Hepatitis Flashcards
Incubation of HAV
2 to 6 weeks
What is the typical sequelae of HAV?
HAV does not cause chronic hepatitis or a carrier state and only uncommonly causes acute hepatic failure
HAV fatality rate
0.1-0.3%
HAV symptoms
nonspecific symptoms such as fatigue and loss of appetite, and often develop jaundice
Where is HAV most prevalent in the world?
occurs throughout the world and is endemic in countries with poor hygiene and sanitation.
HAV family and genotype
HAV is a small, nonenveloped, positive-strand RNA picornavirus of the genus, Hepatovirus
Structure of HAV?
HAV is an icosahedral capsid 27 nm in diameter
How is HAV spread?
HAV is spread by ingestion of contaminated water and foods and is shed in the stool for 2 to 3 weeks before and 1 week after the onset of jaundice. Thus, close personal contact with an infected individual or fecal-oral contamination during this period accounts for most cases and explains the outbreaks in institutional settings such as schools and nurseries, and the water-borne epidemics in places where people live in overcrowded, unsanitary conditions.
Is there a HAV vaccine?
Yes
What is the most likely reason for persons in developed country for contracting HAV?
consumption of raw or steamed shellfish (oysters, mussels, clams), which concentrate the virus from seawater contaminated with human sewage.
Describe the temporal changes in serological markers in acute HAV
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Specific IgM antibody against HAV appears with the onset of symptoms
Fecal shedding of the virus ends as the IgM titer rises
he IgM response usually begins to decline in a few months and is followed by the appearance of IgG anti-HAV
The latter persists for years, perhaps conferring lifelong immunity against reinfection by all strains of HAV
What is the most reliable marker of acute HAV infection?
Specific IgM
Are there routinely available tests for IgG anti-HAV?
No, the presence of IgG anti-HAV is inferred from the difference between total and IgM anti-HAV.
What are the clinical sequelae for HBV?
(1) acute hepatitis followed by recovery and clearance of the virus,
(2) nonprogressive chronic hepatitis,
(3) progressive chronic disease ending in cirrhosis (or hepatocellular carcinoma without cirrhosis),
(4) acute hepatic failure with massive liver necrosis, and
(5) an asymptomatic, “healthy” carrier state.
In almost all cases the infection is self-limited and resolves without treatment. Chronic disease occurs in 5%-10% of infected individuals. Fulminant hepatitis (acute hepatic failure) is rare, occurring in approximately 0.1% to 0.5% of acutely infected individuals.
What determines the chronicity of HBV infection?
age at infection
The younger the age at the time of HBV infection, the higher the probability of chronicity.
How is HBV transmitted in different geographical areas?
In high prevalence regions of the world, transmission during childbirth accounts for 90% of cases.
In areas with intermediate prevalence, horizontal transmission, especially in early childhood, is the dominant mode of transmission (minor breaks in the skin or mucous membranes among children with close bodily contact).
In low prevalence areas, unprotected sex and intravenous drug abuse (sharing of needles and syringes) are the chief modes of spread.
What is the incubation period of HBV?
2 to 26 weeks
HBV remains in the blood until and during active episodes of acute and chronic hepatitis.
Symptoms of HBV
Approximately 65% of adults newly acquiring HBV have mild or no symptoms and do not develop jaundice.
The remaining 25% have nonspecific constitutional symptoms such as anorexia, fever, jaundice, and upper right quadrant pain.
What is the family and virus type of HBV?
Hepadnaviridae, a family of DNA viruses that cause hepatitis in multiple animal species.
of HBV genotypes in the world?
8
What is the structure of HBV?
42-nm, spherical double-layered “Dane particle” that has an outer surface envelope of protein, lipid, and carbohydrate enclosing an electron-dense, 28-nm, slightly hexagonal core.
Describe the genome of HBV
partially double-stranded circular DNA molecule having 3200 nucleotides with 4 open reading frames coding for:
- A nucleocapsid “core” protein (HBcAg, hepatitis B core antigen) and a longer polypeptide transcript with a precore and core region, designated HBeAg (hepatitis B e antigen). The precore region directs the secretion of the HBeAg polypeptide, whereas HBcAg remains in hepatocytes, where it participates in the assembly of complete virions.
- Envelope glycoproteins (HBsAg, hepatitis B surface antigen), which consist of three related proteins: large, middle, and small HBsAg. Infected hepatocytes are capable of synthesizing and secreting massive quantities of noninfective surface protein (mainly small HBsAg).
- A polymerase (Pol) that exhibits both DNA polymerase activity and reverse transcriptase activity. Replication of the viral genome occurs via an intermediate RNA template, through a unique replication cycle: DNA → RNA → DNA
- HBx protein, which is necessary for virus replication and may act as a transcriptional transactivator of both viral genes and a subset of host genes. It has been implicated in the pathogenesis of hepatocellular carcinoma in HBV infection.
Describe the natural course of disease by serological markers
HBsAg appears before the onset of symptoms, peaks during overt disease, and then often declines to undetectable levels in 12 weeks, although it may persist in some individuals for as long as 24 weeks.
Anti-HBs antibody does not rise until the acute disease is over, concomitant with the disappearance of HBsAg.
serologic diagnosis can be made by detection of IgM anti-HBc antibody
Anti-HBs may persist for life, conferring protection; this is the basis for current vaccination strategies using noninfectious HBsAg.
HBeAg, HBV-DNA, and DNA polymerase appear in serum soon after HBsAg, and all signify active viral replication.
IgM anti-HBc antibody becomes detectable in serum shortly before the onset of symptoms, concurrent with the onset of elevated serum aminotransferase levels (indicative of hepatocyte destruction).
Over a period of months the IgM anti-HBc antibody is replaced by IgG anti-HBc. As in the case of anti-HAV, there is no direct assay for IgG anti-HBc; its presence is inferred from decline of IgM anti-HBc in the face of rising total anti-HBc.
What serological antigens signify active viral replication?
HBeAg
HBV-DNA
What marker is an indicator of continued viral replication, infectivity, and probable progression to chronic hepatitis?
HBeAg
What does anti-HBe antibodies imply?
an acute infection has peaked and is on the wane.
What is the main determinant of the outcome of HBV infection?
The host immune response to the virus
Innate immune mechanisms protect the host during the initial phases of the infection, and a strong response by virus-specific CD4+ and CD8+ interferon (IFN)-γ–producing cells is associated with the resolution of acute infection.
What causes hepatocyte injury in HBV infections?
HBV generally does not cause direct hepatocyte injury. Instead, injury is caused by CD8+ cytotoxic T cells attacking infected cells.
What makes HBV so persistent?
The difficulty in achieving cure has been attributed to the ability of the virus to insert itself in the host DNA, thus limiting the development of an effective immune response (HBsAb development)
What is the goal of treatment of chronic HBV infection?
slow disease progression, reduce liver damage, and prevent liver cirrhosis or liver cancer.
Is the HBV vaccine effective in infants and children?
Vaccination induces a protective anti-HBs antibody response in 95% of infants, children, and adolescents.
What are the risk factors for HCV infection?
- Intravenous drug abuse (54%)
- Multiple sex partners (36%)
- Having had surgery within the last 6 month (16%)
- Needle stick injury (10%)
- Multiple contacts with an HCV-infected person (10%)
- Employment in medical or dental fields (1.5%)
- Unknown (32%) - 1/3 of people have no identifiable risk factors
What is the major route of infection for children?
perinatal, but this route of infection with HCV is much lower than for HBV (6% vs. 20%).
HCV genotype and family
member of the Flaviviridae family.
It is a small, enveloped, single-stranded RNA virus with a 9.6-kilobase (kb) genome that codes for a single polyprotein with one open reading frame, which is subsequently processed into functional proteins.
Why does HCV exists as quasispecies in any individual?.
Low fidelity of the HCV RNA polymerase, the virus is inherently unstable, giving rise to multiple genotypes and subtypes.
What protein is are anti-HCV antibodies targeted towards?
The E2 protein of the envelope is the target of many anti-HCV antibodies but is also the most variable region of the entire viral genome, enabling emergent virus strains to escape from neutralizing antibodies.
Is a HCV vaccine available?
No, due to genomic instability and antigenic variability
elevated titers of anti-HCV IgG occurring after an active infection do not confer effective immunity
What is the incubation period of HCV?
4 to 26 weeks, with a mean of 9 weeks.
What are two characteristic feature of HCV infection?
repeated bouts of hepatic damage, the result of reactivation of a preexisting infection or emergence of an endogenous, newly mutated strain, despite the generally asymptomatic nature of acute illness
persistent elevations in serum aminotransferases. Their levels wax and wane but almost never become normal. Even rare patients with normal transaminases are at risk for developing permanent liver damage.
What is the most common clinical sequelae of acute HCV infection?
In about 85% of individuals, the clinical course of the acute infection is asymptomatic and typically missed. The clinical course of acute HCV hepatitis is milder than that of HBV; rare cases may be severe and indistinguishable from HAV or HBV hepatitis.
