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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¸¦ ¾ÇÈ­½ÃŰ´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.