Management of hepatitis C virus in special populations: Patient and treatment considerations
Authors: Robert G. Gish, Nezam H. Afdhal, Douglas T. Dieterich, K. Rajender Reddy
Journal: Clinical Gastroenterology and Hepatology (2005)

The most common chronic blood-borne infection in the United States is caused by hepatitis C virus. An estimated 3.9 million people (1.8%) in the United States have been infected with the hepatitis C virus, excluding certain subpopulations who are at high risk for hepatitis C virus infection. Among these subpopulations are an estimated 255,000 (15%) of prison inmates and 175,000 (22%) of homeless people. Prevalence of hepatitis C virus infection is also high among veterans (6.6% overall and even higher among homeless veterans). The single most important risk factor for hepatitis C virus infection is injection drug use; up to 90% of illicit injection drug users are infected with hepatitis C virus. This review describes the prevalence of hepatitis C virus in special populations and discusses the treatment options for patients with severe disease, transplant recipients, and patients at high risk for infection. Close monitoring and management of therapeutic side effects are required to assist these patients in adhering to therapy. The most common chronic blood-borne infection in the United States is caused by hepatitis C virus. An estimated 3.9 million people (1.8%) in the United States have been infected with the hepatitis C virus, excluding certain subpopulations who are at high risk for hepatitis C virus infection. Among these subpopulations are an estimated 255,000 (15%) of prison inmates and 175,000 (22%) of homeless people. Prevalence of hepatitis C virus infection is also high among veterans (6.6% overall and even higher among homeless veterans). The single most important risk factor for hepatitis C virus infection is injection drug use; up to 90% of illicit injection drug users are infected with hepatitis C virus. This review describes the prevalence of hepatitis C virus in special populations and discusses the treatment options for patients with severe disease, transplant recipients, and patients at high risk for infection. Close monitoring and management of therapeutic side effects are required to assist these patients in adhering to therapy. The most common chronic blood-borne infection in the United States is caused by HCV, an RNA virus transmitted by direct percutaneous exposure to blood.1National Institutes of HealthManagement of hepatitis C 2002.NIH Consens State Sci Statements. 2002; 19: 1-46Google Scholar According to the 1999 National Health and Nutrition Examination Survey (NHANES),2Alter M.J. Kruszon-Moran D. Nainan O.V. et al.The prevalence of hepatitis C virus infection in the United States, 1988 through 1994.N Engl J Med. 1999; 341: 556-562Crossref PubMed Scopus (2463) Google Scholar the overall prevalence of antibody to HCV was 1.8%, which corresponds to an estimated 3.9 million people in the United States having been infected with HCV. On the basis of HCV RNA testing in the population studied, it is estimated that currently 2.7 million individuals in the United States are chronically infected. The prevalence of anti-HCV in groups not evaluated in the NHANES survey, such as the homeless or incarcerated, might be as high as 40%.3Kim W.R. The burden of hepatitis C in the United States.Hepatology. 2002; 36: S30-S34Crossref PubMed Google Scholar Disease progression varies among subpopulations, but up to 85% of HCV infections become chronic, and 20% of cases progress to cirrhosis. Hepatocellular carcinoma (HCC) can be expected in 4% of cases, decompensated cirrhosis in 6%, and death in 3.6%.4Di Bisceglie A.M. Natural history of hepatitis C its impact on clinical management.Hepatology. 2000; 31: 1014-1018Crossref PubMed Scopus (236) Google Scholar Currently, HCV is the reported cause of 10,000–12,000 deaths annually.1National Institutes of HealthManagement of hepatitis C 2002.NIH Consens State Sci Statements. 2002; 19: 1-46Google Scholar The Centers for Disease Control and Prevention estimates that the rate of newly acquired HCV infections dropped from 230,000 cases per year in the 1980s to 25,000 in 2001 after HCV screening of blood donors5Centers for Disease Control and PreventionRecommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease.MMWR Morb Mortal Wkly Rep. 1998; 47: 1-39PubMed Google Scholar and a decrease in specific high-risk behaviors. Although new HCV infections have declined, morbidity and mortality associated with HCV have increased, a trend predicted to continue during the next 2 decades because of the "maturation" of HCV-induced cirrhosis.6Wong J.B. McQuillan G.M. McHutchison J.G. et al.Estimating future hepatitis C morbidity, mortality, and costs in the United States.Am J Public Health. 2000; 90: 1562-1569Crossref PubMed Scopus (530) Google Scholar HCV prevalence rates differ in subpopulations with varied risk factors. The NHANES III reported approximately 937,000 HCV-infected people living below the poverty level and 2.9 million with 12 years or fewer of education (Table 1).2Alter M.J. Kruszon-Moran D. Nainan O.V. et al.The prevalence of hepatitis C virus infection in the United States, 1988 through 1994.N Engl J Med. 1999; 341: 556-562Crossref PubMed Scopus (2463) Google Scholar Prevalence of HCV based on HCV antibody seropositivity among men was 2.5% (95% confidence interval, 2.0–3.2), but among women, it was 1.2% (95% confidence interval, 0.9–1.6). Among minority subpopulations, Mexican Americans were more likely to be HCV seropositive, with an odds ratio of 1.60 (95% confidence interval, 0.92–2.79), as were non-Hispanic blacks with an adjusted odds ratio of 1.44 (95% confidence interval, 0.90–2.30).2Alter M.J. Kruszon-Moran D. Nainan O.V. et al.The prevalence of hepatitis C virus infection in the United States, 1988 through 1994.N Engl J Med. 1999; 341: 556-562Crossref PubMed Scopus (2463) Google Scholar However, neither gender nor race was associated with HCV independent of sociodemographic and behavioral risk factors.2Alter M.J. Kruszon-Moran D. Nainan O.V. et al.The prevalence of hepatitis C virus infection in the United States, 1988 through 1994.N Engl J Med. 1999; 341: 556-562Crossref PubMed Scopus (2463) Google Scholar The most important risk factor for HCV infection is injection drug use, and up to 90% of illegal intravenous drug users (IVDUs) are HCV infected.7Edlin B.R. Prevention and treatment of hepatitis C in injection drug users.Hepatology. 2002; 36: S210-S219Crossref PubMed Google Scholar Coinfection with HCV and HBV or human immunodeficiency virus (HIV) is common as a result of shared routes of infection and might cause accelerated progression to advanced liver disease.1National Institutes of HealthManagement of hepatitis C 2002.NIH Consens State Sci Statements. 2002; 19: 1-46Google ScholarTable 1Prevalence of HCV by Demographic and Potential Risk Factors (NHANES)CharacteristicNumber testedHCV prevalence % (95% CI)Estimated nationwideBelow poverty level5,3453.2 (2.4–4.3)937,000At or above poverty13,9741.6 (1.2–2.0)2,625,00012 y or less of education11,9712.8 (2.1–3.6)2,866,000More than 12 y of education4,5281.3 (0.8–2.0)898,000Men10,0762.5 (2.0–3.2)2,586,000Women11,1651.2 (0.9–1.6)1,289,000Cocaine use more than 10 times51917.8 (12.3–25.8)No cocaine use10,0501.1 (0.8–1.4)Data from Alter et al.2Alter M.J. Kruszon-Moran D. Nainan O.V. et al.The prevalence of hepatitis C virus infection in the United States, 1988 through 1994.N Engl J Med. 1999; 341: 556-562Crossref PubMed Scopus (2463) Google ScholarCI, confidence interval; NHANES, National Health and Nutrition Examination Survey. Open table in a new tab Data from Alter et al.2Alter M.J. Kruszon-Moran D. Nainan O.V. et al.The prevalence of hepatitis C virus infection in the United States, 1988 through 1994.N Engl J Med. 1999; 341: 556-562Crossref PubMed Scopus (2463) Google Scholar CI, confidence interval; NHANES, National Health and Nutrition Examination Survey. HCV is high among specific US subpopulations not included in the NHANES data, 15% of prison inmates, with an estimated 255,000 infected,8Centers for Disease Control and PreventionPrevention and control of infections with hepatitis viruses in correctional settings.MMWR Morb Mortal Wkly Rep. 2003; 52: 1-34PubMed Google Scholar and 22% of homeless people, with an estimated 175,000 infected.9Nyamathi A.M. Dixon E.L. Robbins W. et al.Risk factors for hepatitis C virus infection among homeless adults.J Gen Intern Med. 2002; 17: 134-143Crossref PubMed Scopus (105) Google Scholar Prevalence is also high among veterans (6.6% overall), affecting an estimated 280,000.10Bräu N. Bini E.J. Shahidi A. et al.Prevalence of hepatitis C and coinfection with HIV among United States veterans in the New York City metropolitan area.Am J Gastroenterol. 2002; 97: 2071-2078PubMed Google Scholar Children comprise a special group with a low prevalence of HCV infection (0.1%), affecting an estimated 68,000–100,000 children younger than 19 years of age.11Jonas M.M. Children with hepatitis C.Hepatology. 2002; 36: S173-S178Crossref PubMed Google Scholar Approximately 300,000 HIV-infected patients,3Kim W.R. The burden of hepatitis C in the United States.Hepatology. 2002; 36: S30-S34Crossref PubMed Google Scholar, 8Centers for Disease Control and PreventionPrevention and control of infections with hepatitis viruses in correctional settings.MMWR Morb Mortal Wkly Rep. 2003; 52: 1-34PubMed Google Scholar, 12Staples Jr, C.T. Rimland D. Dudas D. Hepatitis C in the HIV (human immunodeficiency virus) Atlanta VA (Veterans Affairs Medical Center) Cohort Study (HAVACS) the effect of coinfection on survival.Clin Infect Dis. 1999; 29: 150-154Crossref PubMed Scopus (245) Google Scholar 300,000 IVDUs,3Kim W.R. The burden of hepatitis C in the United States.Hepatology. 2002; 36: S30-S34Crossref PubMed Google Scholar, 7Edlin B.R. Prevention and treatment of hepatitis C in injection drug users.Hepatology. 2002; 36: S210-S219Crossref PubMed Google Scholar, 8Centers for Disease Control and PreventionPrevention and control of infections with hepatitis viruses in correctional settings.MMWR Morb Mortal Wkly Rep. 2003; 52: 1-34PubMed Google Scholar, 12Staples Jr, C.T. Rimland D. Dudas D. Hepatitis C in the HIV (human immunodeficiency virus) Atlanta VA (Veterans Affairs Medical Center) Cohort Study (HAVACS) the effect of coinfection on survival.Clin Infect Dis. 1999; 29: 150-154Crossref PubMed Scopus (245) Google Scholar, 13SAMHSA. NHSDA report: injection drug use, 2003. Available at: www.samsha.gov/oas/2k3/ivdrug/ivdrug.cfm. Accessed December 12, 2003.Google Scholar and 240,000 alcoholics3Kim W.R. The burden of hepatitis C in the United States.Hepatology. 2002; 36: S30-S34Crossref PubMed Google Scholar, 7Edlin B.R. Prevention and treatment of hepatitis C in injection drug users.Hepatology. 2002; 36: S210-S219Crossref PubMed Google Scholar, 8Centers for Disease Control and PreventionPrevention and control of infections with hepatitis viruses in correctional settings.MMWR Morb Mortal Wkly Rep. 2003; 52: 1-34PubMed Google Scholar, 12Staples Jr, C.T. Rimland D. Dudas D. Hepatitis C in the HIV (human immunodeficiency virus) Atlanta VA (Veterans Affairs Medical Center) Cohort Study (HAVACS) the effect of coinfection on survival.Clin Infect Dis. 1999; 29: 150-154Crossref PubMed Scopus (245) Google Scholar, 13SAMHSA. NHSDA report: injection drug use, 2003. Available at: www.samsha.gov/oas/2k3/ivdrug/ivdrug.cfm. Accessed December 12, 2003.Google Scholar, 14LaBrecque DR, Sandt L. Hepatitis C choices. Part one: for everyone with hepatitis C. Chapter 2: alcohol and hepatitis C. 2003. Available at: http://www.hepcchallenge.org/manual/alcohol_final.htm. Accessed December 12, 2003.Google Scholar are infected with HCV. The National Institutes of Health (NIH) consensus on HCV management recommended screening all populations at high risk for HCV infection1National Institutes of HealthManagement of hepatitis C 2002.NIH Consens State Sci Statements. 2002; 19: 1-46Google Scholar and considering the treatment of special populations including those with decompensated cirrhosis, transplant recipients, HIV-coinfected patients, and IVDUs. The goal of this review is to describe the prevalence of HCV and treatment options in special populations. Cirrhosis, end-stage liver disease (ESLD), and HCC develop at widely variable intervals after HCV infection. Overall, the rate of progression to cirrhosis is 20% by 20 years after infection, ranging from 2%–4% in women and children and from 20%–30% in blood transfusion subjects.1National Institutes of HealthManagement of hepatitis C 2002.NIH Consens State Sci Statements. 2002; 19: 1-46Google Scholar In patients with cirrhosis the reported risk of HCC at 5 years was 7%, and the risk of decompensation was 18%, with a probability of 5-year survival after the first major complication of only 50%.15Fattovich G. Giustina G. Degos F. et al.Morbidity and mortality in compensated cirrhosis type C a retrospective follow-up study of 384 patients.Gastroenterology. 1997; 112: 463-472Abstract Full Text Full Text PDF PubMed Scopus (1274) Google Scholar Deaths from HCV in the United States are most often due to decompensated cirrhosis, with identified risk factors of age older than 40 years at infection, male gender, moderate alcohol use, fatty liver disease, and HBV coinfection.1National Institutes of HealthManagement of hepatitis C 2002.NIH Consens State Sci Statements. 2002; 19: 1-46Google Scholar Standard HCV therapies, interferon (IFN) or pegylated interferon (PEG-IFN) with ribavirin (RBV), are less effective in cirrhotic patients than in noncirrhotic patients.1National Institutes of HealthManagement of hepatitis C 2002.NIH Consens State Sci Statements. 2002; 19: 1-46Google Scholar Two clinical trials reported that sustained virologic response (SVR) after PEG-IFN and RBV combination therapy was approximately 10% lower for patients with bridging fibrosis/cirrhosis (43%–44%) than for those with minimal fibrosis.16Manns M.P. McHutchison J.G. Gordon S.C. et al.Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C a randomised trial.Lancet. 2001; 358: 958-965Abstract Full Text Full Text PDF PubMed Scopus (5957) Google Scholar, 17Fried M.W. Shiffman M.L. Reddy K.R. et al.Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection.N Engl J Med. 2002; 347: 975-982Crossref PubMed Scopus (5962) Google Scholar PEG-IFN monotherapy resulted in 30% SVR for patients with cirrhosis or bridging fibrosis, which was more effective than standard IFN (8% SVR).18Heathcote E.J. Shiffman M.L. Cooksley W.G. et al.Peginterferon alfa-2a in patients with chronic hepatitis C and cirrhosis.N Engl J Med. 2000; 343: 1673-1680Crossref PubMed Scopus (881) Google Scholar Histologic improvement is seen in the majority of cirrhotic patients treated with high-dose PEG-IFN.18Heathcote E.J. Shiffman M.L. Cooksley W.G. et al.Peginterferon alfa-2a in patients with chronic hepatitis C and cirrhosis.N Engl J Med. 2000; 343: 1673-1680Crossref PubMed Scopus (881) Google Scholar Patients with advanced cirrhosis are at higher risk for decompensation during antiviral therapy, with increased side effects. Although dose maintenance is critical to achieving SVR, dose adjustments might be necessary to manage side effects.19McHutchison J.G. Manns M. Patel K. et al.Adherence to combination therapy enhances sustained response in genotype-1-infected patients with chronic hepatitis C.Gastroenterology. 2002; 123: 1061-1069Abstract Full Text Full Text PDF PubMed Scopus (963) Google Scholar Granulocyte colony-stimulating factor can be used to treat IFN-induced leukopenias, and epoetin alfa has been shown to minimize RBV-induced anemia and increase adherence to RBV therapy, as well as improve quality of life (QOL) (Table 2).1National Institutes of HealthManagement of hepatitis C 2002.NIH Consens State Sci Statements. 2002; 19: 1-46Google Scholar, 20Dieterich D.T. Spivak J.L. Hematologic disorders associated with hepatitis C virus infection and their management.Clin Infect Dis. 2003; 37: 533-541Crossref PubMed Scopus (90) Google Scholar, 21Afdhal N.H. Dieterich D.T. Pockros P.J. et al.Epoetin alfa treatment of anemic HCV-infected patients allows for maintenance of ribavirin dose, increases hemoglobin levels, and improves quality of life vs placebo a randomized, double-blind, multicenter study.Gastroenterology. 2003; 124 (abstr): A-714Google Scholar Supportive care can minimize side effects, improve treatment tolerance, and improve overall health-related QOL for HCV patients.21Afdhal N.H. Dieterich D.T. Pockros P.J. et al.Epoetin alfa treatment of anemic HCV-infected patients allows for maintenance of ribavirin dose, increases hemoglobin levels, and improves quality of life vs placebo a randomized, double-blind, multicenter study.Gastroenterology. 2003; 124 (abstr): A-714Google Scholar Mortality from decompensation is high without transplantation15Fattovich G. Giustina G. Degos F. et al.Morbidity and mortality in compensated cirrhosis type C a retrospective follow-up study of 384 patients.Gastroenterology. 1997; 112: 463-472Abstract Full Text Full Text PDF PubMed Scopus (1274) Google Scholar; however, there is an increasing shortage of donor livers in the United States.22Crippin J.S. McCashland T. Terrault N. et al.A pilot study of the tolerability and efficacy of antiviral therapy in hepatitis C virus-infected patients awaiting liver transplantation.Liver Transpl. 2002; 8: 350-355Crossref PubMed Scopus (312) Google Scholar IFN-based therapy is relatively contraindicated in ESLD when thrombocytopenia and leukopenia are present, and side effects of both IFN and RBV are a major concern. In addition, life-threatening infections can occur during treatment.22Crippin J.S. McCashland T. Terrault N. et al.A pilot study of the tolerability and efficacy of antiviral therapy in hepatitis C virus-infected patients awaiting liver transplantation.Liver Transpl. 2002; 8: 350-355Crossref PubMed Scopus (312) Google ScholarTable 2Management of Common Side Effects of IFN and RBV in HCV-Infected PatientsAdverse eventManagementFlu-like syndromeBedtime injections, prophylactic acetaminophen or other nonsteroidal anti-inflammatory drugs, noncaffeinated fluidsDepressionSelective serotonin reuptake inhibitors, counselingLeukopeniaGranulocyte colony-stimulating factor, IFN/PEG-IFN dose reductionAnemiaEpoetin alfa, RBV dose reductionData from Dieterich.36Dieterich D.T. Treatment of hepatitis C and anemia in human immunodeficiency virus-infected patients.J Infect Dis. 2002; 185: S128-S137Crossref PubMed Scopus (44) Google ScholarIFN, interferon; RBV, ribavirin; PEG-IFN, pegylated interferon. Open table in a new tab Data from Dieterich.36Dieterich D.T. Treatment of hepatitis C and anemia in human immunodeficiency virus-infected patients.J Infect Dis. 2002; 185: S128-S137Crossref PubMed Scopus (44) Google Scholar IFN, interferon; RBV, ribavirin; PEG-IFN, pegylated interferon. In the Low-Accelerating-Dose Regimen trial, patients awaiting transplantation received low-dose IFN/RBV, and the dose was increased at 2-week intervals only if treatment was well tolerated. The first reported SVR rates were 22% and persisted after transplantation. There was no evidence of recurrent HCV after transplantation in patients with an SVR.23Everson G.T. Trotter J.F. Kugelmas M. Long-term outcome of patients with chronic hepatitis C and decompensated liver disease treated with the LADR protocol (Low-Accelerating-Dose Regimen).Hepatology. 2002; 36 (abstr): 297APubMed Google Scholar The majority of decompensated cirrhotic patients required growth factors to avoid anemia and severe leukopenia. The potential for antiviral therapy to slow disease progression in this special population of patients awaiting transplant requires further study. Liver transplantation is the only available option for therapy in many cases of HCV-infected patients with advanced liver disease. However, reinfection with HCV is nearly universal in transplant recipients, and the course of disease is more aggressive, with a lower 5-year patient survival rate of 60%–80%.1National Institutes of HealthManagement of hepatitis C 2002.NIH Consens State Sci Statements. 2002; 19: 1-46Google Scholar Post-transplantation survival rates at longer intervals are decreasing, and the rate of disease progression among recipients is worsening for HCV cases, possibly because of increasing donor age.24Berenguer M. Prieto M. San Juan F. et al.Contribution of donor age to the recent decrease in patient survival among HCV-infected liver transplant recipients.Hepatology. 2002; 36: 202-210Crossref PubMed Scopus (576) Google Scholar, 25Forman L.M. Lewis J.D. Berlin J.A. et al.The association between hepatitis C infection and survival after orthotopic liver transplantation.Gastroenterology. 2002; 122: 889-896Abstract Full Text Full Text PDF PubMed Scopus (966) Google Scholar Variability of disease progression and survival post-transplantation is related to prior antiviral therapy and HCV RNA levels at transplantation. HCV-positive transplant recipients had a 42% probability of decompensation by 1 year after transplantation in some studies, and when followed by decompensation, survival rates dropped to only 41%.26Berenguer M. Prieto M. Rayon J.M. et al.Natural history of clinically compensated hepatitis C virus-related graft cirrhosis after liver transplantation.Hepatology. 2000; 32: 852-858Crossref PubMed Scopus (503) Google Scholar The primary goal of therapy after transplantation is to reduce injury to the allograft, and the secondary goal is to clear HCV. Treatment options include initiating antiviral therapy during acute reinfection or treatment following documentation of disease progression in the allograft.27Reddy R. Fried M. Dickson R. et al.Interferon alfa-2b and ribavirin vs. placebo as early treatment in patients transplanted for hepatitis C end-stage liver disease results of a multicenter, randomized trial.Gastroenterology. 2002; 122; (abstr): A-632Google Scholar PEG-IFN/RBV treatment of transplant recipients reinfected with HCV at 28 weeks after transplantation resulted in an end-of-treatment virologic response of 55%, with sustained results yet to be published.28Dumortier J. Scoazec J.-Y. Chevallier P. et al.Treatment of recurrent hepatitis C after liver transplantation a pilot study of peginterferon alfa-2b and ribavirin combination.J Hepatol. 2004; 40: 669-674Abstract Full Text Full Text PDF PubMed Scopus (204) Google Scholar In this study, the majority of patients required RBV dose reduction because of anemia. Tolerability of combination therapy is a major problem in transplant recipients. Renal insufficiency as a result of immunosuppressive therapy results in reduced clearance of RBV, which can cause severe hemolysis. Preemptive therapy with epoetin alfa has been shown to prevent hemoglobin reductions in nonanemic transplant recipients treated with combination HCV therapy.29Ghalib R.H. Levine C.D. Hollinger B. et al.Changes in hemoglobin during therapy with PEG IFN alfa-2b plus ribavirin in patients with recurrent hepatitis C after liver transplantation. 2003Google Scholar, 30Rahim N. Suggett K. Troppmann C. et al.Hepatitis C RNA drop of two logs at 12 weeks may predict response to treatment of post-transplant HCV. 2003Google Scholar Treatment strategies with improved tolerability are needed for HCV-infected patients undergoing liver transplantation. Benefits of treatment need to be balanced against the potential risk of acute or chronic rejection when treating with IFN.31Saab S. Kalmaz D. Gajjar N.A. et al.Outcomes of acute rejection after interferon therapy in liver transplant recipients.Liver Transpl. 2004; 10: 859-867Crossref PubMed Scopus (92) Google Scholar, 32Stravitz R.T. Shiffman M.L. Sanyal A.J. et al.Effects of interferon treatment on liver histology and allograft rejection in patients with recurrent hepatitis C following liver transplantation.Liver Transpl. 2004; 10: 850-858Crossref PubMed Scopus (124) Google Scholar Prevalence of HIV and HCV coinfection among IVDUs is high, and all HIV-positive patients should be screened for HCV.1National Institutes of HealthManagement of hepatitis C 2002.NIH Consens State Sci Statements. 2002; 19: 1-46Google Scholar With the advent of highly active antiretroviral therapy (HAART), HIV-positive patient survival has dramatically improved, and HCV-induced liver disease among HIV/HCV-coinfected patients has increased. During the pre-HAART era, cause of death from ESLD ranged from 2%–13%. After the introduction of HAART for HIV-positive patients, mortality from ESLD increased to 7%–50% (Table 3).33Soriano V. Sulkowski M. Bergin C. et al.Care of patients with chronic hepatitis C and HIV co-infection recommendations from the HIV-HCV International Panel.AIDS. 2002; 16: 813-828Crossref PubMed Scopus (248) Google Scholar According to one study, HCV infection might also worsen HIV prognosis and decrease CD4+ recovery on antiretroviral treatment.33Soriano V. Sulkowski M. Bergin C. et al.Care of patients with chronic hepatitis C and HIV co-infection recommendations from the HIV-HCV International Panel.AIDS. 2002; 16: 813-828Crossref PubMed Scopus (248) Google Scholar HIV has been shown to accelerate progression of HCV-related liver disease and mortality.34Poles M.A. Dieterich D.T. Hepatitis C virus/human immunodeficiency virus coinfection clinical management issues.Clin Infect Dis. 2000; 31: 154-161Crossref PubMed Scopus (50) Google Scholar, 35Pol S. Vallet-Pichard A. Fontaine H. Hepatitis C and human immune deficiency coinfection at the era of highly active antiretroviral therapy.J Viral Hepat. 2002; 9: 1-8Crossref PubMed Scopus (24) Google ScholarTable 3Mortality Caused by End-Stage Liver Disease Among HIV-Infected IndividualsPre-HAART eraHAART eraNo.YearNo.YearBrescia (Italy)11.5% (35/305)198735% (16/46)1996Madrid (Spain)4.8% (15/312)1991–199545% (9/20)2000Boston (USA)11.5% (3/26)199150% (11/22)1998–1999France1.6% (21/1327)19956.6% (36/543)1997Adapted and reprinted with permission from Soriano et al.33Soriano V. Sulkowski M. Bergin C. et al.Care of patients with chronic hepatitis C and HIV co-infection recommendations from the HIV-HCV International Panel.AIDS. 2002; 16: 813-828Crossref PubMed Scopus (248) Google Scholar Open table in a new tab Adapted and reprinted with permission from Soriano et al.33Soriano V. Sulkowski M. Bergin C. et al.Care of patients with chronic hepatitis C and HIV co-infection recommendations from the HIV-HCV International Panel.AIDS. 2002; 16: 813-828Crossref PubMed Scopus (248) Google Scholar Before HCV treatment of HIV/HCV-coinfected patients, HAART is usually initiated to stabilize CD4+ count. However, patients with advanced liver disease or an intact immune system (ie, high CD4+ counts and no history of opportunistic infection) might require HCV treatment first to prevent hepatotoxicity from HIV treatment.36Dieterich D.T. Treatment of hepatitis C and anemia in human immunodeficiency virus-infected patients.J Infect Dis. 2002; 185: S128-S137Crossref PubMed Scopus (44) Google Scholar HIV-positive patients coinfected with HBV and HCV should be screened for preexisting liver disease before initiating HAART to reduce the risk of toxicity.37Kontorinis N. Dieterich D. Hepatotoxicity of antiretroviral therapy.AIDS Rev. 2003; 5: 36-43PubMed Google Scholar Transaminase levels in patients with preexisting liver disease should be tested every 2 weeks and monthly once patients stabilize. Inflammation and fibrosis should be monitored with regular biopsies and liver enzyme measurement. IFN/RBV combination therapy results in moderate SVR rates for HCV in HIV-coinfected patients.36Dieterich D.T. Treatment of hepatitis C and anemia in human immunodeficiency virus-infected patients.J Infect Dis. 2002; 185: S128-S137Crossref PubMed Scopus (44) Google Scholar PEG-IFN/RBV does not affect HIV RNA levels, and SVR rates for HCV are similar for coinfected patients if CD4+ counts are above 200 cells/μL. Adverse drug interactions, such as fatal lactic acidosis and pancreatitis, are a special concern.38Butt A.A. Fatal lactic acidosis and pancreatitis associated with ribavirin and didanosine therapy.AIDS Read. 2003; 13: 344-348PubMed Google Scholar Further studies evaluating SVR in combination therapies for HIV/HCV-coinfected patients are presented in Table 4.39Chung R.T. Andersen J. Volberding P. et al.Peginterferon alfa-2a plus ribavirin versus interferon alfa-2a plus ribavirin for chronic hepatitis C in HIV-coinfected persons.N Engl J Med. 2004; 351: 451-459Crossref PubMed Scopus (853) Google Scholar, 40Torriani F.J. Rodriguez-Torres M. Rockstroh J.K. et al.Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients.N Engl J Med. 2004; 351: 438-450Crossref PubMed Scopus (1211) Google ScholarTable 4Sustained Virologic Responses to Pegylated Interferon in HIV/HCV-Coinfected PatientsNumber of patientsOverall response (%)Genotype 1 (%)Non-genotype 1 (%)ACTG A5071 (Chung et al)39Chung R.T. Andersen J. Volberding P. et al.Peginterferon alfa-2a plus ribavirin versus interferon alfa-2a plus ribavirin for chronic hepatitis C in HIV-coinfected persons.N Engl J Med. 2004; 351: 451-459Crossref PubMed Scopus (853) Google Scholar Standard interferon + ribavirinaEscalating dose of ribavirin was used in ACTG 5071. Patients were started at a dose of 600 mg/day, which was subsequently increased by 200 mg/day every 4 weeks for a maximum total of 1000 mg/day. Both APRICOT and RIBAVIC started and maintained patients on 800 mg/day ribavirin.6712633 Pegasys + ribavirin66271473APRICOT (Torriani et al)40Torriani F.J. Rodriguez-Torres M. Rockstroh J.K. et al.Peginterferon alfa-2a plus ribavirin