Skip to main content
SpringerLink
Log in

Fibrosis Regression Explains Differences in Outcome in HIV-/HCV-Coinfected Patients with Cirrhosis After Sustained Virological Response

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background and Aims

Fibrosis regression (FR) after sustained virological response (SVR) should produce a better outcome in hepatitis C (HCV)-/HIV-coinfected patients with liver cirrhosis, but there are no specific data in this issue.

Methods

We compared the incidence rate (IR) and the time to develop a liver complication and death in 133 cirrhotic patients according to SVR or/and FR.

Results

Of 42 patients with SVR, 23 (55 %) had FR, in comparison with only 14 of the 91 (15 %) without SVR. During a follow-up of 6.8 years (916.8 person-years), the IR of death, liver-related death, and liver-related complications were 2.45, 0.61, and 1.22 per 100 persons/year among SVR/FR, and 7.6, 5.9, and 6.81 among non-SVR without FR (p < 0.01), respectively. SVR patients without FR had also a lower rate of liver-related complications (1.78 vs 3.25; p = 0.02), but a worse IR of death (5.36) and liver-related death (2.68) than non-SVR patients with FR (1.3, and 0.65; p < 0.01). Moreover, FR was associated with less hospital admissions and decreasing alpha-fetoprotein levels. In Cox analysis, only FR was associated with a lower risk of death (adjusted hazard ratio, HR 0.36; 95 % CI 0.15–0.86), and liver-related death (HR 0.15; 95 % CI 0.03–0.65), whereas both FR (HR 0.09; 95 % CI 0.03–0.3, p < 0.01) and SVR (HR 0.24; 95 % CI 0.07–0.87) decreased the risk of liver-related complications.

Conclusion

Fibrosis regression after SVR is associated with the highest reduction in death of any cause, liver-related mortality, and liver-related complications in HIV-/HCV-coinfected patients with cirrhosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Graham CS, Baden LR, Yu E, et al. Influence of human immunodeficiency virus infection on the course of hepatitis C virus infection: a meta-analysis. Clin Infect Dis. 2001;33:562–569.

    Article  CAS  PubMed  Google Scholar 

  2. Lopez-Dieguez M, Montes ML, Pascual-Pareja JF, et al. The natural history of liver cirrhosis in HIV–hepatitis C virus-coinfected patients. Aids. 2011;25:899–904.

    Article  PubMed  Google Scholar 

  3. Anderson JP, Tchetgen EJT, Lo Re V III, et al. Antiretroviral therapy reduces the rate of hepatic decompensation among HIV- and hepatitis C virus-coinfected veterans. Clin Infect Dis. 2014;58:719–727.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Merchante N, Merino E, Lopez-Aldeguer J, et al. Increasing incidence of hepatocellular carcinoma in HIV-infected patients in Spain. Clin Infect Dis. 2013;56:143–150.

    Article  PubMed  Google Scholar 

  5. Bruno R, Puoti M, Sacchi P, Filice C, Carosi G, Filice G. Management of hepatocellular carcinoma in human immunodeficiency virus-infected patients. J Hepatol. 2006;44:S146–S150.

    Article  CAS  PubMed  Google Scholar 

  6. Berenguer J, Alvarez-Pellicer J, Martin PM, et al. Sustained virological response to interferon plus ribavirin reduces liver-related complications and mortality in patients coinfected with human immunodeficiency virus and hepatitis C virus. Hepatology. 2009;50:407–413.

    Article  CAS  PubMed  Google Scholar 

  7. Barreiro P, Labarga P, Martin-Carbonero L, et al. Sustained virological response following HCV therapy is associated with non-progression of liver fibrosis in HCV/HIV-coinfected patients. Antivir Ther. 2006;11:869–877.

    CAS  PubMed  Google Scholar 

  8. Mira JA, Rivero-Juarez A, Lopez-Cortes LF, et al. Benefits from sustained virologic response to pegylated interferon plus ribavirin in HIV/hepatitis C virus-coinfected patients with compensated cirrhosis. Clin Infect Dis. 2013;56:1646–1653.

    Article  CAS  PubMed  Google Scholar 

  9. Merchante N, Merino E, Rodriguez-Arrondo F, et al. HIV/hepatitis C virus-coinfected patients who achieved sustained virological response are still at risk of developing hepatocellular carcinoma. Aids. 2014;28:41–47.

    Article  CAS  PubMed  Google Scholar 

  10. Aleman S, Rahbin N, Weiland O, et al. A risk for hepatocellular carcinoma persists long-term after sustained virologic response in patients with hepatitis C-associated liver cirrhosis. Clin Infect Dis. 2013;57:230–236.

    Article  CAS  PubMed  Google Scholar 

  11. Morgan TR, Ghany MG, Kim HY, et al. Outcome of sustained virological responders with histologically advanced chronic hepatitis C. Hepatology. 2010;52:833–844.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. Zator ZA, Chung RT. After the cure: management of HCV after achievement of SVR. Curr HIV/AIDS Rep. 2013;10:428–435.

    Article  PubMed  Google Scholar 

  13. European Association for Study of L. EASL clinical practice guidelines: management of hepatitis C virus infection. J Hepatol. 2014;60:392–420.

    Article  Google Scholar 

  14. Casado JL, Quereda C, Moreno A, Perez-Elias MJ, Marti-Belda P, Moreno S. Regression of liver fibrosis is progressive after sustained virological response to HCV therapy in patients with hepatitis C and HIV coinfection. J Viral Hepat. 2013;20:829–837.

    Article  CAS  PubMed  Google Scholar 

  15. Berenguer J, Alvarez-Pellicer J, Carrero A, et al. Clinical effects of viral relapse after interferon plus ribavirin in patients co-infected with human immunodeficiency virus and hepatitis C virus. J Hepatol. 2013;58:1104–1112.

    Article  CAS  PubMed  Google Scholar 

  16. Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group. Hepatology. 1996;24:289–293.

    Article  CAS  PubMed  Google Scholar 

  17. Castera L, Forns X, Alberti A. Non-invasive evaluation of liver fibrosis using transient elastography. J Hepatol. 2008;48:835–847.

    Article  PubMed  Google Scholar 

  18. Bruno S, Crosignani A, Facciotto C, et al. Sustained virologic response prevents the development of esophageal varices in compensated, Child–Pugh class A hepatitis C virus-induced cirrhosis. A 12-year prospective follow-up study. Hepatology. 2010;51:2069–2076.

    Article  CAS  PubMed  Google Scholar 

  19. Berenguer J, Rodriguez E, Miralles P, et al. Sustained virological response to interferon plus ribavirin reduces non-liver-related mortality in patients coinfected with HIV and Hepatitis C virus. Clin Infect Dis. 2012;55:728–736.

    Article  CAS  PubMed  Google Scholar 

  20. Sanchez-Conde M, Miralles P, Bellon JM, et al. Use of transient elastography (FibroScan(R)) for the noninvasive assessment of portal hypertension in HIV/HCV-coinfected patients. J Viral Hepat. 2011;18:685–691.

    Article  CAS  PubMed  Google Scholar 

  21. Roberts S, Gordon A, McLean C, et al. Effect of sustained viral response on hepatic venous pressure gradient in hepatitis C-related cirrhosis. Clin Gastroenterol Hepatol. 2007;5:932–937.

    Article  PubMed  Google Scholar 

  22. Poynard T, Moussalli J, Munteanu M, et al. Slow regression of liver fibrosis presumed by repeated biomarkers after virological cure in patients with chronic hepatitis C. J Hepatol. 2013;59:675–683.

    Article  CAS  PubMed  Google Scholar 

  23. Chen TM, Huang PT, Tsai MH, et al. Predictors of alpha-fetoprotein elevation in patients with chronic hepatitis C, but not hepatocellular carcinoma, and its normalization after pegylated interferon alfa 2a–ribavirin combination therapy. J Gastroenterol Hepatol. 2007;22:669–675.

    Article  CAS  PubMed  Google Scholar 

  24. Perez-Tamayo R. Cirrhosis of the liver: a reversible disease? Pathol Annu. 1979;14:183–213.

    PubMed  Google Scholar 

  25. Serpaggi J, Carnot F, Nalpas B, et al. Direct and indirect evidence for the reversibility of cirrhosis. Hum Pathol. 2006;37:1519–1526.

    Article  PubMed  Google Scholar 

  26. Mallet V, Gilgenkrantz H, Serpaggi J, et al. Brief communication: the relationship of regression of cirrhosis to outcome in chronic hepatitis C. Ann Intern Med. 2008;149:399–403.

    Article  PubMed  Google Scholar 

  27. Pol S, Carnot F, Nalpas B, et al. Reversibility of hepatitis C virus-related cirrhosis. Hum Pathol. 2004;35:107–112.

    Article  CAS  PubMed  Google Scholar 

  28. Friedman SL. Fibrogenic cell reversion underlies fibrosis regression in liver. Proc Natl Acad Sci USA. 2012;109:9230–9231.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Collazos J, Asensi V, de la Fuente B, Carton JA. The effect of unsuccessful treatment with peginterferon and ribavirin on the liver fibrosis course of HIV/HCV-coinfected patients. Curr HIV Res. 2012;10:679–687.

    Article  CAS  PubMed  Google Scholar 

  30. Recio E, Macias J, Rivero-Juarez A, et al. Liver stiffness correlates with Child–Pugh–Turcotte and MELD scores in HIV/hepatitis C virus-coinfected patients with cirrhosis. Liver Int. 2012;32:1031–1032.

    Article  PubMed  Google Scholar 

  31. Merchante N, Rivero-Juarez A, Tellez F, et al. Liver stiffness predicts clinical outcome in human immunodeficiency virus/hepatitis C virus-coinfected patients with compensated liver cirrhosis. Hepatology. 2012;56:228–238.

    Article  PubMed  Google Scholar 

  32. Macias J, Camacho A, Von Wichmann MA, et al. Liver stiffness measurement versus liver biopsy to predict survival and decompensations of cirrhosis among HIV/hepatitis C virus-coinfected patients. Aids. 2013;27:2541–2549.

    Article  PubMed  Google Scholar 

  33. Pineda JA, Recio E, Camacho A, et al. Liver stiffness as a predictor of esophageal varices requiring therapy in HIV/hepatitis C virus-coinfected patients with cirrhosis. J Acquir Immune Defic Syndr. 2009;51:445–449.

    Article  PubMed  Google Scholar 

  34. Foucher J, Chanteloup E, Vergniol J, et al. Diagnosis of cirrhosis by transient elastography (FibroScan): a prospective study. Gut. 2006;55:403–408.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Ana Abad for database management.

Conflict of interest

The authors declare they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Infectious Diseases, Ramon y Cajal Hospital, Cra Colmenar km 9.1, 28034, Madrid, Spain

    José Luis Casado, María Angeles Esteban, Sara Bañón, Ana Moreno, María J. Perez-Elías, Santiago Moreno & Carmen Quereda

  2. Department of Microbiology, Ramon y Cajal Hospital, Madrid, Spain

    María Luisa Mateos

Authors
  1. José Luis Casado
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. María Angeles Esteban
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sara Bañón
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ana Moreno
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. María J. Perez-Elías
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. María Luisa Mateos
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Santiago Moreno
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Carmen Quereda
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to José Luis Casado.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Casado, J.L., Esteban, M.A., Bañón, S. et al. Fibrosis Regression Explains Differences in Outcome in HIV-/HCV-Coinfected Patients with Cirrhosis After Sustained Virological Response. Dig Dis Sci 60, 3473–3481 (2015). https://doi.org/10.1007/s10620-015-3773-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-015-3773-y

Keywords

Search

Navigation