Viral Hepatitis

General

Clinically characterized by malaise, nausea, vomiting, diarrhea, and low-grade fever followed by dark urine, jaundice, and tender hepatomegaly; may be subclinical and detected on basis of elevated aspartate and alanine aminotransferase (AST and ALT) levels. Hepatitis B may be associated with immune-complex phenomena, including arthritis, serum-sickness뻦ike illness, glomerulonephritis, and polyarteritis nodosa. Hepatitis-like illnesses may be caused not only by hepatotropic viruses (A, B, C, D, E) but also by other viruses (Epstein-Barr, CMV, coxsackievirus, etc.), alcohol, drugs, hypotension and ischemia, and biliary tract disease (Table 155-1).

Hepatitis A (HAV)

27-nm picornavirus (hepatovirus) with single-stranded RNA genome.

? ? Clinical Course

? See Fig. 155-1.

? ? Outcome

? Recovery within 6?2 months, occasionally after one or two apparent clinical and serologic relapses; in some cases, pronounced cholestasis suggesting biliary obstruction may occur; rare fatalities (fulminant hepatitis), no chronic carrier state.

? ? Diagnosis

? IgM anti-HAV in acute or early convalescent serum sample.

? ? Epidemiology

? Fecal-oral transmission; endemic in underdeveloped countries; food-borne and waterborne epidemics; outbreaks in day-care centers, residential institutions.

? ? Prevention

? After exposure: immune globulin 0.02 mL/kg IM within 2 weeks to household and institutional contacts (not casual contacts at work). Before exposure: inactivated HAV vaccine 1 mL IM (unit dose depends on formulation); half dose to children; repeat at 6?2 months; target travelers, military recruits, animal handlers, day-care personnel.

Hepatitis B (HBV)

42-nm hepadnavirus with outer surface coat (HBsAg), inner nucleocapsid core (HBcAg), DNA polymerase, and partially double-stranded DNA genome of 3200 nucleotides. Circulating form of HBcAg is HBeAg, a marker of viral replication and infectivity. Multiple serotypes and genetic heterogeneity.

? ? Clinical Course See Fig. 155-2.

? ? Outcome

? Recovery >90%, fulminant hepatitis (<1%), chronic hepatitis or carrier state (only 1?% of immunocompetent adults; higher in neonates, elderly, immunocompromised), cirrhosis, and hepatocellular carcinoma (especially following chronic infection beginning in infancy or early childhood) (see Chap. 157).

? ? Diagnosis

? HBsAg in serum (acute or chronic infection); IgM anti-HBc (early anti-HBc indicative of acute or recent infection). Most sensitive test is detection of HBV DNA in serum; not generally required for routine diagnosis.

? ? Epidemiology

? Percutaneous (needle stick), sexual, or perinatal transmission. Endemic in sub-Saharan Africa and Southeast Asia, where up to 20% of population acquire infection, usually early in life.

? ? Prevention

? After exposure: hepatitis B immune globulin (HBIg) 0.06 mL/ kg IM immediately after needle stick, within 14 days of sexual exposure, or at birth (HbsAg+ mother) in combination with vaccine series. Before exposure: recombinant hepatitis B vaccine 10?0킽 IM (dose depends on formulation); half dose to children, 40-킽 dose for hemodialysis patients and immunocompromised adults; at 0, 1, and 6 months; deltoid, not gluteal injection. Has been targeted to high-risk groups (e.g., health workers, gay men, IV drug users, hemodialysis pts, hemophiliacs, household and sexual contacts of HBsAg carriers, all neonates in endemic areas, or high-risk neonates in lower-risk areas). Universal vaccination of all children is now recommended in the U.S.

Hepatitis C (HCV)

Caused by flavi-like virus with RNA genome of >9000 nucleotides (similar to yellow fever virus, dengue virus); some genetic heterogeneity. Incubation period 7? weeks.

? ? Clinical Course

? Often clinically mild and marked by fluctuating elevations of serum aminotransferase levels; >50% likelihood of chronicity, leading to cirrhosis in >20%.

? ? Diagnosis

? Anti-HCV in serum. Current second- and third-generation enzyme immunoassay detects antibody to epitopes designated C200, C33c, C22- 3; may appear after acute illness but generally present by 3? months after exposure. A positive enzyme immunoassay can be confirmed by recombinant immunoblot assay (RIBA) or by detection of HCV RNA in serum (Fig. 155-3).

? ? Epidemiology

? Percutaneous transmission accounts for >90% of transfusion-associated hepatitis cases. IV drug use accounts >50% of reported cases. Little evidence for frequent sexual or perinatal transmission.

? ? Prevention

? Exclusion of paid blood donors, testing of donated blood for anti-HCV. Anti-HCV detected by enzyme immunoassay in blood donors with normal ALT is often falsely positive (30%); result should be confirmed with RIBA, which correlates with presence of HCV RNA in serum.

Hepatitis D (HDV, Delta Agent)

Defective 37-nm RNA virus that requires HBV for its replication; either co-infects with HBV or superinfects a chronic HBV carrier. Enhances severity of HBV infection (acceleration of chronic hepatitis to cirrhosis, occasionally fulminant acute hepatitis).

? ? Diagnosis

? Anti-HDV in serum (acute hepatitis D뾬ften in low titer, is transient; chronic hepatitis D뾦n higher titer, is sustained).

? ? Epidemiology

? Endemic among HBV carriers in Mediterranean Basin, where it is spread predominantly by nonpercutaneous means. In nonendemic areas (e.g., northern Europe, United States) HDV is spread percutaneously among HbsAg+ IV drug users or by transfusion in hemophiliacs and to a lesser extent among HbsAg+ gay men.

? ? Prevention

? Hepatitis B vaccine (noncarriers only).

Hepatitis E (HEV)

Caused by 29- to 32-nm agent thought to be related to caliciviruses. Enterically transmitted and responsible for waterborne epidemics of hepatitis in India, parts of Asia and Africa, and Central America. Self-limited illness with high (10?0%) mortality rate in pregnant women.

Treatment

Activity as tolerated, high-calorie diet (often tolerated best in morning), IV hydration for severe vomiting, cholestyramine up to 4 g PO qid for severe pruritus, avoid hepatically metabolized drugs; no role for glucocorticoids. Liver transplantation for fulminant hepatic failure and grades III뻀V encephalopathy. Meta-analysis of small clinical trials suggests that treatment of acute HCV infection with -interferon may be effective at reducing the rate of chronicity. Based on these data, many experts feel that acute HCV infection should be treated with the best available regimens currently used to treat chronic HCV infection (see Chap. 156).

1. 간염 바이러스의 종류와 각 형(型)의 역학적 특징을 구분한다.

a. HAV : RNA virus / incubation (15-40, mean 30 days) / acute onset / children, young adults / fecal-oral (m/c) / mild severity, 0.1 % fulminant, no chronicity / no carrier, no cancer, excellent prognosis

b. HBV : DNA virus / incubation (30-180, mean 60-90 days) / insidious or acute onset / young adults (sexual and percutaneous), babies, toddlers/ percutaneous, perinatal, sexual / occasionally severe, 0.1-1 % fulminant, occasional chronicity (1-10 %, 90 % of neonates) / 0.1-30 % carrier, cancer (neonatal infection), worse prognosis with age, debility (쇠약)

c. HCV : RNA virus / incubation (15-160, mean 50 days) / insidious onset / any age, but more common in adults / percutaneous (m/c) / moderate severity, 0.1 % fulminant, common chronicity (50-70 % chronic hepatitis, 80-90 % chronic infection) / 1.5-3.2 % carrier, cancer , moderate prognosis

d. HDV : RNA virus / incubation (30-180, mean 60-90 days) / insidious or acute onset / any age (similar to HBV) / percutaneous, perinatal, sexaul / occasionally severe, 5-20 % fulminant, common chronicity (HBV와 HDV의 coinfection 시에는 HBV infection시와 유사;1-10 % 하지만, HDV superinfection시에는 invariable chronicity) / variable carrier, cancer (+/-), acute (good prognosis); chronic (poor prognosis)

e. HEV : RNA virus / incubation (14-60, mean 40 days) / acute onset / young adults (20-40 yrs) / fecal-oral / mild severity, 1-2 % fulminant (pregnant women에는 10-20 %), no chronicity / no carrier, no cancer, good prognosis

2. 간염 바이러스의 항원, 항체의 특성과 발현양상을 설명한다.

a. HAV : HAV Ag / anti-HAV (acute infection시기에 IgM anti-HAV, past infection 및 long-term immunity시기에 IgG anti-HAV)

b. HBV : ⑴ 3 types of HBV Ag particles : dane particle (완전입자; DNA와 DNA polymerase, HBc Ag, HBs Ag을 각각 1:1:1의 비율) / spherical and long filament (불완전 입자; HBs Ag을 불필요하게 너무 많이 만들어 속이 텅빈 외측 껍질만이 남게 된 것, 즉, 불완전 입자는 HBs Ag 그 자체이다) ⑵ antigen ① HBs Ag : HBV의 표면이기도 하고 불완전입자 그 자체이기도 하다. 현재 HBV에 감염되어 있다. 그러나, 간염이 완전히 소실되더라도 상당 기간 존재한다. 타인에 대한 감염력이 없을 수도 있다. (HBV carrier, not necessarily infective) ② HBc Ag : 혈액에는 존재하지 않고 간조직에만 존재하며, viral replication과 infectivity를 의미 ③ HBe Ag : 완전 입자에 편입되지 못한 HBc Ag을 의미하며, 감염세포가 바이러스를 방출하고 있음을 의미. HBe Ag은 단독으로 혈액중에 존재 가능하지만, HBc Ag은 단독으로 혈액에 존재할 수 없음. 즉, 혈액중에 바이러스가 대량으로 존재하여 타인에게 옮기기 쉽다. Dane particles의 concentration을 반영. (viral replication, high infectivity, high vertical transmission) ⑶ antibody ① anti-HBs : 이미 HBV에 감염되거나, HBV의 vaccine을 접종하여 중화항체가 형성된 상태 (past infection, immunity) ② anti-HBc : 감염 초기부터 양성이 되어 이 상태가 지속. IgM anti-HBc는 acute infection을 의미, IgG anti-HBc with anti-HBs는 immunity를 의미, IgG anti-HBc alone은 immunity를 의미할 수도 있으나 high titers인 경우는 continuing infection을 암시 (serological marker during core window, past infection) ③ anti-HBe : HBs Ag이 양성이고 HBe Ag이 음성인 경우에는 HBV에 감염되었음에도 불구하고 감염력이 매우 약하다. 이런 경우 anti-HBe가 양성이다. (low infectivity, low vertical transmission, integration period)

c. HCV : ⑴ antigen : HCV, C100-3 (1세대 EIA에서 항원으로 이용하여 항체를 측정, 급성기에 진단이 어려움, 특이도가 낮아 위양성의 가능성), C33c와 C22-3 (2세대 EIA에서 항원으로 이용하여 항체를 측정, 급성간염시기에 진단이 가능), NS5 (더욱 일찍 HCV항체를 측정할 수 있으나 위양성의 가능성이 있다) ⑵ antibody : anti-HCV; 중화효과가 highly strain-specific하고 time-limited (오랜 감염을 중화시키지 못함)하여 immunity가 반드시 있다고 할 수 없음.

d. HDV : ⑴ antigen : HBs Ag, HDV Ag ⑵ antibody : anti-HBs, anti-HDV

e. HEV : HEV Ag, anti-HEV