Chronic hepatitis C
1. °³¿ä
- ¸¸¼º CÇü °£¿°ÀÇ 50-70%¿¡¼ ±Þ¼º CÇü °£¿°À» ¾ÎÀºÈÄ ¹ß»ýÇϸç
±Þ¼º CÇü °£¿°¿¡ °É¸°ÈÄ ¸¸¼ºÀ¸·Î ÀÌÇàÇÒ È®·üÀº 85-90%ÀÌ´Ù.
- chronic transfusion-associated hepatitisÀÇ 20%¿¡¼ 10-20³âÈÄ °£°æº¯À¸·Î ÁøÇàÇÏÁö¸¸
long-term prognosis´Â ºñ±³Àû ÁÁÀºµ¥ 10-20³â mortality´Â transfused pt without hepatitis
C¿Í µ¿ÀÏÇÏ´Ù.
- anti-HCV¾ç¼ºÀΠȯÀÚ¿¡¼ ¹«Áõ»óÀ̰í ALT°¡ Á¤»óÀ̶ó ÇÏ´õ¶óµµ Á¶Á÷°Ë»ç¸¦ Çϸé
1/3 - 1/4¿¡¼ chronic hepatitis¼Ò°ßÀ» º¸ÀδÙ.
- hepatic decompensationÀÌ 10³âÈÄ 15%¿¡¼ ¹ß»ýÇÏÁö¸¸ ´ëºÎºÐ(60%)Àº Áõ»óÀÌ ¾øÀ¸¸ç
well-compensated, no clinical sequalae¸¦ º¸À̰í very slowly progressionÇÑ´Ù.
- 1/4Àº °á±¹ end-stage cirrhosis·Î ÁøÇàÇÑ´Ù.
* ProgressionÀÌ ÃËÁøµÇ´Â °æ¿ì
older age
larger duration : most important
advanced histologic grade & stage
genotype 1b
more complex quasispecies, hepatic iron¡è => longer duration¹Ý¿µ
* Best prognostic indicator : liver histology
limited fibrosis, mild necrosis, inflammation
=> excellent Px, limited progression to cirrhosis
moderate to severe necroinflammatory activity or fibrosis(septal or bridging fibrosis)
=> 10-20³âµ¿¾È ¼¼È÷ °£°æº¯À¸·Î ÁøÇà
* Compensated cirrhosis
10 YSR = 80%
mortality : 2-6% / year
decompensation rate : 4-5% / year
HCC : 1-3% / year
2. ÀÓ»óÀû Ư¡
¸¸¼º BÇü °£¿°°ú À¯»çÇϸç fatigue°¡ °¡Àå ÈçÇϰí jaundice´Â µå¹°´Ù.
immune-complex mediated extrahepatic complicationÀº ¸¸¼º BÇü °£¿°º¸´Ù ´ú ÈçÇÏ´Ù.
( essential mixed cryoglobulinemia´Â Á¦¿Ü)
Sjogren's syndrome, lichen planus, porphyria cutanea tarda
3. Lab
- aminotransferase level fluctuationÀÌ ´õ ÈçÇÏ´Ù.
(characteristic episodic pattern of aminotransferase activity)
- °¡²û È¥µ¿½º·± ¼Ò°ßÀÌ º¸À̴µ¥ ¹Ù·Î autoantibody°¡ Á¸ÀçÇÏ´Â °ÍÀÌ´Ù.
µå¹°°Ô autoimmune hepatitis & hyperglobulinemiaȯÀÚ¿¡¼ EIA»ó anti-HCV°¡ À§¾ç¼ºÀÌ
³ª¿À´Â °æ¿ìµµ ÀÖ´Ù.
* circulating anti-LKM(+) : autoimmune hepatitis type 2ȯÀÚ¿¡¼µµ ¹ß°ßµÊ
anti-LKM1ÀÇ Á¸Àç´Â autoimmunity°¡ pathogenesis¿¡ ±â¿©ÇÔÀ» ÀǹÌ.
4. Ä¡·á
1) Interferon monotherapy
- biochemical response(ALT normalize)¿Í virological response(undetectable HCV RNA)
°¡ 30%
- relapse rate : 90%(¼Ò¼ö¸¦ Á¦¿ÜÇϰí´Â Ä¡·á Áß´ÜÈÄ ¹ÝÀÀÀÌ Áö¼ÓÇÏÁö ¾Ê´Â´Ù)
- 6°³¿ù Ä¡·áÈÄ sustained response: 10%
- Ä¡·áÁ¾°áÈÄ response°¡ ¾ø´õ¶óµµ histologic response´Â 3/4¿¡¼ ÀÖ´Ù.
(ÁÖ·Î periportal & lobular activity¡é)
- hepatitis B¿Í ´Þ¸® chronic hepatitis C¿¡¼´Â Ä¡·á¿¡ ´ëÇÑ ¼º°øÀûÀÎ ¹ÝÀÀÀÎ
transient acute hepatitis-like aminotransferase elevationÀÌ ¾ø´Ù.
¹Ý´ë·Î ALT levelÀÌ ¶³¾îÁø´Ù. ¹ÝÀÀÀ» º¸ÀÌ´Â 85-90%°¡ ù 3°³¿ù¿¡ ÀϾ¸ç ±× ÈÄÀÇ
¹ÝÀÀÀº µå¹°´Ù.
¢¼ NIH Consensus Development Conference in 1997 ¢¼
3°³¿ù±îÁö ALTÁ¤»óÈ ¹× HCV RNAÀ½¼ºÀÌ ÀÌ·ç¾îÁöÁö ¾ÊÀ»¸é Ä¡·á¸¦ Áß´ÜÇϵµ·Ï ÇÑ´Ù.
- ¼Ò¼ö(10%)¿¡¼ Ä¡·áµµÁß "Breakthrough"¸¦ °æÇèÇϸç nonresponder·Î ºÐ·ùÇÑ´Ù.
ÀÌ·± °æ¿ì ÀϹÝÀûÀ¸·Î ÀçÄ¡·á¿¡ ¹ÝÀÀÀÌ ¾ø´Ù.
* BreakthroughÇö»óÀÇ ±âÀü
i) interferon Ab »ý¼º
ii) HCV genome mutation
* Responseness¡è
i) brief duration
ii) low HCV quasispecies diversity
iii) immunocompetence
iv) low titer iron level
high level of HCV RNA
histologically advanced liver disease
high quasispecies diversity
=> advanced duration°ú »ó°ü°ü°è(+)
* Duration : interferon¹ÝÀÀ¿¡ °ü°èµÇ´Â single most important variable
- ¹ÝÀÀ·üÀ» ³ôÀÌ´Â °¡Àå È¿°úÀûÀÎ ¹æ¹ýÀº 12°³¿ù ÀÌ»ó Ä¡·áÇÏ´Â °ÍÀÌ´Ù.
À̶§ sustained response = 20%
- higher dose interferon(500-1000¸¸ U) or daily injectionÇÒ ¶§ ¹ÝÀÀ·üÀ» ¾à°£ »ó½ÂÇÏÁö¸¸
ºñ¿ëÀÌ ¸¹ÀÌ µé°í ȯÀÚ°¡ µû¶ó¿ÀÁö ¸øÇÑ´Ù. ±×·¯¹Ç·Î interferon monotherapy¸¦ Çϱâ·Î
°áÁ¤µÇ¸é 300¸¸ U X 12°³¿ù ¿ä¹ýÀÌ ¼±È£µÈ´Ù.
- long-acting interferon(PEG¿¡ °áÇÕ½ÃŲ °Í) - 7¹è Áö¼ÓÇϸç ÀÏÁÖÀÏ¿¡ Çѹø Åõ¿©·Î
interferon-ribavirinº´ÇÕÄ¡·á¿Í ºñ½ÁÇÑ ¼ºÀûÀ» °¡Áø´Ù.
- ÀçÄ¡·áÇϸé ÀϺο¡¼ high-dose·Î ÇßÀ» ¶§ 13%ÀÇ sustained response¸¦ º¸ÀÌÁö¸¸
interferon monotherapy·Î´Â ´õ ÀÌ»ó ¹ÝÀÀ·üÀÌ Áõ°¡ÇÏÁö ¾Ê´Â´Ù.
2) Interferon-Ribavirin combination Tx
IFN + Ribavirin 1000mg(<75kg) - 1200mg(>75kg) / day
: end-treatment response¡è, sustained response¡è
end-treatment response > 50%
sustained response : 6mo - 33%, 12mo - 41%
monotherapyº¸´Ù 2¹è È¿°úÀû.
+- Viral load¡é(2¹é¸¸ copies/ml)
| Genotype non-1
| Minimal fibrosis
| 40¼¼¡é
+- ¿©¼ºÀÎ °æ¿ì sustained response´Â ´õ ³ô´Ù(ÃÖ°í 95%).
24ÁÖ Ä¡·á°¡ 1³â Ä¡·á¿Í µ¿ÀÏÇÔ.
* combination treatment°¡ chronic hepatitis CȯÀÚÀÇ Ä¡·á¿¡¼ choice!!
6°³¿ù°£ monotherapyÈÄ Àç¹ßÇÑ È¯ÀÚ¿¡¼ 6°³¿ù°£ÀÇ combination Tx¸¦ ÇßÀ» ¶§
sustained response rate = 50%
interferon nonresponder¿¡¼´Â È¿°ú¾ø´Ù.
* RibavirinÀÇ ºÎÀÛ¿ë°ú ±Ý±â
i) hemolysis : Hb 2-3gm¡é(Hct 5-10%)
¡Å CBC monitoring
anemia, hemoglobinopathy°¡ ÀÖ´Â °æ¿ì³ª ºóÇ÷ÀÌ coronoary artery disease³ª
cerebrovascular diseaseÀÇ ischemic event¸¦ ¾ÇȽÃŰ´Â °æ¿ì¿¡´Â ±Ý±âÀÌ´Ù.
ii) renal excretion: renal insufficiency¶§´Â ±Ý±â
iii) teratogenic : ÀÓ»êºÎ´Â »ç¿ëÇÏÁö ¾Ê°Å³ª ÇÇÀÓÇϵµ·Ï ÇÑ´Ù.
iv) nasal congestion, pruritus, goutÃ˹ß
3) Indications Tab297-6
- Interferon Tx course´Â ¹Ý¼ö¿¡¼ ¸¸¼ºÈ¸¦ °¨¼Ò½ÃŲ´Ù.
- Compensated cirrhosisµµ Ä¡·á¿¡ ¹ÝÀÀÇÏÁö¸¸ sustained response°¡ ³·´Ù.
- HCCºóµµµµ °¨¼Ò½ÃŲ´Ù.
- liver transplantationÈÄ morbidity, allograft loss or mortality°¡ °ÅÀÇ ¾ø´Ù.
- cutaneous & renal vasculitis of HCV-associated essential mixed cryoglobulinemiaµµ
IFN¿¡ ¹ÝÀÀÇÏÁö¸¸ Ä¡·áÁßÁöÈÄ Áö¼ÓÀûÀÎ ¹ÝÀÀÀº µå¹°´Ù.
- antiviral therapy°¡ È¿°úÀûÀÎ °æ¿ì
: porphyria cutanea tarda, lichen planus associated with hepatitis C
- HIV infection : CD4 count°¡ Á¤»óÀ̸é Ä¡·á¼ºÀûÀº ´Ù¸¥ ±×·ì°ú µ¿ÀÏÇÏ´Ù.