(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% 2.7% 3.2% 3.3% 3.8% 4.6% -HCV 1 2.0% 50-59 3.9% HCV 1b 2a 1b 1a 2b 3b 6 6 1 HCV (1) 1992 -HCV -HCV -HCV -HCV HCV RNA HCV (2) HCV 60%-90% HCV HCV 2 HCV HCV HIV HCV 3 -HCV HCV 2% HCV RNA 4%-7% HIV 20% HCV HCV HCV
5 4 HCV 1-3 HCV RNA HCV 50%-70% -HCV 3 90% -HCV HCV 6 50%-85% 20 2%-4% 20%-30% 10%-15% 40 HCV HCV 40 HIV HBV) 50g/ NASH HCV HCC 30 1%-3% HCC 1%-7% HCC HCC HCC HCC 10 80% 10 25% IFN α ( ) HCC HCV -HCV (ALT) HCV HCV HCV RNA
1 HCV 2-16 7 2 3 ALT -HCV HCV RNA HCV RNA ALT ALT HCV RNA 1+2+3 2+3 1 HCV 6 2 2000 HCV HIV HBV HCV 3 (Sjogren syndrome) 7
B -HCV EIA 99% 4 HCC HCV RIBA HCC 5 HCV HBV HIV 6 HCV HCV HCV 10 5-10 7 /ml HCV RNA 5 10 4-5 10 6 /ml HCV RNA HCV RNA 1 HCV RNA -HCV HCV HCV RNA HCV RNA 98% HCV ALT AST HCV ALT AST HCV 2 HCV RNA qpcr DNA bdna ALT AST PCR HCV RNA HCV RNA PCR Cobas V2.0 SuperQuant LC HCV RNA bdna Versant HCV RNA 2.0 3.0 PCR SFDA 30%ALT 40% 2 HCV RNA /ml IU/ml Cobas ALT V2.0 IU/ml SuperQuant /ml IU/ml=0.854 /ml+0.538 HCV -HCV -HCV -HCV RNA HCV RNA HCV RNA EIA HCV 8 9
HCV HCV RNA Simmonds 1-6 HCV RNA (1) (2) (3) (4) 10
HCV HCC (G 2) (S 2) (2) ALT IFNα HCV IFNα IFN S2 S3 PEG α PEG-IFNα IFNα S0 PEG IFNα S1 3-6 (3) ALT 1 IFNα 9µg IFNα 3MU IFNα ALT PEG-IFNα IFNα IFNα PEG-IFNα-2a ALT PEG-IFNα-2a 180µg PEG-IFNα-2b 1.5µg/kg 1 ALT 48 SVR 54%-56% IFNα 3MU 3 48 SVR 44%-47% PEG-IFNα-2a IFNα 48 SVR PEG-IFNα-2a 180µg 24 SVR 41.5% 1 35.4% 1 IFNα 3MU 1 24 800-1 000mg/d 2 (1) ALT AST 3 (1) Child-Pugh A 25%-39% 12%-19% HCC (2) 66.7% IFNα 4 HCV HCC HCV IFNα HCV RNA 1 IFNα HCV RNA 1 12 13
IFNα 65 70 1 1 HCV IFNα 2 HCV HCC 3. HBV HIV HBV HCC HCV RNA /HBV DNA HCV IFNα HCV HBV DNA HBV / <1.0X10 9 /L <50X10 9 /L Hb<100 g/l HIV HCV Hb<80 g/l CD4 + 6 HAART HCV HAART S2 S3 HCV HIV CD4 + <2 10 8 /L HIV HCV 4 1 ALT AST 2 (1) EVR 12 IFNα HCV RNA 2 (Log) EVR SVR EVR SVR EVR SVR (2) ETVR 14 15
HCV RNA ( ) (3) SVR 48 (3) HCV RNA 24 HCV RNA ( 2 24 24 HCV RNA ) (4) (NR) EVR ETVR SVR (5) (relapse) HCV RNA ( ) HCV RNA (6) breakthrough HCV RNA HCV RNA 3. IFNα IFNα PEG-IFN 3. HCV RNA 1 HCV RNA <2 10 6 /ml 1 PEG-IFNα PEG-IFNα-2a 180µg 1 800mg/d 24 2 IFNα 3MU 3 SVR (1) HCV 2 3 (2) < 2x10 6 /ml (3) <40 (4) (5) HCV (6) (7) (8) (9) HBV HIV (10) PEG-IFNα 48 24 2 IFNα 3-5MU 1 1 000mg/d 48 800-1 000mg/d 24-48 3. IFNα PEG-IFN : (1) PEG-IFNα-2b 1.0 _ 1.5µg/kg PEG-IFNα-2a 180µg 1 48 SVR (2) IFNα IFNα 3-5MU 15-30d 3 HCV RNA (1 1 ) HCV RNA (3) >85kg 1 200mg/d 65-85kg 000mg/d <65kg 800mg/d HCV RNA 1 ( )HCV RNA 2X10 6 /ml >10.6mg/kg 1 PEG-IFNα PEG-IFNα-2a 180µg 1 IFNα PEG-IFNα-2a 1 000mg/d 12 HCV RNA (1) SVR 47% 60% HCV RNA <2 (2) HCV RNA IFNα IFNα PEG-IFNα-2a 16 17
SVR 12%-15% 34%-40% 5 IFNα PEG-IFNα-2a 1 IFNα Hb 100g/L Hb 80g/L 1 2 6 IFNα IFNα 3 2 0.75 10 9 /L <50 10 9 /L IFNα 1-2 0.50 10 9 /L <30 10 9 /L 1. (G-CSF) 1 (GM-CSF) 1 6 3 1 3 2. ALT 6 IFNα 1 HCV ALT IFNα 3. 3 HCV RNA IFNα 6 HCV RNA 4 IFNα 4 6 3-6 18 19
1 Alberti A, Benvegnu L, Management of Hpatitis C. J Hepatol, 2003, 38(suppl.1):S1014-S118. Booth JCL, 0' Grady J, Neuberger J. Clinical guidelines on the management of hepatitis C. Gut, 2001, 49(suppl I):il-i12 3 1 4 suppl.1):s135-s144. 24 1 ALT 5 2 ALT 24 1 Viral Hepat, 2003, 10:210-214. ALT 6 Pharmacol Ther, 2003, 18:1071-1081. 3 3-6 7 AFP B CT MRI HCC randomised trials. BMJ, 2001, 323:1151-1155. 50 AFP 8 1-2 X 2002, 36:(5 Suppl.1) : S3-20. 9 Camma C, Bruno S, Schepis F, et al. Retreatment with Interferon plus ribavirin of chronic hepatitis C non-responders to interferon monotherapy: a meta-analysis of individual patient data. Gut, 2002, 51:864-869. Chander G, Sulkowski MS, Jenckes MW, et al. Treatment of chronic hepatitis C: a systemic review. Hepatology, 2002, 36(5 Di Ciommo V, Russo P, Rava L, et al. Interferon alpha in the treatment of chronic hepatitis C in children: a meta-analysis. J Fabrizi F, Dulai G, Dixit V, et al. Meta-analysis: interferon for the treatment of chronic hepatitis C in dialysis patients. Aliment Kjaergard LL, Krogsgaard K, Gluud C. Interferon alfa with or without ribavirin for chronic hepatitis C: systematic review of National Institute of Health Consensus Development Conference Statement: management of hepatitis C. Hepatology, Papatheodoridis GV, Papadimitropoulos VC, Hadziyannis SJ. Effect of interferon therapy on the development of hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis: a meta-analysis. Aliment Pharmacol Ther, 2001, 15:689-698. 10 Poynard T, McHutchison J, Davis GL, et al. Impact of interferon alfa-2b and ribavirin on progression of liver fibrosis in patients with chronic hepatitis C. Hepatology, 2000, 32:1131-1137. 11,. : ( ), 12,, 13,, 14, Tracy L, 15 2,, 1997:60-71.,.., 1997, 15:71-75.,. HCV., 2004, 12:72-75,.., 2001, 22:99-101..., 2000, 8:324-329. 20 21