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¤»óȵȴÙ.
* 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.