Effects of a Sustained Virologic Response on Outcomes of Patients With Chronic Hepatitis C
2011; Elsevier BV; Volume: 9; Issue: 11 Linguagem: Inglês
10.1016/j.cgh.2011.05.028
ISSN1542-7714
Autores Tópico(s)Hepatitis B Virus Studies
ResumoFor patients with chronic hepatitis C virus infection, the goal of antiviral therapy is to achieve a sustained virologic response (SVR). We review the durability of the SVR and its effects on liver-related mortality, hepatic decompensation, and the development of hepatocellular carcinoma. We performed a systematic review of the effects of the SVR on liver-related hepatic outcomes and found the SVR to be durable (range, 98.4%–100%). An SVR reduced liver-related mortality among patients with chronic hepatitis C (3.3- to 25-fold), the incidence of hepatocellular carcinoma (1.7- to 4.2-fold), and hepatic decompensation (2.7- to 17.4-fold). An SVR can lead to regression of fibrosis and cirrhosis, and has been associated with a reduced rate of hepatic decompensation, a reduced risk for hepatocellular carcinoma, and reduced liver-related mortality. For patients with chronic hepatitis C virus infection, the goal of antiviral therapy is to achieve a sustained virologic response (SVR). We review the durability of the SVR and its effects on liver-related mortality, hepatic decompensation, and the development of hepatocellular carcinoma. We performed a systematic review of the effects of the SVR on liver-related hepatic outcomes and found the SVR to be durable (range, 98.4%–100%). An SVR reduced liver-related mortality among patients with chronic hepatitis C (3.3- to 25-fold), the incidence of hepatocellular carcinoma (1.7- to 4.2-fold), and hepatic decompensation (2.7- to 17.4-fold). An SVR can lead to regression of fibrosis and cirrhosis, and has been associated with a reduced rate of hepatic decompensation, a reduced risk for hepatocellular carcinoma, and reduced liver-related mortality. Hepatitis C virus (HCV) is estimated to infect more than 170 million individuals worldwide.1Butt A.A. Hepatitis C virus infection: the new global epidemic.Expert Rev Anti Infect Ther. 2005; 3: 241-249Crossref PubMed Scopus (36) Google Scholar HCV is a leading cause of decompensated cirrhosis, hepatocellular carcinoma (HCC), liver transplantation, and liver-related death. The prevalence of infection is expected to increase as the survival time of the infected population continues to increase.2Davis G.L. Albright J.E. Cook S.F. et al.Projecting future complications of chronic hepatitis C in the United States.Liver Transplant. 2003; 9: 331-338Crossref PubMed Scopus (511) Google Scholar It is proposed that the proportion of patients with cirrhosis will double by 2020 in the untreated population.2Davis G.L. Albright J.E. Cook S.F. et al.Projecting future complications of chronic hepatitis C in the United States.Liver Transplant. 2003; 9: 331-338Crossref PubMed Scopus (511) Google ScholarTreatment for chronic HCV has been found to be cost effective and is associated with sustained viral clearance in approximately 54%–63% of patients overall.3Zeuzem S. Feinman S.V. Rasenack J. et al.Peginterferon alfa-2a in patients with chronic hepatitis C.N Engl J Med. 2000; 343: 1666-1672Crossref PubMed Scopus (1181) Google Scholar, 4Fried 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 (5859) Google Scholar, 5Hadziyannis S.J. Sette Jr, H. Morgan T.R. et al.Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose.Ann Intern Med. 2004; 140: 346-355Crossref PubMed Scopus (2738) Google Scholar A recent 2010 study using a Markov model to compare the cost effectiveness of interferon (IFN) therapy for HCV over 17 years in a cohort of 4000 patients showed that treatment of hepatitis C with compensated cirrhosis resulted in 119 fewer deaths, 54 fewer HCCs, and 66 fewer transplants when compared with nontreated patients.6Saab S. Hunt D.R. Stone M.A. et al.Timing of hepatitis C antiviral therapy in patients with advanced liver disease: a decision analysis model.Liver Transplant. 2010; 16: 748-759PubMed Google Scholar Treatment for HCV is associated with a reduced risk of liver disease progression, with sustained virologic response (SVR) or without viral eradication.7Nishiguchi S. Shiomi S. Nakatani S. et al.Prevention of hepatocellular carcinoma in patients with chronic active hepatitis C and cirrhosis.Lancet. 2001; 357: 196-197Abstract Full Text Full Text PDF PubMed Scopus (230) Google Scholar, 8Papatheodoridis G.V. Papadimitropoulos V.C. Hadziyannis S.J. Effect of interferon therapy on the development of hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis: a meta-analysis.Aliment Pharmacol Ther. 2001; 15: 689-698Crossref PubMed Scopus (117) Google Scholar, 9International Interferon-Alpha Hepatocellular Carcinoma Study GroupEffect of interferon-alpha on progression of cirrhosis to hepatocellular carcinoma: a retrospective cohort study.Lancet. 1998; 351: 1535-1539Abstract Full Text Full Text PDF PubMed Scopus (318) Google ScholarUse of Sustained Virologic Response as a Marker of Successful Hepatitis C Virus TherapyThe goal of antiviral therapy is achieving an SVR, defined as undetectable HCV RNA levels at the end of 6 months of follow-up evaluation after cessation of treatment for chronic hepatitis C.10Strader D.B. Wright T. Thomas D.L. et al.Diagnosis, management, and treatment of hepatitis C.Hepatology. 2004; 39: 1147-1171Crossref PubMed Scopus (1575) Google Scholar Achieving SVR after treatment has been associated with improvements in disease progression, liver histology, health-related quality of life, and a reduced risk of HCC and liver-related mortality.11Hung C.H. Lee C.M. Lu S.N. et al.Long-term effect of interferon alpha-2b plus ribavirin therapy on incidence of hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis.J Viral Hepat. 2006; 13: 409-414Crossref PubMed Scopus (101) Google Scholar, 12Kasahara A. Tanaka H. Okanoue T. et al.Interferon treatment improves survival in chronic hepatitis C patients showing biochemical as well as virological responses by preventing liver-related death.J Viral Hepat. 2004; 11: 148-156Crossref PubMed Scopus (63) Google Scholar, 13Marcellin 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: 875-881Crossref PubMed Scopus (568) Google Scholar, 14Veldt B.J. Saracco G. Boyer N. et al.Long term clinical outcome of chronic hepatitis C patients with sustained virological response to interferon monotherapy.Gut. 2004; 53: 1504-1508Crossref PubMed Scopus (151) Google ScholarPurposeAs more antiviral treatment regimens are developed and SVR is more easily achievable, the importance of understanding the impact of SVR on patient outcomes will become more pronounced. This article reviews the benefits of SVR on liver-related mortality, development of HCC, and liver disease progression and histologic changes stratified by degree of fibrosis.MethodsData Sources and SearchesWe searched the MEDLINE database for all studies investigating SVR, durability of SVR, and liver-related outcomes for hepatitis C patients. We used combinations of the keywords: "cirrhosis," "liver fibrosis," "liver cancer," "liver malignancy," "hepatic decompensation," "hepatitis C," "durability," "hepatocellular carcinoma," "sustained viral response," and "sustained virological response." We searched all available data from January 1991 through March 2011. We also manually searched references cited in identified articles for additional studies that may have been missed with MEDLINE-assisted strategy.Study SelectionTwo investigators reviewed the contents of 108 abstracts or full-text articles identified from the literature search to determine if they met inclusion criteria. Studies were included if they were published in scientific journals that provided information regarding the benefit of SVR in the development of HCC, liver-related mortality, and hepatic decompensation, along with studies detailing durability of SVR. We included studies that detailed special populations, such as human immunodeficiency virus (HIV) and HCV co-infection, advanced fibrosis, and those with normal serum alanine aminotransferase (ALT) levels. We also searched article reference lists for relevant articles or abstracts. We excluded data with follow-up evaluation of less than 2 years, and also studies with ongoing maintenance therapy, defined as therapy beyond standard acceptable courses (Figure 1) .Data Extraction and Quality AssessmentReviewers abstracted data from the identified studies, and extracted characteristics of each study and its participants. A formal scoring system to rate the study quality of each individual study was not used. Based on inclusion criteria, only studies with a long follow-up period (at least 2 years) were included. Of the studies included, most had cohorts of more than 100 patients, and only 3 cohort studies had fewer than 100 patients studied. Reviewers noted the following as outcomes of interest: rate of SVR, liver-related mortality, development of HCC, and hepatic decompensation. In addition, reviewers noted the degree of fibrosis of the patient population when stratified in the studies.Data SynthesisThe investigators qualitatively synthesized the included studies and summarized the pertinent results into tables, stratifying the discussion of evidence by similar groups such as across all stages of fibrosis, and for those patients with advanced fibrosis.ResultsDurability of Sustained Viral ResponseSustained viral response is considered to be extremely durable. Yu et al15Yu M.L. Dai C.Y. Chen S.C. et al.High versus standard doses interferon-alpha in the treatment of naive chronic hepatitis C patients in Taiwan: a 10-year cohort study.BMC Infect Dis. 2005; 5: 27Crossref PubMed Scopus (19) Google Scholar described a cohort of patients and evaluated different doses of IFN, they showed no statistical dose-dependent difference in durability. A combined 63 of 64 patients maintained SVR, with a mean follow-up period of 6.81 years. Formann et al16Formann E. Steindl-Munda P. Hofer H. et al.Long-term follow-up of chronic hepatitis C patients with sustained virological response to various forms of interferon-based anti-viral therapy.Aliment Pharmacol Ther. 2006; 23: 507-511Crossref PubMed Scopus (66) Google Scholar examined 187 patients who had achieved SVR via IFN, IFN and ribavirin, and pegylated (PEG)-IFN and ribavirin. None of the patients had a relapse with a median follow-up period of 29 months.16Formann E. Steindl-Munda P. Hofer H. et al.Long-term follow-up of chronic hepatitis C patients with sustained virological response to various forms of interferon-based anti-viral therapy.Aliment Pharmacol Ther. 2006; 23: 507-511Crossref PubMed Scopus (66) Google Scholar In a long-term follow-up study of patients previously enrolled in clinical trials,3Zeuzem S. Feinman S.V. Rasenack J. et al.Peginterferon alfa-2a in patients with chronic hepatitis C.N Engl J Med. 2000; 343: 1666-1672Crossref PubMed Scopus (1181) Google Scholar, 4Fried 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 (5859) Google Scholar, 5Hadziyannis S.J. Sette Jr, H. Morgan T.R. et al.Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose.Ann Intern Med. 2004; 140: 346-355Crossref PubMed Scopus (2738) Google Scholar, 17Heathcote 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 (869) Google Scholar, 18Zeuzem S. Diago M. Gane E. et al.Peginterferon alfa-2a (40 kilodaltons) and ribavirin in patients with chronic hepatitis C and normal aminotransferase levels.Gastroenterology. 2004; 127: 1724-1732Abstract Full Text Full Text PDF PubMed Scopus (242) Google Scholar, 19Pockros P.J. Carithers R. Desmond P. et al.Efficacy and safety of two-dose regimens of peginterferon alpha-2a compared with interferon alpha-2a in chronic hepatitis C: a multicenter, randomized controlled trial.Am J Gastroenterol. 2004; 99: 1298-1305Crossref PubMed Scopus (67) Google Scholar, 20Shiffman M.L. Chronic hepatitis C: treatment of pegylated interferon/ribavirin nonresponders.Curr Gastroenterol Rep. 2006; 8: 46-52Crossref PubMed Scopus (26) Google Scholar, 21Fried M.W. Kroner B.L. Preiss L.R. et al.Hemophilic siblings with chronic hepatitis C: Familial aggregation of spontaneous and treatment-related viral clearance.Gastroenterology. 2006; 131: 757-764Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar, 22Torriani 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 (1186) Google Scholar with patients receiving either IFN or IFN and ribavirin, it was found that only 12 of 1343 patients (0.9%) who initially achieved SVR were found to have re-infection during a mean follow-up period of 4.1 years.23Swain M.G. Lai M.Y. Shiffman M.L. et al.A sustained virologic response is durable in patients with chronic hepatitis C treated with peginterferon alfa-2a and ribavirin.Gastroenterology. 2010; 139: 1593-1601Abstract Full Text Full Text PDF PubMed Scopus (256) Google Scholar This large cohort of patients included different patient subsets such as those with normal ALT levels, and those with HIV and HCV co-infection. Desmond et al24Desmond C.P. Roberts S.K. Dudley F. et al.Sustained virological response rates and durability of the response to interferon-based therapies in hepatitis C patients treated in the clinical setting.J Viral Hepat. 2006; 13: 311-315Crossref PubMed Scopus (52) Google Scholar also showed this high durability, with 146 of 147 patients maintaining negative HCV RNA levels over a mean follow-up period of 2.3 years. Giannini et al25Giannini E.G. Basso M. Savarino V. et al.Sustained virological response to pegylated interferon and ribavirin is maintained during long-term follow-up of chronic hepatitis C patients.Aliment Pharmacol Ther. 2010; 31: 502-508Crossref PubMed Scopus (42) Google Scholar studied a cohort of 231 chronic hepatitis C patients with at least 48 weeks of follow-up evaluation after therapy with PEG-IFN and ribavirin, and saw that SVR was maintained in 99% of their cohort (Table 1).Table 1Durability of SVR: Outcomes Reported by Each Primary StudyStudyYearCountryPatients, nGenotypeAntiviral agent usedMean follow-up period, y% SVRYu et al15Yu M.L. Dai C.Y. Chen S.C. et al.High versus standard doses interferon-alpha in the treatment of naive chronic hepatitis C patients in Taiwan: a 10-year cohort study.BMC Infect Dis. 2005; 5: 27Crossref PubMed Scopus (19) Google Scholar2005Taiwan6417 genotype 1b, 47 genotype non-1bIFN6.8163/64 (98.4%)Formann et al16Formann E. Steindl-Munda P. Hofer H. et al.Long-term follow-up of chronic hepatitis C patients with sustained virological response to various forms of interferon-based anti-viral therapy.Aliment Pharmacol Ther. 2006; 23: 507-511Crossref PubMed Scopus (66) Google Scholar2006Austria18791 genotype 1, 92 genotype non-112 Standard IFN73 Standard IFN/RBV102 PEG-IFN/RBV2.4187/187 (100%)Giannini et al25Giannini E.G. Basso M. Savarino V. et al.Sustained virological response to pegylated interferon and ribavirin is maintained during long-term follow-up of chronic hepatitis C patients.Aliment Pharmacol Ther. 2010; 31: 502-508Crossref PubMed Scopus (42) Google Scholar2009Italy23177 genotype 1, 80 genotype 2, 70 genotype 3, 4 genotype 4PEG-IFN/RBV3.2229/231 (99.1%)Swain et al23Swain M.G. Lai M.Y. Shiffman M.L. et al.A sustained virologic response is durable in patients with chronic hepatitis C treated with peginterferon alfa-2a and ribavirin.Gastroenterology. 2010; 139: 1593-1601Abstract Full Text Full Text PDF PubMed Scopus (256) Google Scholar201019 countries1343Not reported166 PEG-IFN1077 PEG-IFN/RBV100 PEG/IFN ± RBV4.11331/1343 (99.1%)Marcellin et al13Marcellin 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: 875-881Crossref PubMed Scopus (568) Google Scholar1997France8023 genotype 1, 11 genotype 2, 33 genotype 3, 2 other genotypesIFN4.096%Desmond et al24Desmond C.P. Roberts S.K. Dudley F. et al.Sustained virological response rates and durability of the response to interferon-based therapies in hepatitis C patients treated in the clinical setting.J Viral Hepat. 2006; 13: 311-315Crossref PubMed Scopus (52) Google Scholar2006Australia14751 genotype 1, 96 genotype 2/334 IFN76 IFN/RBV37 PEG-IFN/RBV2.3146/147 (99.9%)RBV, ribavirin. Open table in a new tab Patients With Normal Serum Aminotransferase LevelsIt is estimated that approximately 30% of patients with chronic hepatitis C have normal serum ALT levels, and it is believed that their rate of disease progression to cirrhosis is reduced compared with patients with higher ALT levels.26Bacon B.R. Treatment of patients with hepatitis C and normal serum aminotransferase levels.Hepatology. 2002; 36: S179-S184Crossref PubMed Google Scholar, 27Martinot-Peignoux M. Boyer N. Cazals-Hatem D. et al.Prospective study on anti-hepatitis C virus-positive patients with persistently normal serum alanine transaminase with or without detectable serum hepatitis C virus RNA.Hepatology. 2001; 34: 1000-1005Crossref PubMed Scopus (142) Google Scholar Gordon et al28Gordon S.C. Fang J.W. Silverman A.L. et al.The significance of baseline serum alanine aminotransferase on pretreatment disease characteristics and response to antiviral therapy in chronic hepatitis C.Hepatology. 2000; 32: 400-404Crossref PubMed Scopus (70) Google Scholar studied 1744 patients with HCV treated with IFN therapy, and 105 patients (6%) had normal serum ALT levels. There was no difference in the SVR rate between patients with normal ALT levels (24.8%) compared with those with increased ALT levels (26.8%). Although most patients with normal ALT levels often have no fibrosis on liver histology, there are some patients with normal ALT levels with advanced fibrosis and cirrhosis on liver biopsy, placing them at increased risk for disease progression, and developing HCC.29Puoti C. Magrini A. Stati T. et al.Clinical, histological, and virological features of hepatitis C virus carriers with persistently normal or abnormal alanine transaminase levels.Hepatology. 1997; 26: 1393-1398Crossref PubMed Scopus (219) Google Scholar Therefore, the decision to treat with IFN should not be based solely on aminotransferase levels.Impact of Pretransplant Sustained Virologic Response After Liver TransplantationIn patients with cirrhosis and advanced liver disease, achievement of SVR before liver transplantation can improve outcomes after transplantation. There have been observations that treatment with IFN therapy for HCV before transplantation can be beneficial in preventing HCV recurrence, particularly if SVR is achieved.30Melero J. Berenguer M. Antiviral therapy in patients with HCV-cirrhosis.Ann Hepatol. 2009; 8: 292-297PubMed Google Scholar However, duration and dose adherence is limited because these patients have difficulty tolerating IFN-based therapy.31Gurusamy K.S. Tsochatzis E. Davidson B.R. et al.Antiviral prophylactic intervention for chronic hepatitis C virus in patients undergoing liver transplantation.Cochrane Database Syst Rev. 2010; 12 (CD006573)PubMed Google ScholarEverson et al32Everson G.T. Trotter J. Forman L. et al.Treatment of advanced hepatitis C with a low accelerating dosage regimen of antiviral therapy.Hepatology. 2005; 42: 255-262Crossref PubMed Scopus (336) Google Scholar followed up 124 patients with advanced cirrhosis who were treated with IFN therapy. Of the 124 patients, 47 patients (37.9%) underwent liver transplantation, and of these 47 patients SVR was achieved in 12 (26%). Of the 4 patients who had achieved SVR before transplantation, none of these patients had recurrence of hepatitis in the long-term follow-up evaluation after liver transplantation. In a separate study by Nudo et al,33Nudo C.G. Cortes R.A. Weppler D. et al.Effect of pretransplant hepatitis C virus RNA status on posttransplant outcome.Transplant Proc. 2008; 40: 1449-1455Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar patients who achieved an SVR, defined using a sensitive viral assay, and no evidence of viral recurrence after liver transplantation. The patients who had undetectable viral levels prior to liver transplantation (without achieving an SVR) were seen to have a significantly decreased risk of recurrent infection after liver transplantation when compared to patients with a measurable viral load at time of liver transplantation.Human Immunodeficiency Virus/Hepatitis C Virus Co-infectionPatients who are co-infected with HIV and HCV often have a higher rate of liver disease progression, cirrhosis, and HCC development.34Giordano T.P. Kramer J.R. Souchek J. et al.Cirrhosis and hepatocellular carcinoma in HIV-infected veterans with and without the hepatitis C virus: a cohort study, 1992–2001.Arch Intern Med. 2004; 164: 2349-2354Crossref PubMed Scopus (150) Google Scholar, 35Graham C.S. Baden L.R. 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: 562-569Crossref PubMed Scopus (836) Google Scholar Successful control of HIV infection with highly active antiretroviral therapy can reduce the rate of liver disease progression.36Verma S. Wang C.H. Govindarajan S. et al.Do type and duration of antiretroviral therapy attenuate liver fibrosis in HIV-hepatitis C virus-coinfected patients?.Clin Infect Dis. 2006; 42: 262-270Crossref PubMed Scopus (74) Google Scholar In a review by Singal et al,37Singal A.K. Anand B.S. Management of hepatitis C virus infection in HIV/HCV co-infected patients: clinical review.World J Gastroenterol. 2009; 15: 3713-3724Crossref PubMed Scopus (45) Google Scholar the SVR rate in HIV/HCV co-infected patients was found to range between 17% and 53%. The pooled SVR rate from 7 randomized controlled trials or prospective cohort studies involving 784 HIV/HCV co-infected patients was 33.3% (range, 27.3%–44.2%) when treated with IFN and ribavirin.38Shire N.J. Welge J.A. Sherman K.E. Response rates to pegylated interferon and ribavirin in HCV/HIV coinfection: a research synthesis.J Viral Hepat. 2007; 14: 239-248Crossref PubMed Scopus (43) Google Scholar When measures are taken to increase treatment monitoring and compliance, SVR rates increased significantly and were equivalent to patients with HCV mono-infection. In a retrospective study conducted in a methadone maintenance treatment program of 73 patients with HCV infection, of whom 32% were co-infected with HIV, it was found that HIV/HCV co-infected patients achieved an SVR rate of 43%, and HCV mono-infected patients had an SVR rate of 46%.39Litwin A.H. Harris Jr, K.A. Nahvi S. et al.Successful treatment of chronic hepatitis C with pegylated interferon in combination with ribavirin in a methadone maintenance treatment program.J Subst Abuse Treat. 2009; 37: 32-40Abstract Full Text Full Text PDF PubMed Scopus (93) Google ScholarLiver-Related Mortality: All Stages of FibrosisMultiple studies have shown a positive effect of SVR on liver-related mortality, regardless of the stage of liver fibrosis (Table 2). Arase et al40Arase Y. Ikeda K. Suzuki F. et al.Long-term outcome after interferon therapy in elderly patients with chronic hepatitis C.Intervirology. 2007; 50: 16-23Crossref PubMed Scopus (49) Google Scholar studied a cohort of 500 patients who received IFN therapy for hepatitis C in which 140 patients (28%) reached SVR and looked at long-term outcomes over a follow-up period of 7.4 years. The number of liver-related deaths was decreased significantly in the group that reached SVR, with 2 liver-related deaths of 9 total deaths in the SVR group (22% of deaths, 1.4% of SVR group) when compared with the group that did not attain SVR, with 32 liver-related deaths of 44 total deaths (73% of deaths, 8.9% of SVR group) (risk ratio, 1/0.13; 95% confidence interval [CI], 0.03–0.59; P = .007).40Arase Y. Ikeda K. Suzuki F. et al.Long-term outcome after interferon therapy in elderly patients with chronic hepatitis C.Intervirology. 2007; 50: 16-23Crossref PubMed Scopus (49) Google Scholar In a study in Australia, 384 patients were followed up for 9 years after IFN therapy for hepatitis C, and of the 384 patients, there were 25 liver-related deaths. The risk of liver-related death was increased at least 3-fold for patients who did not attain SVR.41Coverdale S.A. Khan M.H. Byth K. et al.Effects of interferon treatment response on liver complications of chronic hepatitis C: 9-year follow-up study.Am J Gastroenterol. 2004; 99: 636-644Crossref PubMed Scopus (58) Google Scholar In another retrospective cohort study of 2698 patients who received IFN with follow-up evaluation of more than 6 years, it was seen that the risk of death from liver-related causes was significantly lower for those with SVR than those who were untreated (risk ratio, 0.04; 95% CI, 0.005–0.301; P < .002).12Kasahara A. Tanaka H. Okanoue T. et al.Interferon treatment improves survival in chronic hepatitis C patients showing biochemical as well as virological responses by preventing liver-related death.J Viral Hepat. 2004; 11: 148-156Crossref PubMed Scopus (63) Google Scholar Yoshida et al42Yoshida H. Arakawa Y. Sata M. et al.Interferon therapy prolonged life expectancy among chronic hepatitis C patients.Gastroenterology. 2002; 123: 483-491Abstract Full Text Full Text PDF PubMed Scopus (213) Google Scholar performed a retrospective study of 2430 patients treated with IFN and 459 untreated patients, and found that liver-related mortality was reduced for those with SVR compared with untreated patients (risk ratio, 0.050; 95% CI, 0.012–0.216). A meta-analysis by Singal et al43Singal A.G. Volk M.L. Jensen D. et al.A sustained viral response is associated with reduced liver-related morbidity and mortality in patients with hepatitis C virus.Clin Gastroenterol Hepatol. 2010; 8 (288 e1): 280-288Abstract Full Text Full Text PDF PubMed Scopus (284) Google Scholar quantitatively assessed the reduction in decompensated cirrhosis, development of HCC, and liver-related mortality in patients who achieve SVR compared with those who were nonresponders to therapy. Two investigators independently reviewed 26 studies and pooled rates of decompensated cirrhosis, development of HCC, and liver-related mortality in patients with SVR and nonresponders.12Kasahara A. Tanaka H. Okanoue T. et al.Interferon treatment improves survival in chronic hepatitis C patients showing biochemical as well as virological responses by preventing liver-related death.J Viral Hepat. 2004; 11: 148-156Crossref PubMed Scopus (63) Google Scholar, 40Arase Y. Ikeda K. Suzuki F. et al.Long-term outcome after interferon therapy in elderly patients with chronic hepatitis C.Intervirology. 2007; 50: 16-23Crossref PubMed Scopus (49) Google Scholar, 41Coverdale S.A. Khan M.H. Byth K. et al.Effects of interferon treatment response on liver complications of chronic hepatitis C: 9-year follow-up study.Am J Gastroenterol. 2004; 99: 636-644Crossref PubMed Scopus (58) Google Scholar, 42Yoshida H. Arakawa Y. Sata M. et al.Interferon therapy prolonged life expectancy among chronic hepatitis C patients.Gastroenterology. 2002; 123: 483-491Abstract Full Text Full Text PDF PubMed Scopus (213) Google Scholar, 44Giannini E. Fasoli A. Botta F. et al.Long-term follow up of chronic hepatitis C patients after alpha-interferon treatment: a functional study.J Gastroenterol Hepatol. 2001; 16: 399-405Crossref PubMed Scopus (11) Google Scholar, 45Hayashi K. Kumada T. Nakano S. et al.Incidence of hepatocellular carcinoma in chronic hepatitis C after interferon therapy.Hepatogastroenterology. 2002; 49: 508-512PubMed Google Scholar, 46Ikeda K. Saitoh S. Arase Y. et al.Effect of interferon therapy on hepatocellular carcinogenesis in patients with chronic hepatitis type C: a long-term observation study of 1,643 patients using statistical bias correction with proportional hazard analysis.Hepatology. 1999; 29: 1124-1130Crossref PubMed Scopus (463) Google Scholar, 47Kashiwagi K. Furusyo N. Kubo N. et al.A prospective comparison of the effect of interferon-alpha and interferon-beta treatment in patients with chronic hepatitis C on the incidence of hepatocellular carcinoma development.J Infect Chemother. 2003; 9: 333-340Crossref PubMed Scopus (25) Google Scholar, 48Kim K.I. Sasase N. Taniguchi M. et al.Prediction of efficacy of interferon treatment of chronic hepatitis C and occurrence of HCC after interferon treatment by a new classification.Intervirology. 2005; 48: 52-58Crossref PubMed Scopus (4) Google Scholar, 49Lau D.T. Kleiner D.E. Ghany M.G. et al.10-Year follow-up after interferon-alpha therapy for chronic hepatitis C.Hepatology. 1998; 28: 1121-1127Crossref PubMed Scopus (265) Google Scholar, 50Miyajima I. Sata M. Kumashiro R. et al.The incidence of hepatocellular carcinoma in patients with chronic hepatitis C after interferon treatment.Oncol Rep. 1998; 5: 201-204PubMed Google Scholar, 51Mizui M. Tanaka J. Katayama K. et al.Liver disease in hepatitis C virus carriers identified at blood donation and their outcomes with or without interferon treatment: study on 1019 carriers followed for 5–10 years.Hepatol Res. 2007; 37: 994-1001
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