Hepatite C: Resultados na vida real (Hepatitis C: Real Life Results)

André Castro Lyra

# Prof. Associado e Livre Docente do Depto de Medicina – Universidade Federal da Bahia # Chefe do Serviço de Gastro-Hepatologia do Hospital Universitário Prof. Edgard Santos - UFBA # Coordenador do Serviço de Gastro-Hepatologia do Hospital São Rafael

XXII Workshop de Hepatites Virais de Pernambuco

Sexta-feira - 11/05/2016 – 11:30h as 11:45h

Therapeutic regimen

Therapeutic regimen

PLOS ONE | https://doi.org/10.1371/journal.pone.0184654 October 5, 2017

Co-morbidities

Sofosbuvir based treatment of chronic hepatitis C genotype 3 infections - A Scandinavian real-life study

Olav Dalgard et al. (2017) PLoS ONE 12(7): e0179764. https://doi.org/ 10.1371/journal.pone.0179764

Sustained virological response (SVR) 12 weeks after end of treatment

N=311

Fig. 2 Sustained virological response (SVR) according to liver elasticity levels in patients with chronic HCV genotype 3 infection, treated with a sofosbuvir based

Loreta A. Kondili et al. PLoS ONE 12(10):e0185728. https://doi.org/10.1371/journal. pone.0185728

Table 3. Failure rates following the first DAA regimen, by HCV genotype and treatment regimen in patients who completed the 12 weeks post treatment evaluation (n = 3,830 patients).

Patients who received a second DAA treatment, by type of first regimen and HCV genotype (n = 72 patients).

Patients who received a second DAA treatment, by type of first regimen and HCV genotype (n = 72 patients).

Liver International. 2018;38:602–610.

SVR = 96.6%

Compensated cirrhosis, genotype 1b.

On multivariate analysis:

• lack of IFN pretreatment (P = .02)

• presence of comorbidities (P = .001)

• Increased total bilirubin (P < .001),

• prolonged INR (P = .007)

• ↓ creatinine clearance (P = .001)

non-response to antiviral therapy.

Liver International. 2018;38:733–741.

SVR 73%

suitable for inactivation

and then delisting

Daclatasvir and reduced-dose sofosbuvir: an effective and pangenotypic treatment for hepatitis C in patients with

eGFR <30 ml/min

Amit Goel et al. Nephrology. Ahead of print

Sofosbuvir 200 mg/dia 12 semanas (24 semanas se cirrótico)

DACLA 60 mg/dia

+

Table 1: Clinical and laboratory characteristics of 41 patients with HCV infection treated with daclatasvir and low-dose sofosbuvir

Virological response rates on intention-to-treat basis

Kidney Blood Press Res 2018;43:594-605

Table. Baseline patients’ characteristics

SVR 100% (23 patients)

Table 2. Adverse events overview

w/RBV without/RBV

Serious AE (N. of patients, %)

3 (42.9%) 2 (12.5%)

Afunctional kidney graft rejection

0 (0%) 1 (6.25%)

Renal cyst infection 0 (0%) 1 (6.25%)

Early gastric cancer 1 (14.3%) 0 (0%)

Initiation of haemodialysis

1 (14.3%) 0 (0%)

Salmonellosis 1 (14.3%) 0 (0%)

Baseline characteristics of the entire cohort of 87 patients with posttransplant hepatitis C recurrence and severe fibrosis and of the two treatment groups

The individual treatment schedules were decided by each investigator, and RBV use and dosage was at the physician’s discretion according to tolerability and clinical features.

Sofosbuvir plus daclatasvir with or without ribavirin is safe and effective for post- transplant hepatitis C recurrence and severe fibrosis and cirrhosis: A prospective study

F I G U R E 1. SVR12 according to HCV genotypes overall and in the two treatment groups.

SVR12 among cirrhotic patients according to Child- Pugh class overall and in the two treatment groups.

Patients who received RBV had significantly higher SVR12 than those who did not.

TRATAMENTO DA HEPATITE C COM ESQUEMA LIVRE DE INTERFERON. RESULTADOS PRELIMINARES DE UM REGISTRO

NACIONAL DE TRATAMENTO DE VIDA REAL NO BRASIL

Giovanni Faria Silva em nome do Grupo de Registro de Tratamento da Hepatite C com DAAs na Vida Real

DISTRIBUIÇÃO DOS CENTROS MÉDICOS QUE PARTICIPARAM DO PROGRAMA DE REGISTRO DA SOCIEDADE BRASILEIRA DE HEPATOLOGIA

52 CENTROS 20 ESTADOS

DAAs Population ITT

(N=4336)

Follow up

≥12sem Pos

Tx (n=3435)

Ainda a avaliar RVS

Dados inconsistentes ou

incompletos (n=901)

Genotype 1

(n=2576)

Genotype 2 (n=86) Genotypes 4,5,6 (n=17)

Genotype 3 (n=756)

Sofosbuvir Daclatasir Simeprevir

Sofo+Ledispavir 3D Abbvie

Sofo/Peg+RBV

% TOTAL 75% 22% 3%

Resultados Preliminares do Registro Nacional de Tratamento com Novos Agentes Virais de Ação Direta em Pacientes com Hepatite

C Crônica

Agentes antivirais 2a geração no Brasil

População registrada

ITT (N= 4336)

seguimento≥12s

Pos Tx (n=3435)

Ainda a avaliar dados(n=901)

Genotipo 1

(n=2576) Genotipo 2 (n=86)

Outros (n=17) Genotipo 3

(n=756)

Sofosbuvir Daclatasir Simeprevir

PEGInterferon Ribavirina

N=3435

45,5% Cirrose

9,1% Cirrose Child B e C

54% Experimentados

12% Tx Fígado ou outro órgão 3,75% Co-infectados

4,1% CDK3 (<60ml/min)

% TOTAL 75% 22% 3%

Resultados Preliminares do Registro Nacional de Tratamento com Novos Agentes Virais de Ação Direta em Pacientes com Hepatite C Crônica

100 80 60 40 20 0

%RVS (ITT)

97 89 89

Total Genótipo 1 Genótipo 3 Genótipo 2

95

35 3435 2576 756 84

Resultados Preliminares do Registro Nacional de Tratamento com Novos Agentes Virais de Ação Direta em Pacientes com Hepatite

C Crônica

Resultados Preliminares do Registro Nacional de Tratamento com Novos Agentes Virais de Ação Direta em Pacientes com Hepatite C

Crônica

94 95 96 88

0

10

20

30

40

50

60

70

80

90

100

HCV mono não Tx HCV-HIV HCV+TX CIRR Child B e C

N = 2975 97 363 140

% R

VS

Resposta Virológica Sustentada Nos Principais Genótipos da Hepatite C, de Acordo com a Presença ou Ausência de Cirrose

98 98 93 95

81 85

0

20

40

60

80

100

Genótipo 1 Genótipo 2 Genótipo 3

Não Cirrose Cirrose

43 43

1437 1139

379 377 N=

Genótipo 1 Genótipo 2 Genótipo 3

DISTRIBUIÇÃO DOS DAAs EM PACIENTES CIRRRÓTICOS GENÓTIPOS 1 e 3

GENOTIPO 1 (n=1129)

SOFO + PR / +R 1%

DACLA + SOFO 64%

SOFO + SIME 29%

SOFO + LEDI 3%

3 D 3%

1%

64%

29%

3% 3%

Percentual

SOF/PR/P DACLA/SOF SOFO/SIME

SOFO/LEDI 3D

Genotipo 3 (n=378)

SOFO+DACLA 91%

SOFO+PR; SOFO+R 9%

93 7

Percentual

DACLA+SOFO

SOFO+PR

Obrigado

Resposta virológica sustentada de acordo com o genótipo do HCV

9790

0

20

40

60

80

100

1a 1b 3

91

Poordad F et al. Hepatology. 2016 Jan 11. doi: 10.1002/hep.28446. [Epub ahead of print]

N=10/11 N=9/10 N=30/31

EOT response and SVR (

%)

91 89

100

80

60

40

20

EOT SVR12

• 3 virological breakthroughs and

• 2 relapses • Patients treated with

daclatasvir/simeprevir ± RBV

Fontana RJ et al. Liver Transpl. 2016 Feb 17. doi: 10.1002/lt.24416. [Epub ahead of print]

92

ALL DCV+SOF±RBV

DCV+SMV±RBV

87

72

91

ALL DCV+SOF±RBV

DCV+SMV±RBV

SVR 12 according to liver function post-transplant

SVR

12

(%

) 96-98% 100

80

60

40

20

0 No/compensated

cirrhosis

Moderate hepatic impairment

Severe hepatic impairment

85-88%

60-75%

Gastroenterology 2015;149:649–659

All 6 pts with FCH = SVR

Charlton M et al. Gastroenterol 2015;149:649–659