%PDF-1.3
1 0 obj
<< /Type /Catalog
/Outlines 2 0 R
/Pages 3 0 R >>
endobj
2 0 obj
<< /Type /Outlines /Count 0 >>
endobj
3 0 obj
<< /Type /Pages
/Kids [6 0 R
92 0 R
209 0 R
]
/Count 3
/Resources <<
/ProcSet 4 0 R
/Font << 
/F1 8 0 R
/F2 9 0 R
/F3 10 0 R
/F4 11 0 R
/F5 94 0 R
>>
/XObject << 
/I1 12 0 R
/I2 13 0 R
>>
>>
/MediaBox [0.000 0.000 612.000 792.000]
 >>
endobj
4 0 obj
[/PDF /Text /ImageC ]
endobj
5 0 obj
<<
/Creator (DOMPDF)
/CreationDate (D:20180721150450+00'00')
/ModDate (D:20180721150450+00'00')
/Title (Interleukin-28B genotype testing to determine response to the combination of pegylated-interferon and ribavirin for the treatment of hepatitis C virus � PLOS Currents Evidence on Genomic Tests)
>>
endobj
6 0 obj
<< /Type /Page
/Parent 3 0 R
/Annots [ 14 0 R 16 0 R 18 0 R 20 0 R 22 0 R 24 0 R 26 0 R 28 0 R 30 0 R 32 0 R 34 0 R 36 0 R 38 0 R 40 0 R 42 0 R 44 0 R 46 0 R 48 0 R 50 0 R 52 0 R 54 0 R 56 0 R 58 0 R 60 0 R 62 0 R 64 0 R 66 0 R 68 0 R 70 0 R 72 0 R 74 0 R 76 0 R 78 0 R 80 0 R 82 0 R 84 0 R 86 0 R 88 0 R 90 0 R ]
/Contents 7 0 R
>>
endobj
7 0 obj
<<
/Length 18480 >>
stream

q
375.000 0 0 39.000 222.000 738.000 cm /I2 Do
Q
q
15.000 659.406 577.500 78.594 re W n
0.267 0.267 0.267 rg
BT 15.000 718.042 Td /F2 21.0 Tf  [(Interleukin-28B genotype testing to determine response to the )] TJ ET
BT 15.000 693.094 Td /F2 21.0 Tf  [(combination of pegylated-interferon and ribavirin for the )] TJ ET
BT 15.000 668.146 Td /F2 21.0 Tf  [(treatment of hepatitis C virus)] TJ ET
Q
0.271 0.267 0.267 rg
BT 15.000 650.140 Td /F3 9.8 Tf  [(January 8, 2011)] TJ ET
BT 26.250 638.299 Td /F1 9.8 Tf  [(, )] TJ ET
BT 31.671 638.299 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 37.092 638.299 Td /F1 9.8 Tf  [(Christine M. Nguyen)] TJ ET
0.271 0.267 0.267 rg
BT 125.407 638.299 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 130.829 638.299 Td /F1 9.8 Tf  [(Margaret A.S. Mendes)] TJ ET
0.271 0.267 0.267 rg
BT 228.368 638.299 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 233.788 638.299 Td /F1 9.8 Tf  [(Shirley Tsunoda)] TJ ET
0.271 0.267 0.267 rg
BT 304.232 638.299 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 309.653 638.299 Td /F1 9.8 Tf  [(Joseph D. Ma)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 626.394 Td /F1 9.8 Tf  [(Nguyen CM, Mendes MA, Tsunoda S, Ma JD. Interleukin-28B genotype testing to determine response to the combination of )] TJ ET
BT 26.250 614.490 Td /F1 9.8 Tf  [(pegylated-interferon and ribavirin for the treatment of hepatitis C virus. PLOS Currents Evidence on Genomic Tests. 2011 Jan 8 )] TJ ET
BT 26.250 602.585 Td /F1 9.8 Tf  [(. Edition 1. doi: 10.1371/currents.RRN1207.)] TJ ET
q
15.000 37.421 577.500 562.783 re W n
0.271 0.267 0.267 rg
BT 26.250 573.482 Td /F4 12.0 Tf  [(Abstract)] TJ ET
BT 26.250 553.528 Td /F1 9.8 Tf  [(Hepatitis C virus \(HCV\) is a bloodborne infection that is one of the leading causes of liver disease. If left untreated, HCV can )] TJ ET
BT 26.250 541.623 Td /F1 9.8 Tf  [(lead to cirrhosis, hepatocellular carcinoma, and death. The current standard of care for HCV is a combination of pegylated-)] TJ ET
BT 26.250 529.719 Td /F1 9.8 Tf  [(interferon \(peg-IFN\) and ribavirin \(RBV\) in which the goal of treatment is to decrease complications and death due to HCV. HCV )] TJ ET
BT 26.250 517.814 Td /F1 9.8 Tf  [(displays genetic polymorphism, where patients with HCV genotype 1 may have higher viral replication rates and are less likely )] TJ ET
BT 26.250 505.909 Td /F1 9.8 Tf  [(to respond to treatment. These patients require a longer duration of treatment and a higher RBV dose. The interleukin \(IL\) 28B )] TJ ET
BT 26.250 494.004 Td /F1 9.8 Tf  [(genotype test is associated with a sustained virologic response \(SVR\), defined as an undetectable HCV ribonucleic acid \(RNA\) )] TJ ET
BT 26.250 482.100 Td /F1 9.8 Tf  [(upon completion of treatment and 24 weeks thereafter.)] TJ ET
BT 26.250 445.497 Td /F4 12.0 Tf  [(Clinical Scenario)] TJ ET
BT 26.250 425.543 Td /F1 9.8 Tf  [(The IL28B genotype test can be used to predict response to peg-IFN and RBV in HCV genotype 1 patients. The test result )] TJ ET
BT 26.250 413.638 Td /F1 9.8 Tf  [(indicates whether the patient has an IL28B CC, CT, or TT genotype. Patients who have the IL28B CC genotype are more likely )] TJ ET
BT 26.250 401.733 Td /F1 9.8 Tf  [(to have a SVR with peg-IFN and RBV treatment, whereas patients who have the TT genotype are more likely to be )] TJ ET
BT 26.250 389.829 Td /F1 9.8 Tf  [(nonresponders. This information can help clinicians and patients make informed decisions on how to best manage their HCV )] TJ ET
BT 26.250 377.924 Td /F1 9.8 Tf  [(infection.)] TJ ET
BT 26.250 341.321 Td /F4 12.0 Tf  [(Test Description)] TJ ET
BT 26.250 321.367 Td /F1 9.8 Tf  [(The IL28B polymorphism test is a polymerase chain reaction \(PCR\) analysis of a single nucleotide polymorphism \(SNP\) )] TJ ET
BT 26.250 309.462 Td /F1 9.8 Tf  [(\(rs12979860 C/T\) on chromosome 19q13. )] TJ ET
0.267 0.267 0.267 rg
BT 210.496 309.462 Td /F1 9.8 Tf  [([1])] TJ ET
0.271 0.267 0.267 rg
BT 221.338 309.462 Td /F1 9.8 Tf  [( The test requires either whole blood or buccal swab.)] TJ ET
BT 26.250 272.860 Td /F4 12.0 Tf  [(Public Health Importance)] TJ ET
BT 26.250 252.906 Td /F1 9.8 Tf  [(Chronic liver disease is the tenth leading cause of death in the United States. The Center for Disease Control and Prevention )] TJ ET
BT 26.250 241.001 Td /F1 9.8 Tf  [(\(CDC\) estimates that 40% of chronic liver disease is caused by HCV. )] TJ ET
0.267 0.267 0.267 rg
BT 326.969 241.001 Td /F1 9.8 Tf  [([2])] TJ ET
0.271 0.267 0.267 rg
BT 337.811 241.001 Td /F1 9.8 Tf  [( Treatment of HCV can reduce the risk of developing )] TJ ET
BT 26.250 229.096 Td /F1 9.8 Tf  [(cirrhosis, hepatocellular carcinoma, and death. Treatment also prevents person-to-person transmission. However, SVR does )] TJ ET
BT 26.250 217.191 Td /F1 9.8 Tf  [(not occur in all patients. Two clinical trials have showed that only 41% and 46% of patients with HCV genotype 1 achieved SVR )] TJ ET
BT 26.250 205.287 Td /F1 9.8 Tf  [(with peg-IFN and RBV. )] TJ ET
0.267 0.267 0.267 rg
BT 128.664 205.287 Td /F1 9.8 Tf  [([3])] TJ ET
BT 139.506 205.287 Td /F1 9.8 Tf  [([4])] TJ ET
0.271 0.267 0.267 rg
BT 150.348 205.287 Td /F1 9.8 Tf  [( In addition, many patients do not complete treatment due to adverse events that are associated )] TJ ET
BT 26.250 193.382 Td /F1 9.8 Tf  [(with peg-IFN and RBV. )] TJ ET
0.267 0.267 0.267 rg
BT 128.664 193.382 Td /F1 9.8 Tf  [([2])] TJ ET
BT 139.506 193.382 Td /F1 9.8 Tf  [([5])] TJ ET
0.271 0.267 0.267 rg
BT 150.348 193.382 Td /F1 9.8 Tf  [( Selecting appropriate and motivated patients to treat is important. The IL28B genotype test may )] TJ ET
BT 26.250 181.477 Td /F1 9.8 Tf  [(aid healthcare providers and patients when making decisions on whether or not to start therapy in HCV genotype 1 patients.)] TJ ET
BT 26.250 144.875 Td /F4 12.0 Tf  [(Published Reviews, Recommendations and Guidelines)] TJ ET
BT 26.250 124.920 Td /F4 9.8 Tf  [(Systematic evidence reviews)] TJ ET
BT 26.250 105.516 Td /F1 9.8 Tf  [(None identified)] TJ ET
BT 26.250 86.111 Td /F4 9.8 Tf  [(Recommendations by independent group)] TJ ET
BT 26.250 66.706 Td /F1 9.8 Tf  [(None identified)] TJ ET
Q
q
15.000 659.406 577.500 78.594 re W n
0.267 0.267 0.267 rg
BT 15.000 718.042 Td /F2 21.0 Tf  [(Interleukin-28B genotype testing to determine response to the )] TJ ET
BT 15.000 693.094 Td /F2 21.0 Tf  [(combination of pegylated-interferon and ribavirin for the )] TJ ET
BT 15.000 668.146 Td /F2 21.0 Tf  [(treatment of hepatitis C virus)] TJ ET
Q
0.271 0.267 0.267 rg
BT 15.000 650.140 Td /F3 9.8 Tf  [(January 8, 2011)] TJ ET
BT 26.250 638.299 Td /F1 9.8 Tf  [(, )] TJ ET
BT 31.671 638.299 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 37.092 638.299 Td /F1 9.8 Tf  [(Christine M. Nguyen)] TJ ET
0.271 0.267 0.267 rg
BT 125.407 638.299 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 130.829 638.299 Td /F1 9.8 Tf  [(Margaret A.S. Mendes)] TJ ET
0.271 0.267 0.267 rg
BT 228.368 638.299 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 233.788 638.299 Td /F1 9.8 Tf  [(Shirley Tsunoda)] TJ ET
0.271 0.267 0.267 rg
BT 304.232 638.299 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 309.653 638.299 Td /F1 9.8 Tf  [(Joseph D. Ma)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 626.394 Td /F1 9.8 Tf  [(Nguyen CM, Mendes MA, Tsunoda S, Ma JD. Interleukin-28B genotype testing to determine response to the combination of )] TJ ET
BT 26.250 614.490 Td /F1 9.8 Tf  [(pegylated-interferon and ribavirin for the treatment of hepatitis C virus. PLOS Currents Evidence on Genomic Tests. 2011 Jan 8 )] TJ ET
BT 26.250 602.585 Td /F1 9.8 Tf  [(. Edition 1. doi: 10.1371/currents.RRN1207.)] TJ ET
q
15.000 37.421 577.500 562.783 re W n
0.271 0.267 0.267 rg
BT 26.250 573.482 Td /F4 12.0 Tf  [(Abstract)] TJ ET
BT 26.250 553.528 Td /F1 9.8 Tf  [(Hepatitis C virus \(HCV\) is a bloodborne infection that is one of the leading causes of liver disease. If left untreated, HCV can )] TJ ET
BT 26.250 541.623 Td /F1 9.8 Tf  [(lead to cirrhosis, hepatocellular carcinoma, and death. The current standard of care for HCV is a combination of pegylated-)] TJ ET
BT 26.250 529.719 Td /F1 9.8 Tf  [(interferon \(peg-IFN\) and ribavirin \(RBV\) in which the goal of treatment is to decrease complications and death due to HCV. HCV )] TJ ET
BT 26.250 517.814 Td /F1 9.8 Tf  [(displays genetic polymorphism, where patients with HCV genotype 1 may have higher viral replication rates and are less likely )] TJ ET
BT 26.250 505.909 Td /F1 9.8 Tf  [(to respond to treatment. These patients require a longer duration of treatment and a higher RBV dose. The interleukin \(IL\) 28B )] TJ ET
BT 26.250 494.004 Td /F1 9.8 Tf  [(genotype test is associated with a sustained virologic response \(SVR\), defined as an undetectable HCV ribonucleic acid \(RNA\) )] TJ ET
BT 26.250 482.100 Td /F1 9.8 Tf  [(upon completion of treatment and 24 weeks thereafter.)] TJ ET
BT 26.250 445.497 Td /F4 12.0 Tf  [(Clinical Scenario)] TJ ET
BT 26.250 425.543 Td /F1 9.8 Tf  [(The IL28B genotype test can be used to predict response to peg-IFN and RBV in HCV genotype 1 patients. The test result )] TJ ET
BT 26.250 413.638 Td /F1 9.8 Tf  [(indicates whether the patient has an IL28B CC, CT, or TT genotype. Patients who have the IL28B CC genotype are more likely )] TJ ET
BT 26.250 401.733 Td /F1 9.8 Tf  [(to have a SVR with peg-IFN and RBV treatment, whereas patients who have the TT genotype are more likely to be )] TJ ET
BT 26.250 389.829 Td /F1 9.8 Tf  [(nonresponders. This information can help clinicians and patients make informed decisions on how to best manage their HCV )] TJ ET
BT 26.250 377.924 Td /F1 9.8 Tf  [(infection.)] TJ ET
BT 26.250 341.321 Td /F4 12.0 Tf  [(Test Description)] TJ ET
BT 26.250 321.367 Td /F1 9.8 Tf  [(The IL28B polymorphism test is a polymerase chain reaction \(PCR\) analysis of a single nucleotide polymorphism \(SNP\) )] TJ ET
BT 26.250 309.462 Td /F1 9.8 Tf  [(\(rs12979860 C/T\) on chromosome 19q13. )] TJ ET
0.267 0.267 0.267 rg
BT 210.496 309.462 Td /F1 9.8 Tf  [([1])] TJ ET
0.271 0.267 0.267 rg
BT 221.338 309.462 Td /F1 9.8 Tf  [( The test requires either whole blood or buccal swab.)] TJ ET
BT 26.250 272.860 Td /F4 12.0 Tf  [(Public Health Importance)] TJ ET
BT 26.250 252.906 Td /F1 9.8 Tf  [(Chronic liver disease is the tenth leading cause of death in the United States. The Center for Disease Control and Prevention )] TJ ET
BT 26.250 241.001 Td /F1 9.8 Tf  [(\(CDC\) estimates that 40% of chronic liver disease is caused by HCV. )] TJ ET
0.267 0.267 0.267 rg
BT 326.969 241.001 Td /F1 9.8 Tf  [([2])] TJ ET
0.271 0.267 0.267 rg
BT 337.811 241.001 Td /F1 9.8 Tf  [( Treatment of HCV can reduce the risk of developing )] TJ ET
BT 26.250 229.096 Td /F1 9.8 Tf  [(cirrhosis, hepatocellular carcinoma, and death. Treatment also prevents person-to-person transmission. However, SVR does )] TJ ET
BT 26.250 217.191 Td /F1 9.8 Tf  [(not occur in all patients. Two clinical trials have showed that only 41% and 46% of patients with HCV genotype 1 achieved SVR )] TJ ET
BT 26.250 205.287 Td /F1 9.8 Tf  [(with peg-IFN and RBV. )] TJ ET
0.267 0.267 0.267 rg
BT 128.664 205.287 Td /F1 9.8 Tf  [([3])] TJ ET
BT 139.506 205.287 Td /F1 9.8 Tf  [([4])] TJ ET
0.271 0.267 0.267 rg
BT 150.348 205.287 Td /F1 9.8 Tf  [( In addition, many patients do not complete treatment due to adverse events that are associated )] TJ ET
BT 26.250 193.382 Td /F1 9.8 Tf  [(with peg-IFN and RBV. )] TJ ET
0.267 0.267 0.267 rg
BT 128.664 193.382 Td /F1 9.8 Tf  [([2])] TJ ET
BT 139.506 193.382 Td /F1 9.8 Tf  [([5])] TJ ET
0.271 0.267 0.267 rg
BT 150.348 193.382 Td /F1 9.8 Tf  [( Selecting appropriate and motivated patients to treat is important. The IL28B genotype test may )] TJ ET
BT 26.250 181.477 Td /F1 9.8 Tf  [(aid healthcare providers and patients when making decisions on whether or not to start therapy in HCV genotype 1 patients.)] TJ ET
BT 26.250 144.875 Td /F4 12.0 Tf  [(Published Reviews, Recommendations and Guidelines)] TJ ET
BT 26.250 124.920 Td /F4 9.8 Tf  [(Systematic evidence reviews)] TJ ET
BT 26.250 105.516 Td /F1 9.8 Tf  [(None identified)] TJ ET
BT 26.250 86.111 Td /F4 9.8 Tf  [(Recommendations by independent group)] TJ ET
BT 26.250 66.706 Td /F1 9.8 Tf  [(None identified)] TJ ET
Q
q
15.000 659.406 577.500 78.594 re W n
0.267 0.267 0.267 rg
BT 15.000 718.042 Td /F2 21.0 Tf  [(Interleukin-28B genotype testing to determine response to the )] TJ ET
BT 15.000 693.094 Td /F2 21.0 Tf  [(combination of pegylated-interferon and ribavirin for the )] TJ ET
BT 15.000 668.146 Td /F2 21.0 Tf  [(treatment of hepatitis C virus)] TJ ET
Q
0.271 0.267 0.267 rg
BT 15.000 650.140 Td /F3 9.8 Tf  [(January 8, 2011)] TJ ET
BT 26.250 638.299 Td /F1 9.8 Tf  [(, )] TJ ET
BT 31.671 638.299 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 37.092 638.299 Td /F1 9.8 Tf  [(Christine M. Nguyen)] TJ ET
0.271 0.267 0.267 rg
BT 125.407 638.299 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 130.829 638.299 Td /F1 9.8 Tf  [(Margaret A.S. Mendes)] TJ ET
0.271 0.267 0.267 rg
BT 228.368 638.299 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 233.788 638.299 Td /F1 9.8 Tf  [(Shirley Tsunoda)] TJ ET
0.271 0.267 0.267 rg
BT 304.232 638.299 Td /F1 9.8 Tf  [(, )] TJ ET
0.267 0.267 0.267 rg
BT 309.653 638.299 Td /F1 9.8 Tf  [(Joseph D. Ma)] TJ ET
0.271 0.267 0.267 rg
BT 26.250 626.394 Td /F1 9.8 Tf  [(Nguyen CM, Mendes MA, Tsunoda S, Ma JD. Interleukin-28B genotype testing to determine response to the combination of )] TJ ET
BT 26.250 614.490 Td /F1 9.8 Tf  [(pegylated-interferon and ribavirin for the treatment of hepatitis C virus. PLOS Currents Evidence on Genomic Tests. 2011 Jan 8 )] TJ ET
BT 26.250 602.585 Td /F1 9.8 Tf  [(. Edition 1. doi: 10.1371/currents.RRN1207.)] TJ ET
q
15.000 37.421 577.500 562.783 re W n
0.271 0.267 0.267 rg
BT 26.250 573.482 Td /F4 12.0 Tf  [(Abstract)] TJ ET
BT 26.250 553.528 Td /F1 9.8 Tf  [(Hepatitis C virus \(HCV\) is a bloodborne infection that is one of the leading causes of liver disease. If left untreated, HCV can )] TJ ET
BT 26.250 541.623 Td /F1 9.8 Tf  [(lead to cirrhosis, hepatocellular carcinoma, and death. The current standard of care for HCV is a combination of pegylated-)] TJ ET
BT 26.250 529.719 Td /F1 9.8 Tf  [(interferon \(peg-IFN\) and ribavirin \(RBV\) in which the goal of treatment is to decrease complications and death due to HCV. HCV )] TJ ET
BT 26.250 517.814 Td /F1 9.8 Tf  [(displays genetic polymorphism, where patients with HCV genotype 1 may have higher viral replication rates and are less likely )] TJ ET
BT 26.250 505.909 Td /F1 9.8 Tf  [(to respond to treatment. These patients require a longer duration of treatment and a higher RBV dose. The interleukin \(IL\) 28B )] TJ ET
BT 26.250 494.004 Td /F1 9.8 Tf  [(genotype test is associated with a sustained virologic response \(SVR\), defined as an undetectable HCV ribonucleic acid \(RNA\) )] TJ ET
BT 26.250 482.100 Td /F1 9.8 Tf  [(upon completion of treatment and 24 weeks thereafter.)] TJ ET
BT 26.250 445.497 Td /F4 12.0 Tf  [(Clinical Scenario)] TJ ET
BT 26.250 425.543 Td /F1 9.8 Tf  [(The IL28B genotype test can be used to predict response to peg-IFN and RBV in HCV genotype 1 patients. The test result )] TJ ET
BT 26.250 413.638 Td /F1 9.8 Tf  [(indicates whether the patient has an IL28B CC, CT, or TT genotype. Patients who have the IL28B CC genotype are more likely )] TJ ET
BT 26.250 401.733 Td /F1 9.8 Tf  [(to have a SVR with peg-IFN and RBV treatment, whereas patients who have the TT genotype are more likely to be )] TJ ET
BT 26.250 389.829 Td /F1 9.8 Tf  [(nonresponders. This information can help clinicians and patients make informed decisions on how to best manage their HCV )] TJ ET
BT 26.250 377.924 Td /F1 9.8 Tf  [(infection.)] TJ ET
BT 26.250 341.321 Td /F4 12.0 Tf  [(Test Description)] TJ ET
BT 26.250 321.367 Td /F1 9.8 Tf  [(The IL28B polymorphism test is a polymerase chain reaction \(PCR\) analysis of a single nucleotide polymorphism \(SNP\) )] TJ ET
BT 26.250 309.462 Td /F1 9.8 Tf  [(\(rs12979860 C/T\) on chromosome 19q13. )] TJ ET
0.267 0.267 0.267 rg
BT 210.496 309.462 Td /F1 9.8 Tf  [([1])] TJ ET
0.271 0.267 0.267 rg
BT 221.338 309.462 Td /F1 9.8 Tf  [( The test requires either whole blood or buccal swab.)] TJ ET
BT 26.250 272.860 Td /F4 12.0 Tf  [(Public Health Importance)] TJ ET
BT 26.250 252.906 Td /F1 9.8 Tf  [(Chronic liver disease is the tenth leading cause of death in the United States. The Center for Disease Control and Prevention )] TJ ET
BT 26.250 241.001 Td /F1 9.8 Tf  [(\(CDC\) estimates that 40% of chronic liver disease is caused by HCV. )] TJ ET
0.267 0.267 0.267 rg
BT 326.969 241.001 Td /F1 9.8 Tf  [([2])] TJ ET
0.271 0.267 0.267 rg
BT 337.811 241.001 Td /F1 9.8 Tf  [( Treatment of HCV can reduce the risk of developing )] TJ ET
BT 26.250 229.096 Td /F1 9.8 Tf  [(cirrhosis, hepatocellular carcinoma, and death. Treatment also prevents person-to-person transmission. However, SVR does )] TJ ET
BT 26.250 217.191 Td /F1 9.8 Tf  [(not occur in all patients. Two clinical trials have showed that only 41% and 46% of patients with HCV genotype 1 achieved SVR )] TJ ET
BT 26.250 205.287 Td /F1 9.8 Tf  [(with peg-IFN and RBV. )] TJ ET
0.267 0.267 0.267 rg
BT 128.664 205.287 Td /F1 9.8 Tf  [([3])] TJ ET
BT 139.506 205.287 Td /F1 9.8 Tf  [([4])] TJ ET
0.271 0.267 0.267 rg
BT 150.348 205.287 Td /F1 9.8 Tf  [( In addition, many patients do not complete treatment due to adverse events that are associated )] TJ ET
BT 26.250 193.382 Td /F1 9.8 Tf  [(with peg-IFN and RBV. )] TJ ET
0.267 0.267 0.267 rg
BT 128.664 193.382 Td /F1 9.8 Tf  [([2])] TJ ET
BT 139.506 193.382 Td /F1 9.8 Tf  [([5])] TJ ET
0.271 0.267 0.267 rg
BT 150.348 193.382 Td /F1 9.8 Tf  [( Selecting appropriate and motivated patients to treat is important. The IL28B genotype test may )] TJ ET
BT 26.250 181.477 Td /F1 9.8 Tf  [(aid healthcare providers and patients when making decisions on whether or not to start therapy in HCV genotype 1 patients.)] TJ ET
BT 26.250 144.875 Td /F4 12.0 Tf  [(Published Reviews, Recommendations and Guidelines)] TJ ET
BT 26.250 124.920 Td /F4 9.8 Tf  [(Systematic evidence reviews)] TJ ET
BT 26.250 105.516 Td /F1 9.8 Tf  [(None identified)] TJ ET
BT 26.250 86.111 Td /F4 9.8 Tf  [(Recommendations by independent group)] TJ ET
BT 26.250 66.706 Td /F1 9.8 Tf  [(None identified)] TJ ET
Q
q
0.000 0.000 0.000 rg
BT 291.710 19.825 Td /F1 11.0 Tf  [(1)] TJ ET
BT 25.000 19.825 Td /F1 11.0 Tf  [(PLOS Currents Evidence on Genomic Tests)] TJ ET

Q
endstream
endobj
8 0 obj
<< /Type /Font
/Subtype /Type1
/Name /F1
/BaseFont /Helvetica
/Encoding /WinAnsiEncoding
>>
endobj
9 0 obj
<< /Type /Font
/Subtype /Type1
/Name /F2
/BaseFont /Times-Bold
/Encoding /WinAnsiEncoding
>>
endobj
10 0 obj
<< /Type /Font
/Subtype /Type1
/Name /F3
/BaseFont /Times-Italic
/Encoding /WinAnsiEncoding
>>
endobj
11 0 obj
<< /Type /Font
/Subtype /Type1
/Name /F4
/BaseFont /Helvetica-Bold
/Encoding /WinAnsiEncoding
>>
endobj
12 0 obj
<<
/Type /XObject
/Subtype /Image
/Width 500
/Height 52
/Filter /FlateDecode
/DecodeParms << /Predictor 15 /Colors 1 /Columns 500 /BitsPerComponent 8>>
/ColorSpace /DeviceGray
/BitsPerComponent 8
/Length 144>>
stream
x���1
0���'ݲ؎�"e����{��dz��A��dz��A��dz��A��dz��A��dz��A��dz��A��dz��A��dz��A��dz��A��dz��A��dz��A��dz��A��tlM0\
endstream
endobj
13 0 obj
<<
/Type /XObject
/Subtype /Image
/Width 500
/Height 52
/SMask 12 0 R
/Filter /FlateDecode
/DecodeParms << /Predictor 15 /Colors 3 /Columns 500 /BitsPerComponent 8>>
/ColorSpace /DeviceRGB
/BitsPerComponent 8
/Length 4571>>
stream
x���y�ǝ���[��
b*�TS
��C�
p*���+�T`o����9ZI�dw�M�w����h4=\.�a��\��OW�a��xX�3�|BX�3�|BX�3�|B>R�7M�4�f�0��Ä{Y���h4UU�Qy2�0��0�.����0��~TFq�G��$��B�GQ�Q�1�0z5��b�����۷<�]2
ð�뺮� ��7M3����t:�F��3.L�S���0#c��2���bq�4�z�&��4�z�����*��fff��u����R����-��0�
��=C������,˗�!�}.�p>��W� ���}c�UU��~Q)6���a�ql��5P>8�Ln�S�����d�q_+S���x�}�L&I�P�ݮ�:���,� hv$�s��V�?� �8���4�n>�"0b;���l6��V+���^\�J�Ǯ� @���a�<��CEq�uMG�J� ���OQ�i��e��g��FQt:���m��WR�i�6MӾ�����i۶��N���F[a����֧�}�/��r�<O..MSԁ�'��$Q�(�aH��t:�)�����f,�{?W���z���z�$IBʑb�X�����S�4��W~���x<
!��Y,���p8@���(
�\��ܨ���}�߭V�,��q��,K}�GY���B1F�t]��nѺ>->���ba�����(
{wr��t��GQ4�L~�����ՆA�罼�TU�繢 A0��=�{{{��\��n��y�,��N1�NO�������/��n��������x�����q@�qU�+�i���
A@
r۶�e��x��gGV܌��
�̰
�j���!q��fo	�,��`۶��h�rA�鈞����{=��|[d�]��� %w�����	zh�u��'I��iEP��m�v���r��</�0����f�n�4�se�v��b���n��5��:��0��‚0e��2G2���V�o�UI�g}�B�f���E���a�"�_�5>*�Z��
����6�u�<۶�|�}�|>_�ah��A`I��yݑU�
��jy�7ĥ�zA}�;������������c��;s8�/�M0���ϯ�0}؄;�aE��3��U�5�BE��_]�$�e!҇Q4�a��g��8}�p���	2K�@��
��>�Ϙ��O
;
����kn�PU�jƦ��GI�g/��&k��p�\.��Y6���=���x�~�qYx� He����1�/����?�c����ݶ��2�2L���B�~.�ăI1�T�CȑFw1boiܖ��G�'ܓ$��)�(H���t�L��8���WV�=g���3�\n �|Y�����eJ
��e\ |߇h�/���~U�]�"�
½Om��Od�XD��Q�;�<�aoII�ڧ�I�Z(ï�m��\yB���S��o�h�2�S?+w�.��t:���ޮ��.��4Z���0TT6���I��nyw�l,�u�iH@K�K�|���(��4_mydŽDգBi�
.П�E����dE٧���]6�P�F��Y�F�������c���w�\���?�˻�Eqԃķ�*���	qcp.�ݨk�z0@��h�}�}50�0#\mH۶zG%��^L��2�R����+�l]|�\u��|w�
�&G[������8��%9///��)�D�zhY�����]���{��������}�\�"#����,]��|q�xB;V�M�/f��.�X۵^���%V������eY��_��$l6�$I�D����`�\".�&IoH�'N��	��(
!	�P�B��z��,����r۳,�N9x:�5��	èE�</*���Z��(2N�R�t���>��{��ܪ��w7�Xl�m���5��0��q�NLX1/���vUU��{I�
�p�^w]'��u�N�`X������{�'��������t:�s�0�W�����
�l2^EF����hKi�f����1���A�]��k�~����j:�:��0s+6�.K1�>H���|:��p�޻���v;�,K����v;�W���ӵȋ���A�-���re�)U�e�
!(�-�0��b�����Jq�#0�5�Lʲ��L�In��l�pT��9�����c��r|�Z�����;�3ӟ�.*�s���ftAY��am6�!��fc4��y.��$��c+��ܨ��z����eY��E,{�!D_n}
�A�J�����f#7A~�~}�^_������,Kc��Z,}�X+�
��-̏��.Ě�N�r�Y�M�S	F�f��f�aۦ�p�
9`x?w#t�~���f��Ǐ���iQI���U0�[�����<�|7n7�����7�"���o��uݝ�Ϫ����z\�����|eY�UUQñ݊r
�z{{[����ظ!���*#�!�rǺ���`�\��s!�x<�o��,#حw��>>>�i�����H�Ð�ƪ����XQ��~?�LP�~����nDM�_9-���\��C�� ���{�ڦ�m�gVJ�U7Q�yJ�4�Rd�ݣ�P~RB��齿]ץi��Tm�i3�L���䔰,��l6�Lpn
���0N����0\�]D��e�-#`
�H��Wכ��������d�D!�z�]���a\�_hi�M�t��o�����
>���r-eUW���@7'��S��Jy���A����tP�$I��Y�)�o�������ڣ� 4S)(I%L�%79���:�Ω���Vf�u�<��]%Ce���{�oJ��k\bL�$	5�m[^�`���S�G()��������
�4MUU��f6�}��
z����Y�
�.�p�f��>4��0���r1���|�����ⷑ$�lk*�����1-f5G3��t���ը��(
��u/K
[�@���ᶋ�2EQ ��n�1(�s��E=W�����j���Xi���k�J���>C]O�i�f��E��h�(��\��t���d�n�_�ޝ��4�[AUUx��H��^�(���vX�X��
�{���{E���
�����>�//J��v�3����,�4����+����&����s�V|߿�M��x�����B�X_-���t*oЪ�]���,=��rii���0�aP���j<��#7
j�~����q>�;�K���z����X�e��|�m�,��������F�Q�e7���r	C<[�O�O���r��l60�m�ۦi�g�x<��wb�<�!�&�:��'3�ՍI��V��v�˲L�T���[7!w]0��)Z��1mC��p��
v7�oY"PY���v��1��	]��aH��Xb�4�	��ղ��o:�"[���{&�(\n��?s�C�C��!
�J�O���3rÏ8�g��Rs���~���{9=ϫ�:�s|�Y�9j0�a|�����Oh��(t�9�Z�vד�({2\�1p�M�]Z=xe,!�(`��[F�;l�F��T��]N.'����=TIDZK(�[m��΍��b�_<tcU]l��L��|���r�6w�x@J*K��G�Vl�.��*�0��J`���[��C�͝���^��%��|���q;����m���Ϛ���M%��UZ��F`,Y,�D���*�~'�NN���
˲�,	�|>/�2��a{�e�e+$I�gP~zz����0�頎}�t���B�8�噌 h�Q�o�9ꐦ���JL&����\n�B�&����<��*��=�c�������f�Y�V��
�`4�5U���iB��뺮e}k����Ψy���c!t��i���h4���$�K��?�2o��|[r�w/�W/bB���n��;6�IBS��0��Ί�p+i��oZ9���]��\��g/��^�b���f���X��j��¤��neC���+���ԟ���?>>Zz/�g��n��E�S�`Y�RgA1�����!�zq��u����[����Y���1��G��e�ĥi��YF��+��]�fd��WFK��N'�~W/=~xu]c��p8`�3,Z�+��,#P&�(*��m[�}��b!p��-��8��[^=�r_n��c�0���ʾ��mJ��%�#��|���ew�B�94#�(��3�(G������T�k�*܁b�P���z}(��jJ���з)G]��,x���ʞ��!��*n��х �����-�Z��~B_�FIn�!l�AXZI]��{Y}`�U9R�~�!ܫz� ������	��
�ɷ�(
�G�e�����՟>��5���wO�Jn�j�����<۶%=,�c6�[x�Hqz��]AΎ�Neq�����L��A.� `�V�������֛?>t��p��P��}�P!��d�p��f��S P����C�;�0_���y������зP��yy�˕a��m�
w,��着�k�iP�������>9�0.�P�C�Y.β����G:�k�a�q���۷o$����a��r�pB����i��%Kv�a�3��[�a�����-�0��-�pg����pg����pg����pg����"�A�
endstream
endobj
14 0 obj
<< /Type /Annot
/Subtype /Link
/A 15 0 R
/Border [0 0 0]
/H /I
/Rect [ 15.0000 716.1516 572.6130 736.9416 ]
>>
endobj
15 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/genomictests/article/interleukin-28b-genotype-testing-to-xv5k9xg3o4yu-3/)
>>
endobj
16 0 obj
<< /Type /Annot
/Subtype /Link
/A 17 0 R
/Border [0 0 0]
/H /I
/Rect [ 15.0000 691.2036 534.7290 711.9936 ]
>>
endobj
17 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/genomictests/article/interleukin-28b-genotype-testing-to-xv5k9xg3o4yu-3/)
>>
endobj
18 0 obj
<< /Type /Annot
/Subtype /Link
/A 19 0 R
/Border [0 0 0]
/H /I
/Rect [ 15.0000 666.2556 279.7890 687.0456 ]
>>
endobj
19 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/genomictests/article/interleukin-28b-genotype-testing-to-xv5k9xg3o4yu-3/)
>>
endobj
20 0 obj
<< /Type /Annot
/Subtype /Link
/A 21 0 R
/Border [0 0 0]
/H /I
/Rect [ 37.0920 637.3973 125.4075 647.3179 ]
>>
endobj
21 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/genomictests/author/christinemnguyen/)
>>
endobj
22 0 obj
<< /Type /Annot
/Subtype /Link
/A 23 0 R
/Border [0 0 0]
/H /I
/Rect [ 130.8285 637.3973 228.3675 647.3179 ]
>>
endobj
23 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/genomictests/author/margaretasmendes/)
>>
endobj
24 0 obj
<< /Type /Annot
/Subtype /Link
/A 25 0 R
/Border [0 0 0]
/H /I
/Rect [ 233.7885 637.3973 304.2323 647.3179 ]
>>
endobj
25 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/genomictests/author/shirleytsunoda/)
>>
endobj
26 0 obj
<< /Type /Annot
/Subtype /Link
/A 27 0 R
/Border [0 0 0]
/H /I
/Rect [ 309.6533 637.3973 369.8010 647.3179 ]
>>
endobj
27 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/genomictests/author/josephdma/)
>>
endobj
28 0 obj
<< /Type /Annot
/Subtype /Link
/A 29 0 R
/Border [0 0 0]
/H /I
/Rect [ 210.4957 308.5606 221.3377 318.4812 ]
>>
endobj
29 0 obj
<< /Type /Action
>>
endobj
30 0 obj
<< /Type /Annot
/Subtype /Link
/A 31 0 R
/Border [0 0 0]
/H /I
/Rect [ 326.9692 240.0991 337.8112 250.0197 ]
>>
endobj
31 0 obj
<< /Type /Action
>>
endobj
32 0 obj
<< /Type /Annot
/Subtype /Link
/A 33 0 R
/Border [0 0 0]
/H /I
/Rect [ 128.6640 204.3848 139.5060 214.3055 ]
>>
endobj
33 0 obj
<< /Type /Action
>>
endobj
34 0 obj
<< /Type /Annot
/Subtype /Link
/A 35 0 R
/Border [0 0 0]
/H /I
/Rect [ 139.5060 204.3848 150.3480 214.3055 ]
>>
endobj
35 0 obj
<< /Type /Action
>>
endobj
36 0 obj
<< /Type /Annot
/Subtype /Link
/A 37 0 R
/Border [0 0 0]
/H /I
/Rect [ 128.6640 192.4801 139.5060 202.4007 ]
>>
endobj
37 0 obj
<< /Type /Action
>>
endobj
38 0 obj
<< /Type /Annot
/Subtype /Link
/A 39 0 R
/Border [0 0 0]
/H /I
/Rect [ 139.5060 192.4801 150.3480 202.4007 ]
>>
endobj
39 0 obj
<< /Type /Action
>>
endobj
40 0 obj
<< /Type /Annot
/Subtype /Link
/A 41 0 R
/Border [0 0 0]
/H /I
/Rect [ 15.0000 716.1516 572.6130 736.9416 ]
>>
endobj
41 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/genomictests/article/interleukin-28b-genotype-testing-to-xv5k9xg3o4yu-3/)
>>
endobj
42 0 obj
<< /Type /Annot
/Subtype /Link
/A 43 0 R
/Border [0 0 0]
/H /I
/Rect [ 15.0000 691.2036 534.7290 711.9936 ]
>>
endobj
43 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/genomictests/article/interleukin-28b-genotype-testing-to-xv5k9xg3o4yu-3/)
>>
endobj
44 0 obj
<< /Type /Annot
/Subtype /Link
/A 45 0 R
/Border [0 0 0]
/H /I
/Rect [ 15.0000 666.2556 279.7890 687.0456 ]
>>
endobj
45 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/genomictests/article/interleukin-28b-genotype-testing-to-xv5k9xg3o4yu-3/)
>>
endobj
46 0 obj
<< /Type /Annot
/Subtype /Link
/A 47 0 R
/Border [0 0 0]
/H /I
/Rect [ 37.0920 637.3973 125.4075 647.3179 ]
>>
endobj
47 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/genomictests/author/christinemnguyen/)
>>
endobj
48 0 obj
<< /Type /Annot
/Subtype /Link
/A 49 0 R
/Border [0 0 0]
/H /I
/Rect [ 130.8285 637.3973 228.3675 647.3179 ]
>>
endobj
49 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/genomictests/author/margaretasmendes/)
>>
endobj
50 0 obj
<< /Type /Annot
/Subtype /Link
/A 51 0 R
/Border [0 0 0]
/H /I
/Rect [ 233.7885 637.3973 304.2323 647.3179 ]
>>
endobj
51 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/genomictests/author/shirleytsunoda/)
>>
endobj
52 0 obj
<< /Type /Annot
/Subtype /Link
/A 53 0 R
/Border [0 0 0]
/H /I
/Rect [ 309.6533 637.3973 369.8010 647.3179 ]
>>
endobj
53 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/genomictests/author/josephdma/)
>>
endobj
54 0 obj
<< /Type /Annot
/Subtype /Link
/A 55 0 R
/Border [0 0 0]
/H /I
/Rect [ 210.4957 308.5606 221.3377 318.4812 ]
>>
endobj
55 0 obj
<< /Type /Action
>>
endobj
56 0 obj
<< /Type /Annot
/Subtype /Link
/A 57 0 R
/Border [0 0 0]
/H /I
/Rect [ 326.9692 240.0991 337.8112 250.0197 ]
>>
endobj
57 0 obj
<< /Type /Action
>>
endobj
58 0 obj
<< /Type /Annot
/Subtype /Link
/A 59 0 R
/Border [0 0 0]
/H /I
/Rect [ 128.6640 204.3848 139.5060 214.3055 ]
>>
endobj
59 0 obj
<< /Type /Action
>>
endobj
60 0 obj
<< /Type /Annot
/Subtype /Link
/A 61 0 R
/Border [0 0 0]
/H /I
/Rect [ 139.5060 204.3848 150.3480 214.3055 ]
>>
endobj
61 0 obj
<< /Type /Action
>>
endobj
62 0 obj
<< /Type /Annot
/Subtype /Link
/A 63 0 R
/Border [0 0 0]
/H /I
/Rect [ 128.6640 192.4801 139.5060 202.4007 ]
>>
endobj
63 0 obj
<< /Type /Action
>>
endobj
64 0 obj
<< /Type /Annot
/Subtype /Link
/A 65 0 R
/Border [0 0 0]
/H /I
/Rect [ 139.5060 192.4801 150.3480 202.4007 ]
>>
endobj
65 0 obj
<< /Type /Action
>>
endobj
66 0 obj
<< /Type /Annot
/Subtype /Link
/A 67 0 R
/Border [0 0 0]
/H /I
/Rect [ 15.0000 716.1516 572.6130 736.9416 ]
>>
endobj
67 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/genomictests/article/interleukin-28b-genotype-testing-to-xv5k9xg3o4yu-3/)
>>
endobj
68 0 obj
<< /Type /Annot
/Subtype /Link
/A 69 0 R
/Border [0 0 0]
/H /I
/Rect [ 15.0000 691.2036 534.7290 711.9936 ]
>>
endobj
69 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/genomictests/article/interleukin-28b-genotype-testing-to-xv5k9xg3o4yu-3/)
>>
endobj
70 0 obj
<< /Type /Annot
/Subtype /Link
/A 71 0 R
/Border [0 0 0]
/H /I
/Rect [ 15.0000 666.2556 279.7890 687.0456 ]
>>
endobj
71 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/genomictests/article/interleukin-28b-genotype-testing-to-xv5k9xg3o4yu-3/)
>>
endobj
72 0 obj
<< /Type /Annot
/Subtype /Link
/A 73 0 R
/Border [0 0 0]
/H /I
/Rect [ 37.0920 637.3973 125.4075 647.3179 ]
>>
endobj
73 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/genomictests/author/christinemnguyen/)
>>
endobj
74 0 obj
<< /Type /Annot
/Subtype /Link
/A 75 0 R
/Border [0 0 0]
/H /I
/Rect [ 130.8285 637.3973 228.3675 647.3179 ]
>>
endobj
75 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/genomictests/author/margaretasmendes/)
>>
endobj
76 0 obj
<< /Type /Annot
/Subtype /Link
/A 77 0 R
/Border [0 0 0]
/H /I
/Rect [ 233.7885 637.3973 304.2323 647.3179 ]
>>
endobj
77 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/genomictests/author/shirleytsunoda/)
>>
endobj
78 0 obj
<< /Type /Annot
/Subtype /Link
/A 79 0 R
/Border [0 0 0]
/H /I
/Rect [ 309.6533 637.3973 369.8010 647.3179 ]
>>
endobj
79 0 obj
<< /Type /Action
/S /URI
/URI (https://currents.plos.org/genomictests/author/josephdma/)
>>
endobj
80 0 obj
<< /Type /Annot
/Subtype /Link
/A 81 0 R
/Border [0 0 0]
/H /I
/Rect [ 210.4957 308.5606 221.3377 318.4812 ]
>>
endobj
81 0 obj
<< /Type /Action
>>
endobj
82 0 obj
<< /Type /Annot
/Subtype /Link
/A 83 0 R
/Border [0 0 0]
/H /I
/Rect [ 326.9692 240.0991 337.8112 250.0197 ]
>>
endobj
83 0 obj
<< /Type /Action
>>
endobj
84 0 obj
<< /Type /Annot
/Subtype /Link
/A 85 0 R
/Border [0 0 0]
/H /I
/Rect [ 128.6640 204.3848 139.5060 214.3055 ]
>>
endobj
85 0 obj
<< /Type /Action
>>
endobj
86 0 obj
<< /Type /Annot
/Subtype /Link
/A 87 0 R
/Border [0 0 0]
/H /I
/Rect [ 139.5060 204.3848 150.3480 214.3055 ]
>>
endobj
87 0 obj
<< /Type /Action
>>
endobj
88 0 obj
<< /Type /Annot
/Subtype /Link
/A 89 0 R
/Border [0 0 0]
/H /I
/Rect [ 128.6640 192.4801 139.5060 202.4007 ]
>>
endobj
89 0 obj
<< /Type /Action
>>
endobj
90 0 obj
<< /Type /Annot
/Subtype /Link
/A 91 0 R
/Border [0 0 0]
/H /I
/Rect [ 139.5060 192.4801 150.3480 202.4007 ]
>>
endobj
91 0 obj
<< /Type /Action
>>
endobj
92 0 obj
<< /Type /Page
/Parent 3 0 R
/Annots [ 95 0 R 97 0 R 99 0 R 101 0 R 103 0 R 105 0 R 107 0 R 109 0 R 111 0 R 113 0 R 115 0 R 117 0 R 119 0 R 121 0 R 123 0 R 125 0 R 127 0 R 129 0 R 131 0 R 133 0 R 135 0 R 137 0 R 139 0 R 141 0 R 143 0 R 145 0 R 147 0 R 149 0 R 151 0 R 153 0 R 155 0 R 157 0 R 159 0 R 161 0 R 163 0 R 165 0 R 167 0 R 169 0 R 171 0 R 173 0 R 175 0 R 177 0 R 179 0 R 181 0 R 183 0 R 185 0 R 187 0 R 189 0 R 191 0 R 193 0 R 195 0 R 197 0 R 199 0 R 201 0 R 203 0 R 205 0 R 207 0 R ]
/Contents 93 0 R
>>
endobj
93 0 obj
<<
/Length 30641 >>
stream

0.271 0.267 0.267 rg
q
15.000 36.607 577.500 740.393 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F4 9.8 Tf  [(Guidelines by professional groups)] TJ ET
BT 26.250 748.071 Td /F1 9.8 Tf  [(None identified)] TJ ET
BT 26.250 711.469 Td /F4 12.0 Tf  [(Evidence Overview)] TJ ET
BT 26.250 691.515 Td /F1 9.8 Tf  [(PubMed and Cochrane Review searches were conducted using a combination of the following keywords: IL28 polymorphism )] TJ ET
BT 26.250 679.610 Td /F1 9.8 Tf  [(genotyping, hepatitis C virus, interferon, and ribavirin. The results were limited to English, and yielded a total of nine relevant )] TJ ET
BT 26.250 667.705 Td /F1 9.8 Tf  [(articles.)] TJ ET
BT 26.250 648.300 Td /F5 9.8 Tf  [(Analytic Validity)] TJ ET
BT 101.569 648.300 Td /F1 9.8 Tf  [( No information regarding the analytical validity of the IL28B genotype test was available in either the primary )] TJ ET
BT 26.250 636.396 Td /F1 9.8 Tf  [(literature or on the LabCorp website. )] TJ ET
0.267 0.267 0.267 rg
BT 186.657 636.396 Td /F1 9.8 Tf  [([6])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 616.991 Td /F5 9.8 Tf  [(Clinical Validity)] TJ ET
0.271 0.267 0.267 RG
40.337 600.554 m 
40.337 601.000 40.154 601.444 39.838 601.760 c
39.522 602.076 39.078 602.260 38.631 602.260 c
38.185 602.260 37.741 602.076 37.425 601.760 c
37.109 601.444 36.925 601.000 36.925 600.554 c
36.925 600.107 37.109 599.663 37.425 599.347 c
37.741 599.031 38.185 598.847 38.631 598.847 c
39.078 598.847 39.522 599.031 39.838 599.347 c
40.154 599.663 40.337 600.107 40.337 600.554 c f
BT 45.750 597.586 Td /F1 9.8 Tf  [(Among patients who achieve SVR, the frequency of CC genotype in Caucasian, Hispanics, and African Americans are )] TJ ET
BT 45.750 585.681 Td /F1 9.8 Tf  [(69%, 56%, 48%, respectively.)] TJ ET
0.267 0.267 0.267 rg
BT 174.723 585.681 Td /F1 9.8 Tf  [([7])] TJ ET
0.271 0.267 0.267 rg
40.337 572.994 m 
40.337 573.441 40.154 573.885 39.838 574.201 c
39.522 574.517 39.078 574.700 38.631 574.700 c
38.185 574.700 37.741 574.517 37.425 574.201 c
37.109 573.885 36.925 573.441 36.925 572.994 c
36.925 572.548 37.109 572.104 37.425 571.788 c
37.741 571.472 38.185 571.288 38.631 571.288 c
39.078 571.288 39.522 571.472 39.838 571.788 c
40.154 572.104 40.337 572.548 40.337 572.994 c f
BT 45.750 570.027 Td /F1 9.8 Tf  [(Overall, the SVR rate is higher among patients who have the CC genotype ranging from 60% to 75%.)] TJ ET
0.267 0.267 0.267 rg
BT 482.540 570.027 Td /F1 9.8 Tf  [([8])] TJ ET
BT 493.382 570.027 Td /F1 9.8 Tf  [([9])] TJ ET
0.271 0.267 0.267 rg
BT 504.224 570.027 Td /F1 9.8 Tf  [( As compared to )] TJ ET
BT 45.750 558.122 Td /F1 9.8 Tf  [(patients with the TT genotype, Caucasian and Hispanic patients with the CC genotype have a two-fold likelihood in )] TJ ET
BT 45.750 546.217 Td /F1 9.8 Tf  [(achieving SVR.)] TJ ET
0.267 0.267 0.267 rg
BT 112.401 546.217 Td /F1 9.8 Tf  [([10])] TJ ET
0.271 0.267 0.267 rg
BT 128.664 546.217 Td /F1 9.8 Tf  [( African American patients with the CC genotype have a three-fold likelihood of achieving SVR as )] TJ ET
BT 45.750 534.312 Td /F1 9.8 Tf  [(compared to the TT genotype.)] TJ ET
0.267 0.267 0.267 rg
BT 176.361 534.312 Td /F1 9.8 Tf  [([10])] TJ ET
0.271 0.267 0.267 rg
40.337 521.625 m 
40.337 522.072 40.154 522.516 39.838 522.832 c
39.522 523.148 39.078 523.331 38.631 523.331 c
38.185 523.331 37.741 523.148 37.425 522.832 c
37.109 522.516 36.925 522.072 36.925 521.625 c
36.925 521.179 37.109 520.735 37.425 520.419 c
37.741 520.103 38.185 519.919 38.631 519.919 c
39.078 519.919 39.522 520.103 39.838 520.419 c
40.154 520.735 40.337 521.179 40.337 521.625 c f
BT 45.750 518.658 Td /F1 9.8 Tf  [(There is no difference in the prevalence of the various IL28B genotypes between patients infected with HCV and those who )] TJ ET
BT 45.750 506.753 Td /F1 9.8 Tf  [(are co-infected with HIV.)] TJ ET
0.267 0.267 0.267 rg
BT 151.957 506.753 Td /F1 9.8 Tf  [([9])] TJ ET
BT 162.799 506.753 Td /F1 9.8 Tf  [([11])] TJ ET
BT 179.062 506.753 Td /F1 9.8 Tf  [([12])] TJ ET
0.271 0.267 0.267 rg
BT 195.325 506.753 Td /F1 9.8 Tf  [( However, a recent study showed that co-infected patients with the rs8099917 SNP G )] TJ ET
BT 45.750 494.848 Td /F1 9.8 Tf  [(allele had a higher incidence of treatment failure with Peg-INF and RBV.)] TJ ET
0.267 0.267 0.267 rg
BT 356.804 494.848 Td /F1 9.8 Tf  [([13])] TJ ET
0.271 0.267 0.267 rg
BT 373.067 494.848 Td /F1 9.8 Tf  [( The current IL28B genotype test result does )] TJ ET
BT 45.750 482.943 Td /F1 9.8 Tf  [(not account for any polymorphisms on rs8099917.)] TJ ET
40.337 470.256 m 
40.337 470.703 40.154 471.147 39.838 471.463 c
39.522 471.779 39.078 471.962 38.631 471.962 c
38.185 471.962 37.741 471.779 37.425 471.463 c
37.109 471.147 36.925 470.703 36.925 470.256 c
36.925 469.810 37.109 469.366 37.425 469.050 c
37.741 468.734 38.185 468.550 38.631 468.550 c
39.078 468.550 39.522 468.734 39.838 469.050 c
40.154 469.366 40.337 469.810 40.337 470.256 c f
BT 45.750 467.289 Td /F1 9.8 Tf  [(One study reported the sensitivity, specificity, positive predictive value \(PPV\), and negative predictive value \(NPV\) of the )] TJ ET
BT 45.750 455.384 Td /F1 9.8 Tf  [(CC genotype in predicting SVR in HCV patients who are IFN treatment na�ve.)] TJ ET
0.267 0.267 0.267 rg
BT 380.097 455.384 Td /F1 9.8 Tf  [([14])] TJ ET
0.271 0.267 0.267 rg
BT 396.360 455.384 Td /F1 9.8 Tf  [( Sensitivity: 49.5%; specificity: 85.7%; )] TJ ET
BT 45.750 443.479 Td /F1 9.8 Tf  [(PPV: 90.7%; NPV: 58.8%. Of note, the study included HCV patients regardless of their genotypes.)] TJ ET
BT 26.250 420.324 Td /F5 9.8 Tf  [(Clinical Utility)] TJ ET
40.337 403.887 m 
40.337 404.334 40.154 404.778 39.838 405.094 c
39.522 405.410 39.078 405.593 38.631 405.593 c
38.185 405.593 37.741 405.410 37.425 405.094 c
37.109 404.778 36.925 404.334 36.925 403.887 c
36.925 403.441 37.109 402.997 37.425 402.681 c
37.741 402.365 38.185 402.181 38.631 402.181 c
39.078 402.181 39.522 402.365 39.838 402.681 c
40.154 402.997 40.337 403.441 40.337 403.887 c f
BT 45.750 400.920 Td /F1 9.8 Tf  [(Studies have shown a PPV of the IL28B polymorphism and SVR in HCV genotypes 1 and 4.)] TJ ET
0.267 0.267 0.267 rg
BT 442.994 400.920 Td /F1 9.8 Tf  [([10])] TJ ET
BT 459.257 400.920 Td /F1 9.8 Tf  [([14])] TJ ET
0.271 0.267 0.267 rg
40.337 388.232 m 
40.337 388.679 40.154 389.123 39.838 389.439 c
39.522 389.755 39.078 389.939 38.631 389.939 c
38.185 389.939 37.741 389.755 37.425 389.439 c
37.109 389.123 36.925 388.679 36.925 388.232 c
36.925 387.786 37.109 387.342 37.425 387.026 c
37.741 386.710 38.185 386.526 38.631 386.526 c
39.078 386.526 39.522 386.710 39.838 387.026 c
40.154 387.342 40.337 387.786 40.337 388.232 c f
BT 45.750 385.265 Td /F1 9.8 Tf  [(The CC genotype is more common in HCV genotype 2 or 3 patients who achieve SVR.)] TJ ET
0.267 0.267 0.267 rg
BT 420.199 385.265 Td /F1 9.8 Tf  [([15])] TJ ET
0.271 0.267 0.267 rg
BT 436.462 385.265 Td /F1 9.8 Tf  [( However, the IL28B genotype )] TJ ET
BT 45.750 373.360 Td /F1 9.8 Tf  [(test in these patients may not be necessary as they have a higher SVR rate as compared to HCV genotype 1 or 4 patients.)] TJ ET
0.267 0.267 0.267 rg
BT 45.750 361.455 Td /F1 9.8 Tf  [([3])] TJ ET
BT 56.592 361.455 Td /F1 9.8 Tf  [([4])] TJ ET
0.271 0.267 0.267 rg
40.337 348.768 m 
40.337 349.215 40.154 349.659 39.838 349.975 c
39.522 350.291 39.078 350.475 38.631 350.475 c
38.185 350.475 37.741 350.291 37.425 349.975 c
37.109 349.659 36.925 349.215 36.925 348.768 c
36.925 348.322 37.109 347.878 37.425 347.562 c
37.741 347.246 38.185 347.062 38.631 347.062 c
39.078 347.062 39.522 347.246 39.838 347.562 c
40.154 347.878 40.337 348.322 40.337 348.768 c f
BT 45.750 345.801 Td /F1 9.8 Tf  [(Several SNPs have been studied in clinical trials, including rs12979860 and rs8099917. However the current IL28B )] TJ ET
BT 45.750 333.896 Td /F1 9.8 Tf  [(genotype test only analyzes rs12979860.)] TJ ET
0.267 0.267 0.267 rg
BT 222.976 333.896 Td /F1 9.8 Tf  [([14])] TJ ET
BT 239.239 333.896 Td /F1 9.8 Tf  [([16])] TJ ET
BT 255.502 333.896 Td /F1 9.8 Tf  [([17])] TJ ET
0.271 0.267 0.267 rg
40.337 321.209 m 
40.337 321.655 40.154 322.099 39.838 322.415 c
39.522 322.731 39.078 322.915 38.631 322.915 c
38.185 322.915 37.741 322.731 37.425 322.415 c
37.109 322.099 36.925 321.655 36.925 321.209 c
36.925 320.762 37.109 320.318 37.425 320.002 c
37.741 319.686 38.185 319.503 38.631 319.503 c
39.078 319.503 39.522 319.686 39.838 320.002 c
40.154 320.318 40.337 320.762 40.337 321.209 c f
BT 45.750 318.241 Td /F1 9.8 Tf  [(In the absence of cost-effectiveness analysis, institutions should determine the cost-benefits of using the IL28B genotype )] TJ ET
BT 45.750 306.336 Td /F1 9.8 Tf  [(test in HCV patients based on the available data and test costs.)] TJ ET
BT 26.250 265.984 Td /F4 12.0 Tf  [(Funding Information)] TJ ET
BT 26.250 246.030 Td /F1 9.8 Tf  [(Christine M. Nguyen and Margaret Mendes are funded by the Veterans Affairs San Diego Healthcare System. Shirley Tsunoda )] TJ ET
BT 26.250 234.125 Td /F1 9.8 Tf  [(and Joseph D. Ma are funded by the University of California, San Diego Skaggs School of Pharmacy and Pharmaceutical )] TJ ET
BT 26.250 222.220 Td /F1 9.8 Tf  [(Sciences.)] TJ ET
BT 26.250 185.618 Td /F4 12.0 Tf  [(Competing Interests)] TJ ET
BT 26.250 165.663 Td /F1 9.8 Tf  [(The authors have declared that no competing interests exist.)] TJ ET
BT 26.250 129.061 Td /F4 12.0 Tf  [(References)] TJ ET
BT 26.250 101.607 Td /F1 9.8 Tf  [(1.)] TJ ET
BT 38.132 101.607 Td /F1 9.8 Tf  [(Unit Code 57185: Interleukin 28B \(IL28B0 Polymorphism \(rs12979860\). Available at: www.mayomedicallaboratories.com/test-)] TJ ET
BT 26.250 89.702 Td /F1 9.8 Tf  [(catalog/print.php?unit_code=57185. Accessed 8 Oct 2010.)] TJ ET
BT 26.250 70.297 Td /F1 9.8 Tf  [(2.)] TJ ET
BT 38.132 70.297 Td /F1 9.8 Tf  [(Centers for Disease Control and Prevention. National prevention strategy: a comprehensive strategy for the prevention and )] TJ ET
BT 26.250 58.392 Td /F1 9.8 Tf  [(control of hepatitis C virus infection and its consequences. Available at: )] TJ ET
BT 26.250 46.488 Td /F1 9.8 Tf  [(https://www.cdc.gov/hepatitis/HCV/Strategy/NatHepCPrevStrategy.htm. Accessed 9 Nov 2010.)] TJ ET
Q
q
15.000 36.607 577.500 740.393 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F4 9.8 Tf  [(Guidelines by professional groups)] TJ ET
BT 26.250 748.071 Td /F1 9.8 Tf  [(None identified)] TJ ET
BT 26.250 711.469 Td /F4 12.0 Tf  [(Evidence Overview)] TJ ET
BT 26.250 691.515 Td /F1 9.8 Tf  [(PubMed and Cochrane Review searches were conducted using a combination of the following keywords: IL28 polymorphism )] TJ ET
BT 26.250 679.610 Td /F1 9.8 Tf  [(genotyping, hepatitis C virus, interferon, and ribavirin. The results were limited to English, and yielded a total of nine relevant )] TJ ET
BT 26.250 667.705 Td /F1 9.8 Tf  [(articles.)] TJ ET
BT 26.250 648.300 Td /F5 9.8 Tf  [(Analytic Validity)] TJ ET
BT 101.569 648.300 Td /F1 9.8 Tf  [( No information regarding the analytical validity of the IL28B genotype test was available in either the primary )] TJ ET
BT 26.250 636.396 Td /F1 9.8 Tf  [(literature or on the LabCorp website. )] TJ ET
0.267 0.267 0.267 rg
BT 186.657 636.396 Td /F1 9.8 Tf  [([6])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 616.991 Td /F5 9.8 Tf  [(Clinical Validity)] TJ ET
0.271 0.267 0.267 RG
40.337 600.554 m 
40.337 601.000 40.154 601.444 39.838 601.760 c
39.522 602.076 39.078 602.260 38.631 602.260 c
38.185 602.260 37.741 602.076 37.425 601.760 c
37.109 601.444 36.925 601.000 36.925 600.554 c
36.925 600.107 37.109 599.663 37.425 599.347 c
37.741 599.031 38.185 598.847 38.631 598.847 c
39.078 598.847 39.522 599.031 39.838 599.347 c
40.154 599.663 40.337 600.107 40.337 600.554 c f
BT 45.750 597.586 Td /F1 9.8 Tf  [(Among patients who achieve SVR, the frequency of CC genotype in Caucasian, Hispanics, and African Americans are )] TJ ET
BT 45.750 585.681 Td /F1 9.8 Tf  [(69%, 56%, 48%, respectively.)] TJ ET
0.267 0.267 0.267 rg
BT 174.723 585.681 Td /F1 9.8 Tf  [([7])] TJ ET
0.271 0.267 0.267 rg
40.337 572.994 m 
40.337 573.441 40.154 573.885 39.838 574.201 c
39.522 574.517 39.078 574.700 38.631 574.700 c
38.185 574.700 37.741 574.517 37.425 574.201 c
37.109 573.885 36.925 573.441 36.925 572.994 c
36.925 572.548 37.109 572.104 37.425 571.788 c
37.741 571.472 38.185 571.288 38.631 571.288 c
39.078 571.288 39.522 571.472 39.838 571.788 c
40.154 572.104 40.337 572.548 40.337 572.994 c f
BT 45.750 570.027 Td /F1 9.8 Tf  [(Overall, the SVR rate is higher among patients who have the CC genotype ranging from 60% to 75%.)] TJ ET
0.267 0.267 0.267 rg
BT 482.540 570.027 Td /F1 9.8 Tf  [([8])] TJ ET
BT 493.382 570.027 Td /F1 9.8 Tf  [([9])] TJ ET
0.271 0.267 0.267 rg
BT 504.224 570.027 Td /F1 9.8 Tf  [( As compared to )] TJ ET
BT 45.750 558.122 Td /F1 9.8 Tf  [(patients with the TT genotype, Caucasian and Hispanic patients with the CC genotype have a two-fold likelihood in )] TJ ET
BT 45.750 546.217 Td /F1 9.8 Tf  [(achieving SVR.)] TJ ET
0.267 0.267 0.267 rg
BT 112.401 546.217 Td /F1 9.8 Tf  [([10])] TJ ET
0.271 0.267 0.267 rg
BT 128.664 546.217 Td /F1 9.8 Tf  [( African American patients with the CC genotype have a three-fold likelihood of achieving SVR as )] TJ ET
BT 45.750 534.312 Td /F1 9.8 Tf  [(compared to the TT genotype.)] TJ ET
0.267 0.267 0.267 rg
BT 176.361 534.312 Td /F1 9.8 Tf  [([10])] TJ ET
0.271 0.267 0.267 rg
40.337 521.625 m 
40.337 522.072 40.154 522.516 39.838 522.832 c
39.522 523.148 39.078 523.331 38.631 523.331 c
38.185 523.331 37.741 523.148 37.425 522.832 c
37.109 522.516 36.925 522.072 36.925 521.625 c
36.925 521.179 37.109 520.735 37.425 520.419 c
37.741 520.103 38.185 519.919 38.631 519.919 c
39.078 519.919 39.522 520.103 39.838 520.419 c
40.154 520.735 40.337 521.179 40.337 521.625 c f
BT 45.750 518.658 Td /F1 9.8 Tf  [(There is no difference in the prevalence of the various IL28B genotypes between patients infected with HCV and those who )] TJ ET
BT 45.750 506.753 Td /F1 9.8 Tf  [(are co-infected with HIV.)] TJ ET
0.267 0.267 0.267 rg
BT 151.957 506.753 Td /F1 9.8 Tf  [([9])] TJ ET
BT 162.799 506.753 Td /F1 9.8 Tf  [([11])] TJ ET
BT 179.062 506.753 Td /F1 9.8 Tf  [([12])] TJ ET
0.271 0.267 0.267 rg
BT 195.325 506.753 Td /F1 9.8 Tf  [( However, a recent study showed that co-infected patients with the rs8099917 SNP G )] TJ ET
BT 45.750 494.848 Td /F1 9.8 Tf  [(allele had a higher incidence of treatment failure with Peg-INF and RBV.)] TJ ET
0.267 0.267 0.267 rg
BT 356.804 494.848 Td /F1 9.8 Tf  [([13])] TJ ET
0.271 0.267 0.267 rg
BT 373.067 494.848 Td /F1 9.8 Tf  [( The current IL28B genotype test result does )] TJ ET
BT 45.750 482.943 Td /F1 9.8 Tf  [(not account for any polymorphisms on rs8099917.)] TJ ET
40.337 470.256 m 
40.337 470.703 40.154 471.147 39.838 471.463 c
39.522 471.779 39.078 471.962 38.631 471.962 c
38.185 471.962 37.741 471.779 37.425 471.463 c
37.109 471.147 36.925 470.703 36.925 470.256 c
36.925 469.810 37.109 469.366 37.425 469.050 c
37.741 468.734 38.185 468.550 38.631 468.550 c
39.078 468.550 39.522 468.734 39.838 469.050 c
40.154 469.366 40.337 469.810 40.337 470.256 c f
BT 45.750 467.289 Td /F1 9.8 Tf  [(One study reported the sensitivity, specificity, positive predictive value \(PPV\), and negative predictive value \(NPV\) of the )] TJ ET
BT 45.750 455.384 Td /F1 9.8 Tf  [(CC genotype in predicting SVR in HCV patients who are IFN treatment na�ve.)] TJ ET
0.267 0.267 0.267 rg
BT 380.097 455.384 Td /F1 9.8 Tf  [([14])] TJ ET
0.271 0.267 0.267 rg
BT 396.360 455.384 Td /F1 9.8 Tf  [( Sensitivity: 49.5%; specificity: 85.7%; )] TJ ET
BT 45.750 443.479 Td /F1 9.8 Tf  [(PPV: 90.7%; NPV: 58.8%. Of note, the study included HCV patients regardless of their genotypes.)] TJ ET
BT 26.250 420.324 Td /F5 9.8 Tf  [(Clinical Utility)] TJ ET
40.337 403.887 m 
40.337 404.334 40.154 404.778 39.838 405.094 c
39.522 405.410 39.078 405.593 38.631 405.593 c
38.185 405.593 37.741 405.410 37.425 405.094 c
37.109 404.778 36.925 404.334 36.925 403.887 c
36.925 403.441 37.109 402.997 37.425 402.681 c
37.741 402.365 38.185 402.181 38.631 402.181 c
39.078 402.181 39.522 402.365 39.838 402.681 c
40.154 402.997 40.337 403.441 40.337 403.887 c f
BT 45.750 400.920 Td /F1 9.8 Tf  [(Studies have shown a PPV of the IL28B polymorphism and SVR in HCV genotypes 1 and 4.)] TJ ET
0.267 0.267 0.267 rg
BT 442.994 400.920 Td /F1 9.8 Tf  [([10])] TJ ET
BT 459.257 400.920 Td /F1 9.8 Tf  [([14])] TJ ET
0.271 0.267 0.267 rg
40.337 388.232 m 
40.337 388.679 40.154 389.123 39.838 389.439 c
39.522 389.755 39.078 389.939 38.631 389.939 c
38.185 389.939 37.741 389.755 37.425 389.439 c
37.109 389.123 36.925 388.679 36.925 388.232 c
36.925 387.786 37.109 387.342 37.425 387.026 c
37.741 386.710 38.185 386.526 38.631 386.526 c
39.078 386.526 39.522 386.710 39.838 387.026 c
40.154 387.342 40.337 387.786 40.337 388.232 c f
BT 45.750 385.265 Td /F1 9.8 Tf  [(The CC genotype is more common in HCV genotype 2 or 3 patients who achieve SVR.)] TJ ET
0.267 0.267 0.267 rg
BT 420.199 385.265 Td /F1 9.8 Tf  [([15])] TJ ET
0.271 0.267 0.267 rg
BT 436.462 385.265 Td /F1 9.8 Tf  [( However, the IL28B genotype )] TJ ET
BT 45.750 373.360 Td /F1 9.8 Tf  [(test in these patients may not be necessary as they have a higher SVR rate as compared to HCV genotype 1 or 4 patients.)] TJ ET
0.267 0.267 0.267 rg
BT 45.750 361.455 Td /F1 9.8 Tf  [([3])] TJ ET
BT 56.592 361.455 Td /F1 9.8 Tf  [([4])] TJ ET
0.271 0.267 0.267 rg
40.337 348.768 m 
40.337 349.215 40.154 349.659 39.838 349.975 c
39.522 350.291 39.078 350.475 38.631 350.475 c
38.185 350.475 37.741 350.291 37.425 349.975 c
37.109 349.659 36.925 349.215 36.925 348.768 c
36.925 348.322 37.109 347.878 37.425 347.562 c
37.741 347.246 38.185 347.062 38.631 347.062 c
39.078 347.062 39.522 347.246 39.838 347.562 c
40.154 347.878 40.337 348.322 40.337 348.768 c f
BT 45.750 345.801 Td /F1 9.8 Tf  [(Several SNPs have been studied in clinical trials, including rs12979860 and rs8099917. However the current IL28B )] TJ ET
BT 45.750 333.896 Td /F1 9.8 Tf  [(genotype test only analyzes rs12979860.)] TJ ET
0.267 0.267 0.267 rg
BT 222.976 333.896 Td /F1 9.8 Tf  [([14])] TJ ET
BT 239.239 333.896 Td /F1 9.8 Tf  [([16])] TJ ET
BT 255.502 333.896 Td /F1 9.8 Tf  [([17])] TJ ET
0.271 0.267 0.267 rg
40.337 321.209 m 
40.337 321.655 40.154 322.099 39.838 322.415 c
39.522 322.731 39.078 322.915 38.631 322.915 c
38.185 322.915 37.741 322.731 37.425 322.415 c
37.109 322.099 36.925 321.655 36.925 321.209 c
36.925 320.762 37.109 320.318 37.425 320.002 c
37.741 319.686 38.185 319.503 38.631 319.503 c
39.078 319.503 39.522 319.686 39.838 320.002 c
40.154 320.318 40.337 320.762 40.337 321.209 c f
BT 45.750 318.241 Td /F1 9.8 Tf  [(In the absence of cost-effectiveness analysis, institutions should determine the cost-benefits of using the IL28B genotype )] TJ ET
BT 45.750 306.336 Td /F1 9.8 Tf  [(test in HCV patients based on the available data and test costs.)] TJ ET
BT 26.250 265.984 Td /F4 12.0 Tf  [(Funding Information)] TJ ET
BT 26.250 246.030 Td /F1 9.8 Tf  [(Christine M. Nguyen and Margaret Mendes are funded by the Veterans Affairs San Diego Healthcare System. Shirley Tsunoda )] TJ ET
BT 26.250 234.125 Td /F1 9.8 Tf  [(and Joseph D. Ma are funded by the University of California, San Diego Skaggs School of Pharmacy and Pharmaceutical )] TJ ET
BT 26.250 222.220 Td /F1 9.8 Tf  [(Sciences.)] TJ ET
BT 26.250 185.618 Td /F4 12.0 Tf  [(Competing Interests)] TJ ET
BT 26.250 165.663 Td /F1 9.8 Tf  [(The authors have declared that no competing interests exist.)] TJ ET
BT 26.250 129.061 Td /F4 12.0 Tf  [(References)] TJ ET
BT 26.250 101.607 Td /F1 9.8 Tf  [(1.)] TJ ET
BT 38.132 101.607 Td /F1 9.8 Tf  [(Unit Code 57185: Interleukin 28B \(IL28B0 Polymorphism \(rs12979860\). Available at: www.mayomedicallaboratories.com/test-)] TJ ET
BT 26.250 89.702 Td /F1 9.8 Tf  [(catalog/print.php?unit_code=57185. Accessed 8 Oct 2010.)] TJ ET
BT 26.250 70.297 Td /F1 9.8 Tf  [(2.)] TJ ET
BT 38.132 70.297 Td /F1 9.8 Tf  [(Centers for Disease Control and Prevention. National prevention strategy: a comprehensive strategy for the prevention and )] TJ ET
BT 26.250 58.392 Td /F1 9.8 Tf  [(control of hepatitis C virus infection and its consequences. Available at: )] TJ ET
BT 26.250 46.488 Td /F1 9.8 Tf  [(https://www.cdc.gov/hepatitis/HCV/Strategy/NatHepCPrevStrategy.htm. Accessed 9 Nov 2010.)] TJ ET
Q
q
15.000 36.607 577.500 740.393 re W n
0.271 0.267 0.267 rg
BT 26.250 767.476 Td /F4 9.8 Tf  [(Guidelines by professional groups)] TJ ET
BT 26.250 748.071 Td /F1 9.8 Tf  [(None identified)] TJ ET
BT 26.250 711.469 Td /F4 12.0 Tf  [(Evidence Overview)] TJ ET
BT 26.250 691.515 Td /F1 9.8 Tf  [(PubMed and Cochrane Review searches were conducted using a combination of the following keywords: IL28 polymorphism )] TJ ET
BT 26.250 679.610 Td /F1 9.8 Tf  [(genotyping, hepatitis C virus, interferon, and ribavirin. The results were limited to English, and yielded a total of nine relevant )] TJ ET
BT 26.250 667.705 Td /F1 9.8 Tf  [(articles.)] TJ ET
BT 26.250 648.300 Td /F5 9.8 Tf  [(Analytic Validity)] TJ ET
BT 101.569 648.300 Td /F1 9.8 Tf  [( No information regarding the analytical validity of the IL28B genotype test was available in either the primary )] TJ ET
BT 26.250 636.396 Td /F1 9.8 Tf  [(literature or on the LabCorp website. )] TJ ET
0.267 0.267 0.267 rg
BT 186.657 636.396 Td /F1 9.8 Tf  [([6])] TJ ET
0.271 0.267 0.267 rg
BT 26.250 616.991 Td /F5 9.8 Tf  [(Clinical Validity)] TJ ET
0.271 0.267 0.267 RG
40.337 600.554 m 
40.337 601.000 40.154 601.444 39.838 601.760 c
39.522 602.076 39.078 602.260 38.631 602.260 c
38.185 602.260 37.741 602.076 37.425 601.760 c
37.109 601.444 36.925 601.000 36.925 600.554 c
36.925 600.107 37.109 599.663 37.425 599.347 c
37.741 599.031 38.185 598.847 38.631 598.847 c
39.078 598.847 39.522 599.031 39.838 599.347 c
40.154 599.663 40.337 600.107 40.337 600.554 c f
BT 45.750 597.586 Td /F1 9.8 Tf  [(Among patients who achieve SVR, the frequency of CC genotype in Caucasian, Hispanics, and African Americans are )] TJ ET
BT 45.750 585.681 Td /F1 9.8 Tf  [(69%, 56%, 48%, respectively.)] TJ ET
0.267 0.267 0.267 rg
BT 174.723 585.681 Td /F1 9.8 Tf  [([7])] TJ ET
0.271 0.267 0.267 rg
40.337 572.994 m 
40.337 573.441 40.154 573.885 39.838 574.201 c
39.522 574.517 39.078 574.700 38.631 574.700 c
38.185 574.700 37.741 574.517 37.425 574.201 c
37.109 573.885 36.925 573.441 36.925 572.994 c
36.925 572.548 37.109 572.104 37.425 571.788 c
37.741 571.472 38.185 571.288 38.631 571.288 c
39.078 571.288 39.522 571.472 39.838 571.788 c
40.154 572.104 40.337 572.548 40.337 572.994 c f
BT 45.750 570.027 Td /F1 9.8 Tf  [(Overall, the SVR rate is higher among patients who have the CC genotype ranging from 60% to 75%.)] TJ ET
0.267 0.267 0.267 rg
BT 482.540 570.027 Td /F1 9.8 Tf  [([8])] TJ ET
BT 493.382 570.027 Td /F1 9.8 Tf  [([9])] TJ ET
0.271 0.267 0.267 rg
BT 504.224 570.027 Td /F1 9.8 Tf  [( As compared to )] TJ ET
BT 45.750 558.122 Td /F1 9.8 Tf  [(patients with the TT genotype, Caucasian and Hispanic patients with the CC genotype have a two-fold likelihood in )] TJ ET
BT 45.750 546.217 Td /F1 9.8 Tf  [(achieving SVR.)] TJ ET
0.267 0.267 0.267 rg
BT 112.401 546.217 Td /F1 9.8 Tf  [([10])] TJ ET
0.271 0.267 0.267 rg
BT 128.664 546.217 Td /F1 9.8 Tf  [( African American patients with the CC genotype have a three-fold likelihood of achieving SVR as )] TJ ET
BT 45.750 534.312 Td /F1 9.8 Tf  [(compared to the TT genotype.)] TJ ET
0.267 0.267 0.267 rg
BT 176.361 534.312 Td /F1 9.8 Tf  [([10])] TJ ET
0.271 0.267 0.267 rg
40.337 521.625 m 
40.337 522.072 40.154 522.516 39.838 522.832 c
39.522 523.148 39.078 523.331 38.631 523.331 c
38.185 523.331 37.741 523.148 37.425 522.832 c
37.109 522.516 36.925 522.072 36.925 521.625 c
36.925 521.179 37.109 520.735 37.425 520.419 c
37.741 520.103 38.185 519.919 38.631 519.919 c
39.078 519.919 39.522 520.103 39.838 520.419 c
40.154 520.735 40.337 521.179 40.337 521.625 c f
BT 45.750 518.658 Td /F1 9.8 Tf  [(There is no difference in the prevalence of the various IL28B genotypes between patients infected with HCV and those who )] TJ ET
BT 45.750 506.753 Td /F1 9.8 Tf  [(are co-infected with HIV.)] TJ ET
0.267 0.267 0.267 rg
BT 151.957 506.753 Td /F1 9.8 Tf  [([9])] TJ ET
BT 162.799 506.753 Td /F1 9.8 Tf  [([11])] TJ ET
BT 179.062 506.753 Td /F1 9.8 Tf  [([12])] TJ ET
0.271 0.267 0.267 rg
BT 195.325 506.753 Td /F1 9.8 Tf  [( However, a recent study showed that co-infected patients with the rs8099917 SNP G )] TJ ET
BT 45.750 494.848 Td /F1 9.8 Tf  [(allele had a higher incidence of treatment failure with Peg-INF and RBV.)] TJ ET
0.267 0.267 0.267 rg
BT 356.804 494.848 Td /F1 9.8 Tf  [([13])] TJ ET
0.271 0.267 0.267 rg
BT 373.067 494.848 Td /F1 9.8 Tf  [( The current IL28B genotype test result does )] TJ ET
BT 45.750 482.943 Td /F1 9.8 Tf  [(not account for any polymorphisms on rs8099917.)] TJ ET
40.337 470.256 m 
40.337 470.703 40.154 471.147 39.838 471.463 c
39.522 471.779 39.078 471.962 38.631 471.962 c
38.185 471.962 37.741 471.779 37.425 471.463 c
37.109 471.147 36.925 470.703 36.925 470.256 c
36.925 469.810 37.109 469.366 37.425 469.050 c
37.741 468.734 38.185 468.550 38.631 468.550 c
39.078 468.550 39.522 468.734 39.838 469.050 c
40.154 469.366 40.337 469.810 40.337 470.256 c f
BT 45.750 467.289 Td /F1 9.8 Tf  [(One study reported the sensitivity, specificity, positive predictive value \(PPV\), and negative predictive value \(NPV\) of the )] TJ ET
BT 45.750 455.384 Td /F1 9.8 Tf  [(CC genotype in predicting SVR in HCV patients who are IFN treatment na�ve.)] TJ ET
0.267 0.267 0.267 rg
BT 380.097 455.384 Td /F1 9.8 Tf  [([14])] TJ ET
0.271 0.267 0.267 rg
BT 396.360 455.384 Td /F1 9.8 Tf  [( Sensitivity: 49.5%; specificity: 85.7%; )] TJ ET
BT 45.750 443.479 Td /F1 9.8 Tf  [(PPV: 90.7%; NPV: 58.8%. Of note, the study included HCV patients regardless of their genotypes.)] TJ ET
BT 26.250 420.324 Td /F5 9.8 Tf  [(Clinical Utility)] TJ ET
40.337 403.887 m 
40.337 404.334 40.154 404.778 39.838 405.094 c
39.522 405.410 39.078 405.593 38.631 405.593 c
38.185 405.593 37.741 405.410 37.425 405.094 c
37.109 404.778 36.925 404.334 36.925 403.887 c
36.925 403.441 37.109 402.997 37.425 402.681 c
37.741 402.365 38.185 402.181 38.631 402.181 c
39.078 402.181 39.522 402.365 39.838 402.681 c
40.154 402.997 40.337 403.441 40.337 403.887 c f
BT 45.750 400.920 Td /F1 9.8 Tf  [(Studies have shown a PPV of the IL28B polymorphism and SVR in HCV genotypes 1 and 4.)] TJ ET
0.267 0.267 0.267 rg
BT 442.994 400.920 Td /F1 9.8 Tf  [([10])] TJ ET
BT 459.257 400.920 Td /F1 9.8 Tf  [([14])] TJ ET
0.271 0.267 0.267 rg
40.337 388.232 m 
40.337 388.679 40.154 389.123 39.838 389.439 c
39.522 389.755 39.078 389.939 38.631 389.939 c
38.185 389.939 37.741 389.755 37.425 389.439 c
37.109 389.123 36.925 388.679 36.925 388.232 c
36.925 387.786 37.109 387.342 37.425 387.026 c
37.741 386.710 38.185 386.526 38.631 386.526 c
39.078 386.526 39.522 386.710 39.838 387.026 c
40.154 387.342 40.337 387.786 40.337 388.232 c f
BT 45.750 385.265 Td /F1 9.8 Tf  [(The CC genotype is more common in HCV genotype 2 or 3 patients who achieve SVR.)] TJ ET
0.267 0.267 0.267 rg
BT 420.199 385.265 Td /F1 9.8 Tf  [([15])] TJ ET
0.271 0.267 0.267 rg
BT 436.462 385.265 Td /F1 9.8 Tf  [( However, the IL28B genotype )] TJ ET
BT 45.750 373.360 Td /F1 9.8 Tf  [(test in these patients may not be necessary as they have a higher SVR rate as compared to HCV genotype 1 or 4 patients.)] TJ ET
0.267 0.267 0.267 rg
BT 45.750 361.455 Td /F1 9.8 Tf  [([3])] TJ ET
BT 56.592 361.455 Td /F1 9.8 Tf  [([4])] TJ ET
0.271 0.267 0.267 rg
40.337 348.768 m 
40.337 349.215 40.154 349.659 39.838 349.975 c
39.522 350.291 39.078 350.475 38.631 350.475 c
38.185 350.475 37.741 350.291 37.425 349.975 c
37.109 349.659 36.925 349.215 36.925 348.768 c
36.925 348.322 37.109 347.878 37.425 347.562 c
37.741 347.246 38.185 347.062 38.631 347.062 c
39.078 347.062 39.522 347.246 39.838 347.562 c
40.154 347.878 40.337 348.322 40.337 348.768 c f
BT 45.750 345.801 Td /F1 9.8 Tf  [(Several SNPs have been studied in clinical trials, including rs12979860 and rs8099917. However the current IL28B )] TJ ET
BT 45.750 333.896 Td /F1 9.8 Tf  [(genotype test only analyzes rs12979860.)] TJ ET
0.267 0.267 0.267 rg
BT 222.976 333.896 Td /F1 9.8 Tf  [([14])] TJ ET
BT 239.239 333.896 Td /F1 9.8 Tf  [([16])] TJ ET
BT 255.502 333.896 Td /F1 9.8 Tf  [([17])] TJ ET
0.271 0.267 0.267 rg
40.337 321.209 m 
40.337 321.655 40.154 322.099 39.838 322.415 c
39.522 322.731 39.078 322.915 38.631 322.915 c
38.185 322.915 37.741 322.731 37.425 322.415 c
37.109 322.099 36.925 321.655 36.925 321.209 c
36.925 320.762 37.109 320.318 37.425 320.002 c
37.741 319.686 38.185 319.503 38.631 319.503 c
39.078 319.503 39.522 319.686 39.838 320.002 c
40.154 320.318 40.337 320.762 40.337 321.209 c f
BT 45.750 318.241 Td /F1 9.8 Tf  [(In the absence of cost-effectiveness analysis, institutions should determine the cost-benefits of using the IL28B genotype )] TJ ET
BT 45.750 306.336 Td /F1 9.8 Tf  [(test in HCV patients based on the available data and test costs.)] TJ ET
BT 26.250 265.984 Td /F4 12.0 Tf  [(Funding Information)] TJ ET
BT 26.250 246.030 Td /F1 9.8 Tf  [(Christine M. Nguyen and Margaret Mendes are funded by the Veterans Affairs San Diego Healthcare System. Shirley Tsunoda )] TJ ET
BT 26.250 234.125 Td /F1 9.8 Tf  [(and Joseph D. Ma are funded by the University of California, San Diego Skaggs School of Pharmacy and Pharmaceutical )] TJ ET
BT 26.250 222.220 Td /F1 9.8 Tf  [(Sciences.)] TJ ET
BT 26.250 185.618 Td /F4 12.0 Tf  [(Competing Interests)] TJ ET
BT 26.250 165.663 Td /F1 9.8 Tf  [(The authors have declared that no competing interests exist.)] TJ ET
BT 26.250 129.061 Td /F4 12.0 Tf  [(References)] TJ ET
BT 26.250 101.607 Td /F1 9.8 Tf  [(1.)] TJ ET
BT 38.132 101.607 Td /F1 9.8 Tf  [(Unit Code 57185: Interleukin 28B \(IL28B0 Polymorphism \(rs12979860\). Available at: www.mayomedicallaboratories.com/test-)] TJ ET
BT 26.250 89.702 Td /F1 9.8 Tf  [(catalog/print.php?unit_code=57185. Accessed 8 Oct 2010.)] TJ ET
BT 26.250 70.297 Td /F1 9.8 Tf  [(2.)] TJ ET
BT 38.132 70.297 Td /F1 9.8 Tf  [(Centers for Disease Control and Prevention. National prevention strategy: a comprehensive strategy for the prevention and )] TJ ET
BT 26.250 58.392 Td /F1 9.8 Tf  [(control of hepatitis C virus infection and its consequences. Available at: )] TJ ET
BT 26.250 46.488 Td /F1 9.8 Tf  [(https://www.cdc.gov/hepatitis/HCV/Strategy/NatHepCPrevStrategy.htm. Accessed 9 Nov 2010.)] TJ ET
Q
q
0.000 0.000 0.000 rg
BT 291.710 19.825 Td /F1 11.0 Tf  [(2)] TJ ET
BT 25.000 19.825 Td /F1 11.0 Tf  [(PLOS Currents Evidence on Genomic Tests)] TJ ET

Q
endstream
endobj
94 0 obj
<< /Type /Font
/Subtype /Type1
/Name /F5
/BaseFont /Helvetica-BoldOblique
/Encoding /WinAnsiEncoding
>>
endobj
95 0 obj
<< /Type /Annot
/Subtype /Link
/A 96 0 R
/Border [0 0 0]
/H /I
/Rect [ 186.6570 635.4938 197.4990 645.4144 ]
>>
endobj
96 0 obj
<< /Type /Action
>>
endobj
97 0 obj
<< /Type /Annot
/Subtype /Link
/A 98 0 R
/Border [0 0 0]
/H /I
/Rect [ 174.7230 584.7796 185.5650 594.7002 ]
>>
endobj
98 0 obj
<< /Type /Action
>>
endobj
99 0 obj
<< /Type /Annot
/Subtype /Link
/A 100 0 R
/Border [0 0 0]
/H /I
/Rect [ 482.5403 569.1248 493.3822 579.0454 ]
>>
endobj
100 0 obj
<< /Type /Action
>>
endobj
101 0 obj
<< /Type /Annot
/Subtype /Link
/A 102 0 R
/Border [0 0 0]
/H /I
/Rect [ 493.3822 569.1248 504.2242 579.0454 ]
>>
endobj
102 0 obj
<< /Type /Action
>>
endobj
103 0 obj
<< /Type /Annot
/Subtype /Link
/A 104 0 R
/Border [0 0 0]
/H /I
/Rect [ 112.4010 545.3153 128.6640 555.2359 ]
>>
endobj
104 0 obj
<< /Type /Action
>>
endobj
105 0 obj
<< /Type /Annot
/Subtype /Link
/A 106 0 R
/Border [0 0 0]
/H /I
/Rect [ 176.3610 533.4106 192.6240 543.3312 ]
>>
endobj
106 0 obj
<< /Type /Action
>>
endobj
107 0 obj
<< /Type /Annot
/Subtype /Link
/A 108 0 R
/Border [0 0 0]
/H /I
/Rect [ 151.9567 505.8511 162.7988 515.7717 ]
>>
endobj
108 0 obj
<< /Type /Action
>>
endobj
109 0 obj
<< /Type /Annot
/Subtype /Link
/A 110 0 R
/Border [0 0 0]
/H /I
/Rect [ 162.7987 505.8511 179.0617 515.7717 ]
>>
endobj
110 0 obj
<< /Type /Action
>>
endobj
111 0 obj
<< /Type /Annot
/Subtype /Link
/A 112 0 R
/Border [0 0 0]
/H /I
/Rect [ 179.0617 505.8511 195.3247 515.7717 ]
>>
endobj
112 0 obj
<< /Type /Action
>>
endobj
113 0 obj
<< /Type /Annot
/Subtype /Link
/A 114 0 R
/Border [0 0 0]
/H /I
/Rect [ 356.8043 493.9463 373.0673 503.8669 ]
>>
endobj
114 0 obj
<< /Type /Action
>>
endobj
115 0 obj
<< /Type /Annot
/Subtype /Link
/A 116 0 R
/Border [0 0 0]
/H /I
/Rect [ 380.0970 454.4821 396.3600 464.4027 ]
>>
endobj
116 0 obj
<< /Type /Action
>>
endobj
117 0 obj
<< /Type /Annot
/Subtype /Link
/A 118 0 R
/Border [0 0 0]
/H /I
/Rect [ 442.9943 400.0178 459.2572 409.9384 ]
>>
endobj
118 0 obj
<< /Type /Action
>>
endobj
119 0 obj
<< /Type /Annot
/Subtype /Link
/A 120 0 R
/Border [0 0 0]
/H /I
/Rect [ 459.2572 400.0178 475.5202 409.9384 ]
>>
endobj
120 0 obj
<< /Type /Action
>>
endobj
121 0 obj
<< /Type /Annot
/Subtype /Link
/A 122 0 R
/Border [0 0 0]
/H /I
/Rect [ 420.1988 384.3631 436.4617 394.2837 ]
>>
endobj
122 0 obj
<< /Type /Action
>>
endobj
123 0 obj
<< /Type /Annot
/Subtype /Link
/A 124 0 R
/Border [0 0 0]
/H /I
/Rect [ 45.7500 360.5536 56.5920 370.4742 ]
>>
endobj
124 0 obj
<< /Type /Action
>>
endobj
125 0 obj
<< /Type /Annot
/Subtype /Link
/A 126 0 R
/Border [0 0 0]
/H /I
/Rect [ 56.5920 360.5536 67.4340 370.4742 ]
>>
endobj
126 0 obj
<< /Type /Action
>>
endobj
127 0 obj
<< /Type /Annot
/Subtype /Link
/A 128 0 R
/Border [0 0 0]
/H /I
/Rect [ 222.9758 332.9941 239.2388 342.9147 ]
>>
endobj
128 0 obj
<< /Type /Action
>>
endobj
129 0 obj
<< /Type /Annot
/Subtype /Link
/A 130 0 R
/Border [0 0 0]
/H /I
/Rect [ 239.2388 332.9941 255.5018 342.9147 ]
>>
endobj
130 0 obj
<< /Type /Action
>>
endobj
131 0 obj
<< /Type /Annot
/Subtype /Link
/A 132 0 R
/Border [0 0 0]
/H /I
/Rect [ 255.5018 332.9941 271.7647 342.9147 ]
>>
endobj
132 0 obj
<< /Type /Action
>>
endobj
133 0 obj
<< /Type /Annot
/Subtype /Link
/A 134 0 R
/Border [0 0 0]
/H /I
/Rect [ 186.6570 635.4938 197.4990 645.4144 ]
>>
endobj
134 0 obj
<< /Type /Action
>>
endobj
135 0 obj
<< /Type /Annot
/Subtype /Link
/A 136 0 R
/Border [0 0 0]
/H /I
/Rect [ 174.7230 584.7796 185.5650 594.7002 ]
>>
endobj
136 0 obj
<< /Type /Action
>>
endobj
137 0 obj
<< /Type /Annot
/Subtype /Link
/A 138 0 R
/Border [0 0 0]
/H /I
/Rect [ 482.5403 569.1248 493.3822 579.0454 ]
>>
endobj
138 0 obj
<< /Type /Action
>>
endobj
139 0 obj
<< /Type /Annot
/Subtype /Link
/A 140 0 R
/Border [0 0 0]
/H /I
/Rect [ 493.3822 569.1248 504.2242 579.0454 ]
>>
endobj
140 0 obj
<< /Type /Action
>>
endobj
141 0 obj
<< /Type /Annot
/Subtype /Link
/A 142 0 R
/Border [0 0 0]
/H /I
/Rect [ 112.4010 545.3153 128.6640 555.2359 ]
>>
endobj
142 0 obj
<< /Type /Action
>>
endobj
143 0 obj
<< /Type /Annot
/Subtype /Link
/A 144 0 R
/Border [0 0 0]
/H /I
/Rect [ 176.3610 533.4106 192.6240 543.3312 ]
>>
endobj
144 0 obj
<< /Type /Action
>>
endobj
145 0 obj
<< /Type /Annot
/Subtype /Link
/A 146 0 R
/Border [0 0 0]
/H /I
/Rect [ 151.9567 505.8511 162.7988 515.7717 ]
>>
endobj
146 0 obj
<< /Type /Action
>>
endobj
147 0 obj
<< /Type /Annot
/Subtype /Link
/A 148 0 R
/Border [0 0 0]
/H /I
/Rect [ 162.7987 505.8511 179.0617 515.7717 ]
>>
endobj
148 0 obj
<< /Type /Action
>>
endobj
149 0 obj
<< /Type /Annot
/Subtype /Link
/A 150 0 R
/Border [0 0 0]
/H /I
/Rect [ 179.0617 505.8511 195.3247 515.7717 ]
>>
endobj
150 0 obj
<< /Type /Action
>>
endobj
151 0 obj
<< /Type /Annot
/Subtype /Link
/A 152 0 R
/Border [0 0 0]
/H /I
/Rect [ 356.8043 493.9463 373.0673 503.8669 ]
>>
endobj
152 0 obj
<< /Type /Action
>>
endobj
153 0 obj
<< /Type /Annot
/Subtype /Link
/A 154 0 R
/Border [0 0 0]
/H /I
/Rect [ 380.0970 454.4821 396.3600 464.4027 ]
>>
endobj
154 0 obj
<< /Type /Action
>>
endobj
155 0 obj
<< /Type /Annot
/Subtype /Link
/A 156 0 R
/Border [0 0 0]
/H /I
/Rect [ 442.9943 400.0178 459.2572 409.9384 ]
>>
endobj
156 0 obj
<< /Type /Action
>>
endobj
157 0 obj
<< /Type /Annot
/Subtype /Link
/A 158 0 R
/Border [0 0 0]
/H /I
/Rect [ 459.2572 400.0178 475.5202 409.9384 ]
>>
endobj
158 0 obj
<< /Type /Action
>>
endobj
159 0 obj
<< /Type /Annot
/Subtype /Link
/A 160 0 R
/Border [0 0 0]
/H /I
/Rect [ 420.1988 384.3631 436.4617 394.2837 ]
>>
endobj
160 0 obj
<< /Type /Action
>>
endobj
161 0 obj
<< /Type /Annot
/Subtype /Link
/A 162 0 R
/Border [0 0 0]
/H /I
/Rect [ 45.7500 360.5536 56.5920 370.4742 ]
>>
endobj
162 0 obj
<< /Type /Action
>>
endobj
163 0 obj
<< /Type /Annot
/Subtype /Link
/A 164 0 R
/Border [0 0 0]
/H /I
/Rect [ 56.5920 360.5536 67.4340 370.4742 ]
>>
endobj
164 0 obj
<< /Type /Action
>>
endobj
165 0 obj
<< /Type /Annot
/Subtype /Link
/A 166 0 R
/Border [0 0 0]
/H /I
/Rect [ 222.9758 332.9941 239.2388 342.9147 ]
>>
endobj
166 0 obj
<< /Type /Action
>>
endobj
167 0 obj
<< /Type /Annot
/Subtype /Link
/A 168 0 R
/Border [0 0 0]
/H /I
/Rect [ 239.2388 332.9941 255.5018 342.9147 ]
>>
endobj
168 0 obj
<< /Type /Action
>>
endobj
169 0 obj
<< /Type /Annot
/Subtype /Link
/A 170 0 R
/Border [0 0 0]
/H /I
/Rect [ 255.5018 332.9941 271.7647 342.9147 ]
>>
endobj
170 0 obj
<< /Type /Action
>>
endobj
171 0 obj
<< /Type /Annot
/Subtype /Link
/A 172 0 R
/Border [0 0 0]
/H /I
/Rect [ 186.6570 635.4938 197.4990 645.4144 ]
>>
endobj
172 0 obj
<< /Type /Action
>>
endobj
173 0 obj
<< /Type /Annot
/Subtype /Link
/A 174 0 R
/Border [0 0 0]
/H /I
/Rect [ 174.7230 584.7796 185.5650 594.7002 ]
>>
endobj
174 0 obj
<< /Type /Action
>>
endobj
175 0 obj
<< /Type /Annot
/Subtype /Link
/A 176 0 R
/Border [0 0 0]
/H /I
/Rect [ 482.5403 569.1248 493.3822 579.0454 ]
>>
endobj
176 0 obj
<< /Type /Action
>>
endobj
177 0 obj
<< /Type /Annot
/Subtype /Link
/A 178 0 R
/Border [0 0 0]
/H /I
/Rect [ 493.3822 569.1248 504.2242 579.0454 ]
>>
endobj
178 0 obj
<< /Type /Action
>>
endobj
179 0 obj
<< /Type /Annot
/Subtype /Link
/A 180 0 R
/Border [0 0 0]
/H /I
/Rect [ 112.4010 545.3153 128.6640 555.2359 ]
>>
endobj
180 0 obj
<< /Type /Action
>>
endobj
181 0 obj
<< /Type /Annot
/Subtype /Link
/A 182 0 R
/Border [0 0 0]
/H /I
/Rect [ 176.3610 533.4106 192.6240 543.3312 ]
>>
endobj
182 0 obj
<< /Type /Action
>>
endobj
183 0 obj
<< /Type /Annot
/Subtype /Link
/A 184 0 R
/Border [0 0 0]
/H /I
/Rect [ 151.9567 505.8511 162.7988 515.7717 ]
>>
endobj
184 0 obj
<< /Type /Action
>>
endobj
185 0 obj
<< /Type /Annot
/Subtype /Link
/A 186 0 R
/Border [0 0 0]
/H /I
/Rect [ 162.7987 505.8511 179.0617 515.7717 ]
>>
endobj
186 0 obj
<< /Type /Action
>>
endobj
187 0 obj
<< /Type /Annot
/Subtype /Link
/A 188 0 R
/Border [0 0 0]
/H /I
/Rect [ 179.0617 505.8511 195.3247 515.7717 ]
>>
endobj
188 0 obj
<< /Type /Action
>>
endobj
189 0 obj
<< /Type /Annot
/Subtype /Link
/A 190 0 R
/Border [0 0 0]
/H /I
/Rect [ 356.8043 493.9463 373.0673 503.8669 ]
>>
endobj
190 0 obj
<< /Type /Action
>>
endobj
191 0 obj
<< /Type /Annot
/Subtype /Link
/A 192 0 R
/Border [0 0 0]
/H /I
/Rect [ 380.0970 454.4821 396.3600 464.4027 ]
>>
endobj
192 0 obj
<< /Type /Action
>>
endobj
193 0 obj
<< /Type /Annot
/Subtype /Link
/A 194 0 R
/Border [0 0 0]
/H /I
/Rect [ 442.9943 400.0178 459.2572 409.9384 ]
>>
endobj
194 0 obj
<< /Type /Action
>>
endobj
195 0 obj
<< /Type /Annot
/Subtype /Link
/A 196 0 R
/Border [0 0 0]
/H /I
/Rect [ 459.2572 400.0178 475.5202 409.9384 ]
>>
endobj
196 0 obj
<< /Type /Action
>>
endobj
197 0 obj
<< /Type /Annot
/Subtype /Link
/A 198 0 R
/Border [0 0 0]
/H /I
/Rect [ 420.1988 384.3631 436.4617 394.2837 ]
>>
endobj
198 0 obj
<< /Type /Action
>>
endobj
199 0 obj
<< /Type /Annot
/Subtype /Link
/A 200 0 R
/Border [0 0 0]
/H /I
/Rect [ 45.7500 360.5536 56.5920 370.4742 ]
>>
endobj
200 0 obj
<< /Type /Action
>>
endobj
201 0 obj
<< /Type /Annot
/Subtype /Link
/A 202 0 R
/Border [0 0 0]
/H /I
/Rect [ 56.5920 360.5536 67.4340 370.4742 ]
>>
endobj
202 0 obj
<< /Type /Action
>>
endobj
203 0 obj
<< /Type /Annot
/Subtype /Link
/A 204 0 R
/Border [0 0 0]
/H /I
/Rect [ 222.9758 332.9941 239.2388 342.9147 ]
>>
endobj
204 0 obj
<< /Type /Action
>>
endobj
205 0 obj
<< /Type /Annot
/Subtype /Link
/A 206 0 R
/Border [0 0 0]
/H /I
/Rect [ 239.2388 332.9941 255.5018 342.9147 ]
>>
endobj
206 0 obj
<< /Type /Action
>>
endobj
207 0 obj
<< /Type /Annot
/Subtype /Link
/A 208 0 R
/Border [0 0 0]
/H /I
/Rect [ 255.5018 332.9941 271.7647 342.9147 ]
>>
endobj
208 0 obj
<< /Type /Action
>>
endobj
209 0 obj
<< /Type /Page
/Parent 3 0 R
/Contents 210 0 R
>>
endobj
210 0 obj
<<
/Length 16799 >>
stream

0.271 0.267 0.267 rg
0.271 0.267 0.267 RG
q
15.000 232.834 577.500 544.166 re W n
0.271 0.267 0.267 rg
BT 26.250 759.976 Td /F1 9.8 Tf  [(3.)] TJ ET
BT 38.132 759.976 Td /F1 9.8 Tf  [(Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL Jr, et al. Peginterferon alfa-2a plus ribavirin for chronic )] TJ ET
BT 26.250 748.071 Td /F1 9.8 Tf  [(hepatitis C virus infection. N Engl J Med 2002;347:975-982.)] TJ ET
BT 26.250 728.667 Td /F1 9.8 Tf  [(4.)] TJ ET
BT 38.132 728.667 Td /F1 9.8 Tf  [(Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, et al. Peginterferon alfa-2b plus ribavirin )] TJ ET
BT 26.250 716.762 Td /F1 9.8 Tf  [(compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet )] TJ ET
BT 26.250 704.857 Td /F1 9.8 Tf  [(2001;358:958-965.)] TJ ET
BT 26.250 685.452 Td /F1 9.8 Tf  [(5.)] TJ ET
BT 38.132 685.452 Td /F1 9.8 Tf  [(Yee HS, Currie SL, Darling JM, Wright TL. Management and treatment of hepatitis C viral infection: recommendations from )] TJ ET
BT 26.250 673.548 Td /F1 9.8 Tf  [(the Department of Veterans Affairs Hepatitis C Resource Center program and the National Hepatitis C Program office. Am J )] TJ ET
BT 26.250 661.643 Td /F1 9.8 Tf  [(Gastroenterol 2006;101\(10\):2360-78.)] TJ ET
BT 26.250 642.238 Td /F1 9.8 Tf  [(6.)] TJ ET
BT 38.132 642.238 Td /F1 9.8 Tf  [(LabCorp. Interleukin 28B \(IL28B0 polymorphism \(rs12979860\). Available at: )] TJ ET
BT 26.250 630.333 Td /F1 9.8 Tf  [(https://www.labcorp.com/.EdosPortlet/TestMenuLibrary?libName=File+Library&compName=L8463. Accessed 10 Sept 2010.)] TJ ET
BT 26.250 610.929 Td /F1 9.8 Tf  [(7.)] TJ ET
BT 38.132 610.929 Td /F1 9.8 Tf  [(Thompson AJ, Muir AJ, Sulowski MS, et al. Interleukin-28B polymorphism improves viral kinetics and is the strongest )] TJ ET
BT 26.250 599.024 Td /F1 9.8 Tf  [(pretreatment predictor of sustained virologic response in genotype 1 hepatitis C virus. Gastroenterology 2010;139\(1\):120-129.)] TJ ET
BT 26.250 579.619 Td /F1 9.8 Tf  [(8.)] TJ ET
BT 38.132 579.619 Td /F1 9.8 Tf  [(Montes-Cano MA, Garc�a-Lozano JR, Abad-Molina C, et al. Interleukin-28B genetic variants and hepatitis virus infection by )] TJ ET
BT 26.250 567.714 Td /F1 9.8 Tf  [(different viral genotypes. Hepatology 2010;52\(1\):33-37.)] TJ ET
BT 26.250 548.310 Td /F1 9.8 Tf  [(9.)] TJ ET
BT 38.132 548.310 Td /F1 9.8 Tf  [(Rall�n NI, Naggie S, Benito JM, et al. Association of a single nucleotide polymorphism near the interleukin-28B gene with )] TJ ET
BT 26.250 536.405 Td /F1 9.8 Tf  [(response to hepatitis C therapy in HIV/hepatitis C virus-coinfected patients. AIDS 2010;24:F23-F29.)] TJ ET
BT 26.250 517.000 Td /F1 9.8 Tf  [(10.)] TJ ET
BT 43.553 517.000 Td /F1 9.8 Tf  [(Ge D, Fellay J, Thompson AJ, et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. )] TJ ET
BT 26.250 505.095 Td /F1 9.8 Tf  [(Nature 2009;461:399-401.)] TJ ET
BT 26.250 485.691 Td /F1 9.8 Tf  [(11.)] TJ ET
BT 43.553 485.691 Td /F1 9.8 Tf  [(Thomas DL, Thio CL, Martin MP, et al. Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature )] TJ ET
BT 26.250 473.786 Td /F1 9.8 Tf  [(2009;461\(8\):798-801.)] TJ ET
BT 26.250 454.381 Td /F1 9.8 Tf  [(12.)] TJ ET
BT 43.553 454.381 Td /F1 9.8 Tf  [(Pineda JA, Caruz A, Rivero A, Neukam K, Salas I, Camacho A, et al. Prediction of response to pegylated interferon plus )] TJ ET
BT 26.250 442.476 Td /F1 9.8 Tf  [(ribavirin by IL28B gene variation in patients coinfected with HIV and hepatitis C virus. Clin Infect Dis 2010;51:788-795.)] TJ ET
BT 26.250 423.072 Td /F1 9.8 Tf  [(13.)] TJ ET
BT 43.553 423.072 Td /F1 9.8 Tf  [(Aparicio E, Parera M, Franco S, P�rez-Alvarez N, Tural C, Clotet B, Mart�nez MA. IL28B SNP rs8099917 is strongly )] TJ ET
BT 26.250 411.167 Td /F1 9.8 Tf  [(associated with pegylated interferon-? and ribavirin therapy treatment failure in HCV/HIV-1 coinfected patients. PLoS ONE )] TJ ET
BT 26.250 399.262 Td /F1 9.8 Tf  [(2010;5\(10\):e13771. Available at: https://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0013771. Accessed )] TJ ET
BT 26.250 387.357 Td /F1 9.8 Tf  [(22 Nov 2010.)] TJ ET
BT 26.250 367.953 Td /F1 9.8 Tf  [(14.)] TJ ET
BT 43.553 367.953 Td /F1 9.8 Tf  [(St�ttermayer AF, Stauber R, Hofer H, et al. Impact of IL28B genotype on the early and sustained virologic response in )] TJ ET
BT 26.250 356.048 Td /F1 9.8 Tf  [(treatment-na�ve patients with chronic hepatitis C. Clinc Gastroenterol Hepatol 2010. doi:10.1016/j.cgh.2010.07.019. Accessed )] TJ ET
BT 26.250 344.143 Td /F1 9.8 Tf  [(21 Oct 2010.)] TJ ET
BT 26.250 324.738 Td /F1 9.8 Tf  [(15.)] TJ ET
BT 43.553 324.738 Td /F1 9.8 Tf  [(Mangia A, Thompson AJ, Santoro R, et al. An IL28B polymorphism determines treatment response of hepatitis C virus )] TJ ET
BT 26.250 312.834 Td /F1 9.8 Tf  [(genotype 2 or 3 patients who do not achieve a rapid virologic response. Gastroenterology 2010;139\(3\):821-827.)] TJ ET
BT 26.250 293.429 Td /F1 9.8 Tf  [(16.)] TJ ET
BT 43.553 293.429 Td /F1 9.8 Tf  [(Grebely J, Petoumenos K, Hellard M, et al. Potential role for interleukin-28B genotype in treatment decision-making in )] TJ ET
BT 26.250 281.524 Td /F1 9.8 Tf  [(recent hepatitis C infection. Hepatology 2010;52\(4\):1216-1224.)] TJ ET
BT 26.250 262.119 Td /F1 9.8 Tf  [(17.)] TJ ET
BT 43.553 262.119 Td /F1 9.8 Tf  [(dbSNP website. Available at: https://www.ncbi.nlm.nih.gov/sites/entrez?db=snp&cmd=search&term=rs8099917. Accessed )] TJ ET
BT 26.250 250.215 Td /F1 9.8 Tf  [(on 14 Nov 2010.)] TJ ET
Q
q
15.000 232.834 577.500 544.166 re W n
0.271 0.267 0.267 rg
BT 26.250 759.976 Td /F1 9.8 Tf  [(3.)] TJ ET
BT 38.132 759.976 Td /F1 9.8 Tf  [(Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL Jr, et al. Peginterferon alfa-2a plus ribavirin for chronic )] TJ ET
BT 26.250 748.071 Td /F1 9.8 Tf  [(hepatitis C virus infection. N Engl J Med 2002;347:975-982.)] TJ ET
BT 26.250 728.667 Td /F1 9.8 Tf  [(4.)] TJ ET
BT 38.132 728.667 Td /F1 9.8 Tf  [(Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, et al. Peginterferon alfa-2b plus ribavirin )] TJ ET
BT 26.250 716.762 Td /F1 9.8 Tf  [(compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet )] TJ ET
BT 26.250 704.857 Td /F1 9.8 Tf  [(2001;358:958-965.)] TJ ET
BT 26.250 685.452 Td /F1 9.8 Tf  [(5.)] TJ ET
BT 38.132 685.452 Td /F1 9.8 Tf  [(Yee HS, Currie SL, Darling JM, Wright TL. Management and treatment of hepatitis C viral infection: recommendations from )] TJ ET
BT 26.250 673.548 Td /F1 9.8 Tf  [(the Department of Veterans Affairs Hepatitis C Resource Center program and the National Hepatitis C Program office. Am J )] TJ ET
BT 26.250 661.643 Td /F1 9.8 Tf  [(Gastroenterol 2006;101\(10\):2360-78.)] TJ ET
BT 26.250 642.238 Td /F1 9.8 Tf  [(6.)] TJ ET
BT 38.132 642.238 Td /F1 9.8 Tf  [(LabCorp. Interleukin 28B \(IL28B0 polymorphism \(rs12979860\). Available at: )] TJ ET
BT 26.250 630.333 Td /F1 9.8 Tf  [(https://www.labcorp.com/.EdosPortlet/TestMenuLibrary?libName=File+Library&compName=L8463. Accessed 10 Sept 2010.)] TJ ET
BT 26.250 610.929 Td /F1 9.8 Tf  [(7.)] TJ ET
BT 38.132 610.929 Td /F1 9.8 Tf  [(Thompson AJ, Muir AJ, Sulowski MS, et al. Interleukin-28B polymorphism improves viral kinetics and is the strongest )] TJ ET
BT 26.250 599.024 Td /F1 9.8 Tf  [(pretreatment predictor of sustained virologic response in genotype 1 hepatitis C virus. Gastroenterology 2010;139\(1\):120-129.)] TJ ET
BT 26.250 579.619 Td /F1 9.8 Tf  [(8.)] TJ ET
BT 38.132 579.619 Td /F1 9.8 Tf  [(Montes-Cano MA, Garc�a-Lozano JR, Abad-Molina C, et al. Interleukin-28B genetic variants and hepatitis virus infection by )] TJ ET
BT 26.250 567.714 Td /F1 9.8 Tf  [(different viral genotypes. Hepatology 2010;52\(1\):33-37.)] TJ ET
BT 26.250 548.310 Td /F1 9.8 Tf  [(9.)] TJ ET
BT 38.132 548.310 Td /F1 9.8 Tf  [(Rall�n NI, Naggie S, Benito JM, et al. Association of a single nucleotide polymorphism near the interleukin-28B gene with )] TJ ET
BT 26.250 536.405 Td /F1 9.8 Tf  [(response to hepatitis C therapy in HIV/hepatitis C virus-coinfected patients. AIDS 2010;24:F23-F29.)] TJ ET
BT 26.250 517.000 Td /F1 9.8 Tf  [(10.)] TJ ET
BT 43.553 517.000 Td /F1 9.8 Tf  [(Ge D, Fellay J, Thompson AJ, et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. )] TJ ET
BT 26.250 505.095 Td /F1 9.8 Tf  [(Nature 2009;461:399-401.)] TJ ET
BT 26.250 485.691 Td /F1 9.8 Tf  [(11.)] TJ ET
BT 43.553 485.691 Td /F1 9.8 Tf  [(Thomas DL, Thio CL, Martin MP, et al. Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature )] TJ ET
BT 26.250 473.786 Td /F1 9.8 Tf  [(2009;461\(8\):798-801.)] TJ ET
BT 26.250 454.381 Td /F1 9.8 Tf  [(12.)] TJ ET
BT 43.553 454.381 Td /F1 9.8 Tf  [(Pineda JA, Caruz A, Rivero A, Neukam K, Salas I, Camacho A, et al. Prediction of response to pegylated interferon plus )] TJ ET
BT 26.250 442.476 Td /F1 9.8 Tf  [(ribavirin by IL28B gene variation in patients coinfected with HIV and hepatitis C virus. Clin Infect Dis 2010;51:788-795.)] TJ ET
BT 26.250 423.072 Td /F1 9.8 Tf  [(13.)] TJ ET
BT 43.553 423.072 Td /F1 9.8 Tf  [(Aparicio E, Parera M, Franco S, P�rez-Alvarez N, Tural C, Clotet B, Mart�nez MA. IL28B SNP rs8099917 is strongly )] TJ ET
BT 26.250 411.167 Td /F1 9.8 Tf  [(associated with pegylated interferon-? and ribavirin therapy treatment failure in HCV/HIV-1 coinfected patients. PLoS ONE )] TJ ET
BT 26.250 399.262 Td /F1 9.8 Tf  [(2010;5\(10\):e13771. Available at: https://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0013771. Accessed )] TJ ET
BT 26.250 387.357 Td /F1 9.8 Tf  [(22 Nov 2010.)] TJ ET
BT 26.250 367.953 Td /F1 9.8 Tf  [(14.)] TJ ET
BT 43.553 367.953 Td /F1 9.8 Tf  [(St�ttermayer AF, Stauber R, Hofer H, et al. Impact of IL28B genotype on the early and sustained virologic response in )] TJ ET
BT 26.250 356.048 Td /F1 9.8 Tf  [(treatment-na�ve patients with chronic hepatitis C. Clinc Gastroenterol Hepatol 2010. doi:10.1016/j.cgh.2010.07.019. Accessed )] TJ ET
BT 26.250 344.143 Td /F1 9.8 Tf  [(21 Oct 2010.)] TJ ET
BT 26.250 324.738 Td /F1 9.8 Tf  [(15.)] TJ ET
BT 43.553 324.738 Td /F1 9.8 Tf  [(Mangia A, Thompson AJ, Santoro R, et al. An IL28B polymorphism determines treatment response of hepatitis C virus )] TJ ET
BT 26.250 312.834 Td /F1 9.8 Tf  [(genotype 2 or 3 patients who do not achieve a rapid virologic response. Gastroenterology 2010;139\(3\):821-827.)] TJ ET
BT 26.250 293.429 Td /F1 9.8 Tf  [(16.)] TJ ET
BT 43.553 293.429 Td /F1 9.8 Tf  [(Grebely J, Petoumenos K, Hellard M, et al. Potential role for interleukin-28B genotype in treatment decision-making in )] TJ ET
BT 26.250 281.524 Td /F1 9.8 Tf  [(recent hepatitis C infection. Hepatology 2010;52\(4\):1216-1224.)] TJ ET
BT 26.250 262.119 Td /F1 9.8 Tf  [(17.)] TJ ET
BT 43.553 262.119 Td /F1 9.8 Tf  [(dbSNP website. Available at: https://www.ncbi.nlm.nih.gov/sites/entrez?db=snp&cmd=search&term=rs8099917. Accessed )] TJ ET
BT 26.250 250.215 Td /F1 9.8 Tf  [(on 14 Nov 2010.)] TJ ET
Q
q
15.000 232.834 577.500 544.166 re W n
0.271 0.267 0.267 rg
BT 26.250 759.976 Td /F1 9.8 Tf  [(3.)] TJ ET
BT 38.132 759.976 Td /F1 9.8 Tf  [(Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL Jr, et al. Peginterferon alfa-2a plus ribavirin for chronic )] TJ ET
BT 26.250 748.071 Td /F1 9.8 Tf  [(hepatitis C virus infection. N Engl J Med 2002;347:975-982.)] TJ ET
BT 26.250 728.667 Td /F1 9.8 Tf  [(4.)] TJ ET
BT 38.132 728.667 Td /F1 9.8 Tf  [(Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, et al. Peginterferon alfa-2b plus ribavirin )] TJ ET
BT 26.250 716.762 Td /F1 9.8 Tf  [(compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet )] TJ ET
BT 26.250 704.857 Td /F1 9.8 Tf  [(2001;358:958-965.)] TJ ET
BT 26.250 685.452 Td /F1 9.8 Tf  [(5.)] TJ ET
BT 38.132 685.452 Td /F1 9.8 Tf  [(Yee HS, Currie SL, Darling JM, Wright TL. Management and treatment of hepatitis C viral infection: recommendations from )] TJ ET
BT 26.250 673.548 Td /F1 9.8 Tf  [(the Department of Veterans Affairs Hepatitis C Resource Center program and the National Hepatitis C Program office. Am J )] TJ ET
BT 26.250 661.643 Td /F1 9.8 Tf  [(Gastroenterol 2006;101\(10\):2360-78.)] TJ ET
BT 26.250 642.238 Td /F1 9.8 Tf  [(6.)] TJ ET
BT 38.132 642.238 Td /F1 9.8 Tf  [(LabCorp. Interleukin 28B \(IL28B0 polymorphism \(rs12979860\). Available at: )] TJ ET
BT 26.250 630.333 Td /F1 9.8 Tf  [(https://www.labcorp.com/.EdosPortlet/TestMenuLibrary?libName=File+Library&compName=L8463. Accessed 10 Sept 2010.)] TJ ET
BT 26.250 610.929 Td /F1 9.8 Tf  [(7.)] TJ ET
BT 38.132 610.929 Td /F1 9.8 Tf  [(Thompson AJ, Muir AJ, Sulowski MS, et al. Interleukin-28B polymorphism improves viral kinetics and is the strongest )] TJ ET
BT 26.250 599.024 Td /F1 9.8 Tf  [(pretreatment predictor of sustained virologic response in genotype 1 hepatitis C virus. Gastroenterology 2010;139\(1\):120-129.)] TJ ET
BT 26.250 579.619 Td /F1 9.8 Tf  [(8.)] TJ ET
BT 38.132 579.619 Td /F1 9.8 Tf  [(Montes-Cano MA, Garc�a-Lozano JR, Abad-Molina C, et al. Interleukin-28B genetic variants and hepatitis virus infection by )] TJ ET
BT 26.250 567.714 Td /F1 9.8 Tf  [(different viral genotypes. Hepatology 2010;52\(1\):33-37.)] TJ ET
BT 26.250 548.310 Td /F1 9.8 Tf  [(9.)] TJ ET
BT 38.132 548.310 Td /F1 9.8 Tf  [(Rall�n NI, Naggie S, Benito JM, et al. Association of a single nucleotide polymorphism near the interleukin-28B gene with )] TJ ET
BT 26.250 536.405 Td /F1 9.8 Tf  [(response to hepatitis C therapy in HIV/hepatitis C virus-coinfected patients. AIDS 2010;24:F23-F29.)] TJ ET
BT 26.250 517.000 Td /F1 9.8 Tf  [(10.)] TJ ET
BT 43.553 517.000 Td /F1 9.8 Tf  [(Ge D, Fellay J, Thompson AJ, et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. )] TJ ET
BT 26.250 505.095 Td /F1 9.8 Tf  [(Nature 2009;461:399-401.)] TJ ET
BT 26.250 485.691 Td /F1 9.8 Tf  [(11.)] TJ ET
BT 43.553 485.691 Td /F1 9.8 Tf  [(Thomas DL, Thio CL, Martin MP, et al. Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature )] TJ ET
BT 26.250 473.786 Td /F1 9.8 Tf  [(2009;461\(8\):798-801.)] TJ ET
BT 26.250 454.381 Td /F1 9.8 Tf  [(12.)] TJ ET
BT 43.553 454.381 Td /F1 9.8 Tf  [(Pineda JA, Caruz A, Rivero A, Neukam K, Salas I, Camacho A, et al. Prediction of response to pegylated interferon plus )] TJ ET
BT 26.250 442.476 Td /F1 9.8 Tf  [(ribavirin by IL28B gene variation in patients coinfected with HIV and hepatitis C virus. Clin Infect Dis 2010;51:788-795.)] TJ ET
BT 26.250 423.072 Td /F1 9.8 Tf  [(13.)] TJ ET
BT 43.553 423.072 Td /F1 9.8 Tf  [(Aparicio E, Parera M, Franco S, P�rez-Alvarez N, Tural C, Clotet B, Mart�nez MA. IL28B SNP rs8099917 is strongly )] TJ ET
BT 26.250 411.167 Td /F1 9.8 Tf  [(associated with pegylated interferon-? and ribavirin therapy treatment failure in HCV/HIV-1 coinfected patients. PLoS ONE )] TJ ET
BT 26.250 399.262 Td /F1 9.8 Tf  [(2010;5\(10\):e13771. Available at: https://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0013771. Accessed )] TJ ET
BT 26.250 387.357 Td /F1 9.8 Tf  [(22 Nov 2010.)] TJ ET
BT 26.250 367.953 Td /F1 9.8 Tf  [(14.)] TJ ET
BT 43.553 367.953 Td /F1 9.8 Tf  [(St�ttermayer AF, Stauber R, Hofer H, et al. Impact of IL28B genotype on the early and sustained virologic response in )] TJ ET
BT 26.250 356.048 Td /F1 9.8 Tf  [(treatment-na�ve patients with chronic hepatitis C. Clinc Gastroenterol Hepatol 2010. doi:10.1016/j.cgh.2010.07.019. Accessed )] TJ ET
BT 26.250 344.143 Td /F1 9.8 Tf  [(21 Oct 2010.)] TJ ET
BT 26.250 324.738 Td /F1 9.8 Tf  [(15.)] TJ ET
BT 43.553 324.738 Td /F1 9.8 Tf  [(Mangia A, Thompson AJ, Santoro R, et al. An IL28B polymorphism determines treatment response of hepatitis C virus )] TJ ET
BT 26.250 312.834 Td /F1 9.8 Tf  [(genotype 2 or 3 patients who do not achieve a rapid virologic response. Gastroenterology 2010;139\(3\):821-827.)] TJ ET
BT 26.250 293.429 Td /F1 9.8 Tf  [(16.)] TJ ET
BT 43.553 293.429 Td /F1 9.8 Tf  [(Grebely J, Petoumenos K, Hellard M, et al. Potential role for interleukin-28B genotype in treatment decision-making in )] TJ ET
BT 26.250 281.524 Td /F1 9.8 Tf  [(recent hepatitis C infection. Hepatology 2010;52\(4\):1216-1224.)] TJ ET
BT 26.250 262.119 Td /F1 9.8 Tf  [(17.)] TJ ET
BT 43.553 262.119 Td /F1 9.8 Tf  [(dbSNP website. Available at: https://www.ncbi.nlm.nih.gov/sites/entrez?db=snp&cmd=search&term=rs8099917. Accessed )] TJ ET
BT 26.250 250.215 Td /F1 9.8 Tf  [(on 14 Nov 2010.)] TJ ET
Q
q
0.000 0.000 0.000 rg
BT 291.710 19.825 Td /F1 11.0 Tf  [(3)] TJ ET
BT 25.000 19.825 Td /F1 11.0 Tf  [(PLOS Currents Evidence on Genomic Tests)] TJ ET

Q
endstream
endobj
xref
0 211
0000000000 65535 f 
0000000008 00000 n 
0000000073 00000 n 
0000000119 00000 n 
0000000369 00000 n 
0000000406 00000 n 
0000000722 00000 n 
0000001070 00000 n 
0000019603 00000 n 
0000019710 00000 n 
0000019818 00000 n 
0000019929 00000 n 
0000020042 00000 n 
0000020430 00000 n 
0000025259 00000 n 
0000025386 00000 n 
0000025535 00000 n 
0000025662 00000 n 
0000025811 00000 n 
0000025938 00000 n 
0000026087 00000 n 
0000026214 00000 n 
0000026328 00000 n 
0000026456 00000 n 
0000026570 00000 n 
0000026698 00000 n 
0000026810 00000 n 
0000026938 00000 n 
0000027045 00000 n 
0000027173 00000 n 
0000027209 00000 n 
0000027337 00000 n 
0000027373 00000 n 
0000027501 00000 n 
0000027537 00000 n 
0000027665 00000 n 
0000027701 00000 n 
0000027829 00000 n 
0000027865 00000 n 
0000027993 00000 n 
0000028029 00000 n 
0000028156 00000 n 
0000028305 00000 n 
0000028432 00000 n 
0000028581 00000 n 
0000028708 00000 n 
0000028857 00000 n 
0000028984 00000 n 
0000029098 00000 n 
0000029226 00000 n 
0000029340 00000 n 
0000029468 00000 n 
0000029580 00000 n 
0000029708 00000 n 
0000029815 00000 n 
0000029943 00000 n 
0000029979 00000 n 
0000030107 00000 n 
0000030143 00000 n 
0000030271 00000 n 
0000030307 00000 n 
0000030435 00000 n 
0000030471 00000 n 
0000030599 00000 n 
0000030635 00000 n 
0000030763 00000 n 
0000030799 00000 n 
0000030926 00000 n 
0000031075 00000 n 
0000031202 00000 n 
0000031351 00000 n 
0000031478 00000 n 
0000031627 00000 n 
0000031754 00000 n 
0000031868 00000 n 
0000031996 00000 n 
0000032110 00000 n 
0000032238 00000 n 
0000032350 00000 n 
0000032478 00000 n 
0000032585 00000 n 
0000032713 00000 n 
0000032749 00000 n 
0000032877 00000 n 
0000032913 00000 n 
0000033041 00000 n 
0000033077 00000 n 
0000033205 00000 n 
0000033241 00000 n 
0000033369 00000 n 
0000033405 00000 n 
0000033533 00000 n 
0000033569 00000 n 
0000034099 00000 n 
0000064794 00000 n 
0000064914 00000 n 
0000065042 00000 n 
0000065078 00000 n 
0000065206 00000 n 
0000065242 00000 n 
0000065371 00000 n 
0000065408 00000 n 
0000065538 00000 n 
0000065575 00000 n 
0000065705 00000 n 
0000065742 00000 n 
0000065872 00000 n 
0000065909 00000 n 
0000066039 00000 n 
0000066076 00000 n 
0000066206 00000 n 
0000066243 00000 n 
0000066373 00000 n 
0000066410 00000 n 
0000066540 00000 n 
0000066577 00000 n 
0000066707 00000 n 
0000066744 00000 n 
0000066874 00000 n 
0000066911 00000 n 
0000067041 00000 n 
0000067078 00000 n 
0000067208 00000 n 
0000067245 00000 n 
0000067373 00000 n 
0000067410 00000 n 
0000067538 00000 n 
0000067575 00000 n 
0000067705 00000 n 
0000067742 00000 n 
0000067872 00000 n 
0000067909 00000 n 
0000068039 00000 n 
0000068076 00000 n 
0000068206 00000 n 
0000068243 00000 n 
0000068373 00000 n 
0000068410 00000 n 
0000068540 00000 n 
0000068577 00000 n 
0000068707 00000 n 
0000068744 00000 n 
0000068874 00000 n 
0000068911 00000 n 
0000069041 00000 n 
0000069078 00000 n 
0000069208 00000 n 
0000069245 00000 n 
0000069375 00000 n 
0000069412 00000 n 
0000069542 00000 n 
0000069579 00000 n 
0000069709 00000 n 
0000069746 00000 n 
0000069876 00000 n 
0000069913 00000 n 
0000070043 00000 n 
0000070080 00000 n 
0000070210 00000 n 
0000070247 00000 n 
0000070377 00000 n 
0000070414 00000 n 
0000070542 00000 n 
0000070579 00000 n 
0000070707 00000 n 
0000070744 00000 n 
0000070874 00000 n 
0000070911 00000 n 
0000071041 00000 n 
0000071078 00000 n 
0000071208 00000 n 
0000071245 00000 n 
0000071375 00000 n 
0000071412 00000 n 
0000071542 00000 n 
0000071579 00000 n 
0000071709 00000 n 
0000071746 00000 n 
0000071876 00000 n 
0000071913 00000 n 
0000072043 00000 n 
0000072080 00000 n 
0000072210 00000 n 
0000072247 00000 n 
0000072377 00000 n 
0000072414 00000 n 
0000072544 00000 n 
0000072581 00000 n 
0000072711 00000 n 
0000072748 00000 n 
0000072878 00000 n 
0000072915 00000 n 
0000073045 00000 n 
0000073082 00000 n 
0000073212 00000 n 
0000073249 00000 n 
0000073379 00000 n 
0000073416 00000 n 
0000073546 00000 n 
0000073583 00000 n 
0000073711 00000 n 
0000073748 00000 n 
0000073876 00000 n 
0000073913 00000 n 
0000074043 00000 n 
0000074080 00000 n 
0000074210 00000 n 
0000074247 00000 n 
0000074377 00000 n 
0000074414 00000 n 
0000074481 00000 n 
trailer
<<
/Size 211
/Root 1 0 R
/Info 5 0 R
>>
startxref
91335
%%EOF