2-24 Introduction to the Hepatitis Viruses Flashcards Preview

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Flashcards in 2-24 Introduction to the Hepatitis Viruses Deck (18):
1

What are the hepatitis viruses, and how are they related to one another?

  • 6 variants known to exist: A, B, C, D, E, and G
  • NOT phylogenetically related; instead, share a common host cell type: hepatocyte
  • All cause an initial bout of acute hepatitis on first infection (wide range of severity)
  • From there, pathogenesis depends on the individual virus
  • Avoid a common mistake and rule out pharmaceutical causes before getting too deeply into the virology workup

2

Vaccines are available for which hepatitis viruses?

A, B, and E

3

In all cases of hepatitis, what are some non-infectious causes to rule out?

  • Reactions to prescription meds
  • Med interactions
  • Acetaminophen OD
  • Ecstasy

4

What is the virology of HAV?

  • Picornavirus: (+)ssRNA genome, naked icosahedral capsid
  • Environmentally rugged
  • Single serotyope → no reinfection + VACCINE

5

What is the pathology of HAV?

  • Fecal-oral → infects hepatocytes
  • Often asymptomatic; if symptoms, acute hepatitis (largely immunogenic)
  • >99% recover completely; once virus is cleared, no chronic infection
  • Rare patients develop fulminant hepatitis, 40% mortality
  • Risk factors: elderly, preexisting liver disease
  • Transplant is an option, though most patients eventually recover without

6

What are the exam, labwork, and treatment for HAV?

History: vaccination, foreign travel, daycare, shellfish

Symptoms: Fever, jaundice, gastroenteritis, tenderness around liver, dark urine, pale feces

Serology: IgM = acute, IgG = recovered/vaccinated

Treatment is symptomatic: bed rest, hydration, careful w/ Tylenol

Transmitted human-human: trace contacts, alert local public health authorities

7

What are risk factors for and ways to prevent HAV?

Risk factors: elderly, preexisting liver disease

Prevention is best: handwashing, sanitation, water treatment, HepA vaccine (Twinrix: HAV+HBV)

Prophylaxis is second-best: immune serum globulin (Gammagard)

8

What is the virology of HBV?

  • Human-restricted Hepadnavirus: small, enveloped, DNA virus, partly double-stranded
  • Very “messy” virus:  1000X more HBsAg decoys than virions
  • Unusu. stable for an enveloped virus
  • Only one serotype, HBsAb → no reinfection + vaccine
  • Can establish chrionic infxn
  • Despite DNA genome, carries a RT and replicates via RNA intermediate → leaves integrated copies of viral DNA in hepatocytes

9

What is the pathogenesis of HBV?

  • Transmitted by blood (efficient), sexual/birth contact (less efficient)
  • ~1/3 human pop seropositive worldwide
  • 90% infxns: acute hepatitis, then clear virus
  • Remaining 10% may go fulminant or establish chronic infection

10

What may result from a chronic HBV infection?

  • Cirrhosis → (immunogenic) ongoing cytotoxic attempt to clear virus
  • Accum. of antigen-Ab complexes → kidney damage, arthritis
  • Hepatic cell carcinoma: integrated viral DNA, ongoing hepatocyte replacement in context of virus infection

11

What are the exam and labwork for HBV?

Exam/history

  • Presentation of hepatitis
  • History of vaccination

HBV is the “serum hepatitis”:

  • Serology for infxn timecourse: viral surface antigen (acute), surface antibody, core antibody, E antigen
  • IgG against viral surface antigen = recovered/vaccinated
  • Serum ALT
  • Optional: PCR, biopsy for histology

If infection appears active chronic, perform liver biopsy.

12

How can HBV be treated and prevented?

Treatment

  • Acute infection: supportive
  • Quiescent chronic infection: monitor
  • Damaging chronic infection: discuss interferon therapy: 1yr polymerase inhibitors + 4mo pegylated alpha-interferon (GRUELING)
  • Transplant may be indicated for late stage if treatment fails; watch liver function markers and mental status

Prevention

  • Vaccination
  • Immune globulin prophylaxis

13

What are risk factors for and ways to prevent HBV?

Risk factors:

  • Children
  • Hemophiliacs
  • Men who have sex with men
  • Prostitutes
  • IV drug users
  • Health care workers

Prevention:

  • Patient education
  • Safe sex

14

What is the virology of HCV?

  • Human-restricted Flavivirus: 30-60nm enveloped +RNA genome
  • Just discovered in 1989; anyone who received any blood product before 1994 is at risk
  • ~3 million carriers in the US, many unaware
  • Much higher potential for chronic infxn than HepB → stronger assoc. w/ primary hepatocellular carcinoma (11-19%)
  • NO VACCINE

15

What is the pathogenesis of HCV?

  • Transmitted by blood (efficient), sex (inefficient)
  • Infects hepatocytes (50% in chronic), possibly B lymphocytes (both carry CD81 receptor)
  • Highly mutagenic (rdRNAP has no proofreading), generates quasispecies
  • Can produce 10 trillion new particles/day
  • < 1/2 of infectees clear it, requires strong cytotoxic T response
  • 85% establish chronic infection (liver failure, cirrhosis, hepatocellular carcinoma, 100k deaths/yr worldwide)

16

What is the exam and labwork for HCV?

“non-A, non-B, post-transfusion hepatitis”

Exam:

  • Acute symptoms somewhat milder than HBV
  • Red flag: travel to Egypt (22% HCV+) (blood fluke eradication campaign gone wrong)
  • New infxns in U.S. now usu. from IV drugs, but many old ones still being uncovered

Labwork:

  • Serology: Liver function tests, including ALT levels
  • EIA = real/false pos.; RIBA = confirmation
  • RT-PCR for viral RNA levels to assess success of therapy
  • Liver biopsy not req., but can be helpful for judging severity of disease
  • Screen for HIV, HepB, drug abuse

17

What is RIBA?

Recombinant Immunoblot Assay, used as a follow-up to confirm HCV exposure. A Western blot w/ vendor-provided antigens, 2° Ab, and patient serum for 1° Ab.

A image thumb
18

What is the treatment for HCV?

  • Antibody to HCV is not protective
  • W/ acute infxn, judgment call required: short course of peg-alpha-IFN treatment reduces rates of chronic infxn, BUT infxn may spontaneously clear w/o treatment
  • Multiple serotypes complicate treatment picture
  • Second generation treatments for chronic infxn: ribavirin (viral chain terminator, also immunomodulant) + pegalyted alpha-interferon + HCV protease inhibitors (boceprevir / telaprevir)
  • Third generation treatments: SVR or cure w/ no alpha-interferon
  • Must monitor liver and kidney function, blood, viral RNA levels