: Goyang
country: Korea, Republic of
facility: Local Institution
city: Gwangju
country: Korea, Republic of
facility: Local Institution
city: Gyeonggi-do
country: Korea, Republic of
facility: Local Institution
city: Gyeongju
country: Korea, Republic of
facility: Local Institution
city: Incheon
country: Korea, Republic of
facility: Local Institution
city: Incheon
country: Korea, Republic of
facility: Local Institution
city: Jinju
country: Korea, Republic of
facility: Local Institution
city: Koyang City
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Seoul
country: Korea, Republic of
facility: Local Institution
city: Sungnam-si
country: Korea, Republic of
facility: Local Institution
city: Sungnam
country: Korea, Republic of
facility: Local Institution
city: Suwon-si
country: Korea, Republic of
facility: Local Institution
city: Suwon
country: Korea, Republic of
facility: Local Institution
city: Ulsan
country: Korea, Republic of
facility: Local Institution
city: Wonju
country: Korea, Republic of
facility: Local Institution
city: Saltillo
country: Mexico
facility: Local Institution
state: Coahuila
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Guadalajara
country: Mexico
facility: Local Institution
state: Jalisco
city: Zapopan
country: Mexico
facility: Local Institution
state: Jalisco
city: Zapopan
country: Mexico
facility: Local Institution
state: Jalisco
city: Cuernavaca
country: Mexico
facility: Local Institution
state: Morelos
city: Monterrey, N.l.
country: Mexico
facility: Local Institution
state: Nuevo Leon
city: Monterrey
country: Mexico
facility: Local Institution
state: Nuevo Leon
city: Culiacan, Sin.
country: Mexico
facility: Local Institution
state: Sinaloa
city: Boca Del Rio
country: Mexico
facility: Local Institution
state: Veracruz
city: Distrito Federal
country: Mexico
facility: Local Institution
city: Durango
country: Mexico
facility: Local Institution
city: Cebu City
country: Philippines
facility: Local Institution
city: Davao City
country: Philippines
facility: Local Institution
city: Ermita Manila
country: Philippines
facility: Local Institution
city: Manila
country: Philippines
facility: Local Institution
city: Manila
country: Philippines
facility: Local Institution
city: Metro Manila
country: Philippines
facility: Local Institution
city: Quezon City
country: Philippines
facility: Local Institution
city: Krakow
country: Poland
facility: Local Institution
city: Krakow
country: Poland
facility: Local Institution
city: Lodz
country: Poland
facility: Local Institution
city: Poznan
country: Poland
facility: Local Institution
city: Raciborz
country: Poland
facility: Local Institution
city: Szczecin
country: Poland
facility: Local Institution
city: Zawiercie
country: Poland
facility: Local Institution
city: Braga
country: Portugal
facility: Local Institution
city: Coimbra
country: Portugal
facility: Local Institution
city: Lisbon
country: Portugal
facility: Local Institution
city: Porto
country: Portugal
facility: Local Institution
city: Bucharest
country: Romania
facility: Local Institution
city: Bucharest
country: Romania
facility: Local Institution
city: Bucharest
country: Romania
facility: Local Institution
city: Bucharest
country: Romania
facility: Local Institution
city: Bucharest
country: Romania
facility: Local Institution
city: Constanta
country: Romania
facility: Local Institution
city: Iasi
country: Romania
facility: Local Institution
city: Timisoara
country: Romania
facility: Local Institution
city: Kazan
country: Russian Federation
facility: Local Institution
state: Tatarstan
city: Arkhangelsk
country: Russian Federation
facility: Local Institution
city: Irkutsk
country: Russian Federation
facility: Local Institution
city: Kirov
country: Russian Federation
facility: Local Institution
city: Krasnoyarsk
country: Russian Federation
facility: Local Institution
city: Lipetsk
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Moscow
country: Russian Federation
facility: Local Institution
city: Nizhniy Novgord
country: Russian Federation
facility: Local Institution
city: Nizhniy Novgorod
country: Russian Federation
facility: Local Institution
city: Ryazan
country: Russian Federation
facility: Local Institution
city: Samara
country: Russian Federation
facility: Local Institution
city: Yakutsk
country: Russian Federation
facility: Local Institution
city: Singapore
country: Singapore
facility: Local Institution
city: Granada
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution
city: Madrid
country: Spain
facility: Local Institution
city: Oviedo
country: Spain
facility: Local Institution
city: San Sebastian Guipuzcuoa
country: Spain
facility: Local Institution
city: Sevilla
country: Spain
facility: Local Institution
city: Valencia
country: Spain
facility: Local Institution
city: Kaohsiung
country: Taiwan
facility: Local Institution
city: Kaohsiung
country: Taiwan
facility: Local Institution
city: Taichung
country: Taiwan
facility: Local Institution
city: Taichung
country: Taiwan
facility: Local Institution
city: Taichung
country: Taiwan
facility: Local Institution
city: Tainan
country: Taiwan
facility: Local Institution
city: Taipei
country: Taiwan
facility: Local Institution
city: Taipei
country: Taiwan
facility: Local Institution
city: Taipei
country: Taiwan
facility: Local Institution
city: Young Kang City
country: Taiwan
facility: Local Institution
city: Hatyai
country: Thailand
facility: Local Institution
state: Songkhla
city: Bangkok
country: Thailand
facility: Local Institution
city: Bangkok
country: Thailand
facility: Local Institution
city: Bangkok
country: Thailand
facility: Local Institution
city: Khon Kaen
country: Thailand
facility: Local Institution
city: Pathumthani
country: Thailand
facility: Local Institution
city: Adana
country: Turkey
facility: Local Institution
city: Ankara
country: Turkey
facility: Local Institution
city: Eskisehir
country: Turkey
facility: Local Institution
city: Izmir
country: Turkey
facility: Local Institution
city: Izmir
country: Turkey
facility: Local Institution
city: Kayseri
country: Turkey
facility: Local Institution
city: Trabzon
country: Turkey
facility: Local Institution
Study officials:
affiliation: Bristol-Myers Squibb
name: Bristol-Myers Squibb
role: STUDY_CHAIR
References:
citation: Lim JK, Chang AY, Zaman A, Martin P, Fernandez-Rodriguez CM, Korkmaz M, Rossi S, Ford JM, Noonan T, Cooney E, Navarro V, Colombato L. Clinical Outcome Event Adjudication in a 10-Year Prospective Study of Nucleos(t)ide Analogue Therapy for Chronic Hepatitis B. J Clin Transl Hepatol. 2020 Dec 28;8(4):377-384. doi: 10.14218/JCTH.2020.00039. Epub 2020 Oct 10.
citation: Hou JL, Zhao W, Lee C, Hann HW, Peng CY, Tanwandee T, Morozov V, Klinker H, Sollano JD, Streinu-Cercel A, Cheinquer H, Xie Q, Wang YM, Wei L, Jia JD, Gong G, Han KH, Cao W, Cheng M, Tang X, Tan D, Ren H, Duan Z, Tang H, Gao Z, Chen S, Lin S, Sheng J, Chen C, Shang J, Han T, Ji Y, Niu J, Sun J, Chen Y, Cooney EL, Lim SG. Outcomes of Long-term Treatment of Chronic HBV Infection With Entecavir or Other Agents From a Randomized Trial in 24 Countries. Clin Gastroenterol Hepatol. 2020 Feb;18(2):457-467.e21. doi: 10.1016/j.cgh.2019.07.010. Epub 2019 Jul 12.
citation: Hou JL, Jia JD, Wei L, Zhao W, Wang YM, Cheng M, Tang X, Tan DM, Ren H, Tang H, Cohen D, Llamoso C. Efficacy and safety of entecavir treatment in a heterogeneous CHB population from a 'real-world' clinical practice setting in China. J Viral Hepat. 2013 Nov;20(11):811-20. doi: 10.1111/jvh.12115.