Chapter 3 Acute viral hepatitis
1 Viral hepatitis is the most common cause of liver disease in the world; acute infections with their sequelae are responsible for 1 to 2 million deaths annually.
2 The nonenveloped, enterically transmitted hepatitis viruses (HAV and HEV), in general, are self-limited infections, but severe hepatitis may develop in some cases; rarely, chronic hepatitis E has been reported in organ-transplant recipients. The blood-borne hepatitis viruses (HBV, HDV, and HCV) are enveloped agents frequently associated with persistent infection, prolonged viremia, and the development of chronic liver disease and its sequelae.
3 A wide spectrum of clinical illness is well documented, ranging from asymptomatic, anicteric infection to acute liver failure (fulminant hepatitis); with the exception of acute hepatitis C, no specific or effective treatment of acute viral hepatitis is available; liver transplantation is indicated in acute liver failure when recovery seems unlikely.
4 Highly effective and safe vaccines are available for preexposure immunoprophylaxis of HAV and HBV infection; for postexposure immunoprophylaxis of HAV, HAV vaccine is preferred but immune globulin may be used, whereas for postexposure immunoprophylaxis of HBV, both hepatitis B immune globulin (HBIG) and HBV vaccine are used.
5 Immune globulin preparations are not available for the prevention of HEV or HCV infection. No vaccine for the prevention of HCV infection exists. An effective HEV vaccine is not yet commercially available but remains in development. HBV vaccination prevents HDV infection, but for persons with established HBV infection, vaccines to prevent HDV superinfection are not available.
2. As many as 7% of the global population is chronically infected by the hepatitis B virus (HBV), and 3% are infected by the hepatitis C virus (HCV).
6. The sequelae of chronic infection include cirrhosis, end-stage liver disease, hepatocellular carcinoma, and premature death.
g. Replication in cytoplasm of infected hepatocyte through RNA-dependent RNA polymerase; no definitive evidence of replication in intestine
d. RNA genome with three overlapping open reading frames encoding structural proteins and nonstructural proteins involved in HEV replication:
b. Eight genotypes (A through H): genotype C appears to be associated with more severe chronic disease, and genotype D is less responsive to interferon-based therapy
c. 42-nm spherical particle with
d. HBV core containing circular, partially double-stranded DNA (3.2 kb in length) and
Hepatitis B e antigen (HBeAg), a nonstructural, secretory protein that correlates imperfectly with active HBV replication
e. HBV outer lipoprotein envelope containing
Hepatitis B surface antigen (HBsAg), with three envelope proteins: major, large, and middle proteins
g. HBV mutant viruses as a consequence of poor proofreading ability of reverse transcriptase or emergence of resistance; examples:
a. A defective RNA satellite virus (viroid-like) requiring helper function of HBV for its expression and pathogenicity but not for its replication
c. 35- to 37-nm spherical particle, enveloped by HBV lipoprotein coat (HBsAg)
d. Containing an antigenic nuclear phosphoprotein (HDV antigen)
f. HDV antigenome, a genome complementary, circular RNA found in infected hepatocyte and, to a much lesser extent, in purified HDV particles
h. RNA genome can form an unbranched rodlike structure by folding on itself through intramolecular base pairing
d. HCV genome comprises approximately 9.4 to 9.6 kb, encoding a large polyprotein of approximately 3000 amino acid residues
One third of the polyprotein consisting of a series of structural proteins (an internal nucleocapsid or core [C] protein and two glycosylated envelope proteins, termed E1 and E2, present in the lipid-containing envelope of the virus)
Remaining two thirds of the polyprotein consisting of nonstructural proteins (termed NS2, NS3, NS4A, NS4B, NS5A, and NS5B) involved in HCV replication: a zinc-dependent metalloproteinase in NS2/3, a nucleotide triphosphatase/helicase in NS3, a chymotrypsin-like serine protease in NS3-4A, RNA-dependent RNA polymerase in NS5B, an interferon sensitivity region in NS5A, and an ion channel, P7
e. Only one HCV serotype identified; six major HCV genotypes with multiple subtypes; genotypes variably distributed throughout the world
3. HAV excreted in stools of infected persons for 1 to 2 weeks before and for at least 1 week after onset of illness
4. Viremia short-lived, usually no longer than 3 weeks; occasionally up to 90 days in protracted or relapsing infection
5. Prolonged fecal excretion (months) reported in infected neonates; frequency, level of virus in stool, and epidemiologic importance uncertain
6. Enteric (fecal–oral) transmission predominantly by person-to-person household spread; occasional outbreaks linked to common-source vehicles:
7. Other risk factors including exposure:
11. Overall seroprevalence in the United States: less than 30% and declining rapidly with expanded vaccine use
2. Widely distributed; epidemic and endemic forms but symptomatic infections rare in the United States; nonetheless, seroprevalence in U.S. population of approximately 21%
8. In the United States, imported cases in returning travelers, in recent immigrants from endemic regions; sporadic, rare cases of transmission through undercooked pork products, liver or other organ meats, shellfish, or venison or by transfusion
9. Prolonged viremia or fecal shedding unusual; continued viral shedding possible in rare cases in organ transplant recipients in whom chronic hepatitis develops
3. 1% to 5% of adults, 90% of infected neonates, and 50% of infants developing chronic infection and persistent viremia
4. Persistent infection linked to chronic hepatitis, cirrhosis, hepatocellular carcinoma, and premature mortality
6. Worldwide distribution: HBV carrier prevalence less than 1% in the United States, 5% to 15% in Asia and sub-Saharan Africa; declining incidence in areas where vaccine use has expanded
10. Modes of transmission:
a. Blood-borne transmission
c. Tissue penetrations (percutaneous) or permucosal transfer
2. Endemic in Mediterranean basin, Balkan peninsula, Central Europe, parts of Africa, Middle East, and Amazon basin
6. HDV infections occurring solely in individuals at risk for HBV infection (coinfections or superinfections)
3. Persistent infection etiologically linked to chronic hepatitis, cirrhosis, hepatocellular carcinoma and premature death
4. Seroprevalence of past/present infection 1.3% in the United States, approaching 20% in some communities in Italy and Japan, and up to 40% in some villages in the Nile delta of Egypt
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