Skip to main content

Advertisement

SpringerLink
Log in

The HCV and HIV coinfected patient: What have we learned about pathophysiology?

  • Published:
Current Gastroenterology Reports Aims and scope Submit manuscript

Abstract

Hepatitis C virus (HCV) infection is an important problem in individuals who are also infected with HIV. HCV infection is very common in HIV-infected individuals, occurring in approximately one quarter to one third of this group, presumably as a consequence of shared routes of transmission related to virologic and pathogenic aspects of the viral infections. Although both are single-stranded RNA viruses and share similar epidemiologic properties, there are many important differences. Although the quantity of HIV RNA in plasma is an important prognostic determinant of HIV infection, this has not been shown with HCV. A direct relationship is apparent between HIV-related destruction of CD4 cells and the clinical consequences of the disease resulting from immunodeficiency. The pathogenesis of HCV, which occurs as a consequence of hepatic fibrosis, is much more complex. The hepatic stellate cell, the major producer of the extracellular matrix protein, is the main contributor to hepatic fibrosis, but the mechanism by which HCV induces hepatic fibrosis remains unclear. Treatment of HCV is increasingly important in HIV-infected patients due to improved HIV-associated morbidity and mortality and due to the frequency with which HCV occurs in patients with HIV-HCV coinfection. Timing of treatment initiation, management of side effects, and possible effects of anti-HCV therapy on HIV are among the issues that need consideration. Also, because several issues concerning HCV are unique to coinfected patients, further research is needed to determine optimal management of HCV in this setting.

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

Similar content being viewed by others

References and Recommended Reading

  1. Alter M, Kruszon-Moran D, Nainan O, et al.: The prevalence of hepatitis C virus infection in the United States, 1988 through 1994. N Engl J Med 1999, 341:556–562.

    Article  PubMed  CAS  Google Scholar 

  2. Weekly epidemiological record. WHO Rep 1997, 72:65–72.

  3. Alter MJ, Margolis HS, Krawczynski K, et al.: The natural history of community-acquired hepatitis C in the United States. N Engl J Med 1992, 327:1899–1905.

    Article  PubMed  CAS  Google Scholar 

  4. Sulkowski MS, Mast EE, Seeff LB, Thomas DL: Hepatitis C virus infection as an opportunistic disease in persons infected with human immunodeficiency virus. Clin Infect Dis 2000, 30:S77-S84.

    Article  PubMed  Google Scholar 

  5. Thomas DL, Villano SA, Riester KA, et al.: Perinatal transmission of hepatitis C virus from human immunodeficiency virus type 1-infected mothers: Women and Infants Transmission Study. J Infect Dis 1998, 177:1480–1488.

    Article  PubMed  CAS  Google Scholar 

  6. Soto B, Rodrigo L, Garcia-Bengoechea M, et al.: Heterosexual transmission of hepatitis C virus and the possible role of coexistent human immunodeficiency virus infection in the index case: a multicentre study of 423 pairings. J Intern Med 1994, 236:515–519.

    Article  PubMed  CAS  Google Scholar 

  7. Yeung LTF, King SM, Roberts EA: Mother-to-infant transmission of hepatitis C virus. Hepatology 2001, 34:223–229.

    Article  PubMed  CAS  Google Scholar 

  8. Justice AC, Chang CH, Fusco J, West N: Extrapolating longterm HIV/AIDS survival in the post-HAART era (abstract 1158). Paper presented at the 39th Annual International Conference on Antimicrobial Agents and Chemotherapy. San Francisco, CA, September 26–29, 1999.

  9. Bica I, McGovern B, Dhar R, et al.: Increasing mortality due to end-stage liver disease in patients with human immunodeficiency virus infection. Clin Infect Dis 2001, 32:492–497.

    Article  PubMed  CAS  Google Scholar 

  10. Major ME, Feinstone SM: The molecular virology of hepatitis C. Hepatology 1997, 25:1527–1538.

    Article  CAS  Google Scholar 

  11. Simmonds P: Clinical relevance of hepatitis C virus genotypes. Gut 1997, 40:291–293.

    PubMed  CAS  Google Scholar 

  12. Cerny A, Chisari FV: Pathogenisis of chronic hepatitis C: immunological features of hepatic injury and viral persistence. Hepatology 1999, 30:595–601.

    Article  PubMed  CAS  Google Scholar 

  13. Ramratnam B, Bonhoeffer S, Binley J, et al.: Rapid production and clearance of HIV-1 and hepatitis C virus assessed by large volume plasma apheresis. Lancet 1999, 354:1782–1785.

    Article  PubMed  CAS  Google Scholar 

  14. Mellors JW, Rinaldo CR, Gupta P, et al.: Prognosis in HIV-1 infection predicted by the quantity of virus in plasma. Science 1996, 272:1167–1170.

    Article  PubMed  CAS  Google Scholar 

  15. Friedman SL: Molecular regulation of hepatic fibrosis: an integrated cellular response to tissue injury. J Biol Chem 2000, 275:2247–2250.

    Article  PubMed  CAS  Google Scholar 

  16. Bissell DM, Roulot D, George J: Transforming growth factor B and the liver. Hepatology 2001, 34:859–867.

    Article  PubMed  CAS  Google Scholar 

  17. McHutchinson J, Gordon S, Schiff E, et al.: Interferon alfa-2b alone or in combination with ribavirin as initial treatment for chronic hepatitis C. N Engl J Med 1998, 339:1485–1492.

    Article  Google Scholar 

  18. Cerny A, Chisari FV: Pathogenesis of chronic hepatitis C: immunological features of hepatic injury and viral persistence. Hepatology 1999, 30:595–601.

    Article  PubMed  CAS  Google Scholar 

  19. Gerlach JT, Diepolder HM, Jung M-C, et al.: Recurrence of Hepatitis C virus after loss of virus-specific CD4+ T-cell response in acute hepatitis C. Gastroenterology 1999, 117:933–941.

    Article  PubMed  CAS  Google Scholar 

  20. Thimme R, Oldach D, Chang, K-M, et al.: Determinants of viral clearance and persistence during acute hepatitis C virus infections. J Exp Med 2001, 194:1395–1406.

    Article  PubMed  CAS  Google Scholar 

  21. Rosen HR, Hinrichs DJ, Gretch DR, et al.: Association of multispecific CD4+ response to hepatitis C and severity of recurrence after liver transplantation. Gastroenterology 1999, 117:926–932.

    Article  PubMed  CAS  Google Scholar 

  22. Lechner F, Wong DKH, Dunbar PR, et al.: Analysis of successful immune response in persons infected with hepatitis C virus. J Exp Med 2000, 191:1499–1512.

    Article  PubMed  CAS  Google Scholar 

  23. Takaki A, Wiese M, Maertens G, et al.: Cellular immune responses persist and humoral responses decrease two decades after recovery from a single-source outbreak of hepatitis C. Nat Med 2000, 6:578–582.

    Article  PubMed  CAS  Google Scholar 

  24. Boyer N, Marcellin P, Degott C, et al.: Recombinant interferonalpha for chronic hepatitis C in patients positive for antibody to human immunodeficiency virus. J Infect Dis 1992, 165:723–726.

    PubMed  CAS  Google Scholar 

  25. Marriott E, Navas S, del Romero J, et al.: Treatment with recombinant alpha-interferon of chronic hepatitis C in anti-HIV positive patients. J Med Virol 1993, 40:107–111.

    Article  PubMed  CAS  Google Scholar 

  26. Mauss S, Klinker H, Ulmer A, et al.: Response to treatment of chronic hepatitis C with interferon alpha in patients infected with HIV-1 is associated with higher CD4+ cell count. Infection 1998, 26:16–19.

    PubMed  CAS  Google Scholar 

  27. Soriano V, Bravo R, Samaniego JG, et al.: CD4+ T-lymphocytopenia in HIV-infected patients receiving interferon therapy for chronic hepatitis C. HIV-Hepatitis Spanish Study Group. AIDS 1994, 8:1621–1622.

    Article  PubMed  CAS  Google Scholar 

  28. Vento S, Di Perri G, Cruciani M, et al.: Rapid decline of CD4+ cells after IFN alpha treatment in HIV-1 infection. Lancet 1993, 341:1597.

    Article  Google Scholar 

  29. Benhamou Y, Bochet M, DiMartino V, et al.: Liver fibrosis progression in human immunodeficiency virus and hepatitis C virus coinfected patients. Hepatology 1999, 30:1054–1058. This study evaluated the fibrosis progression rate in 122 HIV-HCV coinfected individuals compared with a matched cohort of 122 HIVnegative HCV-infected individuals. The fibrosis progression rate was defined as the ratio between the fibrosis stage, determined by the METAVIR scoring system, and the HCV duration. In coinfected and HCV monoinfected individuals, the median fibrosis progression rate is 0.153 and 0.106 (P<0.0001) fibrosis units per year, respectively. HIV seropositivity, alcohol consumption, age at HCV infection, and severe immunosuppression were associated with an increase in the fibrosis progression rate.

    Article  PubMed  CAS  Google Scholar 

  30. Soto B, Sanchez-Quijano A, Rodrigo L, et al.: Human immunodeficiency virus infection modifies the natural history of chronic parenterally-acquired hepatitis C with an unusually rapid progression to cirrhosis. J Hepatol 1997, 26:1–5. A cohort of 547 HCV-infected individuals (116 HIV-positive and 431 HIV-negative) was observed to evaluate the effect of HIV infection on the rate of HCV-associated liver disease. The median estimated interval of time from HCV infection to cirrhosis was significantly longer in HIV-negative than in HIV-positive individuals (23.2 vs 6.9 years, P<0.001).

    Article  PubMed  CAS  Google Scholar 

  31. Sanchez-Quijano A, Andreu J, Gavilan F, et al.: Influence of human immunodeficiency virus type 1 infection on the natural history of chronic parenteral-acquired hepatitis C. Eur J Clin Microbiol Infect Dis 1995, 14:949–953.

    Article  PubMed  CAS  Google Scholar 

  32. Puoti M, Bonacini M, Spinetti A, et al.: Liver fibrosis progression is related to CD4 cell depletion in patients coinfected with hepatitis C virus and human immunodeficiency virus. J Infect Dis 2001, 183:134–137. Liver biopsies from 84 HIV-HCV coinfected and 120 HCV monoinfected individuals were evaluated to determine variables associated with increased hepatic fibrosis. This study found a significant association between CD4+ cell counts of less than 500 cells/mm3 and the presence of many fibrous septa independent of HIV infection, suggesting that CD4 depletion is independently associated with the severity of hepatic fibrosis.

    Article  PubMed  CAS  Google Scholar 

  33. Poynard T, Bedossa P, Opolon P, et al.: Natural history of liver fibrosis progression in patients with chronic hepatitis C. Lancet 1997, 349:825–832.

    Article  PubMed  CAS  Google Scholar 

  34. Poynard T, Ratziu V, Charlotte F, et al.: Rates and risk factors of liver fibrosis progression in patients with chronic hepatitis C. Lancet 2001, 34:730–739.

    CAS  Google Scholar 

  35. Benhamou Y, DiMartino V, Colombet G, et al.: Factors affecting liver fibrosis in human immunodeficiency virus and hepatitis C virus coinfected patients: impact of protease inhibitor therapy. Hepatology 2001, 34:283–287.

    Article  PubMed  CAS  Google Scholar 

  36. Talal AH, Yee H, Dieterich DT: Effect of hepatitis C virus and HIV-1 on hepatic parenchymal and mononuclear cell proliferation and apoptosis [abstract]. Gastroenterology 2000, 118:A938.

    Article  Google Scholar 

  37. Canchis W, Fiel I, Chiriboga L, et al.: Hepatocyte and infiltrating hepatic lymphocyte proliferation and apoptosis in HIV/ HCV coinfected individuals [abstract]. Hepatology 2001, 34:438A.

    Article  Google Scholar 

  38. Zajac AJ, Blattman JN Murali-Krishna K, et al.: Viral immune evasion due to persistence of activated T cells without effector function. J Exp Med 1998, 188:2205–2213.

    Article  PubMed  CAS  Google Scholar 

  39. Appay V, Nixon DF, Donahoe SM, et al.: HIV-specific CD8+ T cells produce antiviral cytokines but are impaired in cytolytic function. J Exp Med 2000, 192:63–75.

    Article  PubMed  CAS  Google Scholar 

  40. Gruener NH, Lechner F, Jung M-C, et al.: Sustained dysfunction of antiviral CD8+ T lymphocytes after infection with hepatitis C virus. J Virol 2001, 75:5550–5558.

    Article  PubMed  CAS  Google Scholar 

  41. Friedman SL: The virtuosity of hepatic stellate cells. Gastroenterology 1999, 117:1244–46.

    Article  PubMed  CAS  Google Scholar 

  42. Kamal SM, Rasenack JW, Bianchi L, et al.: Acute hepatitis C without and with schistosomiasis: correlation with hepatitis C-specific CD4+ T-cell and cytokine response. Gastroenterology 2001, 121:646–656.

    Article  PubMed  CAS  Google Scholar 

  43. Schacker T, Collier AC, Hughes J, et al.: Clinical and epidemiologic features of primary HIV infection. Ann Intern Med 1996, 125:257–264.

    PubMed  CAS  Google Scholar 

  44. Orland JR, Wright TL, Cooper S: Acute hepatitis C. Hepatology 2001, 33:321–327.

    Article  PubMed  CAS  Google Scholar 

  45. 1999 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus. Morb Mortal Wkly Rep 1999, 48:1–59.

  46. Bonacini M, Lin HJ, Hollinger FB: Effect of coexisting HIV-1 infection on the diagnosis and evaluation of hepatitis C virus. J Acquire Immunodefic Syndr 2001, 26:340–344.

    CAS  Google Scholar 

  47. Thio CL, Nolt KR, Astemborski J, et al.: Screening for hepatitis C virus in human immunodeficiency virus-infected individuals. J Clin Micro 2000, 38:575–577.

    CAS  Google Scholar 

  48. Miller V, Staszewski S, Sabin C, et al.: CD4 lymphocyte count as a predictor of the duration of highly active antiretroviral therapy-induced suppression of human immunodeficiency virus load. J Infect Dis 1999, 180:530–533.

    Article  PubMed  CAS  Google Scholar 

  49. Bravo AA, She SG, Chopra S: Liver biopsy. N Engl J Med 2001, 344:495–500.

    Article  PubMed  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  51. The METAVIR Cooperative Group: Inter-and intra-observer variation in the assessment of liver biopsy of chronic hepatitis C. Hepatology 1994, 20:15–20.

    Article  Google Scholar 

  52. Brunt EM: Grading and staging the histopathological lesions of chronic hepatitis. Hepatology 2000, 31:241–246.

    Article  PubMed  CAS  Google Scholar 

  53. Stanley AJ, Haydon GH, Piris J, et al.: Assessment of liver histology in patients with hepatitis C and normal aminotransferase levels. Eur J Gastroenterol Hepatol 1996, 8:869–872.

    Article  PubMed  CAS  Google Scholar 

  54. Lau DT, Kleiner DE, Ghany MG, et al: 10-Year follow-up after interferon-alpha therapy for chronic hepatitis C. Hepatology 1998, 28:1121–1127.

    Article  PubMed  CAS  Google Scholar 

  55. Marcellin P, Boyer N, Gervais A, et al.: Long-term histologic improvement and loss of detectable intrahepatic HCV RNA in patients with chronic hepatitis C and sustained response to interferon-alpha therapy. Ann Intern Med 1997, 127:875–881.

    PubMed  CAS  Google Scholar 

  56. Poynard T, Marcellin P, Lee SS, et al.: Randomized trial of interferon alfa-2b plus ribavirin for 48 weeks or for 24 weeks versus interferon alfa-2b plus placebo for 48 weeks for treatment of chronic infection with hepatitis C virus. Lancet 1998, 352:1426–1432.

    Article  PubMed  CAS  Google Scholar 

  57. Rivero J, Faga M, Cancio I, et al.: Long-term treatment with recombinant interferon alpha-2b prolongs survival of asymptomatic HIV-infected individuals. Biotherapy 1997, 10:107–113.

    PubMed  CAS  Google Scholar 

  58. Haas DW, Lavelle J, Nadler JP, et al.: A randomized trial of interferon alpha therapy for HIV type 1 infection. AIDS Res Hum Retroviruses 2000, 16:183–190.

    Article  PubMed  CAS  Google Scholar 

  59. Causse X, Payen JL, Izopet J, et al.: Does HIV-infection influence the response of chronic hepatitis C to interferon treatment? A French multicenter prospective study. J Hepatol 2000, 32:1003–1010.

    Article  PubMed  CAS  Google Scholar 

  60. Landau A, Batisse D, Pickety C, et al.: Long-term efficacy of combination therapy with interferon-a2b and ribavirin for severe chronic hepatitis C in HIV-infected patients. AIDS 2001, 15:2149–2155.

    Article  PubMed  CAS  Google Scholar 

  61. Zylberberg H, Benhamou Y, Lagneaux JL, et al.: Safety and efficacy of interferon-ribavirin combination therapy in HCV-HIV coinfected subjects: an early report. Gut 2000, 47:694–697. This trial evaluated the safety and efficacy of combination therapy using interferon and ribavirin in HIV-HCV coinfected individuals who were nonresponders or relapsers after treatment with standard interferon. The sustained virologic response rate in these patients was 14.3%.

    Article  PubMed  CAS  Google Scholar 

  62. Nasti G, Di Gennaro G, Tavio M, et al.: Chronic hepatitis C in HIV infection: feasibility and sustained efficacy of therapy with interferon alfa-2b and ribavirin. AIDS 2001, 15:1783–1787.

    Article  PubMed  CAS  Google Scholar 

  63. Sauleda S, Juarez A, Esteban JI, et al.: Interferon and ribavirin combination therapy for chronic hepatitis C in human immunodeficiency virus-infected patients with congenital coagulation disorders. Hepatology 2001, 34:1035–1040.

    Article  PubMed  CAS  Google Scholar 

  64. Zeuzem S, Feinman SV, Rasenack J, et al.: Peginterferon alfa-2a in patients with chronic hepatitis. N Engl J Med 2000, 7:1666–1672.

    Article  Google Scholar 

  65. Manns MP, McHutchinson JG, Gordon SC, et al.: Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus randomized trial. Lancet 2001, 358:958–965.

    Article  PubMed  CAS  Google Scholar 

  66. Roberts RB, Hollinger FB, Parks WP, et al.: A multicenter clinical trial of oral ribavirin in HIV-infected people with lymphadenopathy: virologic observations. AIDS 1990, 4:67–72.

    Article  PubMed  CAS  Google Scholar 

  67. Vogt MW, Hartshorn KL, Furman PA, et al.: Ribavirin antagonizes the effect of azidothymidine on HIV replication. Science 1987, 235:1376–1379.

    Article  PubMed  CAS  Google Scholar 

  68. Hoggard PG, Kewn S, Barry MG, et al.: Effects of drugs on 2′3′-didehydrothymidine phosphorylation in vitro. Antimicrob Agents Chemother 1997, 41:1231–1236.

    PubMed  CAS  Google Scholar 

  69. Poynard T, McHutchinson J, Goodman Z, et al.: Is an ‘a la carte’ combination interferon alfa-2b plus ribavirin regimen possible for the first line treatment in patients with chronic hepatitis C? Hepatology 2000, 31:211–218.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Weill Medical College of Cornell University, 525 East 68th Street, A354, 10021, New York, NY, USA

    Andrew H. Talal MD, MPH, P. Wilfredo Canchis MD & Ira M. Jacobson MD

Authors
  1. Andrew H. Talal MD, MPH
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. Wilfredo Canchis MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ira M. Jacobson MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Talal, A.H., Canchis, P.W. & Jacobson, I.M. The HCV and HIV coinfected patient: What have we learned about pathophysiology?. Curr Gastroenterol Rep 4, 15–22 (2002). https://doi.org/10.1007/s11894-002-0033-z

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11894-002-0033-z

Keywords

Search

Navigation