1. 간질환의원인에상관없이만성간질환은간경변으로진행하며간세포암발생의위험성이높다. 2. 만성간질환의원인이 2 가지이상중복되는경우, 간경변으로의진행이빠르고간세포암의발생위험성증가 2

간담도계질환의이해 가톨릭대학교의과대학성모병원내과 한준열 1

( 간 ) 비장종대식도정맥류문맥압항진복수혼수등 ( 간동맥 ) ( 문맥 ) : 5-10 mmhg ( 담낭 ) ( 담관 ) 3

간의위치 4

간의혈액공급 6

간의혈액공급 간동맥 (hepatic artery) - oxygen rich - 25% 문맥 (portal vein) - nutrient rich - 75% - 5-10 mmhg 7

2006 년사망원인통계연령별사망원인순위 연령 1 위 2 위 3 위 4 위 5 위 전체 암 뇌혈관질환 심장질환 당뇨병 자살 65909(134.8) 30036(61.4) 20282(41.5) 11600(23.7) 10688(23.0) <1세 출생전후기질환 선천기형 영아급사증후군 암 심장질환 857(204.4) 338(80.6) 77(18.4) 21(5.0) 16(3.8) 1~9세 운수사고 암 선천기형 익수사고 추락사고 232(4.5) 166(3.2) 87(1.7) 47(0.9) 42(0.8) 10대 운수사고 자살 암 익수사고 심장질환 357(5.3) 233(3.5) 227(3.4) 76(1.1) 44(0.7) 20대 자살 운수사고 암 심장질환 타살 1044(13.8) 744(9.8) 418(5.5) 157(2.1) 96(1.3) 30대 암 자살 간및운수사고간내담관암 심장질환 간질환 1634(18.6) 1480(16.8) 854(9.7) (2.8) 433(4.9) 409(4.7) 40대암자살간질환간뇌혈관질환및간내담관암운수사고수막 5506(65.4), 뇌및기타 2093(24.9) 1894(22.5) 1323(15.7) (18.4) 1320(15.7) 50대중추신경계통의암뇌혈관질환간질환간및심장질환간내담관암자살악성신생물 10400(192.2) (3.0) 2190(40.5) 2104(38.9) 1945(35.9) (51.3) 1817(33.6) 60대 암 뇌혈관질환 심장질환 당뇨병 자살 17465(471.8) 5439(146.9) 3437(92.8) 2855(77.1) 1744(47.1) >70세 암 뇌혈관질환 심장질환 당뇨병 만성하기도질환 30070(1108.8) 20657(761.7) 12937(477.0) 6788(250.3) 5717(210.8) 8

30.0 간질환과간암의사망률추이, 1996-2006 년 25.0 20.0 15.0 간질환간암 10.0 5.0 0.0 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 9

악성신생물의사망률추이, 1996-2006 년 35.0 30.0 25.0 20.0 15.0 10.0 5.0 입술, 구강및인두암식도암위암대장암간암췌장암후두암폐암유방암자궁암 1) 전립샘암 2) 방광암뇌암백혈병 0.0 1996 1998 2000 2002 2004 2005 2006 10

2006 년악성신생물원인별사망 120.0 100.0 80.0 60.0 40.0 위의악성신생물 결장, 직장및항문의악성신생물간및간내쓸개관 ( 담관 ) 의악성신생물췌장 ( 이자 ) 의악성신생물 기관, 기관지및폐의악성신생물 20.0 0.0 20 30 40 50 60 11

남자에서의 10 대암의발생분율 여자에서의 10 대암의발생분율 12

2002 년도한국중앙암등록사업연례보고서 13

15 Suh DJ.Intervirology 2006;49:70 75

Fig. 2. Fibrosis progression according to gender. Panel A: transition rates to cirrhosis (stage 4) in females. Panel B: transition rates to cirrhosis in males. Panel C: transition rates to septal fibrosis (stage 2) in females. Panel D: transition rates to septal fibrosis in males. Poynard T et al. Journal of Hepatology 38 (2003) 257 265 남자에비하여여자에서의 Fibrosis progression: Slower: HBV, HCV, Genetic hemochromatosis, Primary biliary cirrhosis Rapid : Alcoholic liver disease 16

Gender-specific incidence of liver cancer in the world. Data on age standardized incidence of liver cancer was obtained from Cancer Incidence in Five Continents Vol. Ⅷ Shimizu I et al. World J Gastroenterol. 2007. 28;13: 4295 Hepatocellular carcinoma 의 incidence 가남자에비하여여자에서적다 17

Hepatocellular Carcinoma 세계적으로암발생 5 위, 암사망원인 3 위 지역적차이 * 동남아시아, 중국남부, 사하라남쪽아프리카 - 인구 10 만명당 20 명이상 * 북유럽, 북미, 영국, 호주 - 인구 10 만명당 5 명이하 우리나라 : 2006 년인구 10 만명당 22.4 명사망 - 남자 : 33.9/100,000; 여자 : 10.9/100,000 여자보다남자에흔함 (F:M=1:4) 대개 cirrhotic liver 에서발생 Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet 2003; 362: 1907 17 Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma. Lancet 2003; 362: 18 1907 17

Figure Incidence (per 100,000 population) of hepatocellular carcinoma (HCC) in the USA from 1976 to 1996 (from El-Serag and Mason 1999). 19

Liver Function 단백질합성 : 알부민, 응고인자 (II,V,VII,IX,X,XI,XII,XIII), 당단백 ( 세룰로프라스민, 알파 -1- 항트립신 ) 등 대사 : 지단백, 콜레스테롤, 호르몬, 탄수화물, 아미노산, 암모니아 생전환 : 해독작용 ( 지용성 à 수용성 ) Serum albumin Prothrombin time 담즙염생성과담즙형성 망상내피기능 기타 : Total & direct bilirubin Alkaline phosphatase Gamma-GTPGTP 20

간기능검사 (liver function test) 1. AST (SGOT) : hepatocyte injury 2. ALT (SGPT) : hepatocyte injury 3. ALP : bile flow interference 4. Total bilirubin : excretory function 5. Direct bilirubin : excretory function 6. Total protein : synthetic function 7. Albumin : synthetic function 8. Prothrombin time : synthetic function 9. Gamma-GTP : bile flow interference 21

Hepatocellular liver disease Intrahepatic cholestasis Extrahepatic cholestasis 22

간질환진단 원인진단 (diagnosis) 심한정도 (grading) 진행정도 (stage) 24

Liver Diseases Inherited hyperbilirubinemia Gilbert's syndrome Crigler-Najjar syndrome, types I and II Dubin-Johnson syndrome Rotor syndrome Viral hepatitis Hepatitis A Hepatitis B Hepatitis C Hepatitis D Hepatitis E Others (mononucleosis, herpes, adenovirus hepatitis) Cryptogenic hepatitis Immune and autoimmune liver diseases Primary biliary cirrhosis Autoimmune hepatitis Sclerosing cholangitis Overlap syndromes Graft-vs-host disease Allograft rejection Genetic liver diseases α 1 Antitrypsin deficiency Hemochromatosis Wilson's disease Benign recurrent intrahepatic cholestasis (BRIC) Familial intrahepatic cholestasis (FIC), types I-III Others (galactosemia, tyrosinemia, cystic fibrosis, Niemann-Pick disease, Gaucher's disease) Alcoholic liver disease Acute fatty liver Acute alcoholic hepatitis Laennec's cirrhosis Nonalcoholic fatty liver Steatosis Steatohepatitis Acute fatty liver of pregnancy Liver involvement in systemic diseases Sarcoidosis Amyloidosis Glycogen storage diseases Celiac disease Tuberculosis Myobacterium avium intracellulare Cholestatic syndromes Benign postoperative cholestasis Jaundice of sepsis Total parenteral nutrition (TPN)-induced jaundice Cholestasis of pregnancy Cholangitis and cholecystitis Extrahepatic biliary obstruction (stone, stricture, cancer) Biliary atresia Caroli's disease Cryptosporidiosis Drug-induced liver disease Hepatocellular patterns (isoniazid, acetaminophen) Cholestatic patterns (methyltestosterone) Mixed patterns (sulfonamides, phenytoin) Micro- and macrovesicular steatosis (methotrexate, fialuridine) Vascular injury Venoocclusive disease Budd-Chiari syndrome Ischemic hepatitis Passive congestion Portal vein thrombosis Nodular regenerative hyperplasia Mass lesions Hepatocellular carcinoma Cholangiocarcinoma Adenoma Focal nodular hyperplasia Metastatic tumors Abscess Cysts 25

Table 295-3 Important Diagnostic Tests in Common Liver Diseases Disease Diagnostic Test Hepatitis A Anti-HAV IgM Hepatitis B Acute HBsAg, anti-hbc IgM Chronic HBsAg, HBeAg and/or HBV DNA Hepatitis C Anti-HCV, HCV RNA Hepatitis D (delta) HBsAg, anti-hdv Hepatitis E Anti-HEV Autoimmune hepatitis ANA, SMA, IgG, liver biopsy Primary biliary cirrhosis AMA, IgM, liver biopsy Primary sclerosing cholangitis P-ANCA, cholangiography Drug-induced liver disease History Alcoholic liver disease History, liver biopsy Nonalcoholic steatohepatitis Ultrasound or CT, liver biopsy α 1 Antitrypsin disease α 1 antitrypsin, PiZZ or PiSZ Wilson disease ceruloplasmin, urinary Cu ; hepatic Cu Hemochromatosis iron saturation, ferritin ; HFE gene Hepatocellular cancer α-fetoprotein >500; ultrasound or CT 26

Grading of chronic hepatitis Descriptive Dx Score Lobular activity Porto-Periportal activity None 0 No necrosis < mild portal inflammation Minimal 1 Sinusoidal lymphocytosis mild portal inflammation +/- 1 or less necrosis per +/- focal PMN in a few 10x objective field portal tracts Mild 2 2 5 necrosis per 10x PMN, focal in some or objective field most portal tracts, or PMN, around < 50% in a few portal tracts Moderate 3 6 10 necrosis per 10x PMN, around < 50% in objective field most portal tracts, or PMN, around > 50% in a few or some portal tracts Severe 4 More than 10 necrosis per PMN, around > 50% in 10x objective field, or most portal tracts/ septal confluent necrosis (zone 3) surfaces, or bridging necrosis 27 대한병리학회소화기병리연구회

Staging of chronic hepatitis Descriptive diagnosis Score Definition No fibrosis 0 Normal connective tissue Portal fibrosis 1 Fibrous portal expansion Periportal fibrosis 2 Periportal fibrosis with short septa extending into lobules or rare portoportal septa (intact architecture) Septal fibrosis 3 Fibrous septa reaching adjacent portal tracts and terminal hepatic venule (architectural distortion but no obvious cirrhosis Cirrhosis 4 Diffuse nodular formation 28 대한병리학회소화기병리연구회

Table Child-Pugh Classification of Cirrhosis Factor 1 2 3 Serum bilirubin (mg/dl) <2.0 2.0-3.0 >3.0 Serum albumin (g/dl) >3.5 3.0-3.5 <3.0 Ascites None Easily controlled Poorly controlled Neurologic disorder None Minimal Advanced coma Prothrombin time second prolonged 0-4 4-6 >6 INR <1.7 1.7-2.3 >2.3 Child-Pugh class A : 5-6, B : 7-9, C : >10 29

Model for End-stage Liver Disease (MELD) Scoring Equation MELD score for TIPS = 0.957 log e (creatinine [mg/dl]) + 0.378 log e (bilirubin [mg/dl]) + 1.120 log e (INR) +.643 (cause of liver disease) [ ] MELD score for liver transplantation = 0.957 log e (creatinine [mg/dl]) + 0.378 log e (bilirubin [mg/dl]) + 1.120 log e (INR) +.643 30

QUANTITATIVE TESTS OF LIVER FUNCTION Indocyanine green clearance Galactose elimination capacity Aminopyrine breath test Antipyrine clearance Monoethylglycinexylidide (MEGX) Caffeine clearance 31

Features of Hepatitis A virus infection Incubation (days) 15 45, mean 30 Onset Acute Age preference Children, young adults Transmission Fecal-oral +++ Percutaneous Unusual Perinatal Sexual ± Clinical Severity Mild Fulminant 0.1% Progression to chronicity None Carrier None Cancer None Prognosis Excellent Prophylaxis IG Inactivated vaccine Therapy None 33

Figure 298-2 Scheme of typical clinical and laboratory features of hepatitis A. 34

Chronic hepatitis B Prevalence of chronic hepatitis B Chronic hepatitis B Cirrhosis 로사망 HCC 로사망 4 억명 20 만명 /yr 30 만명 /yr 35

Infection 시기에따른 chronic HBV 발생률 Perinatal infection 90% Infection in childhood 20 30% Infection in adulthood <1% 36

37 Joo KR et al. Kor J Gastroenterol 1999;33:642-652

Joo KR et al. Kor J Gastroenterol 1999;33:642-652 38

Jang MK et al. Korean J Med 58:608-615, 2000 39

핵 간세포 HBV is not direct cytopathic40

Mechanism of Hepatocyte Injury Liver Cirrhosis Fibrinogenesis Cellular Immune System Hepatocyte AST ALT Injury HLA Regeneration 41

만성 B 형간염의자연경과 10 8-10 12 10 6-10 10 10 4-10 8 <10 4 HBV DNA ( 바이러스양 ) HBeAg negative (precore) mutant ALT HBsAg (+) HBeAg (+) HBeAb ( ) 바이러스증식됨 경증간염 (+) (+) ( ) Funtioning Hepatocytes (hepatic reserve) 바이러스증식됨 활동성간염 (+) (+) Fibrosis à Cirrhosis ( ) ( ) ( /+) (+) 바이러스증식없음 관해, 간경변 ( ) ( ) (+) 면역관용기 면역제거기 융합기 resolved 0 10 20 30 40 50 60 70 세 42

HBeAg seroconversion [HBeAg(+) à HBeAg(-)] Seroconversion rate : 약 65% ALT 가증가한성인 : 10 15%/yr Caucasian adults: 10 년 follow-up 동안 90% (18%/yr) Spontaneous HBeAg seroconversion - older age - higher ALT - genotypes B (vs. C) & A (vs. versus D) - Asian이아닌 ethnicity 43

Reactivation in Inactive HBsAg carrier Inactive carrier: HBeAg (-), anti-hbe(+), HBV DNA<2000 IU/ml) HBeAg negative chronic hepatitis: 15 24% 1-3%/yr HBeAg positivity chronic hepatitis: 1 17% 44

Spontaneous HBsAg clearance Inactive carrier state에서의 Spontaneous HBsAg clearance low endemic areas (Caucasian): 1 2%/yr high endemic areas(perinatal): 0.05 0.8%/yr asymptomatic adult Chinese: cumulative rate 40% spontaneous HBsAg seroclearance와연관있는 factors: - older age - sustained remission 45

Cirrhosis incidence rates in chronic hepatitis B Clinical Geographic area No. Male Cirrhosis Status patients (%) incidence (%/yr) Asymptomatic carriers Taiwan 5077 72 0.9 Chronic hepatitis HBeAg positive Europe 77 69 3.8 Taiwan, Korea 1198 80 1.6 HBeAg negative Europe 30 85 g 9.7 Taiwan 62 79 2.8 Inactive carrier Europe 296 68 0.01 Taiwan 184 79 0.07 Fattovich G et al. J Hepatol. 2008, 48:335-352 46

Hepatocellular carcinoma incidence rates in chronic hepatitis B Clinical Geographic area No. males HCC incidence Status patients (%) (%/yr) Asymptomatic carrier Europe, North America 6089 73 0.04 Taiwan, China, Korea, Japan 27807 88 0.5 Inactive carrier Europe 364 79 0.02 Taiwan 189 79 0.2 Chronic hepatitis Europe, United States 732 77 i 0.3 Taiwan, China, Korea, Japan 5661 70 0.6 Compensated cirrhosis l Europe, United States 540 82 2.2 Taiwan, Singapore, Japan 1160 83 3.7 Fattovich G et al. J Hepatol. 2008, 48:335-352 47

Liver-related death rates in chronic hepatitis B infection Clinical Geographic area No. males Liver-related Status patients (%) death rate (%/yr) Asymptomatic carrier Europe, North America 6181 73 0.09 Taiwan, China, Japan 6690 84 0.8 Inactive carrier Europe 387 79 0.03 Chronic hepatitis Europe 105 76 0 China 246 84 0.6 Compensated cirrhosis Europe 179 89 3.3 Taiwan, China, Japan 410 84 2.9 Fattovich G et al. J Hepatol. 2008, 48:335-352 48

Clevudine Terrault NA. Semin Liver Dis. 2007;27(S1):18-24 49

Chronic hepatitis C v 만성감염자수 전세계 :1 억 7 천만명 ( 전체인구의약 3%) 미국약 3 천 200 만명 ( 전체인구의약 1.3%) v 대개우연히발견 v 전파 : Blood v 효과적인백신이없다 v 1992 년 : 효과적인 HCV tests 개발 v 미국 : 1990 년에비하여 2015 년에 HCV 로인한 chronic liver disease 가 4 배증가할것으로추정 50

Suh DJ.Intervirology 2006;49:70 75 51

Maheshwari A et al. Lancet 2008; 372: 321 32 53

Outcomes in persons who develop hepatitis C infection. Seeff LB, Am J Med. 1999;107(6B): 10S 15S. 54

C 형간염에대한 Screening 을해야하는경우 Unexplained abnormal aminotransferase levels Children born to HCV-infected mothers Needle stick or mucosal exposure to HCV(+) blood Current sexual partners of HCV-infected persons AASLD guideline. Strader DB et al. Hepatology. 2004; 39:1147-1171 55

Diagnosis Screening: Anti-HCV (+) Diagnosis: HCV RNA PCR (+) * HCV(+) mother 의 Infants: 생후 15 개월이전에는 maternal antibody 때문에 EIA 검사에서는 false-positive 일수있다 * 빨리진단을해야하는경우생후 1-2 개월에 PCR test 를한다 Anti-HCV(+), HCV RNA PCR(-) 인경우 - spontaneously cleared acute infection - autoimmune disease Anti-HCV Folse negative 인경우 - immune deficiencies - hemodialysis 56

Treatment 57

59 Suh DJ.Intervirology 2006;49:70 75

Alcoholic liver disease 여자는남자보다 alcoholic liver disease 의발생위험성이높으며, 더빨리진행한다. 여자 : 10-40 g/day 남자 : 40-80 g/day 10 년이상 Sleisenger 8 th ed. 알코올의양에대한일치하는견해나연구결과가없음. 개인차가크기때문에, 위의알코올양을모든사람에게적용될수는없음 AASLD: non-alcoholic fatty liver disease: < 20 g/d 60

Table 302-2 Complications of Cirrhosis Portal hypertension Gastroesophageal varices Portal hypertensive gastropathy Splenomegaly, hypersplenism Ascites Spontaneous bacterial peritonitis Hepatorenal syndrome Type 1 Type 2 Hepatic encephalopathy Hepatopulmonary syndrome Portopulmonary hypertension Malnutrition Coagulopathy Factor deficiency Fibrinolysis Thrombocytopenia Bone disease Osteopenia Osteoporosis Osteomalacia Hematologic abnormalities Anemia Hemolysis Thrombocytopenia Neutropenia 61

62 Suh DJ.Intervirology 2006;49:70 75

Surveillance for HCC in High-Risk Patients 대상 남자 30 세, 여자 40 세이상으로아래의위험인자를가지고있는대상자에게간암검진을권고함 - B 형또는 C 형간염바이러스에의한만성간질환환자 - 간경변및기타간암발생고위험군 검진주기 : 6 개월 검진방법 : 복부초음파검사와혈청알파태아단백 64

Imaging procedures 초음파검사 : ultrasound 초음파검사, CT, MRI, 간동맥조영술 초음파검사 - Surveillance for high-risk populations - 간암의심환자에서의첫검사 비교적싸고, sensitive 65

전산화단층촬영 (CT) 동맥상 (arterial phase) 초기 : 조영증강 문맥상 (portal phase): 조영증강을보이지않는 hypodense 종양진단과병기결정 (staging): 초음파검사보다정확 조영증강으로민감도증가 간문맥침범을진단할수있음 Lipiodol CT: 진단하는데가장민감한방법은간동맥조영술후 lipiodol 을주입하고, 2-3 주후 CT 로간내 lipiodol 을확인하는것으로 0.2-0.3cm 크기의작은종양까지확인이가능하다. 67

자기공명영상 (MRI) T1 영상 : 저음영 T2 영상 : 고음영 조영증강 CT 보다우수하지않음 최근에는 superparamagnetic iron oxide (SPIO), mangafodipir trisodium, gadobenate dimeglumine 등을이용한조영증강 MRI 로간암의진단민감도향상 지방간이동반되어있을때유용 70

치료 외과적절제술 : 가장이상적인치료 - 절제가능한경우가매우적음 (3-30%) 간이식 : 재발과전이가잦음 국소치료법 : - 경피적알코올주사 (percutaneous ethanol injection) - 극초단파응고술 (microwave coagulation) - 경피적고주파열치료 (percutaneous radiofrequency) - 냉동제거술 (ultrasound guided cryoablation) - cyberknife, tomotherapy 등방사선치료 - HIFU - 간동맥색전술 (trans-catheter arterial embolization) 화학요법, 면역요법, 유전자치료등 72

급성 B 형간염 (Acute hepatitis B) 전파 : 혈액 일부는만성간염으로이행 효과적인백신이있음 임신중의급성 B 형간염경과 : 임신하지않은경우와동일 급성간염은대부분 6 개월이내에완치 태아에게전염될위험성 : 감염시기 - 1st trimester: 태아의전염위험성적음 - 2nd or 3rd trimester: 신생아에게전염 Chronic HBV carrier 82

만성 B 형간염 (Chronic hepatitis B) 수직감염 : 대부분출생시발생 수직감염 : 대부분 Chronic HBV carrier 가됨 3rd trimester 의급성 B 형간염과, chronic HBV carrier mother à 출생즉시신생아에게면역글로부린 (HBIG) + B 형간염백신 HBIG + B 형간염백신 : 5-10% 에서만수직감염 Infection 의 source 가됨 Infant 만성간염, 간경변, 간암등공중보건문제 83

만성 B 형간염 (Chronic hepatitis B) Mother 임신중의경과는임신하지않은경우와동일 임신중에악화되는경우는자연경과임 모유 : HBIG과백신을시작한신생아에게는모유수유 임산부에서도 B형간염백신을할수있음 84

RISK FACTORS 1. 1992 년전에 transfusions 이나 transplants 를받은사람 2. Injection drug use 3. Sexual transmission: controversial Terrault NA. (Hepatology. 2002;36:S99-105) Monogamous partnerships: 0-0.6% / yr : minimal risk Multiple partners: 0.4-1.8% /yr : unreported injectiondrug use? 85

4. Mother-to-child transmission Perinatal transmission Average infection rate: 5-6% High HCV-RNA levels: 17% HIV와 coinfected mothers: 14% * HCV-RNA: 출생 2-3 개월이내에 detect됨 * HCV infected children: - symptoms이나타나거나 liver enzymes이증가하는경우는드물다. - 심한 liver disease로 progression하는것이성인보다늦다. 86

5. Household transmission 가족들사이의 nonsexual transmission Percutaneous or permucosal exposure Nonsexual household contacts: 평균 4% Controversial 87

Nosocomial transmission 6. needle stick or sharp exposure: 1.8% (0-7%) Puro V et al. (Am J Infec Cont. 1995;23(5):273 277) - Hollow-bore needle injury: 1.2% - Sharp objects injuries: no - Mucosa or nonintact skin 의 contamination: no 7. Hemodialysis: 평균 10% 8. Iatrogenic HCV: unsafe therapeutic injection practices - contaminated multiple-dose medication vials - saline bags from reinsertion of used syringes - 혈당검사기 : spring-loaded finger-stick devices * 대부분선진국에서발생 88

Counseling * Risk factor 가없는 pregnant women: HCV routine testing 은하지않는다 임신중이거나임신을고려중인 HCV(+) women 1. Pregnancy 나 breastfeeding 을피할필요없음 2. Perinatal infection rate: 약 5% - 예방법없음 - Cesarean vs. Vaginal delivery: 차이없음 3. HCV(+) infants 와 children - adults 보다 symptoms 이적음 - liver disease 는더서서히발생 - 성인보다 HCV 의 spontaneous clearance 가더흔함 4. Nipples 손상이나출혈 : breastfeeding 중단을고려 5. Breastfeeding 은 HCV 를 transmit 하지않는것으로생각됨 (*) 89

정상적인부부생활 전염위험성이낮다 이미오랫동안부부생활을한사람에서 sexual practices 를바꿀필요는없다. 즉 condoms 같은 barrier forms 의 protection 을시작할필요가없다. 단, multiple sexual partners, short-term relationships: risk 가높다 90

HCV (+) 인사람 다른사람에게전염되는것을최소화 다른사람에게 blood 의접촉예방 - cover any bleeding wound - toothbrushes and dental or shaving equipment sharing 금지 Blood, organs, tissues, semen donation 금지 Injection drug user: stop - syringes, needles, water, cotton 등의재사용이나 sharing 금지 - clean the injection site with a new alcohol swab - dispose safely of syringes and needles after one use 91

Alcohol: HCV와 synergistic effects가있기때문에금주 Weight control: Fatty liver는 HCV liver disease의 progression과연관 - body mass index >25 kg/m 2 : 체중조절필요 HBV & HAV vaccination: Fulminant hepatitis 와 coinfection 의 risk 92

Hormonal Therapy in Postmenopause 93

남자보다여자에서 HBe seroconversion 이더흔하다 HBeAg à anti-hbe; HbsAg àanti-hbs (Alward WL et al. J Infect Dis 1985; 151: 604-609, Zacharakis GH et al. J Med Virol 2005; 77: 173-179) 여자는남자보다 cellular and humoral immune reactions 이강하다 - autoimmune diseases 의 incidence 가높다. (Ansar Ahmed S et al. Am J Pathol 1985; 121: 531-551, Grossman CJ. Science 1985; 227: 257-261) Estradiol: - lymphocytes에서 interferon (INF)-γ production을 induce (Fox HS et al. J Immunol 1991; 146: 4362-4367) - human PBMC 에서 antigen-specific primary antibody response 를증진 (Clerici E et al. J Clin Lab Immunol 1991; 34: 71-78) * IFN-γ: immunomodulatory and antiproliferative properties à 여자가남자보다 HBeAg 과 HBsAg 에대한 antibodies 를더잘생성 ( 특히 menopause 전 ) 94

Oxidative stress Estradiol 은 liver 와 serum 에서 lipid peroxide levels 을감소시키는 strong endogenous antioxidants 이다. 95

Estrogens and Hepatic Fibrosis Estradiol Male rats 의 hepatic fibrosis model - hepatic fibrosis 를억제 - collagen 감소, procollagen typeⅠ 과 Ⅲ mrna expression 감소 Yasuda M et al. Hepatology 1999;29:719-727 Shimizu I et al. Gut 1999; 44:127-136 Lu G et al. Life Sci 2004; 74:897-907 Male rats 에서 estradiol 에대한 neutralizing antibody 투여 - fibrogenesis 가 enhance Female rats 에서 ovarectomy - fibrogenesis 가 enhance Yasuda M et al. Hepatology 1999; 29: 719-727 96

Non-alcoholic fatty liver disease Prevalence of NAFLD by age and gender Visceral fat이 subcutaneous fat보다더 harmful Menopausal women: estrogen 이낮으면 subcutaneous fat loss, visceral fat을 gain Male-to-female transsexuals: estrogen treatment à subcutaneous fat 증가 Estrogen으로 treated한 women은 adipose tissue의 visceral accumulation이낮다 Tamoxifen: fatty liver와 NASH의 risk를증가 97

Females and HCC Comparison of male-to-female ratio between two age groups of HBV related HCC patients without HCV infection Rats 의 chemical hepatocarcinogenesis 에서 estradiol 이 suppressive effect Shimizu I et al. Gut 1998; 42: 112-119 98

A 형간염 (Hepatitis A) 만성간염으로이행하지않음 임신중의경과 : 임신하지않은환자와동일 전파 : 대변 - 경구감염 거의대부분후유증없이치유 : 드물게전격간염 주산기감염은매우드물다 임신중에도필요한경우에는 A 형간염백신과면역글로부린을투여 모유제한필요없음 99

A 형간염 (Hepatitis A) (2) 임신의경우특별한조치필요없음 전파경로 : 대변 - 경구감염 신생아를통한감염이가장흔함 임신말기에감염된경우, 타인에게전파예방을위한조치필요 100