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
Vaccines are available for which hepatitis viruses?
A, B, and E
In all cases of hepatitis, what are some non-infectious causes to rule out?
- Reactions to prescription meds
- Med interactions
- Acetaminophen OD
What is the virology of HAV?
Picornavirus: (+)ssRNA genome, naked icosahedral capsid
- Environmentally rugged
- Single serotyope → no reinfection + VACCINE
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
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
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)
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
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
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
What are the exam and labwork for HBV?
- 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.
How can HBV be treated and prevented?
- 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
- Immune globulin prophylaxis
What are risk factors for and ways to prevent HBV?
- Men who have sex with men
- IV drug users
- Health care workers
- Patient education
- Safe sex
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
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)
What is the exam and labwork for HCV?
“non-A, non-B, post-transfusion hepatitis”
- 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
- 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
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.
What is the treatment for HCV?