**Hepatitis Disease** Any **inflammation of the liver** caused by **infectious or toxic** agents...
1. Infectious Hepatitis
1.1. Indirect causes
1.1.1. Viral
1.1.1.1. VZV
1.1.1.2. Yellow Fever Virus
1.1.1.3. During Chicken Pox
1.1.1.4. Following infection of T cells
1.1.1.5. CMV and EBV
1.1.1.5.1. mononucleosis
1.1.2. Bacterial
1.1.2.1. Pyogenic Liver Abscesses
1.1.2.1.1. E. Coli
1.1.2.1.2. Klebsiella pneumoniae
1.1.2.2. Acute Hepatitis
1.1.2.2.1. Neisseria
1.1.2.2.2. Salmonella
1.1.2.2.3. Borrelia
1.1.2.2.4. Bartonella
1.1.2.2.5. Campylobacter
1.1.2.3. Chronic Granulomatous Hepatitis
1.1.2.3.1. Mycobacteria
1.1.2.3.2. Rickettsia
1.1.3. Parasites - Protozoan
1.1.3.1. Plasmodium (Malaria)
1.1.3.2. Leishmania
1.1.3.3. Trypanosomes
1.2. Hepatitis Viruses
1.2.1. Direct infection of
1.2.1.1. hepatocytes
1.2.1.1.1. Disease is primarily associated with this process
1.2.2. A
1.2.2.1. Genomic Composition
1.2.2.1.1. Family
1.2.2.1.2. + ssRNA
1.2.2.1.3. Geometry
1.2.2.1.4. Non-Enveloped
1.2.2.2. Route of Transmission / Acquisition
1.2.2.2.1. Fecal-Oral
1.2.2.3. At Risk Groups
1.2.2.3.1. Contaminated food
1.2.2.3.2. Majority of US cases have no identifiable risk factors
1.2.2.4. Disease Course
1.2.2.4.1. Clinical Course
1.2.2.4.2. Diagnosis
1.2.2.4.3. Infectious Course
1.2.2.5. Pattern of Infection, Disease and Serology
1.2.2.5.1. Most clear within 2 months
1.2.2.5.2. Infection:Disease ratio
1.2.2.5.3. Icteric phase
1.2.2.6. Structural Proteins
1.2.2.7. Prevention and Treatment
1.2.2.7.1. Vaccine
1.2.2.7.2. HAV - Immunoglobulin
1.2.3. B
1.2.3.1. Genomic Composition
1.2.3.1.1. DNA Virus
1.2.3.1.2. Enveloped
1.2.3.1.3. Nuclear Replication
1.2.3.1.4. Pleomorphic structure
1.2.3.1.5. Smallest of enveloped animal viruses
1.2.3.2. Route of Transmission / Acquisition
1.2.3.2.1. Person to Person
1.2.3.3. At Risk Groups
1.2.3.4. Disease Course
1.2.3.4.1. Acute Hepatitis
1.2.3.4.2. Chronic Hepatitis
1.2.3.4.3. Hepatic Cancer
1.2.3.5. Pattern of Infection, Disease and Serology
1.2.3.5.1. Diagnosis
1.2.3.5.2. Immunology
1.2.3.6. Structural Proteins
1.2.3.6.1. Infectious
1.2.3.6.2. Non-Infectious
1.2.3.7. Prevention and Treatment
1.2.3.7.1. Vaccine
1.2.3.7.2. Therapy
1.2.4. C
1.2.4.1. Genomic Composition
1.2.4.1.1. Genus
1.2.4.1.2. + ssRNA
1.2.4.1.3. Enveloped
1.2.4.1.4. Life CYcle
1.2.4.2. Route of Transmission / Acquisition
1.2.4.2.1. Percutaneous exposure to Infectious Blood
1.2.4.2.2. Less frequent
1.2.4.3. At Risk Groups
1.2.4.4. Disease Course
1.2.4.5. Pattern of Infection, Disease and Serology
1.2.4.5.1. Initial Replication
1.2.4.5.2. Asymptomatic / Mild symptoms are typical
1.2.4.5.3. 25% of infections are symptomatic
1.2.4.5.4. > 75% become chronically infected and don't clear the virus
1.2.4.5.5. Serologic Pattern
1.2.4.6. Structural Proteins
1.2.4.7. Prevention and Treatment
1.2.4.7.1. Screening
1.2.4.7.2. Vaccine
1.2.4.7.3. Goal of Treatment
1.2.4.7.4. Treatment Regimen determined by
1.2.4.7.5. Life cycle of Hep C and points of drug action
1.2.4.7.6. Basic treatment regimen
1.2.5. D
1.2.5.1. Genomic Composition
1.2.5.1.1. Enveloped
1.2.5.1.2. Satellite virus
1.2.5.1.3. Genome
1.2.5.1.4. Replication
1.2.5.1.5. Reading frame
1.2.5.2. Route of Transmission / Acquisition
1.2.5.2.1. Parenteral
1.2.5.3. At Risk Groups
1.2.5.4. Disease Course
1.2.5.4.1. Associated diseaes
1.2.5.5. Pattern of Infection, Disease and Serology
1.2.5.5.1. Diagnosis
1.2.5.6. Structural Proteins
1.2.5.7. Prevention and Treatment
1.2.5.7.1. None
1.2.5.7.2. Eliminate HBV
1.2.5.7.3. Vaccine
1.2.6. E
1.2.6.1. Genomic Composition
1.2.6.1.1. Family
1.2.6.1.2. Genus
1.2.6.1.3. + ssRNA
1.2.6.1.4. Icosahedral
1.2.6.1.5. Non-Enveloped
1.2.6.1.6. 4 genotypes, 1 serotype
1.2.6.2. Route of Transmission / Acquisition
1.2.6.2.1. Fecal-Oral
1.2.6.2.2. Zoonosis
1.2.6.3. At Risk Groups
1.2.6.3.1. Developing countries with poor sanitation
1.2.6.4. Disease Course
1.2.6.4.1. Frequently subclinical
1.2.6.4.2. May fulminate
1.2.6.4.3. Symptoms
1.2.6.4.4. Major cause of acute hepatitis worldwide
1.2.6.4.5. Clinical Course
1.2.6.5. Pattern of Infection, Disease and Serology
1.2.6.5.1. Viremia
1.2.6.5.2. Incubation
1.2.6.6. Structural Proteins
1.2.6.7. Prevention and Treatment
1.2.6.7.1. Supportive Care
1.2.6.7.2. Precautions while traveling; no vaccine in US but recombinant vaccine is used in CHina
1.2.7. G
1.2.7.1. Structural Proteins
1.2.7.2. Genomic Composition
1.2.7.3. Route of Transmission / Acquisition
1.2.7.4. At Risk Groups
1.2.7.5. Disease Course
1.2.7.6. Pattern of Infection, Disease and Serology
1.2.7.7. Prevention and Treatment
1.2.8. Need to know features
1.2.8.1. Viral and other pathogen-associated cancers
1.2.8.1.1. Group 1
1.2.8.1.2. Group 2
1.2.8.1.3. Inflammation and regenerative capccity with buildup of mutations
1.2.8.1.4. Hep B
1.2.8.1.5. Hep C
2. Spectrum of Hepatitis Disease
2.1. Acute Hepatitis
2.1.1. < 6 mo duration
2.1.2. 3 phases
2.1.2.1. Prodromal phase
2.1.2.1.1. General flu-like symptoms
2.1.2.2. Jaundice Phase
2.1.2.2.1. 2 weeks after prodromal; lasts up to 4 weeks
2.1.2.3. Recovery Phase
2.1.2.3.1. within 6 months
2.2. Fulminant Hepatitis
2.2.1. complication of acute hepatitis
2.2.2. massive hepatic cell death and necrosis
2.3. Chronic Hepatitis
2.3.1. Persistent progressive necroinflammatory process with fibrosis
2.3.2. Progression
3. Lab Findings
3.1. LFT
3.1.1. Proteins and enzymes in the blood that indicate proper liver function, or are released when hepatocytes are damaged or diseased
3.1.1.1. Bilirubin test
3.1.1.1.1. Bilirubin is made when RBCs break down
3.1.1.1.2. Liver usually cleans bilirubin out of the body
3.1.1.1.3. High Bilirubin in the blood = jaundice = probably liver damage
3.1.1.2. Total Serum Protein / Albumin
3.1.1.2.1. Low levels
3.1.1.2.2. Liver makes two proteins: albumin and globulin
3.1.1.3. Prothrombin Time / Partial Thromboplastin Time Test
3.1.1.3.1. Measure blood clotting factors produced in liver
3.1.1.3.2. Measures how long it takes blood to clot
3.1.1.3.3. taking a long time to clot?
3.1.1.4. ALT test
3.1.1.4.1. Enzyme that helps break down proteins
3.1.1.4.2. cytosolic enzyme, mainly in liver
3.1.1.4.3. High levels
3.1.1.5. AST
3.1.1.5.1. mitochondrial enzyme, liver and other tissues
3.1.1.5.2. High levels
3.1.1.6. ALP
3.1.1.6.1. Enzyme in
3.1.1.6.2. High levels
3.1.1.7. GGT
3.1.1.7.1. High levels
3.2. Understanding Viral Hepatitis Panels
3.2.1. Reasoning
3.2.1.1. Treatment protocls and potential outcomes vary for each hepatitis virus, so how do we diagnose specific pathogens?
3.2.2. Concepts of viral hepatitis diagnostic panels
3.2.2.1. Are they infected and with which specific hepatitis virus?
3.2.2.1.1. Depends on
3.2.2.1.2. Detection of viral antigen (Ag)
3.2.2.1.3. Detection of viral genome
3.2.2.1.4. Detection of Antibodies to pathogen
3.2.2.2. Patterns of infection, antigen detection, and antibody generation for each specific virus can provide insights into disease staging and status
3.2.2.2.1. Coupling serological tests with liver function biochemical tests give an idea of disease status and progression
3.2.2.3. ELISA Assay
3.2.2.3.1. Detects viral antigens
3.2.2.3.2. Detects specific antibodies to the virus
3.2.2.3.3. Hep A example
3.2.2.3.4. HCV +, HBV Vaccinated
3.2.2.3.5. HCV+, Early HBV
3.2.2.4. Pre-Vaccination Testing
3.2.2.4.1. Determine HAV infection status - cost-effective in MSM b/c high risk of HAV infection
3.2.2.4.2. Determine HBV infection status - cost-effective because MSM have high risk of HBV infection
3.2.2.4.3. HCV - not indicated. MSM at no greater risk of HCV infection than general population
3.2.2.5. Implications for HBsAg positive
3.2.2.5.1. Asymptomatic person
3.2.2.5.2. Unvaccinated sex partners and household contacts should be tested for susceptibility to HBV infection and vaccinated if susceptible
3.2.2.5.3. HBsAg positive test is reportable in most states
3.2.2.5.4. HBsAg positive person should be further assessed for chronic liver disease
3.2.3. Cases
3.2.3.1. 1. Diagnosis of acute viral hepatitis, the most appropriate serologic tests to order would be?
3.2.3.1.1. IgM anti HAV
3.2.3.1.2. IgM anti HBc
3.2.3.1.3. HBsAg
3.2.3.1.4. Anti HCV