Viral Hepatitis Flashcards
What is viral hepatitis?
Inflammation of the liver caused by a virus. Symptoms include jaundice, fatigue, abdominal pain, loss of appetite. Some people don’t have symptoms.
Hepatitis Viruses
Numerous and genetically distinct. However, they cause similar symptoms, infect hepatocytes, and are primarily/exclusively associated with liver disease. They often have diverse clinical features like onset, severity and chronicity
Hepatitis A
AKA Infectious hepatitis, is a picornavirus. Abrupt onset, mild severity and no chronicity
Hepatitis B
AKA serum hepatitis, is a hepadnavirus. Slow onset, occasionally severe, chronic
Hepatitis C
AKA non A non B hepatitis, is a member of the flaviviridae family. Slow onset, usually subclinical but chronic.
Hepatitis delta
AKA delta agent, is a delta virus. Abrupt onset, occasionally severe, chronic.
Hepatitis E Virus
AKA enteric non A non B hepatitis, is a hepevirus. Abrupt onset, severe in pregnant women, not chronic.
Which hepatitis viruses have a vaccine?
Hep A, Hep B.
Which hepatitis viruses have a therapy?
Hep B (rarely cures), Hep C.
High risk for HBV?
Drug users.
HBV virology
Hepadnaviridae, genus orthohepadnavirus. Enveloped protein is major antigen (HBsAg)
HBV genome
Partially double stranded, circular DNA genome. Smallest genome of a replication competent human virus. Replication occurs via an RNA intermediate (reverse transcription)
Three antibodies produced in response to HBV?
anti-HBsAg, anti-HBeAg, anti-HBcAg
What leads to chronic HB?
Anti-HBsAg
How is hepatocellular carcinoma induced?
Virus theory - viral products act as oncogenes, inducing cancer from the integration of genome and disruption of cellular gene expression.
Indirect theory- chronic hepatic injury and subsquent repair processes lead to genetic changes in cells and subsequent uncontrolled growth.
Treatment for chronic HBV?
Pegylated interferon alpha (antiviral cytokine), successful in 30% of patients but difficult to tolerate during 48 week therapy. Reverse transcriptase inhibitors
HBV antivirals
Are RT inhibitors– lamivudine (Nucleoside analog), entecavir, tenofovir
HBV vaccines
Use non-glycosylated HBsAg produced in yeast and the adjuvant alum. Safe, but requires multiple vaccinations.
Hepatitis Delta Virus
Subiviral satellite virus, requires HBV to provide envelope proteins required for assembly, only affects individuals with HBV, greatly exacerbates HBV disease and increases chances of cancer.
Fulminant hepatitis
Rare complication that frequently ends in death.
HCV
Leading indication for liver transplants in the US, frequently from drug use and sexually transmitted.
HCV Genome
Flaviviridae genus hepacivirus, single stranded positive sense RNA
Why does HCV have a high error rate?
Because of an error prone RNA polymerase, so it exists as a quasispecies, allowing it to escape immune responses and be resistant to treatment.
Outcome of HCV infection
Can lead to liver failure, cancer, transplant or death in 4% of people over 20-30 years.
What enzyme spikes during infection?
ALT
How to assess HCV infection
Serology (look for antibodies to NS3, NS5, core, 6-8 weeks after exposure)
RT-PCR
Liver Biopsy to assess injury
How to treat HCV?
Curable, many drugs like interferon alpha, simepravir
Hepatitis A virus
Transmission is person-person via oral fecal route, 3 week selflimited disease that is often subclinical. symptoms of acute viral hepatitis occur and detection of HAV-specific IgM antibody. Supportive therapy. Prevent with vaccine.
Hepatitis E virus
Clinical presentation similar to HAV. Predominantly found in developing countries with fecal contamination of drinking water. Less widespread than HAV. Self limiting viral infection followed by recovery. Prolinged viremia or fecal shedding are unusual and chronic infection does not occur.