Abstract

 Background: Hepatitis B virus (HBV) infection is a global problem and >350 million HBV carriers in the world. HBV infection causes chronic hepatitis and can lead to liver cirrhosis and hepatocellular carcinoma (HCC).

Aim: To evaluate safety and efficacy  of Tenofovir and Entecavir medications in liver disease course in HBV-decompensated cirrhosis patients

Patients & Methods: The study was carried out in hepatology  Out-Patient Clinic, Amiri hospital, Kuwait. Forty six HBV decompensated cirrhosis patients were classified into 2 groups; Tenofovir group (n=23) and Entecavir group (n=23). All patients underwent clinical examination, laboratory data (liver profile, HBV DNA, eGFR, Phosphate) and Assessment of Child-Pugh (CP) score, Model for end stage liver disease (M ELD) score before and after treatment.

Results: Baseline HBV DNA and liver enzymes of both groups  showed no significant difference before treatment. 21 (91.3%) of patients of in each group had undetectable HBV DNA at 12 months. CP and MELD scores among the 2 groups showed improvement in both scores after treatment with similar changes in both scores between the 2 medications at any time. Comparison of eGFR among the 2groups showed no changes at any time in eGFR at each group and in between the 2 groups.

Conclusion: Both antivirals (Tenofovir and Entecavir) were well tolerated; none of the patients discontinued therapy, while eGFRs were not different between Tenofovir and Entecavir groups during the follow up period, the patients had excellent virological response without viral breakthrough and with improvement in severity of liver disease.

Keywords: Tenofovir, Entecavir, chronic hepatitis B, Decompensated cirrhosis.

1.      Ismail S,  Abdel Hafez H,Darweesh S, Esmat G, (2014), Virologic response and breakthrough in chronic hepatitis B Egyptian patients receiving lamivudine therapy,Ann Gastroenterol.; 27(4): 380–386

2.      Huang YW, Chayama K, Kao JH, Yang SS. Detectability and clinical significance of serum hepatitis B virus ribonucleic acid. Hepato Biliary SurgNutr,  2015; 4(3): 197- 202. http://www.thehbsn.org/article/-view/5288/7322

3.      Mast EE, Margolis HS, Fiore AE, Brink EW, Goldstein ST, Wang SA, Moyer LA, Bell BP, Alter MJ; Advisory Committee on Immunization Practices (ACIP), (2005), A comprehensive immunization strategy to eliminate transmission of hepatitis B virus infection in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP) part 1: immunization of infants, children, and adolescents.MMWR Recomm Rep.  Dec 23;54(RR-16):1-31.

4.      Kwon  B., HS Lee, MJ Park, SG Shim  (2015),Comparison of the efficacy of tenofovir and entecavir for the treatment of nucleos(t) ide‑naïve patients with chronic hepatitis, Nigerian Journal of Clinical Practice   Vol 18, No 6 .

5.      EvangelosCholongitasa, George V. Papatheodoridisb, John Goulis (2015), The impact of newer nucleos(t)ide analogues on patients with hepatitis B decompensated cirrhosis,Annals of Gastroenterology  28, 109-117.

6.      Shaikh S, Ghani H, Memon  S, and Shaikh  K, (2010), MELD Era: Is This Time to Replace The Original Child-Pugh Score in Patients with Decompensated Cirrhosis of Liver. Journal of the College of Physicians and Surgeons Pakistan, Vol. 20 (7): 432-435.

7.      Chang TT, Gish RG, de Man R, Gadano A, Sollano J, et al. (2006), A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. N Engl J Med 354(10): 1001-1010.

8.      Lai CL, Shouval D, Lok AS, Chang TT, Cheinquer H, et al. (2006),Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B. N Engl J Med 354(10): 1011-1020.

9.      Tenney DJ, Rose RE, Baldick CJ, Pokornowski KA, Eggers BJ, et al. (2009), Long-term monitoring shows hepatitis B virus resistance to entecavir in nucleoside-naïve patients is rare through 5 years of therapy. Hepatology 49(5): 1503-1514.

10.  Marcellin P, Heathcote EJ, Buti M, Gane E, de Man RA, et al. (2008), Tenofovir disoproxilfumarate versus adefovir dipivoxil for chronic hepatitis B. N Engl J Med 359(23): 2442-2455.

11.  Manns M, Jeffers L, Dalekos G, Berg T, Trepo C, et al. (2009), Safety and efficacy of 96 weeks of tenofovir disoproxilfumarate therapy in lamivudine experienced patients. J Hepatol 50(S1): S335-336.

12.  Berg, T, Moller B, Trinh H, Chan S, Marcellin P, et al. (2009), Tenofovir disoproxilfumarate (TDF) versus emtricitabine plus TDF (FTC/TDF) for treatment of chronic hepatitis b (CHB) in patients with persistent viral replication receiving adefovirdipivoxil. J Hepatol 50(S1): S328.

13.  Rajinder JG, Vries-Slulls T, Hansen BE, Zaaijer HL, Prinsj M, et al. (2009), Five-year tenotovii therapy is associated with maintained virologic response but significant decline in renal function in HIV-HBV infected patients. Hepatology 50: abstract 506A.

14.  Constable C, Childs K, Bachon ML, Camero DC, Mullen MR, et al. (2009) Does tenofovlr increase the risk of abnormal bone and calcium metabolism? Hepatology 51: abstract 518.

15.  Liaw YF, Sheen IS, Lee CM, Akarca US, Papatheodoridis GV, et al. (2011), Tenof-ovir disoproxilfumarate (TDF), emtrici-tabine/TDF, and entecavir in patients with decompensated chronic hepatitis B liver disease. Hepatology 53(1): 62-72

16.  Surude R,  Parikh P,  Choksey A,  Patel B,  Phadke A  Sawant P, A Randomized Comparative Study of Efficacy of Lamivudine and Adefovir Combination versus Tenofovir versus Entecavir in Decompensated Cirrhotic Patients of Hepatitis B Adv Res GastroenteroHepatol 1(1): ARGH.MS.ID.555553 (2015) DOI: 10.19080/ARGH.2015.01.555553

17.  Centeno BL,  Borrell RC,  Encinas MP,  Gutiérrez-García ML,  Fenollera PS,  Comparison of the effectiveness and renal safety of tenofovir versusentecavir in patients with chronic hepatitis B. Farm Hosp. 2016;40(4):279-286. DOI: 10.7399/fh.2016.40.4.10492

18.  Fan XH, Geng JZ, Wang LF, Zheng YY, Lu XY, et al. (2011), De novo combination therapy with lamivudine and adefovirdipivoxil in chronic hepatitis B patient. World J Gastroenterol 17(43): 4804-4809.

19.  Shim JH, Lee HC, Kim KM, Lim YS, Chung YH, et al. (2010), Efficacy of entecavir in treatment-naive patients with hepatitis B virus-related decompensated cirrhosis. J Hepatol 52(2): 176-182.

20.  Liaw YF, Raptopoulou-Gigi M, Cheinquer H, Sarin SK, Tanwandee T, et al. (2011), Efficacy and safety of entecavir versus adefovir in chronic hepatitis B patients with hepatic decompensation: a randomized, open-label study. Hepatology 54(1): 91-100.

21.  Chan HL, Chen YC, Gane EJ, Sarin SK, Suh DJ, et al. (2012), Randomized clinical trial: efficacy and safety of telbivudine and lamivudine in treatment-naïve patients with HBV-related decompensated cirrhosis. J Viral Hepat 19(10): 732-743.

22.  Schiff ER, Lai CL, Hadziyannis S, Neuhaus P, Terrault N, et al. (2007), Adefovirdipivoxil for wait-listed and post-liver transplantation patients with lamivudine-resistant hepatitis B: final long-term results. Liver Transpl 13(3): 349-360.

23.  Koklu S, Tuna Y, Gulsen MT, et al (2013), Long-term efficacy and safety of lamivudine, entecavir, and tenofovir for treatment of hepatitis B virus-related cirrhosis. Clin Gastroenterol Hepatol ;11:88-94.

24.  Chiu YC, Liao SF, Wu JF, Lin CY, Lee WC, Chen HL, Ni YH, Hsu HY, Chang MH(2014),Factors affecting the natural decay of hepatitis B surface antigen in children with chronic hepatitis B virus infection during long-term follow-upJ Pediatr. 2014 Oct;165(4):767-72.e1.

25.  MyoNyeinAung, WattanaLeowattana, KhineNweWin ,NoppadonTangpukdee , SantMuangnoicharoen (2013):Chronic hepatitis B prognostic markers other than pre-treatment viral load predicted composite treatment outcome. J Infect DevCtries 2013; 7(7):541-549