Role of Growth Factors in the Treatment of Patients With HIV/HCV Coinfection and Patients With Recurrent Hepatitis C Following Liver Transplantation

Abstract

Hepatitis C (HCV) contributes significantly to the morbidity and mortality of patients coinfected with human immunodeficiency virus (HIV) and those with recurrent hepatitis C after successful liver transplantation. Treatment of hepatitis C in these patient populations, while crucial, can be quite challenging. Baseline cytopenias, in particular, may limit dosing of interferon and/or ribavirin or preclude therapy entirely when standard guidelines are followed. Concomitant medications, opportunistic infections, and other bone marrow insults account for the anemia, neutropenia, and thrombocytopenia frequently encountered in these patients. Sustained virologic response rates in published series for HIV/HCV and post-transplantation HCV have not reached those seen in treatment of HCV alone, despite the highly selected patient populations chosen for these studies. Hematopoietic growth factors such as erythropoietin and granulocyte-colony stimulating factors may be used to improve the anemia and neutropenia seen during treatment of HCV. Reported experience with these growth factors is limited in HIV/HCV coinfected patients, but studies are underway to determine if growth factors improve adherence to therapy and perhaps virologic response rates. Post-transplantation studies of HCV therapy have reported more liberal use of growth factors; however, discontinuation rates have been high and virologic response rates have been disappointing. Further study of growth factors as a means to increase sustained virologic response rates and maintain adequate dosing and duration of interferon and ribavirin therapy in these patient populations is needed.

Spontaneous clearance of hepatitis C virus after liver transplantation in two patients coinfected with hepatitis C virus and human immunodeficiency virus

“…To date, response rates to HCV treatment in the posttransplant HIV-HCVcoinfected population are lower than those seen in recipients solely infected with HCV. 6 In HIV-HCV-coinfected individuals, host genetic factors appear to play a role in both the development of fibrosis and the response to HCV therapy. Allelic variations in proteins critical to the inflammatory response found in these patients may alter hepatic response to HCV and thus alter the severity of infection.…”

Rational Guide to the Use of Erythropoietin in the Treatment of HCV Infection

“…The use of growth factors in this population is addressed in only a few studies, most of which have small sample sizes [36,[44][45][46][47]. Most of these papers merely mention EPO in passing, and Shergill et al [45] comment on the usefulness of EPO for RBV dose maintenance, but did not allow for dose increase.…”

“…Unfortunately, because of the paucity of information on the use of erythropoietic growth factors in these populations, definitive conclusions cannot be drawn, especially because no current studies have examined the role of EPO in the post-liver transplant patient. However, Frederick and Hassanein [36] make note of the fact that this patient population has a less vigorous response to growth factors in general.…”

“…About 15% to 30% of patients infected with HIV are coinfected with HIV, whereas only 5% to 10% of patients with HCV are coinfected with HIV [36]. In the coinfected patient, highly active antiretroviral treatment medications (eg, zidovudine), can further contribute to anemia.…”

“…Most of these papers merely mention EPO in passing, and Shergill et al [45] comment on the usefulness of EPO for RBV dose maintenance, but did not allow for dose increase. Frederick and Hassanein [36] examine the literature regarding the use of hematopoietic growth factors in both the coinfected patients and the postliver transplant patient. Unfortunately, because of the paucity of information on the use of erythropoietic growth factors in these populations, definitive conclusions cannot be drawn, especially because no current studies have examined the role of EPO in the post-liver transplant patient.…”