Hepatitis A 소화기 내과 R4 박재현

INTRODUCTION Hepatitis A virus is a 27 nm, nonenveloped, icosahedral, heat-,acid- and ether-resistant RNA virus classified in the Hepatovirus genus of the Picornaviridae family.

EPIDEMIOLOGY

연도별 발생현황 연령별 발생현황 2009 년 1 월부터 5 월까지 5200 명 발생 !

우리나라 지역별 발생 현황

Age and Gender Distribution in Patients with Acute Hepatitis A (KMC) Age and Gender Distribution in Patients with Acute Hepatitis A (KMC)

Annual Incidence of Acute Hepatitis A from 1996 to 2009 (KMC)

Comparison of Mean Age (KMC) Comparison of Mean Age (KMC) p < 0.05

급성 바이러스성 간염 Etiology of acute viral hepatitis in Seongnam area, 2006~2007 (N:245)

최근 A 형 간염의 폭발적 증가 원인은 ? 우리나라 성인의 연령별 A 형 간염 항체 보 유율 외식 ? 해외여행 ? 외국인의 유입 증가 ?

spread via the fecal-oral route more prevalent in low socioeconomic areas Human is only reservoir EPIDEMIOLOGY EPIDEMIOLOGY

PATHOGENESIS Injury to the liver is secondary to the host's immune response. Panlobular infiltration of mononuclear cells, hyperplasia of Kupffer cells, hepatic cell necrosis, variable degree of cholestasis.

CLINICAL MANIFESTATION Acute, self-limited illness and only rarely leads to fulminant hepatic failure Manifestations also vary with age 1)Usually silent or subclinical in children 2)Vary in severity from a mild flu-like illness to fulminant hepatitis in adult Incubation period : averages 30 days Prodromal symptom :fatigue, malaise, nausea, vomiting, anorexia, fever, and right upper quadrant pain

CLINICAL MANIFESTATION Two most common physical examination findings; jaundice and hepatomegaly Laboratory findings 1) marked elevations of serum aminotransferases (usually >1000 IU/dL), serum total and direct bilirubin, and alkaline phosphatase 2) ALT>AST 3) aminotransferase elevations precede the bilirubin elevation 4) Serum bilirubin levels above 10 mg/dL are uncommon

우리나라 급성 A 형간염 환자의 임상 양상 내원 당시 IgM anti-HAV 가 음성이 었으나 추적 검사에서 양성으로 나와 A 형간염으로 진단된 경우가 15 예 (6.7%) 였으며, 이들에서는 내원 당시 발열 (80%) 및 복부 통증 (54%) 등의 증상이 더 빈번하였다.

CLINICAL MANIFESTATION

Diagnosis : Serum IgM anti-HAV is the gold standard HAV detection is possible in stool and body fluids by electron microscopy and HAV RNA detection in stool, body fluids, serum, and liver tissue. IgM anti-HAV antibodies in adults without clinical features of viral hepatitis does not necessarily indicate acute infection..

TREATMENT AND PROGNOSIS Treatment is supportive. Patients who develop fulminant infection require aggressive supportive therapy, and should be transferred to a center capable of performing liver transplantation. 85 percent of individuals with hepatitis A have full clinical and biochemical recovery within three months. Fatality rates are 0.1 percent in infants and children, 0.4 percent between the ages of 15 and 39, and 1.1 percent in those over age 40. (Centers for Disease Control. Hepatitis Surveillance Report 1990; 53:23 )

ATYPICAL MANIFESTATION 1)Cholestatic hepatitis -Marked elevation of the serum bilirubin (often >10 mg/dL) and alkaline phosphatase, an elevated serum cholesterol, minimal elevation of serum aminotransferases - Duration: more than 12 week - Treatment Supportive Corticosteroid (30mg/day)  Gastrointestinal and Liver Disease, p.1129 Cholestyramine

ATYPICAL MANIFESTATION 2) Relapsing hepatitis -The clinical course is usually preceded by an apparent full clinical recovery with near normalization of the serum aminotransferases lasting 4 to 15 weeks, followed by biochemical and, in some cases, clinical relapse, which is often milder than the initial episode. -Incidence : 6~10 % -HAV can frequently be recovered from stool during relapse. - The prognosis in the relapsing form of hepatitis A is excellent.

ATYPICAL MANIFESTATION 3)ARF - 기전 : Prerenal type ATN : hyperbilirubinemia retention of bile salt virus-induced endotoxemia Nephron Clin Pract 2008;109:c127–c132 ARF : 12/208 (5.7%) HD : 8/12 (66%)

ATYPICAL MANIFESTATION 4)Fulminant hepatitis - incidence : < 1% -The consequence of severe liver injury complicated by the development of hepatic encephalopathy within 8 weeks of the onset of the jaundice. -Fatality rate of fulminant hepatitis is about 50~80%. -Long-term survival after liver transplantation of patients with fulminant hepatitis has been relatively poor in comparison with survival after liver transplantation for other conditions.

전격성 간염의 생존 예측인자 HEPATOLOGY 2006;44:

ATYPICAL MANIFESTATION 4) EXTRAHEPATIC MANIFESTATIONS Leukocytoclastic vasculitis Glomerulonephritis Arthritis Cryoglobulinemia Toxic epidermal necrolysis Myocarditis Optic neuritis Transverse myelitis Thrombocytopenia Aplastic anemia Red cell aplasia

VACCINATION AND PROPHYLAXIS Vaccination indication 1) A 형간염 유행지역을 여행하거나 유행지역에서 군인으로 복무할 경우 2) 만성간질환 환자 3) 혈우병환자 4) 마약중독자나 동성연애자 5) 직업적으로 A 형간염에 노출되는 실험실 종사자

VACCINATION AND PROPHYLAXIS Recommended Dose, Schedules of Inactivated Hepatitis A Vaccines Available in Korea

World Health Organization (WHO) states that “travelers should be vaccinated 4 weeks before departure if possible.” The Centers for Disease Control and Prevention(CDC) recommend that “travelers who need optimal protection earlier than 4 weeks after the first dose of vaccine should also receive immune globulin with the first vaccine dose.”

POSTEXPOSURE PROPHYAXIS Standard : IG 0.02mL/kg N Engl J Med 2007;357: