Date of Publication: 30-Nov--0001
Response to Pegylated Interferon in Hepatitis B patients with HBe Ag-Negative: Long-Term Results and Predictors of Sustained-Off Virological Response
Author: Younes Cherradi, Mustapha Benazzouz, Hanaa Benbrahim, Abdellah Essaid, Rajaa Afifi
Category: JMSR Gastroenterology
Introduction: Chronic Hepatitis B (CHB) is a major public health problem in Morocco and worldwide. According to our real-life experience, genotype D and mutant phenotype are prominent in Moroccan population. In this study, we aimed to evaluate the place of PEG INF in HBe Ag Negative patients and to define good responders__ampersandsign#39; profile.
Methods: It__ampersandsign#39;s a mono-centric study including all naive HBV-carriers treated by PEG INF since 2004. Patients with treatment failure and relapsers were not excluded. Patients with less than 24Wof regular follow-up after end of treatment and patients with HIV or HCV co-infection were excluded. Considered data were: age, gender, body mass index (BMI), initial ALT rates, initial viral loads, histological activity and fibrosis according to METAVIR score. The major endpoints of the study were Virological response (VR) and sustained off-treatment virological response (SVR) rates.
Results: From a total of 80 treated patients, 50 were considered for the study. Mean age was 41 years old and 74% of patients were male. HVB genotyping was performed in only 28 patients. Four patients were genotype A and 24 were genotype D. Ten patients were obese. Hepatic fibrosis was severe (F3- F4) in 6 patients. Treatment failure and relapse were reported in 9 patients (18%) and then only 41 patients achieved 48 weeks of treatment. They all achieved 72 weeks of regular follow-up. HBV DNA was undetectable by polymerase chain reaction in respectively 10% and 6% of patients at both 72W and 96W (respectively n=5/50 and n=3/50). Virological response was achieved by 34% of patients at 72W (n= 17/50) and SVR was obtained in 18% at 96W (n=9/50). No HBs seroconversion was reported. Gender, age< 50 years old, genotype and initial cytolysis were not significant predictors of SVR. Low initial DNA viral level (<4log) was the only significant factor associated to SVR (p= 0,002)
Conclusion: The advantage of PEG- INF is the short duration of treatment. In our population - where HBe antigen negative profile and genotype D are prominent-, DNA negativation rates were very low (only 6%) and SVR was achieved in 18%. A national randomized study will help to assess the efficacy of extended PEG-INF treatment duration in our HBe Ag negative CHB patients with genotype D.
Keywords: Ag Hbe negative, Chronic Hepatitis B (CHB), Pegylated interferon (PEG-IFN), Sustained-off virological response (SVR).
1- Y. Cherradi, et al. Hepatocellular Carcinoma screening is indicated Even After Sustained Virological Response: -Moroccan University Hospital Experience-Journal of Medical and Surgical research (JMSR) 2016; III, 1: 223-228 doi: 10.46327/msrjg.1.000000000000064
2- Saikia N., Talukdar R, Mazumder S, Khanna S and Tandon R. Management of patients with HBe Agnegative chronic hepatitis B Postgrad Med J. 2007 Jan; 83(975): 32-39.
3- WHO media center: http://www.who.int/mediacentre/factsheets/fs204/en/
4-Guo-Feng Chen, Cheng Wang, George Lau. Treatment of Chronic Hepatitis B infection Liver International Vol 37, Issue S1 January 2017, 59-66.
5- Bennani A, Baha W, Dersi N,Ennaji M, Lazaar F, El Malki A,1 and all. Hepatitis B & C epidemiology in Morocco. BMC Proc. 2011; 5(Suppl 1): P20.
6- Kitab B., Afifi R, Essaid A, Benazzouz M, SalihAlj H, Rebbani K and all. Genetic variability of Hepatitis B virus in Morocco. BMC Proc. 2011; 5(Suppl 1): P22.
7- Cherradi Y, Afifi R, Derdabi O, Essamri W, Benjelloun S, RazineR and all. Génotypes de l'hépatite virale B et réponse à l'interféron pégylé. JFHOD 2013, P 303.http://www.snfge.org/content/genotypes-delhepatite-virale-b-et-reponse-l
8-Kitab B, El Feydi AE, Afifi R, Derdabi O, Cherradi Y, Benazzouz M and all. Hepatitis B genotypes/ subgenotypes and MHR variants among Moroccan chronic carriers. J. Infect. 2011 Jul;63(1):66-75.
9-Wang H, Xi Lu, Xudong Yang and Nan Xu. The efficacy and safety of tenofovir alafenamide versus tenofovir disoproxilfumarate in antiretroviral regimens for HIV-1 therapy. Medicine (Baltimore). 2016 Oct; 95(41): e5146.
10- Grimm D, Thimme R and Blum H.E.HBV life cycle and novel drug targets. Hepatol Int. 2011 Jun; 5(2): 644- 653.
11-Testoni B, Durantel D, Zoulim F. Novel targets for hepatitis B virus therapy. Liver Int. 2017 Jan;37Suppl 1:33-39.
12- EASL Clinical Practice Guidelines: Management of chronic hepatitis B virus infection. Journal of Hepatology 2012; 57: 167-185
13- EASL Clinical Practice Guidelines on the management of hepatitis B virus infection. Journal of Hepatology 2017.
14- Lampertico P, Viganò M and Colombo M. Why do I treat HBeAg-negative chronic hepatitis B patients with pegylated interferon? Liver Int. 2013 Feb;33Suppl 1:15763.
15- Santantonio T A, Fasano M. Chronic hepatitis B: Advances in treatment. World J Hepatol 2014 May 27; 6(5): 284-292
16-WJG Hepatitis B virus genotypes: Global distribution and clinical importance https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4017058 /pdf/WJG-20-5427.pdf
17- Moucari R, Mackiewicz V, Lada O, Ripault MP, Castelnau C, Martinot-Peignoux M and all. Early Serum HBsAg Drop: A Strong Predictor of Sustained Virological Response to Pegylated Interferon Alfa-2a in HBeAg-Negative Patients. Hepatology 2009, 49 (X).
18- Lampertico P, Viganò M, Di Costanzo GG, Sagnelli E, Fasano M, Di Marco V and all. Randomised study comparing 48 and 96 weeks peginterferon α-2a therapy in genotype D HBe Ag-negative chronic hepatitis B. Gut 2013; 62: 290-298
19-EunJu Cho, Jeong-Hoon Lee J-H, and Jung-Hwan Yoon. Combination of Pegylated Interferon and Nucleos(t)ide Therapy: Toward a Cure of Hepatitis B Virus Infection? Gut Liver. 2016 Jul; 10(4): 497-498.
20-Chih-Lin Lin and Jia-Horng KaoNew perspectives of biomarkers for the management of chronic hepatitis B. Clin Mol Hepatol. 2016 Dec; 22(4): 423-431.
21- Marcellin P, CihanYurdaydin F, Hadziyannis S, Moucari R, Kapprell H-P and all. Hepatitis B surface antigen levels: association with 5-year response to peginterferon alfa-2a in hepatitis B e-antigen-negative patients. Hepatol Int. 2013 Mar; 7(1): 88-97.
22- Wiegand J, Wedemeyer H, Finger A, Heidrich B, Rosenau J, Michel G and all. A decline in hepatitis B virus surface antigen (HBs Ag) predicts clearance, but does not correlate with quantitative HBs Ag or HBV DNA levels. Antivir Ther. 2008;13(4):547-54.