how to optimize hcv treatment in china-2017 and...

How to Optimize HCV Treatment

in China-2017 and beyond?

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

(Edin, Lond), FAASLD (US)

Chairman

Humanity and Health Medical Group, Hong Kong SAR, CHINA

Director and Consultant

Division of Gastroenterology and Hepatology, Humanity and Health

Medical Center, Hong Kong SAR, CHINA

Director and Professor

The Institute of Translational Hepatology

Beijing 302- HK Humanity and Health Hepatitis C center

Liver Fibrosis Diagnosis and Treatment Center

Beijing 302 Hospital, Beijing, CHINA

CHC treatment in China-

2017 and beyond

Efficacy (SVR12) of DAA-based therapy by 2017

No cirrhosis Cirrhosis

FDA-approved HCV therapy

Genoty

pe TN TE TN TE

12 wks SOF+IFN w/wo RBV GT1 87-100% 79-100% 81% -

GT2 93-100% 100% 94% -

GT3 90-100% 86% 91% 86%

GT4-6 82-100%

12 wks SOF+SMV GT1 88-100% 85-98% 66-92% 80-100%

GT4 98% 97% 81% 89-100%

12 wks SOF+LDV Harvoni® GT1 95-100% 91-100% 97-100% 91-100%

GT3-6 77-100% 84-100%

12 wks ombitasvir, paritaprevir,

ritonavir, and dasabuvir AbbVie 3D GT1 87-99% 99-100% 100% 100%

12 wks SOF+DCV w/wo RBV GT1 100% 98% 80-100% 93-100%

GT3 98-100% 94-100% 50-58% 70-88%

12 wks Grazoprevir+Elbasvir Zepatier® GT1 91-100% 90-94% 93-100% 93-100%

GT4 88-100% 100%

GT5-6 20-80%

12 wks SOF+Velpatasvir Epclusa® GT1 98-100% 96-100%

GT2 99-100% 100%

GT3 93-98% 91-100% 93% 88-89%

GT4-6 86-100% 100%

Adapted from Li et al, Antiviral Research, 2017

Current recommendation for CHC GT1-6

12-24 weeks pan-oral DAAs

(plus RBV in cirrhotic)

1. Omata M, Kanda T, Wei L, et al. APASL consensus statements and recommendation on

management of hepatitis C. Hepatol Int. 2016 Sep;10(5):702-26.

2. AASLD IDSA HCV GUIDANCE PANEL. Hepatitis C guidance: AASLD-IDSA recommendations

for testing, managing, and treating adults infected with hepatitis C virus. Hepatology

2015;62:932-954.

3. European Association for the Study of the Liver. Electronic address eee. EASL

Recommendations on Treatment of Hepatitis C 2015. J Hepatol 2015;63:199-236.

12-weeks ribavirin-free DAAs for treatment experienced

Chinese with GT1b CHC( including cirrhotic patients)

Ji D, …, Lau G. Hepatol Int (2016) 10:789–798

SVR -DAAs Vs PR72

Ji D, …, Lau G. Hepatol Int (2016) 10:789–798

DCV + ASV: firstly approved DAAs in China

DCV + ASV for CHC GT1b

- A phase 3, open-label study in Asian patients

Wei L, et al. J Gastroenterol Hepatol. 2016 Nov;31(11):1860-1867

Factors affecting sustained virologic

response (SVR24)

Wei L, et al. J Gastroenterol Hepatol. 2016 Nov;31(11):1860-1867

Efficacy and safety of DCV + ASV for HCV GT1b

- in Japanese real-life settings

SVR12 rates by baseline RAVs

Sezaki H, et al. Liver Int. 2017 Feb 8. doi: 10.1111/liv.13384

HCV drug resistance associated substitutions observedwith treatment

NS3 Protease

(180 aa)

NS5A Domain 1

(213 aa)

NS5B Polymerase (591 aa)

- Nucleotide Analog

NS5B Polymerase (591 aa)

- Non-nucleotide Analog

Lontok E, et al. Hepatology 2015;62(5): 1623 -1632

Mean Fold-Change in Resistance Compared to Wild-

Type Replicon of Clinically Relevant NS3 Protease

Resistance–Associated Substitutions

Virological response based on baseline RAV

HCV NS3

Protease AA and

Position

Resistance-

Associated

Substitution(s)

Mean Fold Change in Resistance Compared to

Wild-Type Replicon

SMV ASV

D168 D168A 784 127

D168E 38 78

D168H 401 98

D168I 1800

D168N 5.5

D168T 334

D168V 3100 280

D168Y 651 238

Q80R+D168A 2660

Q80H+D168A 145

Q80R+D168A 418


Mean Fold-Change in Resistance Compared to Wild-

Type Replicon of Clinically Relevant NS5A

Resistance–Associated Substitutions

HCV NS5A Amino

Acid and Position

Resistance-Associated

Substitution(s)

Mean Fold Change in

Resistance Compared to

Wild-Type Replicon

DCV

L31 L31M 3

L31V 15

L31M + Y93H 4227

L31V + Y93H 5425

Y93 Y93H 12


Koizumi Y, et al. PNAS 2017

Nucleoside polymerase inhibitor (Sofosbuvir) has the

largest potential to inhibit viral replication

Quantification of the instantaneous inhibitory potential (IIP) of single-HCV drugs

Triple DAAs is superior to dual DAAs-enhanced antiviral activity and lower probability of drug resistance

Koizumi Y, et al. PNAS 2017

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

Response-guided therapy – study design

• 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

Pat

ien

t ra

nd

om

ly a

ssig

ne

d

Group 3:

SOF+DCV+ASVN=8

Plasma HCV RNA < 500 IU/ml by

Day 2


Treatment response (ITT)

1/6

100 100 100 100 100 100 100

2/6

0/6 0/62/6

5/6 2/64/6

6/6 5/66/6

6/6 6/66/6

6/6 6/66/6

6/6 6/66/6

6/6

% p

atie

nts

wit

h H

CV

RN

A <

LLO

Q (

ITT)


Cost effectiveness of RGT in Chinese CHC Cost-savings by price per bottle

3 log

reduction

Current price (96729) 2 log

reduction

1 log

reduction

Even the price could be reduced by 3 log to US$96 per bottle, the

government could still save US$240 million if using response-

guided therapy.

Chen GF, Oral presentation, APASL 2017, Shanghai

Other ultra-short SOF-based DAAs trials in CHC GT1

6 weeks SVR % Clinical Trial

Odalasvir 100 (12/12) PROXY

Ledipasvir+ GS-9669 95 (19/20) SYNERGY

Ledipasvir+ GS-9451 95 (19/20) SYNERGY

Ledipasvir 68 (17/25) ELECTRON

Velpatasvir+Voxilaprevir (GS-9857) 93 (14/15) LEPTON

Grazoprevir+Elbasvir 87 (26/30) C-SWIFT

Daclatasvir+Asunaprevir+Beclabuvir 57 (8/14) FOURward


Velpatasvir+Voxilaprevir 87 (13/15) LEPTON

Ledipasvir+GS-9451 72 (18/25) SYNERGY

Velpatasvir+ Voxilaprevir 67 (20/30) LEPTON

Ledipasvir+GS-9451 80 (20/25) SYNERGY

Emmanuel B, …, Lau G. Lancet Gastroenterol Hepatol 2017 (In press)

4 weeksLedipasvir+GS-9451 40 (10/25) SYNERGY

Ledipasvir+GS-9451+GS-9669 20 (5/25) SYNERGY


Velpatasvir+Voxilaprevir 27 (4/15) LEPTON

Daclatasvir+Asunaprevir+Beclabuvir 29 (4/14) FOURward

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,or NS5B RAV

Presence of ≥1 NS3, NS5A, or NS5B RAV

SV

R1

2 (

%)

0

10

20

30

40

50

60

70

80

90

100

Absence of NS3, NS5A, orNS5B RAV with >20-fold

resistance

Presence of NS3, NS5A, orNS5B RAV with >20-fold

resistance

SV

R1

2 (

%)

11/29

4/21

15/40

0/10

P = 0.35 P = 0.022

HBV reactivation after DAAs

treatment

FDA Drug Safety Communication: FDA warns about the risk of hepatitis B reactivating in some patients treated with direct-acting antivirals for hepatitis C

Safety Announcement

[10-04-2016] The U.S. Food and Drug Administration (FDA) is warning about the risk of

hepatitis B virus (HBV) becoming an active infection again in any patient who has a current or

previous infection with HBV and is treated with certain direct-acting antiviral (DAA) medicines

for hepatitis C virus. In a few cases, HBV reactivation in patients treated with DAA medicines

resulted in serious liver problems or death.

As a result, we are requiring a Boxed Warning, our most prominent warning, about the risk of

HBV reactivation to be added to the drug labels of these DAAs directing health care

professionals to screen and monitor for HBV in all patients receiving DAA treatment. This

warning will also be included in the patient information leaflet or Medication Guides for these

medicines.

Direct-acting antiviral medicines are used to treat chronic hepatitis C virus (HCV) infection, an

infection that can last a lifetime. These medicines reduce the amount of HCV in the body by

preventing HCV from multiplying, and in most cases, they cure HCV. Without treatment, HCV

can lead to serious liver problems including cirrhosis, liver cancer, and death (see List of Direct-

Acting Antivirals).

Health care professionals should screen all patients for evidence of current or prior HBV

infection before starting treatment with DAAs, and monitor patients using blood tests for HBV

flare-ups or reactivation during treatment and post-treatment follow-up. It is currently unknown

why the reactivation occurs.

Patients should tell your health care professional if you have a history of hepatitis B infection or

other liver problems before being treated for hepatitis C. Do not stop taking your DAA medicine

without first talking to your health care professional. Stopping treatment early could result in

your virus becoming less responsive to certain hepatitis C medicines. Read the patient

information leaflet or Medication Guide that comes with each new prescription because the

information may have changed. Contact your health care professional immediately if you

develop fatigue, weakness, loss of appetite, nausea and vomiting, yellow eyes or skin, or light-

colored stools, as these may be signs of serious liver problems.

We identified 24 cases of HBV reactivation reported to FDA1 and from the published literature

in HCV/HBV co-infected patients treated with DAAs during the 31 months from November 22,

2013 to July 18, 2016.2-7

This number includes only cases submitted to FDA, so there are likely

additional cases about which we are unaware. Of the cases reported, two patients died and one

FDA Drug Safety Communication: FDA warns about the risk of hepatitis B reactivating in some patients treated with direct-acting antivirals for hepatitis C

Safety Announcement

[10-04-2016] The U.S. Food and Drug Administration (FDA) is warning about the risk of

hepatitis B virus (HBV) becoming an active infection again in any patient who has a current or

previous infection with HBV and is treated with certain direct-acting antiviral (DAA) medicines

for hepatitis C virus. In a few cases, HBV reactivation in patients treated with DAA medicines

resulted in serious liver problems or death.

As a result, we are requiring a Boxed Warning, our most prominent warning, about the risk of

HBV reactivation to be added to the drug labels of these DAAs directing health care

professionals to screen and monitor for HBV in all patients receiving DAA treatment. This

warning will also be included in the patient information leaflet or Medication Guides for these

medicines.

Direct-acting antiviral medicines are used to treat chronic hepatitis C virus (HCV) infection, an

infection that can last a lifetime. These medicines reduce the amount of HCV in the body by

preventing HCV from multiplying, and in most cases, they cure HCV. Without treatment, HCV

can lead to serious liver problems including cirrhosis, liver cancer, and death (see List of Direct-

Acting Antivirals).

Health care professionals should screen all patients for evidence of current or prior HBV

infection before starting treatment with DAAs, and monitor patients using blood tests for HBV

flare-ups or reactivation during treatment and post-treatment follow-up. It is currently unknown

why the reactivation occurs.

Patients should tell your health care professional if you have a history of hepatitis B infection or

other liver problems before being treated for hepatitis C. Do not stop taking your DAA medicine

without first talking to your health care professional. Stopping treatment early could result in

your virus becoming less responsive to certain hepatitis C medicines. Read the patient

information leaflet or Medication Guide that comes with each new prescription because the

information may have changed. Contact your health care professional immediately if you

develop fatigue, weakness, loss of appetite, nausea and vomiting, yellow eyes or skin, or light-

colored stools, as these may be signs of serious liver problems.

We identified 24 cases of HBV reactivation reported to FDA1 and from the published literature

in HCV/HBV co-infected patients treated with DAAs during the 31 months from November 22,

2013 to July 18, 2016.2-7

This number includes only cases submitted to FDA, so there are likely

additional cases about which we are unaware. Of the cases reported, two patients died and one

HBV reactivation: Case reportsAuthor HCV GT HBV status DAAs HBV Rx Outcome

Ende AR1 1b HBsAg-, anti-HBs-, anti-HBc+ SMV+SOF+RBV TDF OLTx

Takayama H2 1b HBsAg+, HBV DNA 1.7 log IU/ml ASV+DCV ETV Anicteric

hepatitis

Collins JM3

1a HBsAg+, HBeAg-

HBV DNA 3.36 log IU/ml

SMV+SOF TDF+FT

C

Icteric hepatitis

1a HBsAg-, anti-HBs-, anti-HBc+ SMV+SOF TDF No hepatitis

De Monte A4* 4d HBsAg+, HBV 8.9 log IU/mL LDV+SOF TDF Icteric hepatitis

Wang C5 1b HBsAg+, HBeAg-, HBV 7 log

IU/mL

LDV+SOF ETV Icteric hepatitis

1b HBsAg+, HBeAg-, HBV 3 log

IU/mL

LDV+SOF nil Icteric hepatitis

1b HBsAg+, HBeAg-, HBV 3 log

IU/mL

Viekera Pak ETV Hepatic failure

Pillai6 1b HBsAg+, HBV 3 log IU/mL SMV+SOF ETV Icteric hepatitis

1a HBsAg-, HBsAb-, HBcAb+, HBV <

1.3 log IU/mL

SMV+SOF TDF No hepatitis

Seto K.72a HBsAg+, HBeAg-, HBV 1.8 log

IU/mL

SOF+RBV None No hepatitis

1b HBsAg+, HBeAg-, HBV 1.8 log

IU/mL

Abbie 3D None No hepatitis

1Ende AR, et al. J Med Case Rep 2015; 2Takayama H, et al. Hepatol Res 2015. 3Collins JM, et al; Clin Infect Dis 2015;; 4De Monte

A, et al. J Clin Virol 2016; 5 Wang C et al. Clin Gastroentrol Hepatol 2017; 6 Pillai AA et al, Am J Gastroenterol. 2016, 7Seto K., et al.

Hepatol Res 2017

* HBV/HCV/HIV coinfection

327 Consecutive CHC Chinese Adults Treated With Brand-name Pan-oral DAAs - Prospective Observational Cohort Study

395 consecutive Chinese with CHC referred to

Humanity and Health Medical Centre (Hong Kong)

Refuse therapy (n=9)

327 pts. received Pan-oral DAAs

regimen

HBsAg negative (n=317)HBsAg positive (n=10)

HBsAb

positive

(n=31,

25.0%)

48 weeks pegylated interferon and

ribavirin (n=54)

HBsAb

negative

(n=93,

75.0%)

HBcAb

positive

(n=93,

75.0%)

HBcAb

negative

(n=31,

25.0%)

OBI

(n=124, 39.%)

Non-OBI

(n=193, 60.9%)

HBV/HCV coinfection patients who

were on anti-HBV treatment before

DAAs anti-HCV TREATMENT (n=5)

OBI=Occult HBV infection

Serum HBsAg negative, HBV DNA + by PCR

(>10 copies/ml)

Wang et al. Clin Gastroentrol Hepatol 2017

Hepatitis Due To HBV Reactivation In

HBsAg+ CHC Chinese


0 7 14 28 42 56 84 112 140 168

0

20

40

60

80

100

120

0

1

2

3

4

5

6

7

8

AL

T (

U/L

)&

TB

IL(u

mo

l/L

)

HC

V R

NA

&

HB

V D

NA

lo

g1

0 IU

/mL

Time (days)

Female 46 yrs

HCV GT1b

FS 5

HBsAg +

HBeAg -

SOF-LDV

ETV

Patient ID: 2493

0 7 28 42 70 84 98112 140 168 196 224 252

0

200

400

600

800

1000

1200

1400

0

1

2

3

4

5

6

7

8

9

AL

T (

U/L

) &

TB

IL(u

mo

l/L

)

HC

V R

NA

& H

BV

DN

A l

og

10 IU

/mL

Time (days)

VIEKIRA PAK

ETV

Patient ID: 2419

Male 52 yrs

HCV GT1b

FS 17

HBsAg +

HBeAg -

0 7 14 28 42 56 70 84 112 140 168

0

5

10

15

20

25

30

35

40

45

50

0

1

2

3

4

5

6

7

8

AL

T (

U/L

) &

TB

IL(u

mo

l/L

)

HC

V R

NA

& H

BV

DN

A l

og

10 IU

/mL

Time (days)

SOF-LDV Patient ID: 2222

Female 52 yrs

HCV GT1b

FS 6

HBsAg +

HBeAg -

Survival Free From Hepatitis In HBsAg Positive Patients

And HBsAg Negative Patients With And Without OBI


!

!!!!!!!!!!!!!!!

!!!!!

Figure 3. Survival free from hepatitis in H BsAg positive patients, and H BsAg negative patients with and without OBI

A. Cumulative proportion for free of hepatitis in all 327 patients who underwent DAAs treatment. p<0.001 by log rank test.

Compared to HBsAg negative patients without OBI, the risk of hepatitis was not significantly increased in HBsAg negative patients with OBI (hazard

ratio = 1.2, 95%CI: 0.3 - 5.2, p=0.84) but significantly increased in HBsAg positive patients (hazard ratio = 16.0, 95%CI: 3.6-71.8, p<0.001)

B. Cumulative proportion for free of hepatitis in 39 patients who underwent 8 weeks of DAAs treatment. p<0.001 by log rank test.


ratio = 1.5, 95%CI: 0.09 - 24.0, p=0.77) but significantly increased in HBsAg positive patients (hazard ratio = 17.2, 95%CI: 1.05-282.4, p=0.046)

C. Cumulative proportion for free of hepatitis in 276 patients who underwent 12 weeks of DAAs treatment. p<0.001 by log rank test.


ratio = 1.5, 95%CI: 0.2 - 10.8, p=0.68) but significantly increased in HBsAg positive patients (hazard ratio = 24.9, 95%CI: 3.5-177.1, p=0.001)

D. Cumulative proportion for free of hepatitis in 12 patients who underwent 24 weeks of DAAs treatment. p<0.001 by log rank test.

Only one HBsAg negative patient without OBI experienced hepatitis.

A B

C D

Cumulative proportion for free of hepatitis in all 327 patients who underwent DAAs treatment. p<0.001 by log rank test.

Compared to HBsAg negative patients without OBI, the risk of hepatitis was not significantly increased in HBsAg negative patients with OBI (hazard ratio = 1.2, 95%CI: 0.3 - 5.2,

p=0.84) but significantly increased in HBsAg positive patients (hazard ratio = 16.0, 95%CI: 3.6-71.8, p<0.001)

Bersoff-Matcha SJ, et al. Ann Intern Med 2017

Pooled incidence rate of HBV reactivation was similar when comparing IFN-based therapy to DAAs

the pooled incidence rate of HBV reactivation 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 between-

group heterogeneity). CHC SVR was not affected by HBV reactivation (p=0.27).

Chen et al, Hepatology. 2017 Feb 13. doi: 10.1002/hep.29109. [Epub ahead of print]

Pooled incidence rate of hepatitis due to HBV reactivation was significantly higher with DAAs

The pooled incidence rate of hepatitis due to HBV reactivation was significantly higher

with DAAs (12.2%, 95%CI: 0.2-33.2, p=0.03) than with interferon-based therapy (0%;

p=0.009 for between-group heterogeneity).

Chen et al, Hepatology. 2017 Feb 13. doi: 10.1002/hep.29109. [Epub ahead of print]

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

AASLD1 EASL2 US FDA3 PRAC4

Screening for

HBV serology

✔ ✔ ✔ ✔

Preemptive

NUCs

Only active

CHB

ALL HBsAg+

or OBI

Consult

Hepatologist

According to

guidelines

According to

guidelines

Monitoring ✔ ✔ ✔ ✔

1. AASLD/ISDA. HCV guidance: recommendations for testing, managing, and treating hepatitis C. Updated September 16, 2016. Pawlotsky JM et al.

2. EASL recommendations on treatment of hepatitis C 2016. Journal of Hepatology, in press, 2016.

3. The U.S. Food and Drug Administration. FDA Drug Safety Communication: FDA warns about the risk of hepatitis B reactivating in some patients

treated with direct-acting antivirals for hepatitis C. 2016 [Nov, 2016]. http://www.fda.gov/Drugs/DrugSafety/ucm522932.htm.

4. PRAC Warns Of Risk Of Hepatitis B Re-activation With Direct-acting Antivirals For Hepatitis C. http://www.benzinga.com/news/16/12/8764261/prac-

warns-of-risk-of-hepatitis-b-re-activation-with-direct-acting-antivirals

Current recommendations

Post SVR management

and complications

Does DAA therapy really increase the risk of HCC?

J Hepatol.2016;65(4):719-26.

HCC occurrence=3.2%,recurrence=28.8%HCC recurrence=27.6%

344 cirrhotic patientsmedian fu=6mon

J Hepatol.2016;65(4):727-33.

58 HCC patientsmedian fu=5.7mon

Ji D,…Lau G. EASL 2017 (oral presentation)

Patients studied

CHC patients who attended Beijing 302-Hong Kong

Humanity and Health Hepatitis C Diagnosis and

Treatment Centre

(n=1498)

patients excluded due to (n=116):

- Non-GT1b (n=90)

- Baseline HCC (n=4)

- Non-SVR (n=13)

- Patients developed HCC before SVR

or within 3 month after SVR (n=2)

- Loss of follow-up post SVR (n=7)

Treated with DAAs

(n=440)

Patients achieved SVR

included in the analysis

(n=324)

Treated with PR

(n=1058)

Patients excluded due to (n=661):

- Non-GT1b (n=236)

- Baseline HCC (n=5)

- Non-SVR (n=392)

- Patients developed HCC before SVR

or within 3 month after SVR (n=3)

- Loss of follow-up post SVR (n=25)

Patients achieved SVR

included in the analysis

(n=397)


p=0.28 by log-rank test

0.0

00.2

50

.50

0.7

51.0

0S

urv

ival

fre

e f

rom

HC

C

0 2 4 6 8Follow-up years post-SVR

DAAs PR

Liver stiffness, comorbid with DM and age are the risk factors of HCC in Chinese with GT1b HCV who achieved an SVR

DM

AHR: 3.0

(95%CI: 1.1-8.8)

p=0.04

Liver

Stiffness AHR: 1.03

(95%CI:

1.01-1.07)

p=0.045

AgeAHR: 1.07

(95%CI:

1.02-1.13)

p=0.008

Risk

Factors

Compared to IFN, DAAs was NOT a risk factor of HCC (AHR: 1.5, 0.4 – 5.6,

p=0.50) in the cohort (n=721), with adjustment of age, sex, liver stiffness, DM, ALT

and APRI score.

AHR: Adjusted Hazard Ratio; 95%CI: 95% confidence interval of AHR; APRI: AST to Platelet Ratio Index.


NO increase in occurrence of HCC post-SVR in patients treated with DAAs compared to IFN in a matched sub-cohort

Risk factors at baseline of HCC in the matched

sub-cohort

TreatmentAdjusted Hazard

Ratio (95% CI)P value

IFN 1

DAAs 2.51 (0.40-15.9) 0.33

IFN

(n=168)

DAAs

(n=168)

Age

Liver stiffness

DM

Age

Liver stiffness

DM

1:1 Matched

±2

±2

Exact

p=0.40 by log-rank test

0.0

00.2

50

.50

0.7

51.0

0S

urv

ival

fre

e f

rom

HC

C

0 2 4 6Follow-up years post-SVR

DAAs PR


What I feel?

❖Major barriers✓ Slow progress of DAAs registration ✓ RAV problem✓ HBV reactivation✓ Post SVR management

❖ Strategy✓ Response-guided therapy with viral (and

immune) response to shorten the treatment duration

✓ RAV sequencing✓ Preemptive HBV treatment✓ Frequent monitoring

Collaborators

❖ 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

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