INFO: Numerous factors affect success of interferon treatment for hepatitis C

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Numerous factors affect success of interferontreatment for hepatitis CA new study on predicting outcomes of standardtreatment for hepatitis C virus (HCV) infection found that a number offactors impacted responses, including the form of the interferon given. However, forsome genotypes of the disease, few of these factors play a role.The results of this study appear in the July2007 issue of Hepatology, the official journal of the American Association forthe Study of Liver Diseases (AASLD). Published by Wiley & Sons, Inc.,Hepatology is available online via Wiley InterScience athttp://www.interscience.wiley.com/journal/hepatology.Over three million people in the U.S. havechronic HCV infection, which accounts for approximately 40 percent of allchronic liver disease and is the most frequent indication for liver transplants. Thecurrent standard of care for HCV is the combination of pegylated interferonalfa (PEG-INF) and ribavarin, but this treatment can be difficult to tolerate.Many patients have side effects that include fatigue, flu-like symptoms,depression, fever and anemia. These can be severe enough to cause these patients todiscontinue treatment.Led by I. Backus, of the Center for QualityManagement in Public Health located at the Veterans Affairs Palo Alto HealthCare System in

Palo Alto, CA, researchers conducted a large retrospectivestudy to analyze predictors of sustained virologic response (SVR), orundetectable virus in the blood six months after finishing treatment. For this study,the researchers used a time frame of three months or later to determine an SVR,because a previous study showed that 98 percent of relapses occur withinthree months of stopping treatment. The study included 5,944 predominantly malepatients receiving care at VA medical facilities.The researchers were able to identify severalindependent predictors of achieving SVR after treatment. “In many of theprevious trials only a few of these factors

were identified,†they state. “Theexpanded range of predictors may assist clinicians and patients in more accuratelyassessing the likelihood of an SVR and thus in making more informed treatmentdecisions.†The results confirmed previous trials that identified lowlevels of HCV in the blood, absence of cirrhosis, genotype other than genotype 1, andelevated levels of the liver enzyme ALT as independent predictors of SVR. Theyalso confirmed significantly lower SVR rates amongAfrican-Americans compared with Caucasians and among patients who had not responded to priornon-pegylated interferon. The results provided new information indicating that thePEG-INF form may affect the likelihood of an SVR: Patients treated withPEG-INF 2A (as opposed to 2B) were 40% more likely to have an SVR. The two forms differin pharmacokinetic properties, side effects, and method of determining dosage.In

addition, the study identified low baseline cholesterol as a negativepredictor of an SVR. “Low cholesterol may indicate more severe liverdisease and subsequent reduced treatment response,†the researchers note.Patients included in the study were 80 percentgenotype 1, but few of the significant SVR predictors for this genotypeimpact the rate for genotype 2 patients and even fewer do so for genotype 3patients. The results suggest that genotype 2 patients are more likely to respond toHCV treatment than genotype 3 patients, and that SVR predictors differedbetween these two genotypes, as well as from those for genotype 1.“Our findings serve as a reminder thatresponse rates in routine medical practice may be lower than those in clinicaltrials,†the researchers state. This may be due to the fact that a substantialpercentage of the study patients would have been excluded from

clinical trials forfactors that negatively predict an SVR, and the study showed highertreatment discontinuation rates than in clinical trials, possibly because patients intrials are generally extremely motivated and usually agree to continue treatmentregardless of their response.The researchers conclude that “with thedemonstrated efficacy of PEG-INF/ribavarin against HCV, it is increasinglyimportant to understand the predictors of response to this treatment. Just as SVR ratesdiffer substantially by genotype, so too do the significant SVRpredictors.†###The research was supported by the U.S.Department of Veterans Affairs.Article: “Predictors of Response of U.S.Veterans to Treatment for the Hepatitis C Virus,†I. Backus, B.Boothroyd, Barbara R. , Larry A. Mole, Hepatology; July 2007; (DOI:10.1002/hep.21662).

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Numerous factors affect success of interferontreatment for hepatitis CA new study on predicting outcomes of standardtreatment for hepatitis C virus (HCV) infection found that a number offactors impacted responses, including the form of the interferon given. However, forsome genotypes of the disease, few of these factors play a role.The results of this study appear in the July2007 issue of Hepatology, the official journal of the American Association forthe Study of Liver Diseases (AASLD). Published by Wiley & Sons, Inc.,Hepatology is available online via Wiley InterScience athttp://www.interscience.wiley.com/journal/hepatology.Over three million people in the U.S. havechronic HCV infection, which accounts for approximately 40 percent of allchronic liver disease and is the most frequent indication for liver transplants. Thecurrent standard of care for HCV is the combination of pegylated interferonalfa (PEG-INF) and ribavarin, but this treatment can be difficult to tolerate.Many patients have side effects that include fatigue, flu-like symptoms,depression, fever and anemia. These can be severe enough to cause these patients todiscontinue treatment.Led by I. Backus, of the Center for QualityManagement in Public Health located at the Veterans Affairs Palo Alto HealthCare System in

Palo Alto, CA, researchers conducted a large retrospectivestudy to analyze predictors of sustained virologic response (SVR), orundetectable virus in the blood six months after finishing treatment. For this study,the researchers used a time frame of three months or later to determine an SVR,because a previous study showed that 98 percent of relapses occur withinthree months of stopping treatment. The study included 5,944 predominantly malepatients receiving care at VA medical facilities.The researchers were able to identify severalindependent predictors of achieving SVR after treatment. “In many of theprevious trials only a few of these factors

were identified,†they state. “Theexpanded range of predictors may assist clinicians and patients in more accuratelyassessing the likelihood of an SVR and thus in making more informed treatmentdecisions.†The results confirmed previous trials that identified lowlevels of HCV in the blood, absence of cirrhosis, genotype other than genotype 1, andelevated levels of the liver enzyme ALT as independent predictors of SVR. Theyalso confirmed significantly lower SVR rates amongAfrican-Americans compared with Caucasians and among patients who had not responded to priornon-pegylated interferon. The results provided new information indicating that thePEG-INF form may affect the likelihood of an SVR: Patients treated withPEG-INF 2A (as opposed to 2B) were 40% more likely to have an SVR. The two forms differin pharmacokinetic properties, side effects, and method of determining dosage.In

addition, the study identified low baseline cholesterol as a negativepredictor of an SVR. “Low cholesterol may indicate more severe liverdisease and subsequent reduced treatment response,†the researchers note.Patients included in the study were 80 percentgenotype 1, but few of the significant SVR predictors for this genotypeimpact the rate for genotype 2 patients and even fewer do so for genotype 3patients. The results suggest that genotype 2 patients are more likely to respond toHCV treatment than genotype 3 patients, and that SVR predictors differedbetween these two genotypes, as well as from those for genotype 1.“Our findings serve as a reminder thatresponse rates in routine medical practice may be lower than those in clinicaltrials,†the researchers state. This may be due to the fact that a substantialpercentage of the study patients would have been excluded from

clinical trials forfactors that negatively predict an SVR, and the study showed highertreatment discontinuation rates than in clinical trials, possibly because patients intrials are generally extremely motivated and usually agree to continue treatmentregardless of their response.The researchers conclude that “with thedemonstrated efficacy of PEG-INF/ribavarin against HCV, it is increasinglyimportant to understand the predictors of response to this treatment. Just as SVR ratesdiffer substantially by genotype, so too do the significant SVRpredictors.†###The research was supported by the U.S.Department of Veterans Affairs.Article: “Predictors of Response of U.S.Veterans to Treatment for the Hepatitis C Virus,†I. Backus, B.Boothroyd, Barbara R. , Larry A. Mole, Hepatology; July 2007; (DOI:10.1002/hep.21662).