George KK LauMBBS (HK), MRCP(UK), FHKCP, FHKAM (GI), MD(HK), FRCP (Edin, Lond)

Liver Disease In Chinese-Perspective from a practisingHepatologist

Chairman, Humanity and Health Medical Group, Hong Kong SAR, ChinaConsultant in Gastroenterology & Hepatology, Humanity and Health Medical Centre, Hong Kong SAR, China

Director, Beijing 302-Hong Kong Humanity and Health Hepatitis C Diagnosis and Treatment Center, Beijing, ChinaCo-director, Institute of Translational Hepatology, 302 Hospital, Beijing, China

HEP DART 2017, Kona, Hawaii

Hong Kong-mainland China

Beijing – Hong Kong close collaboration

Beijing 302-Hong Kong Humanity and Health Hepatitis C Diagnosis and Treatment Centre

Beijing Team

Institute of Translational Hepatology, 302 Hospital, Beijing, China

National Scientific and Technological Progress Second Class Award-2015

HBV reactivation after DAAs treatment

Hepatitis due to HBV reactivation in HBsAg+ CHC Chinese treated with pan-oral DAAs

Female 46 yrsHCV GT1bFS 5HBsAg + HBeAg -

SOF-LDVETV

Patient ID: 2493

VIEKIRA PAK

ETVPatient ID: 2419

Male 52 yrsHCV GT1bFS 17HBsAg + HBeAg -

SOF-LDV Patient ID: 2222

Female 52 yrsHCV GT1bFS 6HBsAg + HBeAg -

Wang C et al. Clin Gastroentrol Hepatol 2017;15: 132-136

US FDA Box warning for HBV reactivation after DAAs therapy for CHC

Time to HBV reactivation was significantly shorter with DAAs

DAAs-based:Mean time: 8 weeksp<0.01 for the comparison

IFN-based: Mean time:42 weeks

Chen et al, APASL (Oral presentation) Shanghai 2017

Outline

Disease Burden

CHC-Science meet Public Health

CHB-a “cure”?

Disease burden

Increasing Deaths Due To Chronic Liver Disease In China

46% 45%37%

23%

7%

26%

10%6%

0%

13%

25%

38%

50%

Liver cancer Cirrhosis

HBV HCV Alcohol Other

Causes of Death from CLD China, 2010

0

55000

110000

165000

220000

1990 1995 2000 2005 2010 2013

Liver cancer-HBV Cirrhosis-HBVLiver Cancer-HCV Cirrhosis-HCV

Causes of CLD deaths, China

54%46%

19% 21%18% 22%

8% 11%

0%

15%

30%

45%

60%

Liver cancer Cirrhosis

HBV HCV Alcohol Other

Causes of Death from CLD China, 2013

Global Burden of Disease Study 2013 Collaborators, and others.Lancet 2015; 386Cowie et al. AASLD, 2013

Birth Dose Vaccination Is Effective In Prevention Of MTCT In China

Fan R, et al. Lancet Infectious Disease 2016;16:1103-1105Cui FQ et al, Emerging Infectious Diseases 2017; 23

Reported HCV Cases Increased In China

Duan ZP et al. J Clin Gastroenterol 2014;48:679–686

Prevalence of NAFLD And Obesity, T2DM And MS Among NAFLD

Younossi et al, Hepatology. 2016 Jul;64(1):73-84. doi: 10.1002/hep.28431. Epub 2016 Feb 22

NAFLD Obesity

T2DM MS

T2DM: Type 2 Diabetes; MS: Metabolic Syndrome

Prevalence of NASH Increased In The Past 10 Years In China

Ji D, et al. Unpublished data

HCV therapy: science meets public health

Adapted from Falade-Nwulia et al. Ann Intern Med. 2017;166:637-648.

50

60

70

80

90

100

1a 1b 2 3 4 5 6

SVR

12(%

)

Genotype

Efficacy from Clinical trials

Heterogeneity between groups: p = 0.933Overall (I^2 = 88.805%, p = 0.000);

Ji

Tapper

Subtotal (I^2 = 84.429%, p = 0.000)

12

Terrault

Crespo

Backus

BackusTerrault

Ji

Subtotal (I^2 = 92.631%, p = 0.000)

Kowdley

Crespo

8

Author

2016

2016

2016

2016

2016

20162016

2016

2017

2016

Year

37

1432

271

32

1223

2475881

153

622

335

SVR12

37

1521

305

34

1333

2615971

156

634

349

Total

0.948 (0.929, 0.964)

1.000 (0.905, 1.000)

0.941 (0.928, 0.953)

0.945 (0.927, 0.962)

0.889 (0.848, 0.922)

0.941 (0.803, 0.993)

0.917 (0.901, 0.932)

0.946 (0.937, 0.955)0.907 (0.887, 0.925)

0.981 (0.945, 0.996)

0.952 (0.901, 0.986)

0.981 (0.967, 0.990)

0.960 (0.934, 0.978)

ES (95% CI)

0.948 (0.929, 0.964)

1.000 (0.905, 1.000)

0.941 (0.928, 0.953)

0.945 (0.927, 0.962)

0.889 (0.848, 0.922)

0.941 (0.803, 0.993)

0.917 (0.901, 0.932)

0.946 (0.937, 0.955)0.907 (0.887, 0.925)

0.981 (0.945, 0.996)

0.952 (0.901, 0.986)

0.981 (0.967, 0.990)

0.960 (0.934, 0.978)

ES (95% CI)

.5 .65 .85 1Proportion (%)

SVR12 rate (ITT)

Effectiveness from real-world studies

F Li…G Lau, APASL 2017, Oral presentation

Lack of diagnosisRequirement for viral load assessment

and genotypingTreatment delivery

Lau G. Lancet Gastroenterol Hepatol. 2017

PR 48• Not covered by health insurance in most

parts of China, and even in some areas where it is covered, patients still need to be hospitalized to get reimbursement.

• Out-of-pocket cost- ranges from US$ 2,500 to 10,000.

14%

30%

12,40%

0,60%

43%

Outpatient insurance coverage for anti-HCV treatment

Government employee programGovernment public program, urbanGovernment public program, ruralOther types of health insurance

Zhou et al. Hepatology, Medicine and Policy. 2016: 1:7

Drug company-driven initiatives such as tiered pricing and voluntary licensing have demonstrated insufficient benefit, and act as a barrier to universal access to essential medications compared with unfettered generic drug competition.

http://www.thebody.com/content/75438/generic-drug-registration-licensing-anda-trip-to-g.html

Swathi Iyengar, WHO, 2016

HCV RNA <15 IU/ml, n/n (%)

SOF + LDV + RBV 12 weeks (n = 63, LC)

SOF + LDV + RBV 8 weeks (n = 65, CHC)

SOF + LDV 8 weeks(n = 64, CHC) p value*

During treatmentWeek 1 10/61(16.4) 33/64 (51.6) 32/63 (50.8) 0.932Week 2 28/61 (45.9) 46/64 (71.9) 44/63 (69.8) 0.801Week 3 49/61 (80.3) 60/64 (93.8) 59/63 (93.7) 1.000Week 4 58/61 (95.1) 64/64 (100) 63/63 (100) naWeek 8 na 63/63 (100) 63/63 (100) naWeek 12 61/61 (100) na na naAfter treatmentWeek 4 61/63 (96.8) 63/65 (96.9) 62/64 (96.9) 1.000Week 8 61/63 (96.8) 63/65 (96.9) 62/64 (96.9) 1.000Week 12 (SVR 12, ITT) 61/63 (96.8) 63/65 (96.9) 62/64 (96.9) 0.989On-treatment virologic breakthrough, n 0 0 0 naRelapse after therapy, n 0 0 1 naWithdrew consent, n 2 2 1 naLost to follow-up, n 2 1 1 naCHC, chronic hepatitis C; HCV, hepatitis C virus; ITT, intention-to-treat analysis; LC, liver cirrhosis; LDV, ledipasvir; n.a., not applicable; RBV, ribavirin; SOF, sofosbuvir; SVR,sustained virologic response.

Zeng et al, Journal of Hepatology 2017

Ledipasvir-sofosbuvir (Hepcinat LP) approved by Gilead Sciences earlier in 2015 and produced by Indian Natco Pharma Limited was used.

200.100

17.425.000

- 2.000.000 4.000.000 6.000.000 8.000.000

10.000.000 12.000.000 14.000.000 16.000.000 18.000.000 20.000.000

Treated with DAAs Estimated number of HCVpatients

Only 1% of the patients were treated with DAAs by Sept 2016

WHO. Global report on access to hepatitis C treatment. Focus on overcoming barriers. 2016.Messina et al. Global distribution and prevalence of hepatitis C virus genotypes. Hepatology 2015;61:77-87

Approved Pan-oral DAAs for HCV in China, 2017: Still Expensive

3D Viekirax®

Paritaprevir 75 mg/Ritonavir 50 mg + Ombitasvir 12.5 mg+Exviera®

Dasabuvir 250mg

12 weeks ¥ 58968 CNY(USD ~9000)

Daklinza® + Sunvepra®

Daclatasvir 60mg +

Asunaprevir 100mg

24 weeks ¥ 57800 CNY(USD~8700)

Sovaldi®

Sofosbuvir 400mg

12 weeks ¥ 58,980 CNY(USD ~9000)

Comparison between HnH and TARGET in patients treated with Harvoni

8 week p value 12 week p valueHnH Target HnH Targetn=43 n=305 n=182 n=971

Sex, Male, N (%) 25 (58) 134 (44) 0.08 97 (53) 570 (59) 0.13Age, yr median (range) 49 (22-75) 58 (18-84) 0.003* 52 (20-83) 60 (21-87) <0.001*Genotype <0.001 <0.0011a 0 (0) 197 (65) 1 (0.5) 646 (67)1b 37 (86) 97 (32) 155 (85) 270 (28)Other 6 (14) 11 (4) 26 (14) 55 (6)

HCV RNA Log10 IU/mL, median (range) 6.6 (1.4-7.6) 6.0 (0-7) 0.009* 6.5 (1.4-7.7) 6.3 (0-8) <0.001*HCV RNA >=6 million IU/mL N (%) 13 (30) 13 (4) <0.001 67 (37) 177 (18) <0.001Albumin g/dl, median (range) 4.1 (2.9-5.6) 4.1 (2.6-5.1) 0.35* 3.9 (1.6-5.1) 4.1 (1.3-6.9) 0.005*Albumin>=3.5 g/dl N (%) 39 (91) 267 (88) 0.56 134 (74) 730 (75) 0.77T Bilirubin mg/dl, median (range) 0.8 (0.2-2.3) 0.5 (0.1-2.3) 0.58 0.9 (0.1-13.7) 0.6 (0.1-7.0) <0.001*T Bilirubin <=1.2 mg/dl N (%) 34 (79) 288 (94) <0.001* 131 (72) 773 (80) 0.015Platelets, median (range) 143 (53-381) 228 (62-581) <0.001* 124 (18-359) 186 (6-647) <0.001*Cirrhosis 12 (33) 3 (1) <0.001 88 (52) 259 (27) <0.001IL28bC/C 23 (56) - 120 (72) -C/T 18 (44) - 46 (27) -T/T 0 (0) - 1 (0.6) -

ITT SVR12 rate, % (95%CI)95.3 (87.2-

99.4) 88.8 (85.3-92.3) 0.19 98.3 (95.2-99.6)90.7 (88.9-

92.5) <0.001* significance test by two-sample t-test was done to compare the difference between mean

BL, D2, D4, wk 1,2,4,8 and 12

1 Division of Gastroenterology & Hepatology, Humanity & Health Medical Centre, Hong Kong, Hong Kong SAR, China.2 Second Liver Cirrhosis Diagnosis and Treatment Center, 302 Hospital, Beijing, 100039, China. 3 Service d’Hépatologie, Hôpital Pitié-Salpêtrière, Paris, France.4 Institute of Infectious Disease, 302 Hospital, Beijing, 100039, China.5 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, 510515, China6 Hong Kong Molecular Pathology Diagnostic Centre, Hong Kong SAR, China.7 Center for AIDS Research, Department of Pediatrics, Emory University School of Medicine and Veterans Affairs Medical Center, Atlanta, GA, 30322, USA8 Theoretical Biology and Biophysics, MS-K710, Los Alamos National Laboratory, Los Alamos, NM 87545, USA9 Department of Mathematics, North Carolina State University, Raleigh, NC 27695, USA

Lau G. Lancet Gastroenterol Hepatol. 2016

• Sofosbuvir (SOF, NS5B inhibitor) 400 mg/ledipasvir (LDV, NS5A inhibitor) 90 mg once daily• Daclatasvir (DCV, NS5A inhibitor) 60 mg once daily• Simeprevir (SMV, a protease/ NS3/4 inhibitor) 150 mg once daily• Asunaprevir (ASV, a protease/ NS3/4 inhibitor) 100 mg twice daily

Day 0 3521 1052

GT-1bNon-

cirrhotic Chinese

N=26

Group 1: SOF+LDV+ASV N=12

Group 2: SOF+DCV+SMV N=6

Follow up

Follow up

Follow up

Group 1: SOF+LDV+ASV N=6

Group 2: SOF+DCV+SMV N=6

Group 3: SOF+DCV+ASVN=6

Patie

nt ra

ndom

ly a

ssig

ned

Group 3: SOF+DCV+ASVN=8

Plasma HCV RNA < 500 IU/ml by Day 2

Lau G. Lancet Gastroenterol Hepatol. 2016

0

10

20

30

40

50

60

70

80

90

100

Day 2 Day 4 Day 7 Week 2 Week 3 Fu_Week 4 Fu_Week 12

16,7

83,3

100 100 100 100 100

33,3 33,3

66,7

0 0

33,3

83,3

SVR

12(%

)

SOF+LDV+ASV(Group 1)SOF+DCV+SMV(Group 2)SOF+DCV+ASV(Group 3)

1/6

100 100 100 100 100 100 100

2/60/6 0/6

2/65/6 2/6

4/66/6 5/6

6/66/6 6/6

6/66/6 6/6

6/66/6 6/6

6/66/6

% p

atie

nts w

ith H

CV R

NA

< LL

OQ

(IT

T)

Lau G. Lancet Gastroenterol Hepatol. 2016

Duration(weeks) Treatment-naive cirrhosis

Sustainedvirological

response (n [%])Sofosbuvir and odalasvir (PROXY) 6 Yes No 12 (100%)Ledipasvir, sofosbuvir, GS-9669 (SYNERGY) 6 Yes No 19(95%)Ledipasvir, sofosbuvir, GS-9451 (SYNERGY) 6 Yes No 19(95%)Sofosbuvir, ledipasvir, ribavirin (ELECTRON) 6 Yes No 17(68%)Sofosbuvir, velpatasvir, voxilaprevir (formerly GS-9857; LEPTON) 6 Yes No 14(93%)

Grazoprevir, elbasvir, sofosbuvir (C-SWIFT) 6 Yes No 26 (87%)Daclatasvir, asunaprevir, beclabuvir, sofosbuvir(FOURward) 6 Yes No 8 (57%)

Sofosbuvir, velpatasvir, voxilaprevir (LEPTON) 6 No Yes 20 (67%)Ledipasvir, sofosbuvir, GS-9451 (SYNERGY) 6 No Yes (48%) 20 (80%)Grazoprevir, elbasvir, sofosbuvir (C-SWIFT) 6 Yes Yes 16 (80%)Sofosbuvir, velpatasvir, voxilaprevir (LEPTON) 6 Yes Yes 13 (87%)Ledipasvir, sofosbuvir, GS-9451 (SYNERGY) 6 Yes Yes (40%) 18 (72%)Ledipasvir, sofosbuvir, GS-9451 (SYNERGY) 4 Yes No 10 (40%)Ledipasvir, sofosbuvir, GS-9451, GS-9669 (SYNERGY) 4 Yes No 5 (20%)Grazoprevir, elbasvir, sofosbuvir (C-SWIFT) 4 Yes No 10 (32%)Sofosbuvir, velpatasvir, voxilaprevir (LEPTON) 4 Yes No 4 (27%)Daclatasvir, asunaprevir, beclabuvir, sofosbuvir(FOURward) 4 Yes No 4 (29%)

Sofosbuvir, ledipasvir, asunaprevir (SODAPI) 3 Yes (50%) No 6 (100%)Sofosbuvir, ledipasvir, asunaprevir (SODAPI) 3 Yes (67%) No 6 (100%)Sofosbuvir, ledipasvir, asunaprevir (SODAPI) 3 Yes (83%) No 6 (100%)

Emmanuel B, …, Lau G. Lancet Gastroenterol Hepatol. 2017

SYNERGY study:SOF + LDV + GS9451 ± GS9669 for 4 weeks

Virological response based on baseline RAV

Kohli A, et al. Ann Intern Med. 2015;163:899-907

0

10

20

30

40

50

60

70

80

90

100

Absence of any NS3, NS5A, orNS5B RAV

Presence of ≥1 NS3, NS5A, or NS5B RAV

SVR1

2 (%

)

0

10

20

30

40

50

60

70

80

90

100

Absence of NS3, NS5A, or NS5BRAV with >20-fold resistance

Presence of NS3, NS5A, or NS5BRAV with >20-fold resistance

SVR1

2 (%

)

11/29

4/21

15/40

0/10

P = 0.35 P = 0.022

Resistant Associated Variants (RAVs) with drug resistance have emerged both in vitro and in clinical trials, leading guidance to recommend resistance testing in patients in whom treatment has failed and in selected regimens at baseline.

Niebel M et al. Lancet Gastroenterol Hepatol. 2017; 2.

NS3 protease sequences

NS5A sequences

NS5B polymerase sequences

Chen GF et al, APASL 2017, Oral presentation

3 logreduction

Current price(96729)

2 logreduction

1 logreduction

172,2

17,11,77 0,24

020406080

100120140160180200

Price per bottle

Cost savings (US$ Billion)

130

172193

225

0

50

100

150

200

250

40% 67% 80% 100%Proportion of patients who can achieve HCV

RNA<500 IU/mL by day 2

Cost savings (US$ Billion)

Even the price could be reduced by 3 log to US$96 per bottle, the government could stillsave US$240 million using Response-Guided Therapy.

Ceiling prices restrict market negotiations by setting maximum prices purchasers can pay for drugs

Reference prices use local or international price comparisons of drugs classified in a group as therapeutically similar to determine a single or maximum price for all drugs in that group

Profit limits control how much profit a drug manufacturer may earn per product or within a specified period of time.

John E. Dicken. An Overview of Approaches to Negotiate Drug Prices Used by Other Countries and U.S. Private Payers and Federal Programs. Thursday, January 11, 2007

A MUST: Strong recommendation by WHO

WHO. Guidelines for the screening, care and treatment of persons with hepatitis C infection.2014Duan et al. J Clin Gastroenterol. 2014; 48: 8

What is the real burden of HCV

Bland–Altman bias plot of differences(A) Compared with the Abbott RealTime assay in plasma

(B) Xpert HCV Viral Load assay for HCV RNA detection in finger-stick capillary whole-blood samples compared with the Abbott RealTime assay in plasma

Grebely et al, Lancet Gastroenterol Hepatol 2017; 2: 514–20

• Major barriers– Lack of diagnosis– Requirement for viral load assessment and genotyping– Treatment delivery

Strategy Point-to-care Short treatment duration Government efforts to negotiate with better price

Lau G. Lancet Gastroenterol Hepatol. 20

Therapies For Chronic Hepatitis B

Conventional/Peg-IFN α-2a: • Sustained off-therapy

response (immune control)• Low HBV DNA level (<2000 IU/ml)

and Normal ALT level• Finite therapy Relapse

Sustained Remission (<20%)

Chronic Hepatitis B

Nucleos(t)ide analogues (NUCs):• Maintained on-treatment response (viral control)• Undetectable HBV DNA level and Normal ALT• Lifelong or indefinite

There are 30 approved registration for generic Tenofovir in China

TenofovirBrand Name Viread Ke Lao Er Bei Xin

Packaging

Company GSK Aahui Biochem Bio-Pharmaceutical Co., Ltd. Brilliant

Dosage form Tablets Tablets Dispersible Tablets

Price / month US$ 74 US$ 64 US$ 74

TenofovirBrand Name Qing Zhong Fu Gan Ding

Packaging

Company Chitai Tianqing Fujian Consunter Pharmaceutical

Dosage form Tablets Capsules

Price / month US$ 70 US$ 67

EntecavirBrandName Baraclude Leiyide Run Zhong Tian Ding

Packaging

Company BMS Dawnrays Pharmaceutical Chiatai Tianqing Chiatai Tianqing

Dosageform Tablets Dispersible tablets Dispersible Tablets Tablets

Price /month US$ 105 ~ 150 US$ 83 US$ 48 ~ 60 US$ 52

EntecavirBrandName Gan Ze Wei Li Qing En Gan Ding Bei Shuang Ding

Packag-ing

Company Chiatai Tianqing Qingfeng Pharmaceutical Fujian ConsunterPharmaceutical

Aahui Biochem Bio-Pharmaceutical Co., Ltd.

DosageForm Capsules Dispersible tablets Capsules Dispersible Tablets

Price /Month US$ 56.76 US$ 64.28 US$ 28.28 US$ 30.17

There are 35 approved registration for generic Entecavir in China

Estimated number of diagnosed with HBV ontreatment in China

Global Hepatitis Report 2017. Geneva: World Health Organization; 2017.Cui Y, Jia JD. Journal of Gastroenterology and Hepatology 2013; 28

120 million CHB

patients

9% know their diagnosis

864,000 on treatment

8%on

treatment

Do we need an HBV cure?

Nayagam S, et al. Lancet Infect Dis 2016;16:1399-408

Impact on Total Cost of Global Eradication

CURE reduce total costs by >10% (> USD $5 Billion)

Non-invasive Method To Screen Liver Fibrosis In General Population: Example From China

Distribution of Liver Fibrosis In Chinese General Population (N= 174,314)

90,2 87,583,7

79,685,4

7,5 9,4 11,5 13,810,5

1,6 2,1 3,1 4,1 2,70,6 0,8 1,2 1,8 1,00,1 0,2 0,5 0,6 0,40,0

25,0

50,0

75,0

100,0

18-29 30-44 45-59 60-75 TotalAge group

F0F1 (<=7.3) F2 (7.3-9.7) F2F3 (9.7-12.4) F3F4 (12.4-17.5) F4 (>=17.5)

Usefulness of screening in general population

Advanced fibrosis with normal ALTAdvanced fibrosis with normal

ALT, HBsAg-N = 566 N=150

Male 408 (72.1) 124 (82.7)Age, years 52.5 (22-75) 52 (25-74)BMI>24 kg/m2 404 (71.4) 114 (76.0)

n=404 n=114Liver steatosis (UAP) 257.2 (187-400) 262.5 (216-377)Minimal (<240) 124 (30.7) 28 (24.6)Mild (240-264) 99 (24.5) 31 (27.2)Moderate (265-294) 86 (21.3) 22 (19.3)Severe (>=295) 95 (23.5) 33 (29)GGT>=50 84 (20.1) 25 (21.9)Impaired glucose (FBG>=6.1) 72 (17.8) 17 (14.9)Total Cholestrol>5.2 158 (39.1) 41 (36.0)HDL>1.42 119 (29.4) 31 (27.2)LDL<2.1 61 (15.1) 23 (20.2)Triglyceride>1.7 187 (46.3) 58 (50.9)HBsAg- 114 (28.2)+ 13 (3.2)Unknown 277 (68.6)

Continous variables are presented as median (range); Categorical variables are presented as number (percentage).

• Collaboration platform for professionals from mainland China, Taiwan, Hong Kong and Macau to research fatty liver disease• Targets to prevent and control the rapidly increased prevalence of fatty liver disease in the region•http://www.gc-flc.or

Greater China Fatty Liver Consortium (GC-FLC)

What we need in the near future?

Biological samples and paired biopsy specimenNext-generation functional genomics-

PNPLA3ProteinomicsLipid profilingmiRNA-miRNA-12213-carbon isotope

❖ Humanity & Health Medical Group, Hong Kong

❖ Vanessa Wu❖ Yudong Wang❖ Cheng Wang❖ Jing Chen❖ Catherine Lok❖ April Wong

❖ 302 Hospital, Beijing❖ Wang FS❖ Guofeng Chen❖ Zhang Zheng ❖ Qing Shao❖ Jin Li❖ Dong Ji❖ Bing Li❖ Jialiang Liu❖ Xiaxiao Niu❖ Shiying Ding

❖ Nanfang Hospital, Guangzhou❖ Jinlin Hou❖ Jian Sun❖ Zhang Xiao Yong

❖ Hôpital Pitié-Salpêtrière, Paris ❖ Yves Benhamou

❖ Hong Kong Molecular Pathology Diagnostic Centre

❖ Chris L.P. Wong❖ Stella T.Y. Tsang

❖ Los Alamos National Laboratory❖ Alan S. Perelson❖ Ruian Ke❖ Ruy M. Ribeiro

❖ Emory University❖ Raymond F. Schinazi❖ Leda Bassit❖ Hui-Mien Hsiao

❖ Patients

❖ ABL SA, Luxembourg❖ Chalom B. Sayada❖ Dimitri Gonzalez❖ Ronan Boulmé

Ethics Science Quality

Look Forward to future collaboration