F3 F4, HIV HBV HCV (, HCV,,, (F2) (F0~F1) A1 -HCV A1 -HCV B1 -HCV HCV RNA A1 HCV HCV HCV liver cirrhosis LC hepatocellular carcinoma HCC A1

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1 European Association for the Study of the Liver EASL 2015 HCV Journal of Hepatology GRADE A B C HCV PegIFN-α2a PegIFN-α2b Ribavirin Sofosbuvir Simeprevir Daclatasvir Sofosbuvir/ledipasvir Paritaprevir/ombitasvir/ritonavir Dasabuvir 2 HCV HCV 160 -HCV HCV A1 HCV RNA A1 -HCV HCV RNA A1 -HCV HCV RNA 3 HCV RNA A1 A B C HCV PegIFN-α2a PegIFN-α2a, 180 μg 135 μg 90 μg, 180 μg( ) PegIFN-α2b PegIFN-α2b 50 μg/0.5 ml, 1.5 μg/kg( ) (Ribavirin) 200 mg <75 kg 2, 3 ;>75 kg, 3, 3 (Sofosbuvir) 400 mg/,1 /, (Simeprevir) 150 mg/ ( ),1 /, (Daclatasvir) 30 mg/ 60 mg/,1 /, Sofosbuvir/ledipasvir 400 mg +90 mg /,1 /, Paritaprevir/ombitasvir/ Paritaprevir 75 mg/ombitasvir 12.5 mg/ritonavir 50 mg,2 /, ritonavir Dasabuvir 250 mg/,1 / ( 1 ) DOI: /cma.j.issn dryanjie@gmail.com

μg 90 μg, 180 μg( ) PegIFN-α2b PegIFN-α2b 50 μg/0.5 ml, 1.

2 F3 F4, HIV HBV HCV (, HCV,,, (F2) (F0~F1) A1 -HCV A1 -HCV B1 -HCV HCV RNA A1 HCV HCV HCV liver cirrhosis LC hepatocellular carcinoma HCC A HCV RNA 15 IU/ml [ sustained virological response SVR ] A1 HCV HCC HCC A1 HCV B2 HCV A1 A1 A1 A1 15 IU/ml HCV RNA A1 HCV 1 1a/1b A1 direct antiviral agents DAAs 28B interleukin 28B IL28B A1 -HCV SVR -1a PegIFN-α simeprevir A1 HCV A1 METAVIR F3 F4 A1 Child-Pugh B C A1 HBV HIV HCV A1 A1 METAVIR F2 A2 METAVIR F0 F1 HIV B1 B1 3 HCV

HCV A1 A1 A1 A1 15 IU/ml HCV RNA A1 HCV 1 1a/1b A1 direct antiviral agents DAAs 28B interleukin 28B IL28B A1 -HCV SVR -1a

3 B1 Cobicistat HIV Simeprevir HIV A1 HIV Daclatasvir 30 mg/d Daclatasvir 90 mg/d B2 Sofobuvir A2 / / darunavir/ritonavir lopinavir/ritonavir elvitegravir/ cobicista B1 ritonavir-boosted paritaprevir ombitasvir dasabuvir efavirenz etravirine nevirapine rilpivirine Atazanavir darunavir B1 Child-Pugh A 7 10 HIV HCV HCV A1 HIV/HCV HCV Child-Pugh A Child-Pugh B C A1 HIV HCV HCV A1 1 HCV HCV HCV PegIFN-α PegIFN-α Telaprevir Boceprevir EASL 1 1 HCV PegIFN-α/ 75 kg mg/d 75 kg mg/d Sofosbuvir 400 mg/d 12 A1 2 1 HCV PegIFN-α/ 75 kg mg/d 75 kg mg/d Simeprevir 150 mg/d A1 NS3 Q80K 1a A1 PegIFN-α 12 PegIFN-α PegIFN-α B1 HCV RNA HCV RNA 25 IU/ml A2 1 1 HCV Sofobuvir 400 mg Ledipasvir 90 mg A1 12 A1 HCV RNA IU/ml 8 F3 HCV RNA 8 SVR B kg mg/d 75 kg mg/d A1 Sofobuvir Ledipasvir 24 B /μl 24 B2 2 1 HCV ombitasvir 75 mg paritaprevir 12.5 mg ritonavir 50 mg

paritaprevir ombitasvir dasabuvir efavirenz etravirine nevirapine rilpivirine Atazanavir darunavir B1 Child-Pugh A 7 10 HIV HCV HCV A1 HIV/HCV HCV Child-Pugh A Child-Pugh B C A1 HIV HCV HCV A1 1 HCV

4 2943 dasabuvir 250 mg A1 1b 12 A1 1b 75 kg mg/d 75 kg mg/d 12 A1 1a 75 kg mg/d 75 kg mg/d 24 A1 3 1 HCV Sofosbuvir 400 mg/d Simeprevir 150 mg/d 12 A1 75 kg mg/d 75 kg mg/d B1 24 B1 4 1 HCV Sofosbuvir 400 mg/d Daclatasvir 60 mg/d 12 A1 75 kg mg/d 75 kg mg/d B1 24 B1 2 HCV 2 HCV sofosbuvir PegIFN-α EASL 1 2 HCV 75kg mg/d 75 kg mg/d Sofosbuvir 400 mg/d 12 A B1 2 PegIFN-α 75 kg mg/d 75 kg mg/d Sofosbuvir 400 mg/d 12 B1 3 Sofosbuvir 400 mg/d Daclatasvir 60 mg/d 12 B1 3 HCV 3 HCV 3 Sofosbuvir 3 HCV PegIFN-α Daclatasvir 3 HCV 3 Ledipasvir Daclatasvir Ledipasvir Ledipasvir PegIFN-α EASL 1 3 HCV PegIFN-α/ 75 kg mg/d 75 kg mg/d Sofosbuvir 400 mg/d 12 B1 Sofosbuvir SVR B1 2 3 HCV 75 kg mg/d 75 kg mg/d Sofosbuvir 400 mg/d 24 A1 B1 3 3 HCV Sofosbuvir 400 mg/d Daclatasvir 60 mg/d 12 A1 3 HCV 75 kg mg/d 75 kg mg/d B1 4 HCV HCV PegIFN-α EASL 1 4 HCV PegIFN-α/ 75 kg mg/d 75 kg mg/d Sofosbuvir 400 mg/d

Sofosbuvir 400 mg/d 12 A1 16 20 B1 2 PegIFN-α 75 kg 1 000 mg/d 75 kg 1 200 mg/d Sofosbuvir 400 mg/d 12 B1 3 Sofosbuvir 400 mg/d Daclatasvir 60 mg/d 12 B1 3 HCV 3 HCV 3 Sofosbuvir 3 HCV PegIFN-α

5 B1 2 4 HCV PegIFN-α/ 75 kg mg/d 75 kg mg/d Simeprevir 150 mg/d B1 Simeprevir PegIFN-α PegIFN-α B1 HCV RNA HCV RNA 25 IU/ml A2 1 4 HCV Sofobuvir 400 mg Ledipasvir 90 mg A1 12 A1 1 HCV 75 kg mg/d 75 kg mg/d 12 B1 Sofobuvir Ledipasvir 24 B1 1 HCV /μl Sofobuvir Ledipasvir 24 B1 2 4 HCV [Ombitasvir 75 mg Paritaprevir 12.5 mg Ritonavir 50 mg 2 / ] 75 kg mg/d 75 kg mg/d Dasabuvir 12 B1 4 HCV B1 3 4 HCV 400 mg/d 150 mg/d 12 B2 75 kg mg/d 75 kg mg/d B2 24 B2 4 4 HCV 400 mg/d 60 mg/d 12 B2 75 kg mg/d 75 kg mg/d B2 24 B2 5 6 HCV 5 6 HCV 3 PegIFN-α Sofosbuvir Sofosbuvir Ledipasvir Sofosbuvir Daclatasvir PegIFN-α HCV PegIFN-α/ 75 kg mg/d 75 kg mg/d Sofosbuvir 400 mg/d 12 B HCV Sofosbuvir 400 mg Ledipasvir 90 mg A1 12 B1 1 HCV 75 kg mg/d 75 kg mg/d 12 B1 24 B1 1 HCV /μl 24 B HCV 400 mg/d Daclatasvir 60 mg/d 12 B1 Sofosbuvir 75 kg mg/d

5 mg Ritonavir 50 mg 2 / ] 75 kg 1 000 mg/d 75 kg 1 200 mg/d Dasabuvir 12 B1 4 HCV B1 3 4 HCV 400 mg/d 150 mg/d 12 B2 75 kg 1 000 mg/d 75 kg 1 200 mg/d B2 24 B2 4 4 HCV 400 mg/d 60 mg/d 12 B2 75 kg 1

6 kg mg/d B1 24 B1 1. PCR 15 IU/ml HCV RNA A1 PegIFN-α HCV RNA A2 PegIFN-α 12 PegIFN-α HCV RNA A HCV RNA A2 2. PegIFN-α HCV RNA 25 IU/ml A2 B1 A A1 PegIFN-α A1 B1 ALT A1 A1 estimated glomerular filtration egfr 30 ml min m 2-1 B2 B2 B2 4. A1 HCV B1 HCV A1 HCV SVR A1 B2 A1 HCV B2 A1 A1 SVR SVR 48 ALT HCV RNA ALT HCV RNA B1 SVR 6 1 HCC B1 SVR A2 B1 B1 SVR HCV RNA HCV B2 SVR PegIFN-α A1 PegIFN-α 1 HCV

2 4 12 24 12 24 HCV RNA A2 2. PegIFN-α 4 12 24 HCV RNA 25 IU/ml A2 B1 A1 3.

7 A1 A1 DAA PegIFN-α F3 F4 B2 PegIFN-α Paritaprevir Ombitascir Dasabuvir 1 Paritaprevir Ombitasvir 4 B2 PegIFN-α 4 HCV B2 PegIFN-α B2 1 4 B B2 1 Ritonavir/Paritaprevir Ombitasvir Dasabuvir Simeprevir daclatasvir Ledipasvir Paritaprevir Ombitasvir Dasabuvir 1 B2 Ritonavir-boosted paritaprevir Ombitasvir 4 B2 A1 NS3 NS5A B2 HCV DAAs B2 1. Child-Pugh B Child-Pugh C 12 Sofosbuvir 2 Sofosbuvir Ledipasvir sofosbuvir Daclatasvir 12 B1 Sofosbuvir Ledipasvir Sofosbuvir Daclatasvir 24 B1 2. HCV B2 3. HCV A1

Paritaprevir Ombitasvir Dasabuvir 1 B2 Ritonavir-boosted paritaprevir Ombitasvir 4 B2 A1 NS3 NS5A B2 HCV DAAs B2 1.

8 2947 B A1 Child-Pugh A HCC ritonavir-boosted paritaprevir Ombitasvir Dasabuvir 1b 12 1a B1 Child-Pugh A PegIFN-α 12 B2 Child-Pugh B C Child-Pugh C 12 MELD 20 A1 B2 B2 4. HCV A1 A1 HCV A1 Child-Pugh A A1 Child-Pugh A Ritonavir-boosted paritaprevir Ombitasvir Dasabuvir 1b 12 1a A B1 Child-Pugh B C mg/d B A2 A A2 Ritonavir-boosted paritaprevir Ombitasvir Dasabuvir 0.5 mg/ 0.2 mg A 5 mg/d mtor A2 1. HBV HCV B1 HCV HBV B1 2. HCV HCV SVR B B1 HCV

HCV A1 A1 HCV 12 24 A1 Child-Pugh A 2 12 1 4 5 6 12 12 A1 Child-Pugh A Ritonavir-boosted paritaprevir Ombitasvir Dasabuvir 1b 12 1a 24 4 12 24 1

9 2948 HCV HCV SVR B1 3. B B1 the combination of ritonavirboosted paritaprevir ombitasvir dasabuvir A1 egfr 30 ml min m 2-1 B2 B1 4. HCV 12 Child-Pugh A 24 egfr 30 ml min m 2-1 B1 HCV B2 5. PWID HCV B1 PWID opiate substitution treatment OST B1 HCV B1 PWID A1 PWID B2 PWID HCV A1 PWID A1 SVR B1 SVR B1 B1 PWID PWID HCV B1 B1 OST OST B1 6. HCV HCV A1 B1 HCV B1 B2 7. HCV HCV A1 HCV HIV A1 HCV A1 A1 HCC A1 PegIFN-α PegIFN-α2a 180 μg/ PegIFN-α2b 1.5 μg kg %

HCV 12 Child-Pugh A 24 egfr 30 ml min -1 1.73 m 2-1 B1 HCV B2 5.

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13 2952 SVR A1 HIV PegIFN-α PegIFN-α2a 180 μg/ PegIFN-α2b 1.5 μg kg kg mg/d 75 kg mg/d 24 B1 SVR B1 HCV B1 European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu. EASL Recommendations on Treatment of Hepatitis C 2015[S]. J Hepatol, pii: S (15) doi: /j.jhep J/CD

Study of the Liver. Electronic address: easloffice@easloffice.eu.

plx-005/04

plx-005/04 (HCV) (HCC) 3 2 HCV HCV Flaviviridae) RNA 6 HCV ( 1a 2b 3c ) 1 HCV 70% HCV quasispecies HCV HCV ORF 10 NS NS3 / NS5B RNA RNA HCV HCV 100 5min 60 10h WHO HCV 3% 1.7 HCV 3.5 -HCV 3.2% -HCV 3.6% 2.9% 2.5%