Study to Evaluate the Safety and Efficacy of Switching to Tenofovir Alafenamide (TAF) From Tenofovir Disoproxil Fumarate (TDF) and/or Other Oral Antiviral Treatment (OAV)
- Registration Number
- NCT03180619
- Lead Sponsor
- Gilead Sciences
- Brief Summary
The primary objective of this study is to evaluate the safety and tolerability and virologic response of tenofovir alafenamide (TAF) in virologically suppressed chronic hepatitis B participants with renal and/or hepatic impairment.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 124
All Participants (Parts A and B):
- Adult male or non-pregnant female individuals
- Documented evidence of chronic HBV infection
- Alanine aminotransferase (ALT) ≤ 10 × upper limit of normal (ULN)
Part A Only (renal impairment):
-
Maintained on TDF and/or other OAV treatment(s) for CHB for at least 48 weeks and with viral suppression (HBV deoxyribonucleic acid [DNA] < lower limit of quantitation [LLOQ]) for ≥ 6 months prior to screening
- All individuals must have HBV DNA < 20 International units per milliliter (IU/mL) at screening by central laboratory
- Both Hepatitis B e-Antigen (HBeAg) positive and negative individuals are eligible to participate
-
Moderate renal impairment (30 milliliters per minute [mL/min] ≤ estimated glomerular filtration rate by the cockcroft-gault formula [eGFRcg] ≤ 59 mL/min), severe renal impairment (15 mL/min ≤ eGFRcg < 30 mL/min) or end stage renal disease (ESRD) (eGFR < 15 mL/min) maintained on hemodialysis (HD)
-
Stable renal function (for participants with moderate or severe impairment): serum creatinine measured at least once within three months prior to screening. The measurement difference between the value measured within three months prior to screening versus the screening value must be ≤ 25% of the screening value
Part B Only (hepatic impairment):
-
Maintained on TDF and/or other OAV(s) for CHB for at least 48 weeks and with viral suppression (HBV DNA < LLOQ) for ≥ 6 months prior to screening
- All individuals must have HBV DNA < 20 IU/mL at screening by central laboratory
- Both HBeAg positive and negative individuals are eligible to participate
-
Child-pugh-turcotte (CPT) score of 7-12 (inclusive) OR a past history of CPT score ≥ 7 and any CPT score ≤ 12 at screening
-
eGFRCG ≥ 30 mL/min using the Cockcroft-Gault equation
Key
All Individuals (Parts A & B):
- Women who are breastfeeding or who believe they may wish to become pregnant during the course of the study
- Males and females of reproductive potential who are unwilling to use an "effective", protocol-specified method(s) of contraception during the study
- Co-infection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), or hepatitis D virus (HDV)
- Prior Interferon (IFN) use within 6 months of screening
- Evidence of hepatocellular carcinoma
- Received solid organ or bone marrow transplant
- Significant cardiovascular, pulmonary, or neurological disease
- Malignancy within 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (basal cell skin cancer, etc.). Individuals under evaluation for possible malignancy are not eligible
- Currently receiving therapy with immunomodulators (e.g. corticosteroids), nephrotoxic agents, or agents capable of modifying renal excretion
- Known hypersensitivity to study drugs, metabolites, or formulation excipients
- Current alcohol or substance abuse judged by the investigator to potentially interfere with individual's compliance
- Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the individual unsuitable for the study or unable to comply with dosing requirements.
Part A Only (Renal Impairment):
-
Current or historical evidence of clinical hepatic decompensation (e.g., ascites, encephalopathy or variceal hemorrhage)
-
Abnormal hematological and biochemical parameters, including:
- Hemoglobin < 9 grams per deciliter (g/dL)
- Absolute neutrophil count < 750/cubic millimeter (mm^3)
- Platelets ≤ 50,000/mm^3
- Aspartate aminotransferase (AST) > 10 × ULN
- Albumin < 3.0 g/dL
- Total bilirubin > 2.5 × ULN
- International normalized ratio of prothrombin time (INR) > 1.5 × ULN (unless stable on anticoagulant regimen)
-
Individuals with ESRD (i.e. eGFRcg < 15 mL/min) not on HD, or those on other forms of renal replacement therapy (i.e. peritoneal dialysis)
Part B Only (Hepatic Impairment):
-
Active variceal bleeding within 6 months or prior placement of a portosystemic shunt (such as transjugular intrahepatic portosystemic shunt [TIPS])
-
History of hepatorenal syndrome, hepatopulmonary syndrome, Grade 3 or Grade 4 hepatic encephalopathy, or spontaneous bacterial peritonitis within 6 months of screening
-
Grade 2 hepatic encephalopathy at screening
-
Model for end-stage liver disease (MELD) score ≥ 30
-
Abnormal hematological and biochemical parameters, including
- Absolute neutrophil count < 750/mm^3
- Platelets < 30,000/mm^3
- Hemoglobin < 8.0 g/dL
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part A (Renal Impairment): Moderate or Severe Renal Impairment TAF Participants with chronic hepatitis B (CHB) and moderate or severe renal impairment who were virologically suppressed and taking tenofovir disoproxil fumarate (TDF), a TDF-containing anti-hepatitis B virus (HBV) regimen, or other oral antivirals (OAVs), will switch to tenofovir alafenamide (TAF) and receive TAF 25 milligram (mg) tablet once daily orally for 96 weeks. Part A (Renal Impairment): End Stage Renal Disease TAF Participants with CHB and end stage renal disease who were virologically suppressed and taking TDF, a TDF-containing anti-HBV regimen, or OAVs, will switch to TAF and receive TAF 25 mg tablet once daily orally for 96 weeks. Part B: Hepatic Impairment TAF Participants with CHB and moderate or severe hepatic impairment who were virologically suppressed and taking TDF, a TDF-containing anti-HBV regimen, or OAVs, will switch to TAF and receive TAF 25 mg tablet once daily orally for 96 weeks.
- Primary Outcome Measures
Name Time Method Percentage of Participants Who Experienced Graded Treatment-Emergent Adverse Events (AEs) at Week 24 Week 24 Treatment-emergent AEs were defined as:
* Any AEs with an onset date on or after the study drug start date and no later than the study drug stop date + 3 days after permanent discontinuation of study drug;
* Any AEs with onset date on or after the study drug start date for those who have not permanently discontinued study drug;
* Any AEs leading to premature discontinuation of study drug.
The most severe graded AE from all tests was counted for each participant.Percentage of Participants Achieving Virologic Response (Plasma Hepatitis B Virus [HBV] Deoxyribonucleic Acid [DNA] < 20 IU/mL) at Week 24 Week 24 The percentage of participants with HBV DNA \< 20 IU/mL at Week 24 was determined by the Missing = Failure (M = F) approach.
Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 24 Week 24 Graded treatment-emergent laboratory abnormalities were defined as values that increased at least 1 toxicity grade from baseline at any postbaseline visit, up to and including the date of last dose of study drug + 3 days for participants who permanently discontinued study drug or the last available date in the database snapshot for participants who were on treatment at the time of the analysis.
The most severe graded abnormality from all tests was counted for each participant.
- Secondary Outcome Measures
Name Time Method Percentage of Participants Achieving Virologic Response (Plasma HBV DNA < 20 IU/mL) at Week 96 Weeks 96 The percentage of participants with HBV DNA \< 20 IU/mL at Week 48 was determined by the Missing = Failure (M = F) approach.
Percent Change From Baseline in Spine BMD at Week 24 Baseline, Week 24 Percent change = Change from baseline at a postbaseline visit/baseline \* 100%.
Percentage of Participants Who Experienced Graded Treatment-Emergent AEs at Week 96 Week 96 Treatment-emergent AEs were defined as: Any AEs with an onset date on or after the study drug start date and no later than the study drug stop date + 3 days after permanent discontinuation of study drug; Any AEs with onset date on or after the study drug start date for those who have not permanently discontinued study drug; Any AEs leading to premature discontinuation of study drug. The most severe graded AE from all tests was counted for each participant.
Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 48 Week 48 Graded treatment-emergent laboratory abnormalities were defined as values that increased at least 1 toxicity grade from baseline at any postbaseline visit, up to and including the date of last dose of study drug + 3 days for participants who permanently discontinued study drug or the last available date in the database snapshot for participants who were on treatment at the time of the analysis.
The most severe graded abnormality from all tests was counted for each participant.Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 24 Baseline, Week 24 Percent change = Change from baseline at a postbaseline visit/baseline \* 100%.
Percent Change From Baseline in Hip BMD at Week 48 Baseline, Week 48 Percent change = Change from baseline at a postbaseline visit/baseline \* 100%.
Percent Change From Baseline in Hip BMD at Week 96 Baseline, Week 96 Percent change = Change from baseline at a postbaseline visit/baseline \* 100%.
Percent Change From Baseline in Spine BMD at Week 48 Baseline, Week 48 Percent change = Change from baseline at a postbaseline visit/baseline \* 100%.
Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Detected (≥ Lower Limit of Detection [LLOD]) at Week 24 Week 24 The percentage of participants with HBV DNA \< 20 IU/mL and target detected (≥ LLOD; i.e. 10 IU/mL) at Week 24 was determined by the M = F approach.
Percentage of Participants With Serological Response: Seroconversion to Anti-HBe in HBeAg-Positive Participants at Week 24 Week 24 HBeAg seroconversion was defined as HBeAg loss and HBeAb test changing from negative/missing at baseline to positive at a postbaseline visit. The M = F approach was used for this analysis.
Percentage of Participants With Serological Response: Seroconversion to Anti-HBe in HBeAg-Positive Participants at Week 96 Week 96 HBeAg seroconversion was defined as HBeAg loss and HBeAb test changing from negative/missing at baseline to positive at a postbaseline visit. The M = F approach was used for this analysis.
Change From Baseline in FibroTest® Score at Week 96 Week 96 The FibroTest® score is used to assess liver fibrosis. Scores range from 0.00 to 1.00, with higher scores indicating a greater degree of fibrosis. Change from baseline was calculated as the value at Week 96 minus the value at Baseline.
Percentage of Participants Who Experienced Graded Treatment-Emergent AEs at Week 48 Week 48 Treatment-emergent AEs were defined as: Any AEs with an onset date on or after the study drug start date and no later than the study drug stop date + 3 days after permanent discontinuation of study drug; Any AEs with onset date on or after the study drug start date for those who have not permanently discontinued study drug; Any AEs leading to premature discontinuation of study drug. The most severe graded AE from all tests was counted for each participant.
Change From Baseline in Estimated Glomerular Filtration Rate by the Cockcroft-Gault Formula (eGFRcg) in Participants With Moderate or Severe Renal Impairment and Hepatically Impaired Participants at Week 24 Baseline, Week 24 GFR is a measure of the rate at which blood is filtered by the kidney. Cockcroft-Gault is an equation (calculation) used to estimate GFR based on serum creatinine, weight, and gender. eGFRcg = (140 - age in years) x (body weight in kg) x (0.85 if female) divided by 72 x serum creatinine in mg/dL.
Moderate renal impairment= 30 mL/min ≤ eGFRCG ≤ 59 mL/min Severe renal impairment= 15 mL/min ≤ eGFRCG \< 30 mL/min Change from baseline was calculated as the value at Week 24 minus the value at Baseline.Change From Baseline in eGFRcg in Participants With Moderate or Severe Renal Impairment and Hepatically Impaired Participants at Week 48 Baseline, Week 48 GFR is a measure of the rate at which blood is filtered by the kidney. Cockcroft-Gault is an equation (calculation) used to estimate GFR based on serum creatinine, weight, and gender. eGFRcg = (140 - age in years) x (body weight in kg) x (0.85 if female) divided by 72 x serum creatinine in mg/dL.
Moderate renal impairment= 30 mL/min ≤ eGFRCG ≤ 59 mL/min Severe renal impairment= 15 mL/min ≤ eGFRCG \< 30 mL/min Change from baseline was calculated as the value at Week 48 minus the value at Baseline.Change From Baseline in eGFRcg in Participants With Moderate or Severe Renal Impairment and Hepatically Impaired Participants at Week 96 Baseline, Week 96 GFR is a measure of the rate at which blood is filtered by the kidney. Cockcroft-Gault is an equation (calculation) used to estimate GFR based on serum creatinine, weight, and gender. eGFRcg = (140 - age in years) x (body weight in kg) x (0.85 if female) divided by 72 x serum creatinine in mg/dL.
Moderate renal impairment= 30 mL/min ≤ eGFRCG ≤ 59 mL/min Severe renal impairment= 15 mL/min ≤ eGFRCG \< 30 mL/min Change from baseline was calculated as the value at Week 96 minus the value at Baseline.Percent Change From Baseline in Spine BMD at Week 96 Baseline, Week 96 Percent change = Change from baseline at a postbaseline visit/baseline \* 100%.
Percentage of Participants Who Experienced Graded Treatment-Emergent Laboratory Abnormalities at Week 96 Week 96 Graded treatment-emergent laboratory abnormalities were defined as values that increased at least 1 toxicity grade from baseline at any post-baseline visit, up to and including the date of last dose of study drug + 3 days for participants who permanently discontinued study drug or the last available date in the database snapshot for participants who were on treatment at the time of the analysis. The most severe graded abnormality from all tests was counted for each participant.
Percentage of Participants Achieving Virologic Response (Plasma HBV DNA < 20 IU/mL) at Week 48 Weeks 48 The percentage of participants with HBV DNA \< 20 IU/mL at Week 48 was determined by the Missing = Failure (M = F) approach.
Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Detected (≥ LLOD) at Week 48 Week 48 The percentage of participants with HBV DNA \< 20 IU/mL and target detected (≥ LLOD; i.e. 10 IU/mL) at Week 48 was determined by the M = F approach.
Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Detected (≥ LLOD) at Week 96 Week 96 The percentage of participants with HBV DNA \< 20 IU/mL and target detected (≥ LLOD; i.e. 10 IU/mL) at Week 96 was determined by the M = F approach.
Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Not Detected (< LLOD) at Week 24 Week 24 The percentage of participants with HBV DNA \< 20 IU/mL and target not detected (\< LLOD; i.e. 10 IU/mL) at Week 24 was determined by the M = F approach.
Percentage of Participants With Serological Response: Seroconversion to Anti-HBe in HBeAg-Positive Participants at Week 48 Week 48 HBeAg seroconversion was defined as HBeAg loss and HBeAb test changing from negative/missing at baseline to positive at a postbaseline visit. The M = F approach was used for this analysis.
Percentage of Participants With Normal ALT at Week 96 by Central Laboratory and the AASLD Criteria Week 96 Central laboratory ULN for ALT were as follows: ≤ 43 U/L for males aged 18 to \< 69 years and ≤ 35 U/L for males aged ≥ 69 years; ≤ 34 U/L for females aged 18 to \< 69 years and ≤ 32 U/L for females aged ≥ 69 years. The ULN for ALT using the 2018 AASLD normal range was 25 U/L for females and 35 U/L for males. The M = F approach was used for this analysis.
Percentage of Participants With Normalized ALT at Week 48 by Central Laboratory and the AASLD Criteria Week 48 ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit. Central laboratory ULN for ALT were as follows: ≤ 43 U/L for males aged 18 to \< 69 years and ≤ 35 U/L for males aged ≥ 69 years; ≤ 34 U/L for females aged 18 to \< 69 years and ≤ 32 U/L for females aged ≥ 69 years. The ULN for ALT using the 2018 AASLD normal range was 25 U/L for females and 35 U/L for males. The M = F approach was used for this analysis.
Percentage of Participants With Normalized ALT at Week 96 by Central Laboratory and the AASLD Criteria Week 96 ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit. Central laboratory ULN for ALT were as follows: ≤ 43 U/L for males aged 18 to \< 69 years and ≤ 35 U/L for males aged ≥ 69 years; ≤ 34 U/L for females aged 18 to \< 69 years and ≤ 32 U/L for females aged ≥ 69 years. The ULN for ALT using the 2018 AASLD normal range was 25 U/L for females and 35 U/L for males. The M = F approach was used for this analysis.
Percentage of Participants With Serological Response: Loss of Hepatitis B s-Antigen (HBsAg) at Week 24 Week 24 HBsAg loss was defined as HBsAg changing from positive at baseline to negative at a postbaseline. The M = F approach was used for this analysis.
Percentage of Participants With Serological Response: Seroconversion to Anti-HBs at Week 24 Week 24 HBsAg seroconversion was defined as HBsAg loss and HBsAb test changing from negative/missing at baseline to positive at a postbaseline visit. The M = F approach was used for this analysis.
Percentage of Participants With Serological Response: Loss of HBeAg in HBeAg-Positive Participants at Week 48 Week 48 HBeAg loss was defined as HBeAg changing from positive at baseline to negative at a postbaseline. The M = F approach was used for this analysis.
Change From Baseline in Child-Pugh-Turcotte (CPT) Score in Hepatically Impaired Participants at Week 24 Baseline, Week 24 CPT scores grade the severity of cirrhosis and are used to determine the need for liver transplantation. Scores can range from 5 to 15, with higher scores indicating a greater severity of disease.
Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Not Detected (< LLOD) at Week 96 Weeks 96 The percentage of participants with HBV DNA \< 20 IU/mL and target not detected (\< LLOD; i.e. 10 IU/mL) at Week 96 was determined by the M = F approach.
Percentage of Participants With Serological Response: Loss of HBsAg at Week 96 Week 96 HBsAg loss was defined as HBsAg changing from positive at baseline to negative at a postbaseline. The M = F approach was used for this analysis.
Percentage of Participants With Serological Response: Loss of HBeAg in HBeAg-Positive Participants at Week 24 Week 24 HBeAg loss was defined as HBeAg changing from positive at baseline to negative at a postbaseline. The M = F approach was used for this analysis.
Percentage of Participants With Normal Alanine Aminotransferase (ALT) at Week 24 by Central Laboratory and the American Association for the Study of Liver Diseases (AASLD) Criteria Week 24 Central laboratory ULN for ALT were as follows: ≤ 43 U/L for males aged 18 to \< 69 years and ≤ 35 U/L for males aged ≥ 69 years; ≤ 34 U/L for females aged 18 to \< 69 years and ≤ 32 U/L for females aged ≥ 69 years. The ULN for ALT using the 2018 AASLD normal range was 25 U/L for females and 35 U/L for males. The M = F approach was used for this analysis.
Change From Baseline in FibroTest® Score at Week 24 Baseline, Week 24 The FibroTest® score is used to assess liver fibrosis. Scores range from 0.00 to 1.00, with higher scores indicating a greater degree of fibrosis. Change from baseline was calculated as the value at Week 24 minus the value at Baseline.
Percentage of Participants With Serological Response: Loss of HBsAg at Week 48 Week 48 HBsAg loss was defined as HBsAg changing from positive at baseline to negative at a postbaseline. The M = F approach was used for this analysis.
Percentage of Participants With Serological Response: Seroconversion to Anti-HBs at Week 48 Week 48 HBsAg seroconversion was defined as HBsAg loss and HBsAb test changing from negative/missing at baseline to positive at a postbaseline visit. The M = F approach was used for this analysis.
Percentage of Participants With Serological Response: Seroconversion to Anti-HBs at Week 96 Week 96 HBsAg seroconversion was defined as HBsAg loss and HBsAb test changing from negative/missing at baseline to positive at a postbaseline visit. The M = F approach was used for this analysis.
Percentage of Participants With Serological Response: Loss of HBeAg in HBeAg-Positive Participants at Week 96 Week 96 HBeAg loss was defined as HBeAg changing from positive at baseline to negative at a postbaseline. The M = F approach was used for this analysis.
Percentage of Participants With Normal ALT at Week 48 by Central Laboratory and the AASLD Criteria Week 48 Central laboratory ULN for ALT were as follows: ≤ 43 U/L for males aged 18 to \< 69 years and ≤ 35 U/L for males aged ≥ 69 years; ≤ 34 U/L for females aged 18 to \< 69 years and ≤ 32 U/L for females aged ≥ 69 years. The ULN for ALT using the 2018 AASLD normal range was 25 U/L for females and 35 U/L for males. The M = F approach was used for this analysis.
Change From Baseline in FibroTest® Score at Week 48 Baseline, Week 48 The FibroTest® score is used to assess liver fibrosis. Scores range from 0.00 to 1.00, with higher scores indicating a greater degree of fibrosis. Change from baseline was calculated as the value at Week 48 minus the value at Baseline.
Percentage of Participants With Normalized ALT at Week 24 by Central Laboratory and the AASLD Criteria Week 24 ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit. Central laboratory ULN for ALT were as follows: ≤ 43 U/L for males aged 18 to \< 69 years and ≤ 35 U/L for males aged ≥ 69 years; ≤ 34 U/L for females aged 18 to \< 69 years and ≤ 32 U/L for females aged ≥ 69 years. The ULN for ALT using the 2018 AASLD normal range was 25 U/L for females and 35 U/L for males. The M = F approach was used for this analysis.
Change From Baseline in CPT Score in Hepatically Impaired Participants at Week 96 Baseline, Week 96 CPT scores grade the severity of cirrhosis and are used to determine the need for liver transplantation. Scores can range from 5 to 15, with higher scores indicating a greater severity of disease.
Change From Baseline in MELD Score in Hepatically Impaired Participants at Week 48 Baseline, Week 48 MELD scores are used to assess prognosis and suitability for liver transplantation. Scores can range from 6 to 40, with higher scores indicating greater disease severity.
Change From Baseline in CPT Score in Hepatically Impaired Participants at Week 48 Baseline, Week 48 CPT scores grade the severity of cirrhosis and are used to determine the need for liver transplantation. Scores can range from 5 to 15, with higher scores indicating a greater severity of disease.
Change From Baseline in Model for End-Stage Liver Disease (MELD) Score in Hepatically Impaired Participants at Week 24 Baseline, Week 24 MELD scores are used to assess prognosis and suitability for liver transplantation. Scores can range from 6 to 40, with higher scores indicating greater disease severity.
Change From Baseline in MELD Score in Hepatically Impaired Participants at Week 96 Baseline, Week 96 MELD scores are used to assess prognosis and suitability for liver transplantation. Scores can range from 6 to 40, with higher scores indicating greater disease severity.
Percentage of Participants With Plasma HBV DNA < 20 IU/mL and Target Not Detected (< LLOD) at Week 48 Weeks 48 The percentage of participants with HBV DNA \< 20 IU/mL and target not detected (\< LLOD; i.e. 10 IU/mL) at Week 48 was determined by the M = F approach.
Trial Locations
- Locations (30)
Harborview Medical Center
🇺🇸Seattle, Washington, United States
University of Calgary Liver Unit
🇨🇦Calgary, Canada
Centre de Recherche du Centre Hospitalier de l'Universite de Montreal
🇨🇦Montreal, Canada
Prince of Wales Hospital
🇭🇰Shatin, NT, Hong Kong
Auckland Clinical Studies
🇳🇿Grafton, Auckland, New Zealand
Changhua Christian Hospital
🇨🇳Changhua, Taiwan
Kaohsiung Chang Gung Memorial Hospital
🇨🇳Kaohsiung City, Taiwan
Yonsei University Health System, Severance Hospital
🇰🇷Seoul, Korea, Republic of
Nottingham University Hospital
🇬🇧London, United Kingdom
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Veterans General Hospital-Taipei
🇨🇳Taipei, Taiwan
Coalition of Inclusive Medicine
🇺🇸Los Angeles, California, United States
Silicon Valley Research Institute, Inc
🇺🇸San Jose, California, United States
Toronto Liver Centre
🇨🇦Toronto, Canada
(G.I.R.I.) GI Research Institute
🇨🇦Vancouver, Canada
University Health Network,Toronto general Hospital,Toronto centre for liver disease
🇨🇦Toronto, Canada
Princess Margaret Hospital
🇭🇰Kowloon, Hong Kong
Alice Ho Miu Ling Nethersole Hospital
🇭🇰Tai Po, Hong Kong
Dipartimento di Scienze Mediche e Chirurgiche (DIMEC) AOU Policlinico S.Orsola-Malpighi di Bologna
🇮🇹Bologna, Italy
U.O. Medicina Generale Epatologia IRCCS Humanitas Centro di Ricerca Traslazionale in Epatologia
🇮🇹Rozzano, Milan, Italy
UOC Gastroenterol-Epatol.-Fondazione IRCCS Ca Granda
🇮🇹Milan, Italy
Pusan National University Hospital
🇰🇷Busan, Korea, Republic of
Dong-A University Hospital
🇰🇷Busan, Korea, Republic of
Taichung Veterans Genl Hosp
🇨🇳Taichung, Taiwan
Kaohsiung Medical University Chung-Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
Ditmanson Medical Foundation Chia-Yi Christian Hospital
🇨🇳Chiayi City, Taiwan
Chang Gung Medical Foundation, Linkou Chang Gung Memorial Hospital
🇨🇳Taoyuan City, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
King's College Hospital NHS Foundation Trust
🇬🇧London, United Kingdom
Asan Medical Center
🇰🇷Seoul, Korea, Republic of