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1 [1] (HBV) DNA (hepadnaviridae) 3.2kb DNA HBV HBV DNA DNA DNA (cccdna) cccdna RNA II mrna 3.5kb mrna HBV DNA RNA HBV DNA DNA HBV DNA DNA DNA HBV DNA cccdna cccdna ( ) [1, 2] HBV (ORF) S S C C P X S/S ( S1 S2 S) ( S2 S) (S) 3 C/C HBeAg HBcAg P X X C (BCP) HBeAg C G1896A (TAG) HBeAg BCP A1762T/G1764A C mrna HBeAg [3] P POL/RT (349~692 aa rt1~rt344) (YMDD) YMDD YIDD (rtm204i) YVDD (rtm204v) rtl180m [4] ( ) S HBV (occult HBV infection) HBsAg HBV ( HBV DNA < 10 4 /ml) [5] HBV 8% S 4% HBV A~H 8 A D B C A D B C [6] ( ) ( ) HBV HBV 1

2 2 (quasispecies) HBV h 10 min HBV HBV HBV 20 HBV 3.5 HBV 100 HBV (HCC) [7] HBV HBsAg 9.09% HBsAg 4.51% 9.51% [8] ( ) HBV adrq+ adw2 ayw3 ( ) C B [9] HBV [7] ( ) HBV ( ) [1, 10] ( -2) ( ) ( ) HBV HBV ( ) HBsAg HBV ( ) HBV ( ) HBV 6 HBV ( ) HBV 90% 25%~30% [11] ( ) HBV 3 [12] HBV HBsAg HBeAg HBV DNA (>10 5 /ml) (ALT) HBV DNA >10 5 /ml ALT/ (AST) ( ) HBeAg -HBe HBV DNA (PCR ) ALT AST HBV 5%~10% ( ) ( ) HBV ( ) HBV HBeAg C C HBV HBeAg HBeAg 5 10 ( ) 50% 70% [13,14] ( -3, -2) ( ) HBV [8] % [15] HBeAg 9 (1~18.4 ) HCC 23% 4.4% [16,17] HBeAg ALT HCV HDV HIV [18-20] (I) HBeAg HBeAg [1,10, 15] ( -2) 3% 5 16% [10] ( ) 5 0%~2% 14%~20% 70%~86%

3 3 [10] ( -2) HBeAg HBV DNA ALT [10, 21] (, -3,) HBV HCC HBsAg HBeAg HCC HBsAg [22] ( -2) HCC HCV HDV HBeAg HBV DNA ( 10 5 /ml ) [10] ( ) 6 25% HCC [23] -2 HBV HCC HCC HBV [24] ( -3) HBV [25] ( HBsAg ) h 87.8% [26] ( -3) HBsAg 24 h (HBIG) 12 h 100 IU 10 µg µg (CHO) [10, 26, 27] ( -3) 12 h 1 HBIG 1 2 HBIG 10 µg µg CHO ( 10 µg µg CHO ) [28] 12 h HBIG HBsAg [29] (III) HBsAg 5µg µg CHO 5µg µg CHO 20µg µg CHO ~2 -HBs 12 -HBs -HBs -HBs< 10 miu/ml [30] ( ) ( ) ( ) HBsAg HBsAg ( ) HBV [31] HBV

4 4 1 HBsAg -HBs ALT HBs 10 miu/ml -HBs <10 miu/ml -HBs HBIG 200~400 IU (20µg) ( 20µg) ( ) (CDC) HBsAg -HBc -HBs ( 3 ) () HBV HBsAg ( ) ( ) HBV DNA ALT AST HBsAg 6 HBsAg ( ) HBV DNA HBV HBV HBV ( ) 1 HBeAg HBsAg HBV DNA HBeAg -HBe ALT 2 HBeAg HBsAg HBV DNA HBeAg -HBe ALT ( 2000 [32] ) ( ) 1 Child-Pugh A ALT AST 2 Child-Pugh B C 35g/L 35 mol/l ALT AST (PTA) <60% 2001 [32] ( ) 1 HBV HBsAg HBV DNA HBeAg -HBe 1 3 ALT AST HBV DNA 2 HBsAg HBsAg HBeAg -HBe HBV DNA (PCR ) 1 3 ALT

5 Knodell ( HAI) <4 ( ) HBsAg ( ) HBV DNA -HBs -HBe ( ) -HBc 20% HBV DNA HBV ( ) 1 ALT AST ALT AST 2 1 (ULN) 10 ULN ALT AST 3 (PT) PTA PT PTA PT PTA 40% <20% (INR) INR PTA (AFP) HCC HCC AFP AFP ALT AST B ( ) HBV HBV HBsAg -HBs HBeAg -HBe -HBc -HBc Ig M (EIA) (RIA) (MEIA) HBsAg HBV -HBs HBV HBsAg -HBs HBsAg HBeAg HBV -HBe HBV ( C ) HBeAg -HBe HBeAg -HBc IgM HBV -HBc -HBc IgG, HBV HBV (HDV) HDAg -HDV -HDV IgM HDV RNA ( ) HBV DNA 1 HBV DNA HBV HBV DNA 2 HBV (1) PCR (2) (RFLP) (3) (INNO-LiPA) (4) PCR (5) (SFDA) HBV [33, 34] 3 HBV (1) HBV (2) (RFLP) (3) PCR (4) B (CT) (MRI) HCC 5

6 6 (interface hepatitis ) (piecemeal necrosis) HBsAg HBcAg HBsAg HBcAg HBV HBsAg HBcAg HBV (G) (S) 2001 [32] Knodell HAI Ishak Scheuer Chevallier [35-38] HBV HCC [39-42] (1) HBV DNA 10 5 /m l (HBeAg 10 4 /ml) (2) ALT 2 ULNALT 10 ULN<2 ULN (3) ALT <2 ULN Knodell HAI 4 G2 (1) (2) (3) HBV DNA ALT (III) ALT ALT AST ALT AST [39-42] ( ) 1 (virological response) HBV DNA (PCR ) 2 log 10 2 (serological response) HBeAg HBeAg HBsAg HBsAg 3 (biochemical response) ALT AST 4 (histological response) ( ) 1. (initial or early response) 12 2 (end-of-treatment response) 3 (sustained response) (maintained response) HBV DNA (PCR ) ALT

7 7 5 (breakthrough) HBV DNA ALT ALT AST ALT AST 6 (relapse) HBV DNA ALT AST ALT AST (combined response) 1 (complete response, CR) HBeAg ALT HBV DNA (PCR ) HBeAg HBeAg ALT HBV DNA (PCR ) 2 (partial response, PR) HBeAg ALT HBV DNA <10 5 /ml HBeAg 3 (non- response, NR) HBeAg α ( IFN α) 4~6 HBV DNA ( ) 37% 17% HBeAg 33% 12% HBsAg 7.8% 1.8% ALT [39] ( ) HBeAg 4 38%~90% 10%~47% ( 24%) [40, 41] ( ) IFNα 1 [42-44] IFN α (5MU 1 ) ALT <1% [45] ( ) α-2a (PegIFNα-2a) (40 KD) HBeAg (87% ) HBeAg 32% [46, 47] HBeAg (60% ) HBV DNA < /ml 43% [48] 48 42% II 1 PegIFN α-2a (40 KD) HBeAg IFN (32%:25% P<0.05) [49] PegIFN α-2b (12 KD) HBeAg HBeAg 29% [6] PegIFN α-2a (40 KD) IFN IFN [42, 50] ( ) α PegIFNα-2a ( ) (III) ( ) (1) ALT (2) HBV DNA< ml (3) (4) (5) (6) (7) (8) HCV HDV HIV HBV DNA ALT [51-54] II 12 ( ) (1) ALT AST (2) (3) HBsAg HBeAg -HBe HBV DNA (4) (5) (6) (HCG) (1) 1 1~2 1 1 (2) ALT AST (3) 3 1 HBsAg HBeAg -HBe HBV DNA (4) 3 1 (5)

8 8 ( ) [53] 1 IFN α (III) 2 ( ) /L < /L IFN α 1~ /L < /L (G-CSF) (GM-CSF) ( ) 3 (III) IFN α 4 () 5 ( ) ( ) ( ) ( ) / < /L < /L >51 µmol/l ( ) (lamivudine) 100 mg HBV DNA HBeAg HBeAg 16% 17% 23% [55] ALT HBeAg [56-60] [1, 2] HCC [21] [61-63] [64, 65] HBIG HBV HBIG ( % 38% 49% 66%) [55, 66, 67], [68] HBV DNA ALT [69] SFDA ( ) (adefovir dipivoxil) 5 - HBeAg HBV DNA [70], HBV DNA

9 (<1000 /ml) 28% 45% 56% HBeAg12% 29% 43% 0% 1.6% 3.1% [71] HBeAg % 3.0% 5.9%~11% [72-74] [75, 76] 10 mg [77] 10 mg 48~96 2%~3% >0.5mg /dl (44.2 µmol/l) SFDA ( ) (entecavir) II/III 0.5 mg HBV DNA [78, 79] III YMDD 1mg HBV DNA [80] 1 0 YMDD 1 5.8% [81] SFDA ( ) ( ) (1) ALT AST(2) HBeAg -HBe HBV DNA (3) (1) (2) 3 1 HBsAg HBeAg -HBe HBV DNA (3) HBeAg 1 HBV DNA HBV DNA <2 log 10 ( 1~3 ) 1 ( ) 1 1.6mg 2 6 (II-3) ( ) HBV [82-84] HBV 1 HBeAg (I) IFN α ( -2) 2 (I) ( ) 9

10 10 ( ) HBV HBsAg HBV Knodell HAI 4 G2 HBsAg 3~6 ALT 2 ULN HBV DNA IFN α ( ) ( -2) ( ) HBeAg HBV DNA /ml ALT 2 ULN ALT<2 ULN Knodell HAI 4 G2 IFN α (ALT <10 ULN) ( ) HBV DNA /ml 3 HBV DNA ALT (III) 1 IFN α 5 MU ( ) (I) 1 [52] (II) 6 2 PegIFN α-2a 180 µg 1 1 (I) mg 1 1 HBV DNA (PCR ) ALT HBeAg -HBe HBeAg 2 ( 6 ) [85] (II) 4 10 mg 1 [85] (II) 5 0.5mg ( 1mg) 1 ( ) HBeAg HBV DNA /ml ALT 2 ULN ALT<2ULN Knodell HAI 4 G2 HBV DNA (PCR ) ALT 1 (I) IFN α (ALT <10 ULN) ( ) HBV DNA ALT (III) 1 IFN α 5MU (I) 2 PegIFN α-2a 180µg 1 1 (I) 3 10 mg ( 6 ) HBV DNA (PCR ) ALT [87] II mg 1 1 [87] (II) 5 0.5mg ( 1mg) 1 ( ) HBeAg HBV DNA 10 5 /ml HBeAg HBV DNA 10 4 /ml ALT HCC mg mg 1 3 (III) ( )

11 11 HBV DNA ALT ( ) ( ) (II 2) ( ) () HBsAg HBV DNA ALT mg (II-1, II-3) ( ) ( ) ( ) HBV 1~3 100 mg HBIG HBIG ( IU 800 IU) -HBs HBIG ( -HBs 100~150 miu/ml 500 miu/ml) (II-1) ( ) ( ) 1 IFN IFN IFN α ( ) PegIFNα-2a ( ) (III) 2 IFN α 2~3 3 ( ) 3. ( ) ( ) (I) 1~3 HBV DNA IFN-α ( 1~3 ) 4 ( ) ( ) IFNα (III) ( ) 12 IFNα [53] 3~6 MU/m 2 10 MU/m 2 ( ) (I) ( -2 II-3) ALT ALT IFNα ( )

12 (GCP) HBV ( ) HBeAg HBeAg ( ) 2 1 ALT AST ( ) HBV HBV DNA 3~ ALT HBV DNA 6 HBV DNA ALT AFP B ALT HBV DNA 3 1 HBV DNA ALT 6 AFP B HCC ( 40 AFP ) 3~6 AFP B ( CT MRI) HCC 1~2 X HBeAg HBeAg ALT 2 ULN HBV DNA /ml ALT <2 ULN ALT 2 ULN HBV DNA /ml ( ) IFN α PegIFN α-2a ALT IFN α PegIFN α-2a 12

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中国肝脏病杂志 ( 电子版 ) 2010 年第 2 卷第 4 期指南 55 1 诊断 1.1 临床表现肝纤维化患者的临床表现无特异性, 差异较大常见的临床表现有 : 疲倦乏力食欲不振大便异常肝

中国肝脏病杂志 ( 电子版 ) 2010 年第 2 卷第 4 期指南 55 1 诊断 1.1 临床表现肝纤维化患者的临床表现无特异性, 差异较大常见的临床表现有 : 疲倦乏力食欲不振大便异常肝 54 指南中国肝脏病杂志 ( 电子版 ) 2010 年第 2 卷第 4 期肝纤维化中西医结合诊疗指南中国中西医结合学会肝病专业委员会肝纤维化在国际疾病分类 (international classification of disease,icd-10) 中可作为一种病名 (K74.001),