Advertisement

Management of HCV-related decompensated cirrhosis with direct-acting antiviral agents: who should be treated?

  • Amr Shaaban HanafyEmail author
  • Mohamed A. Bassiony
  • Mohammad Abd Alkhalik Basha
Original Article

Abstract

Background

Medical treatment of decompensated cirrhosis due to hepatitis C virus (HCV) remains a clinical challenge even in the era of direct-acting antiviral drugs (DAAs). We evaluated the efficacy and safety of DAAs in the management of HCV genotype 4-related decompensated cirrhosis.

Methods

The study included a treatment group (n = 160) composed of HCV patients with decompensated cirrhosis who received DAAs for 3 months and a matched control group (n = 80) who preferred not to receive DAAs, follow-up was for 24–31 months.

Results

In treatment group; there were improvements in platelet count, albumin, CTP (p = 0.001) and MELD scores (p = 0.03), a significant reduction in the frequency of hepatic encephalopathy (HE). SVR was achieved in 90%. Hepatocellular carcinoma (HCC) developed in 10% (n = 18) within 6.8 ± 2.5 months after DAAs, survival was higher in the treated vs. the control group (28.9 ± 0.95 vs. 11.4 ± 2.2 months, p = 0.001). Liver volume by ultrasound at a cutoff 495 ml was predictive of complications after DAAs therapy mainly HCC and reduced survival with sensitivity 93.2%, specificity 72%.

Conclusion

HCV with decompensated cirrhosis and adequate liver volume had a 90% SVR with improved CTP&MELD and survival. Clinical trial: (NCT03547895).

Keywords

HCV Decompensated cirrhosis DAAs Liver volume 

Notes

Author contribution

Amr Shaaban Hanafy was responsible for the study concept and design and he is the Guarantor of the article. Mohamed Bassiony was responsible for data acquisition and recording, Mohammad Abd Alkhalik supervised radiological investigations. All authors had full access to all data in the study, and take responsibility for the integrity of the data and the accuracy of the analysis. Amr Hanafy wrote the manuscript and performed statistical analysis. All authors were responsible for the critical review and had approved the final draft submitted.

Compliance with ethical standards

Conflict of interest

Amr Shaaban Hanafy, Mohamed A. Bassiony and Mohammad Abd Alkhalik Basha declare that they have no conflict of interest.

Ethical approval

The study was approved by Zagazig university institutional research committee at the 3rd of May 2015. Written, informed consent was obtained from each patient included in the study. The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by the institution’s human research committee.

Supplementary material

12072_2019_9933_MOESM1_ESM.jpg (161 kb)
Supplementary material 1 (JPEG 160 kb)

References

  1. 1.
    Kwo P, Agrawal S. Treating hepatitis C virus in patients with decompensated cirrhosis: why is it so difficult and does a sustained response rate rescue the patient from liver transplantation? Clin Liver Dis. 2015;6(6):133–5.CrossRefGoogle Scholar
  2. 2.
    Babusis DM, Curry MP, Denning J, Park Y, Murakami E, Afdhal N, et al. Nucleotide analog levels in liver explants from HCV infected subjects undergoing liver transplantation after up to 24 weeks sofosbuvir (GS-7977) with ribavirin treatment. Hepatology. 2013;58:111.Google Scholar
  3. 3.
    Lens S, Rincón D, García-Retortillo M, Albillos A, Calleja JL, Bañares R, et al. Association between severe portal hypertension and risk of liver decompensation in patients with hepatitis C, regardless of response to antiviral therapy. Clin Gastroenterol Hepatol. 2015;13:1846–53.CrossRefGoogle Scholar
  4. 4.
    Burchill MA, Golden-Mason L, Wind-Rotolo M, Rosen HR. Memory re-differentiation and reduced lymphocyte activation in chronic HCV-infected patients receiving direct-acting antivirals. J Viral Hepat. 2015;22(12):983–91.CrossRefGoogle Scholar
  5. 5.
    Van der Meer AJ, Veldt BJ, Feld JJ, Wedemeyer H, Dufour JF, Lammert F, et al. Association between sustained virological response and all-cause mortality among patients with chronic hepatitis C and advanced hepatic fibrosis. JAMA. 2012;308:2584–93.CrossRefGoogle Scholar
  6. 6.
    Ohkoshi S, Hirono H, Yamagiwa S. Direct antiviral agent treatment of decompensated hepatitis C virus-induced liver cirrhosis. World J Gastrointest Pharmacol Ther. 2015;6(4):114–9.CrossRefGoogle Scholar
  7. 7.
    Wiesner R, Edwards E, Freeman R, Harper A, Kim R, Kamath P, et al. Model for end-stage liver disease (MELD) and allocation of donor livers. Gastroenterology. 2003;124(1):91–6.CrossRefGoogle Scholar
  8. 8.
    Bouchardeau F, Cantaloube JF, Chevaliez S, Portal C, Razer A, Lefrère J, et al. Improvement of hepatitis C virus (HCV) genotype determination with the new version of the INNO-LiPA HCV assay. J Clin Microbiol. 2007;45(4):1140–5.CrossRefGoogle Scholar
  9. 9.
    Bushberg JT, Seitbert JA, Leidholt JE, Boone JM, editors. Ultrasound: the essential physics of medical imaging. 3rd ed. Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins; 2012. p. 500–75.Google Scholar
  10. 10.
    Leung NW, Farrant P, Peters TJ. Liver volume measurement by ultrasonography in normal subjects and alcoholic patients. J Hepatol. 1986;2(2):157–64.CrossRefGoogle Scholar
  11. 11.
    Ferenci P, Lockwood A, Mullen K, Tarter R, Weissenborn K, Blei AT. Hepatic encephalopathy—definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, 1998. Hepatology. 2002;35(3):716–21.CrossRefGoogle Scholar
  12. 12.
    Vilstrup H, Amodio P, Bajaj J, Cordoba J, Ferenci P, Mullen KD, et al. Hepatic encephalopathy in chronic liver disease: 2014 practice guideline by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology. 2014;60:715–35.CrossRefGoogle Scholar
  13. 13.
    Afdhal N, Zeuzem S, Kwo P, Choijkier M, Gitlin N, Puoti M, et al. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014;370:1889–98.CrossRefGoogle Scholar
  14. 14.
    Reddy R, Lim JK, Kuo A, Di Bisceglie AM, Vargas HM, Galati JS, et al. All oral HCV therapy is safe and effective in patients with decompensated cirrhosis: interim report from the HCV-target real world experience. J Hepatol. 2015;62:S193.CrossRefGoogle Scholar
  15. 15.
    Manolakopoulos S, Zacharakis G, Zissis M, Giannakopoulos V. Safety and efficacy of daclatasvir in the management of patients with chronic hepatitis C. Ann Gastroenterol. 2016;29(3):282–96.Google Scholar
  16. 16.
    Flamm SL, Everson GT, Charlton MR, Denning JM, Arterburn S, Brandt-Sarif T, et al. Ledipasvir/sofosbuvir with ribavirin for the treatment of HCV in patients with decompensated cirrhosis: preliminary results of a prospective, multicenter study. Hepatology (Baltimore, MD). 2014;60:320A.Google Scholar
  17. 17.
    Manns M, Forns X, Samuel D, Denning J, Arterburn S, Brandt-Sarif T, et al. ledipasvir/sofosbuvir with ribavirin is safe and efficacious in decompensated and post-liver transplantation patients with HCV infection: preliminary results of the prospective solar 2 trial. J Hepatol. 2015;62:S187–8.CrossRefGoogle Scholar
  18. 18.
    Poordad F, Schiff ER, Vierling JM, Landis C, Fontana RJ, Yang R, et al. Daclatasvir, sofosbuvir, and ribavirin combination for HCV patients with advanced cirrhosis or post-transplant recurrence: ALLY-1 phase 3 study. J Hepatol. 2015;62:S261.CrossRefGoogle Scholar
  19. 19.
    Afdhal N, Everson GT, Calleja JL, McCaughan GW, Bosch J, Brainard DM, et al. Effect of viral suppression on hepatic venous pressure gradient in hepatitis C with cirrhosis and portal hypertension. J Viral Hepat. 2017;24(10):823–31.CrossRefGoogle Scholar
  20. 20.
    Foster G, McLauchlan J, Irving W, Cheung M, Hudson B, Verma S, et al. Treatment of decompensated HCV cirrhosis in patients with diverse genotypes: 12 weeks sofosbuvir and NS5A inhibitors with/without ribavirin is effective in HCV genotypes 1 and 3. J Hepatol. 2015;62:S190–1.CrossRefGoogle Scholar
  21. 21.
    Guarino M, Morisco F, Valvano MR, Ippolito AM, Librandi M, Andriulli N, et al. Systematic review: interferon-free regimens for patients with HCV-related child C cirrhosis. Aliment Pharmacol Ther. 2017;45(9):1193–200.CrossRefGoogle Scholar

Copyright information

© Asian Pacific Association for the Study of the Liver 2019

Authors and Affiliations

  1. 1.Internal Medicine Department, Hepatology DivisionZagazig UniversityZagazigEgypt
  2. 2.Diagnostic RadiologyZagazig UniversityZagazigEgypt
  3. 3.ZagazigEgypt

Personalised recommendations