HCV CHRONIC INFECTION TREATMENT WITH DAA:

WHO ARE THE PATIENTS THAT ARE NOT ACHIEVING

SUSTAINED VIROLOGIC RESPONSE?

R U I V A L E N T E 1 , R I TA G R Á C I O 2 , M I G U E L A C H E G A 3 , A N A C L Á U D I A M I R A N D A 4 ,

T E R E S A B A P T I S TA 4 , J A I M E N I N A 4 , F E R N A N D O V E N T U R A 4 , S U S A N A P E R E S 4 ,

I S A B E L A L D I R 4 , F E R N A N D O B O R G E S 4 , I S A B E L A N T U N E S 4 , M A R I A J O S É

C A M P O S 5 , J O Ã O P E R E I R A 6 ,

K A M A L M A N S I N H O 4

1 Serviço de Medicina Interna - Hospital Beatriz Ângelo

2 Serviço de Medicina I - Centro Hospitalar de Leiria

3 Serviço de Medicina II - Hospital Prof. Dr. Fernando da Fonseca

4 Serviço de Infecciologia e Medicina Tropical - Hospital de Egas Moniz – Centro Hospitalar de Lisboa

Ocidental

5 Serviço de Urgência – Centro Hospitalar de Lisboa Ocidental

6 Serviço de Medicina 1 – Hospital de Egas Moniz - Centro Hospitalar de Lisboa Ocidental

BACKGROUND

Hepatitis C virus (HCV) is a major healthcare problem.

Recent advances in the HCV treatment after the introduction of direct acting antiviral (DAA) brought a change in the quality of life and life expectancy of these patients.

The aim of this study is to characterize the

patients treated with DAA for chronic

hepatitis C who did not achieve sustained

virological response (SVR), with special

focus on those HIV co-infected.

MATERIALS & METHODS

Retrospective, observational study.

Individual clinical file review of HCV chronically

infected patients, with regular follow-up on an out-

patient Infectious Diseases clinic who were

eligible to start DAA treatment.

From1st January 2015 to 30 April 2017.

Demographic and HCV infection features, liver

disease staging, therapeutic regimen and

response to therapy.

Data was analyzed using Microsoft Office Excel

2010.

RESULTS

532 patients proposed to hepatitis C DAA treatment

1st January 2015 - 30 April 2017

Tabela

DEMOGRAPHICS

Mean age [min;max] 49,8 years [33;78]

Men / Women (%) 76% / 24%

Mean time HCV

diagnosis 14,2 years [1;30]

HIV co-infection (n, %) 338 (63,5)

HCV treatment

experienced (n, %) 157 (29)

TRANSMISSION n (%)

IV drug use 353 (66%)

Sexual 37 (7%)

Transfusional 6 (1%)

Unkown 37 (7%)

NA 99 (18%)

HCV GENOTYPE n (%)

G1 323 (60%)

G2 9 (1,2%)

G3 99 (18%)

G4 100 (18%)

G6 1 (0,1%)

FIBROSIS

(METAVIR) n (%)

≤ F2 222 (42%)

F3 246 (46%)

F4 54 (10%)

MELD SCORE >= 10 63 (12%) NA: Not available

RESULTS

532 patients proposed to hepatitis C DAA treatment

464 (87%) started DAA 68 (13%) did not start

DAA

5 (7%) lost

to follow up 430 (81%) completed tx

359 (67,5%) performed

12/24 week post tx

evaluation

58 (85%)

waiting tx

1st January 2015 - 30 April 2017

5 (7%) died

Sepsis n=2*

Lung Cancer n=1*

Lymphoma n=1*

Chronic liver disease

n=1*

Global SVR 96,1%

(345/359)

3 died

31 OT

Sepsis n=1

ESLD n=1*

HCC n=1*

* HIV coinfected

18%

0 50 100 150 200 250 300 350 400

OMB/PTVr/DBV+RBV

OMB/PTVr/DBV

SOF+DAC

Other

SOF/LED+RBV

SOF+RBV

SOF/LED

HIV/HCV HCV Global

RESULTS

532 patients proposed for hepatitis C DAA treatment

74%

1st January 2015 - 30 April 2017

RESULTS

532 patients proposed for hepatitis C DAA treatment

98% 100% 100% 100%

84%

100% 97% 97% 100% 98% 96%

0%

G1a G1b G2 G3 G4 G6

VHC VHC/VIH

430 (81%) completed tx 359 (67,5%) performed 12/24 w

post tx evaluation SVR

Global SVR

96,1%

1st January 2015 - 30 April 2017

55/56

13/16 48/50 1/1

25/25 55/56 118/122 31/30

4/4 4/4

26/26 38/39

13/16 48/50

1/1

RESULTS

DEMOGRAPHICS

Mean age

[min;max] 54 [43;78]

Men / Women 93% / 7%

HIV co-infection 9 (64 %)

HCV treatment

experienced 11 (78%)

TRANSMISSION n (%)

IV drug use 8 (57,14)

NA 2 (14,2)

Transfusional 1 (7,14)

Unkown 3 (21,4)

14 (3,9%) patients did not achieve sustained virologic response

(SVR)

GENOTYPE n (%)

G1 5 (35)

G2 1 (7)

G3 4 (28)

G4 4 (28)

FIBROSIS (METAVIR) n (%)

≤ F2 7 (50)

≥ F3 7 (50)

MELD SCORE > 10 0

RESULTS

14 (3,9%) patients did not achieve sustained virologic response

(SVR)

4

1 1

4 4

G1a G1b G2 G3 G4

2

5

6

1

F2 F2/F3 F3 F4

GENOTYPE FIBROSIS SCORE

50%

RESULTS

14 (3,9%) patients did not achieve sustained virologic response

(SVR)

SOFOSBUVIR+LEDIPASVIR SOFOSBUVIR+RIBAVIRIN

DAA ORIGINAL REGIMEN

9 Patients (G1/G4)

5 Cirrhotic - 24 Wks

4 non Cirrhotic - 12 Wks

4 Patients (G2/G3)

4 Cirrhotic - 24 Wks

SOFOSBUVIR+DACLATASVIR

1 Patient (G3)

Non-Cirrhotic - 12 Wks

RESULTS

14 (3,9%) patients did not achieve sustained virologic response

(SVR)

SOF+LE

D

SOF+RB

V

ORIGINAL REGIMEN PROPOSED RETREATMENT

24 wks

12 wks

3

5

SOF+DAC+RBV

SOF+GZV/EBR+RBV

RETREATMENT REGIMENS WERE SOLICITED FOR 8 PATIENTS AT

PRESENT DATE

CONCLUSIONS

The treatment of hepatitis C virus infection was

revolutionized by the introduction of the direct antiviral

agents, which achieve high rates of virologic response.

Although the treatment is very effective there are still

patients who do not respond to therapy.

The present study reveals a low relapse rate (3,9%) and

the majority of non-responders were men, previously

treated with PEGIFN+RIB, HCV infected by intravenous

drug use, co-infected with HIV and have

moderate/advanced hepatic fibrosis (F2-F3).

Acknowledgements

Fernando Borges

Fernando Ventura

Jaime Nina

Isabel Antunes

Isabel Aldir

Teresa Baptista

Ana Cláudia Miranda

Susana Peres

Virginia Moneti

Telma Azevedo

Director: Kamal Mansinho

Molecular Biology: Perpétua Gomes

Pharmaceutical: João Rijo, Helena Farinha

Secretary: Hermínia Calixto

Pedro Brogueira

Joana Silva

João Vaz Alves

Karen Pereira

Sara Grazina

João Torres

Margarida Cardoso

Miguel Achega

Rita Grácio