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05 Deja Review-Micro Hepatitis

Terms in this set (46)

What are the five main clinically relevant hepatitis viruses?
1. Hepatitis A
2. Hepatitis B
3. Hepatitis C
4. Hepatitis D
5. Hepatitis E
Mnemonic: HAV causes Puking (Picor- navirus), HBV causes Hepatitis (Hepadnavir- us), HCV most Fatal (Flaviviridae), HDV is Deficient (Delta virus), HEV is bad for Expectant mothers (HEpadenavirus)
To what virus family does hepatitis A virus (HAV) belong? Describe its morphology:
Picornavirus. Smallest (27-nm diameter) nonenveloped icosahedral single-stranded positive-sense RNA virus
How many immunological strains of HAV are there? How is HAV transmitted?
Although HAV genome may vary by 20%, there is only one serotype. Infection confers immunity from all HAV strains. HAV is transmitted by fecal-oral route.
How common is HAV infection?
HAV is almost universal in developing nations and in about one-third of adults in the United States have evidence of past infection.
Is there a chronic HAV carrier state?
No. HAV usually causes a self-limited acute reaction with complete recovery.
How is it possible to distinguish between active and past HAV infections?
Active HAV infection is characterized by anti-HAV immunoglobulin M (IgM) and elevated serum aminotransferases.
Past HAV infection is characterized by anti-HAV immunoglobulin G (IgG).
How can HAV infection be prevented?
Active immunization with an attenuated vaccine or passive immunization with anti-HAV IgG
In which season do most HAV infections occur?
Autumn
Hepatitis B virus (HBV) belongs to which family of viruses?
Hepadnavirus
What is unique about the genome of HBV compared to all other hepatitis viruses?
HBV has a partially single-stranded and partially double-stranded DNA genome where-as all other hepatitis viruses have an RNA genome.
What is unique about the replicative strategy of HBV?
HBV relies on an RNA-dependent DNA polymerase (reverse transcriptase [RT]) to replicate its genome.
Describe the replication cycle of HBV:
1. HBV binds to the hepatocyte membrane.
2. Virion uncoats and the DNA genome enters the
nucleus.
3. DNA genome gets repaired to form a covalently closed circular DNA (cccDNA).
4. DNA-dependent RNA polymerase forms messenger RNA (mRNA) and pregenomic RNA
from cccDNA.
5. Pregenomic RNA, nucleocapsid, polymerase
proteins are encapsulated in the virus core particle in cytoplasm.
6. RT forms genomic DNA (double-and single-stranded) within virus core particle.
7. Virus core particle can reinfect the same nucleus to form more cccDNA or be secreted as
virion.
How does the function of RT differ between HBV and retroviruses?
RT forms genomic DNA within the viral core particle in HBV. Human immunode- ficiency virus (HIV) requires RT to form DNA immediately after fusion. HBV re- quires RT to form progeny; HIV requires RT to integrate into genome and produce viral proteins.
What is unique about the size of the HBV genome?
HBV has a small (3.2 kb) genome that has four overlapping genes: S encodes hepatitis B surface antigen (HBsAg); C encodes hepatitis B envelope antigen (HBeAg) and hepatitis B core antigen (HBcAg); P codes for DNA polymerase; and × encodes hepatitis B × antigen (HBxAg).
How common is HBV infection? How is HBV transmitted?
More than 350 million are HBV carriers worldwide and approximately 1.2 million HBV carriers in the United States. Vertical (maternal-infant) transmission in endemic areas (Southeast Asia, China, and sub-Saharan Africa). Horizontal (transfusions, sexually, intravenous [IV] drug) transmission in areas of low prevalence
Does HBV cause acute or chronic hepatitis?
Both. Ninety percent of perinatally acquired HBV develop chronic HBV infection whereas less than 5% of immunocompetent adults develop chronic HBV after infection.
How can HBV infection be diagnosed?
Most commonly serologically using HBsAg, but diagnosis can also be obtained using immunohistochemistry, in situ hybridization, or PCR
What are the commonly used serological markers for HBV?
HBsAg, HBeAg, anti-HBc IgM, anti-HBc IgG, anti-HBs (HBsAb), anti-HBe (HBeAb), and HBV DNA
What is the significance of HBsAg?
Presence of HBsAg in serum is diagnostic for HBV infection. HBsAg typically appears in the blood in 1 to 10 weeks after infection. Persistence of HBsAg for over 6 months is diagnostic for chronic HBV infection.
What is the significance of hepatitis B surface antibody (HBsAb)?
HBsAb is protective against HBV infection and detectable HBsAb correlates to resolution of an acute HBV infection, past HBV infection, or successful immunization.
What is the significance of anti-HBc?
Anti-HBc IgM develops before HBsAb and is usually diagnostic for acute HBV infection. Anti-HBc IgM is detectable during the window period. Anti-HBc IgG is indicative of past acute or chronic HBV infection and may persist longer than HBsAb.
What is the window period?
In acute HBV infection, there may be a win- dow period following the disappearance of HBsAg in the serum but before the appearance of HBsAb. During this period, anti HBc IgM is usually detectable. However, as the laboratory sensitivities for detection
of HBsAg and HBsAb have improved, this window period is now rarely clinically significant.
What is the significance of HBeAg?
HBeAg is a marker of HBV replication and infectivity. Anti-HBe may be detected in both patients with acute or chronic HBV infection.
What are clinical serological markers for hepatitis?
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT). In general, viral hepatitis ALT is greater than AST, whereas alcoholic hepatitis AST is greater than ALT.
What is fulminant hepatitis?
Unusual (0.1%-0.5%) outcome following HBV infection that results from massive immunemediated lysis of infected hepatocytes. More than 50% of all fulminant hepatitis cases are related to HBV but usually with underlying hepatitis D virus (HDV) or hepatitis C virus (HCV) coinfection.
What cancer is associated with HBV infection?
Hepatocellular carcinoma
What is the treatment of HBV infection?
Adult-acquired acute HBV infection usually does not require treatment. Neonates born to HBsAg-positive mothers should receive HBV vaccine and HBsAb immediately following birth. Chronic HBV patients may be treated with α-interferon or lamivudine (RT inhibitor).
Who should get the HBV vaccine?
Everybody should be vaccinated as it has been shown to be safe and cost-effective.
To what virus family does hepatitis C virus (HCV) belong? Describe its morphology.
Flaviviridae. Spherical (40-60 mn), enveloped, single-stranded positive-sense RNA virus
How many different genotypes of HCV are there?
At least six genotypes identified. With a rapid mutation rate, there appears to be no effective long-term neutralizing antibodies. Past infection does not confer immunity.
How common is HCV infection?
An estimated 4 million (1.8% of population) in the United States and 170 million world-wide (up to 22% in Egypt). Most have
chronic infections. New acute HCV infections are uncommon.
How is HCV usually transmitted?
HCV was associated with 90% of transfusion-related hepatitis prior to 1992 in the United States and was referred to as non- A, non-B hepatitis. Since identification, transfusion-related HCV has dramatically decreased and IV drugs use is the most com- mon form of transmission. Sexual and peri-natal transmission is also possible but signi- ficantly less likely.
What are the chances of acquiring HCV through an accidental needlestick from an HCV-infected patient?
3%
What percentage of acute HCV infections de- velops into chronic HCV infections?
60% to 80%
How is HCV diagnosed?
Detection of antibodies to HCV polypep- tides by anti-HCV-ELISA (90%-95% sensitive) or direct detection of HCV RNA (gold-standard)
What are common sequelae of HCV infection?
Cirrhosis (20% after 20 years of HCV infection) and hepatocellular carcinoma (1%-4% per year in HCV cirrhotic patients)
What are the treatments for both acute and chronic HCV infection?
For both, the treatment of choice is α-interferon and ribavirin.
How can HCV infection be prevented?
Avoid needlesticks, IV drugs, and screen transfusion blood. There is no vaccine available for HCV.
To what virus family does hepatitis D virus (HDV) belong? Describe its morphology:
Delta virus. Defective single-stranded negative polarity circular RNA (smallest gen- ome 1.7 kb)
HDV infection can only occur in the presence of which other virus? Why?
HBV HDV requires the outer envelope HBsAg for assembly.
Mnemonic: HDV is Defective and therefore needs HBV to help it.
How common is HDV infection?
HDV is endemic among HBV-infected people in the Mediterranean, North Africa, and South America and patients who receive frequent transfusions. Globally 5% of HBV- infected people are coinfected with HDV.
What are important sequelae of HDV infection?
HDV increases the severity of HBV infec- tion and can transform asymptomatic chronic HBV infection into severe chronic hepatitis. HDV is also associated with fulminant hepatitis. However, HDV does not increase the frequency with which acute HBV infection progresses to chronic HBV infection.
How can you prevent HDV infection?
By HBV vaccine
To what virus family does hepatitis E virus (HEV) belong? Describe its morphology:
Most similar to calcivirus family, although recently, HEV has been classified as its own hepevirus family. Nonenveloped single-stranded positive-sense RNA
How is HEV predominately transmitted? Where do HEV infections occur?
Through fecal-oral route. Southeast and Central Asia, the Middle East, and North and West Africa. In the United States, linked to travel to endemic areas
Why is HEV infection particularly bad for pregnant women?
HEV infections in pregnant women have a fatality rate of 15%-25%, compared to only 1%-3% overall fatality rate
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