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Chronic hepatitis B

1. °³¿ä

chronicityÁ¤µµ´Â °¨¿°µÈ ³ªÀÌ¿¡ µû¶ó ´Ù¸£´Ù.

(at birth: 90%, immunocompetent adulthood: 1%)

°£¼Õ»óÀÇ Á¤µµ(grade)¿¡ µû¶ó ¹«Áõ»ó-°æÁõ-Áߵ-ÁßÁõ±îÁö ´Ù¾çÇÏ´Ù.

chronic hepatitis BȯÀÚ¿¡¼­ ¿¹ÈÄ¿Í °ü·ÃÇÏ¿© º¸´Ù Áß¿äÇÑ °ÍÀº histology´Üµ¶º¸´Ù´Â

HBV replicationÁ¤µµÀÌ´Ù.

* replicative phase : HBeAg(+), HBV DNA(+)

intrahepatocyte HBcAg(+)

high infectivity, liver injury

°£³» HBV DNA(+) - extrachromosomal

* nonreplicative phase : HBeAg(-), anti HBe(+)

intrahepatocytic HBcAg(-)

limited infectivity, minimal liver injury

°£³» HBV DNA(+) - host genome³»¿¡ integration

¸Å³â 10-15% spontaneous seroconversionÀÌ ÀϾ¸ç À̶§ ÀϽÃÀûÀÎ

aminotransferase activity»ó½ÂÀÌ ÀÖ´Ù.

2. ÀÓ»óÀû Ư¡ - broad

fatigue - common sx

persistent or intermittent jaundice - severe, advanced cases

* extrahepatic manifestations

±Þ¼º BÇü °£¿°ÀÇ Àü±¸±â¿Í À¯»çÇϸç

circulating HBsAg-Ab immune complexÄ§Âø°ú °ü·ÃÀÖ´Ù.

arthralgia or arthritis(common)

more rare - purpuric cutaneous lesion(leukocytoclastic vasculitis),

immune complex GN, generalized vasculitits(PAN)

3. Lab

aminotransferase : 100-1000 units

ALT > AST : cirrhosis°¡ ÁøÇàµÇ¸é ALT < AST ¿ªÀü

ALP : normal or ¾à°£¡è

severe case : Bil»ó½Â 3-10mg/dL

Alb¡é, PT¡è : severe or end-stage

circulating autoantibody(-)

4. Ä¡·á

viral replicationÁ¤µµ¿¡ µû¶ó Ä¡·á°¡ °áÁ¤µÈ´Ù.

* °¡Àå ÈçÇÑ Ä¡·áÀûÀÀÁõ

i) HBeAg(+), HBV DNA(+)

ii) ALT¡è

iii) Liver Bx»ó chronic hepatitis

iv) immunocompetent adult

1) Interferon-¥á

¸ÅÀÏ 500¸¸ ´ÜÀ§ SC 16ÁÖ È¤Àº ÁÖ 3ȸ 1000¸¸ ´ÜÀ§ SC 16ÁÖ

-> seroconversion : 35% (À̶§ histologyµµ È£Àü)

anti HBe : 20%

HBs Ag loss : 8 %

IFNÄ¡·á°¡ ¼º°øÀûÀ̰í seroconversionÀÌ ÀϾ ¶§ acute hepatitis-like ALT elevationÀÌ

ÀϾ´Ù.

¡ñ HBV-infected hepatocyte¿¡¼­ cytotoxic T cell clearance°¡ ÃËÁøµÇ±â ¶§¹®

<Âü°í>

¸¸¼º CÇü °£¿°ÀÇ ¼º°øÀû Ä¡·á¶§´Â ÀÌ·± Çö»óÀÌ ¾ø°í ALT°¡ Á¤»óÈ­µÈ´Ù.

* InterferonÄ¡·á°¡ È¿°úÀûÀÌÁö ¸øÇÑ °æ¿ì

i) young children( infected at birth )

ii) immunosuppressed

iii) Asian with minimal-to-mild ALT elevation

iv) pre-core mutant

v) decompensated chronic hepatitis B

* Complications of IFN Tx

i) flulike sx

ii) marrow suppression

iii) emotional lability(irritability)

iv) autoimmune reaction(autoimmune thyroiditis)

v) ±âŸ - alopecia, rash, diarrhea, numbness, tingling sensation

autoimmeun thyroiditis¸¦ Á¦¿ÜÇϰí´Â interferonÁß´Ü È¤Àº ¿ë·®°¨¼Ò½Ã reversible

2) Glucocorticoid

HBV replication¡è

cytotoxic T cell¾ïÁ¦

IFN´Üµ¶º¸´Ù È¿°ú ¾ø´Ù.

3) Nucleoside analogue

Famciclovir, Ganciclovir - limited activity

Lamivudine - reverse transcriptase activity¾ïÁ¦

* Lamivudine 12°³¿ù Ä¡·áÈ¿°ú

HBe Ag loss : 32-33%

HBeAg seroconversion : 16-20%

ALT normalization : 40%

histology improvement : 50%

fibrosis retardation : 20%

- HBe Ag responder¿¡¼­ 1³âÀÌ»ó °æ°ú°üÂûÇϸé 70-80%°¡ responseÁö¼Ó

- HBe Ag seroconversion : 2³â - 27%, 3³â - 44%

- pre-core mutant : DNA¾ïÁ¦, ALT normalization - 65%

histologyÈ£Àü - 60%

- Ä¡·áÁߴܽà reactivationÀÌ ÈçÇÔ. µû¶ó¼­ long-term txÇÊ¿ä

- long-term monotherapy½Ã YMDD mutation¹ß»ýÇÔ

15-30%/ 1³â

38% / 2³â

50% / 3³â

- YMDD mutationÀÌ ÀϾ´õ¶óµµ immunocompetent pt¿¡¼­ HBV DNA & ALT levelÀº

baselineº¸´Ù ³·´Ù.

- immunosuppressed pt¿¡¼± hepatic decompensationÀÌ ÀϾ´Ù.