The Regression of Liver Fibrosis in HCV Cirrhotic Patients Who Registered SVR after DAA Therapy

Transcription

1 The Regression of Liver Fibrosis in HCV Cirrhotic Patients Who Registered SVR after DAA Therapy Leustean Anca 1,2, Nastase Raluca 1, Molagic Violeta 1, Radulescu Mihaela 1,2, Munteanu Daniela 1,2, Tiliscan Catalin 1,2, Catana Remulus 1,2, Stratan Laurentiu 1, Orfanu Alina 1,2, Carp Codruta 1, Ciresa Alexandra 1, Badea Alexandra 1, Arama Sorin 2, Arama Victoria 1,2 1 "Matei Bals" National Institute for Infectious Diseases, Bucharest Bucharest, Romania 2 "Carol Davila" University of Medicine and Pharmacy Bucharest, Bucharest, Romania

2 Introduction Worldwide, it is estimated that the prevalence of chronic hepatitis with HCV is million people (2-2.5% of the world population). 1 With Interferon-free regimens (Direct Acting Antivirals): the rate of SVR in patients with HCV genotype 1:> 95% 2 so far, insufficient data have been collected on the progression of fibrosis in patients who have acheived SVR a perfect method for assessing the liver fibrosis and its dynamics has not been established SVR = sustained virologic response 1. Mauss S, Berg T, Rockstroh J, Sarrazin C, Wedemeyer H, Kamps BS. Hepatology-A clinical textbook. 2.Poordad F, et al. EASL Abstract O163. Poordad F, et al. N Engl J Med. 2014;370: Ombitasvir/paritaprevir/ritonavir and dasabuvir

3 In Romania Interferon-free treatment with paritaprevir/ritonavir-ombitasvir-dasabuvir (PrOD) ± ribavirin was approved since November 2015 for patients with advanced liver fibrosis. According to the local protocol, the assessment of the liver fibrosis was made by using the Fibromax test (BioPredictive). In the last 2 years, patients with HCV hepatitis and various stages of liver fibrosis (except F0) have been receiving interferon-free treatment.

4 Objective to evaluate the dynamics of liver fibrosis in patients with HCV compensated cirrhosis who achieved SVR after direct acting antivirals (DAA) therapy to determine the diagnostic value of simple and less costly fibrosis scores: APRI and FIB-4

5 Methods A prospective study conducted in Matei Bals National Institute for Infectious Diseases, Bucharest, Romania Third Department, between November 2015 and June 2018 The patients were evaluated: at the beginning of the therapy at 6 months after the end of treatment (post-eot) at 1 year post-eot at 2 years post-eot, using Fibromax, AST to Platelet Ratio Index (APRI) and Fibrosis-4 score (FIB-4). Inclusion criteria: HCV liver cirrhosis - Child A patients who registered SVR after Interferon-free therapy: Ombitasvir / Paritaprevir / r + Dasabuvir +/- Ribavirin patient signature of an informed consent

6 Results 175 patients with Child A liver cirrhosis - initial FibroMax: F3-F4 18 patients F4 157 patients Initial FibroMax (N=175) FibroMax at 6 months post EOT (N=72) Score, mean ± SD 0.84 ± ± 0.15 Grade, n (%) F4 157 (89.7) F3-F4 18 (10.3) F4 27 (37.5) F3-F4 3 (4.16) F3 21 (29.16) F2 14 (19.44) F1-F2 6 (8.33) F0-F1 1 (1.38) FibroMax at 12 months post EOT (N=42) FibroMax at 24 months post EOT (N=17) Score, mean ± SD 0.67 ± ± 0.17 Grade, n (%) F4 15 (35.71) F3-F4 5 (11.9) F3 11 (26.19) F2 7 (16.66) F1-F2 3 (7.14) F1 1 (2.38) F4 5 (29.41) F3-F4 2 (11.76) F3 7 (41.17) F2 1 (5.88) F1-F2 2 (11.76)

7 Fibrosis dynamic(1) 100% 90% 80% 10,3 1,38 2,38 8,33 7,14 11,76 19,44 16,66 5,88 70% 60% 50% 40% 30% 20% 10% 89,7 29,16 4,16 11,9 37,5 35,7 26,19 41,17 11,76 29,4 F0-F1 F1 F1-F2 F2 F3 F3-F4 F4 0% Initiere Initiation 6 months la 6 luni postpost-eot 12 months la 12 luni postpost-eot 24 months la 24 luni postpost-eot

8 Fibrosis dynamic(2) p=0.047 p=0.933 p=0.163 p<0.001 p<0.001 p=0.002

9 APRI at initiation (N=175) Score, mean ± SD >2 1-2 <1 APRI at 6 months post EOT (N=72) APRI at 12 months post EOT (N=42) APRI at 24 months post EOT (N=17) ± ± ± ± (30.85%) 51 (29.14%) 70 (40%) APRI and FIB-4 dynamic 0 (0%) 5 (6.95%) 67 (93.05%) 0 (0%) 5(11.9%) 37 (88.1%) 0 (0%) 2 (11.77%) 15 (88.23%) FIB-4 at initiation (N=175) FIB-4 at 6 months post EOT (N=72) FIB-4 at 12 months post EOT (N=42) FIB-4 at 24 months post EOT (N=17) Score, mean ± SD 4.22 ± ± ± ± 2.03 > < (53.14%) 68(38.85%) 14 (8%) 11 (15.27%) 44 (61.11%) 17 (23.61%) 8 (19.05%) 21 (50%) 13 (30.95%) 5 (29.41%) 10 (58.82%) 2 (11.76%)

10 APRI dynamic 100% 90% 80% 70/ % 60% 50% 40% 51/ /72 37/42 15/17 <1 1-2 >2 30% 20% 10% 0% 54/ 175 Initiere 5/72 5/4 2 la 6 luni post-eot la 12 luni post-eot la 24 luni post-eot Initiation 6 months post EOT 12 months post EOT 24 months post EOT 2/1 7 Scores statistically decreased between: - Initiation and 6 months post EOT: p< Initiation and 12 months post EOT: p< Initiation and 24 months post EOT: p=0.002

11 FIB-4 dynamic 100% 90% 80% 14/175 68/175 17/72 13/42 2/17 70% 60% 50% 40% 44/72 21/42 10/17 < > % 93/175 20% 10% 11/72 8/42 5/17 0% Initiere la 6 luni post-eot la 12 luni post-eot la 24 luni post-eot Initiation 6 months post EOT 12 months post EOT 24 months post EOT Scores statistically decreased between: - Initiation and 6 months post EOT: p< Initiation and 12 months post EOT: p< Initiation and 24 months post EOT: p=0.003

12 Correlations between fibrosis scores At Interferon-free initiation APRI FibroTest: r=0.121, p=0.123 FIB-4 - FibroTest r=0.310, p<0.001 APRI FIB-4: r=0.732, p<0.001 At 6 months post EOT: APRI FibroTest: r=0.205, p=0.086 FIB-4 - FibroTest r=0.364, p=0.002 APRI FIB-4: r=0.842, p<0.001 At 12 months post EOT: APRI FibroTest: r=0.134, p=0.409 FIB-4 - FibroTest r=0.355, p=0.025 APRI FIB-4: r=0.879, p<0.001 At 24 months post EOT: APRI FibroTest: r=0.476, p=0.054 FIB-4 - FibroTest r=0.557, p=0.020 APRI FIB-4: r=0.895, p<0.001

13 Conclusions According to FibroMax (used by the national protocol for stratification of fibrosis), there is a statistically significant decrease between baseline and months after the completion of antiviral therapy. The score FIB-4, highly correlated with FibroMax, proves to be a useful non-invasive tool in screening the patients and monitoring the dynamic of liver fibrosis. Aknowledgement A part of the FibroMax tests used in this study were performed with BioPredictive support

14 Thank you!