Viral Hepatitis

  1. Routes of transmission of Hepatitis A, B, C
    • Orofecal: A, B (possible)
    • Sexual: A, B, C (rare)
    • Blood: A (rare), B, C
  2. Risk factors for getting Hep A, B, C
    A: travelers to regions with high rates of Hep A, sex contacts, MSM, household members or caregivers of infected person, illegal drug users (injection and non injection), pt with clotting factor disorders

    B: infants of infected mothers, sex partners (or those with multiple partners or MSM), those with STDs, IVDUs, household contacts of infected person, healthcare workers exposed to blood on the job, hemodialysis patients, residents and staff of facilities for developmentally disabled persons, travelers to endemic regions

    C: Current or former IVDUs, recipients of clotting factors prior to 1987 or of blood transfusions or organ donations before 1992, long-term hemodialysis pts, persons with known exposures to HCV, HIV pts, infants of infected mothers
  3. What are the 3 types of acute hepatitis? Describe each.
    • Asymptomatic - Rise in LFTs and serologic markers present
    • Symptomatic - 4 phases - 1. incubation period, 2. pericteric phase, 3. icteric phase, 4. convalescent phase
    • Fulminant - severe liver failure that develops w/in 8 weeks of sx onset. Liver cell destruction leading to coagulopathy and hepatic encephalopathy
  4. Describe each of the phases of symptomatic hepatitis
    • 1. incubation period - time from infx to onset of sx
    • 2. pericteric phase - lasts days to 3 weeks - nonspecific influenza like sx - malaise, aches, fever - conjugated bilirubin rises, dark urine
    • 3. icteric phase - lasts 7-30 d - jaundice in sclera, pale stools, pruritis reported in 40% of pts
    • 4. convalescent phase - may take up to 6 mo - fatigue and weakness
  5. What is the incubation period for HAV, B, C?
    • A: 28 d
    • B: 120 d
    • C: 45 d
  6. Describe chronic viral hepatitis
    • hepatocellular necrosis and inflammation, often with fibrosis, lasting 6+ months
    • not caused by HAV
    • mild to severe
    • can result in cirrhosis, portal HTN, hepatocellular carcinoma
    • liver injury is d/t cytolytic t-cell response to virus-infected hepatocytes (not from the virus itself being cytopathic)
  7. Which Hepatitis viruses are transmitted enterally, which are transmitted parenterally?
    • Enterally - A, E (not in chronic carrier state)
    • Parenterally - B, C, D (exist in chronic carrier state)
  8. Serologic test results for HBV
    • HBc (core particle) - indicates replicating HBV
    • HBsAg (surface antigen) - the immunogenic component of the vaccine

    If pt is negative for HBsAg, anti-HBc, and anti-HBs they are susceptible

    If pt is negative for HBsAg, but positive for anti-HBc and anti-HBs, they are immune d/t natural infection (have cleared the infx)

    If pt is negative for HBsAg and anti-HBc, but positive for anti-HBs, they're immune d/t HBV vaccine

    If pt is positive for HBsAg, anti-HBc, IgM anti-HBc, and negative for anti-HBs, they are acutely infected (can tell b/c IgM goes up first)

    If pt is positive for HBsAg and anti-HBc, and negative for IgM anti-HBc and anti-HBs, they are chronically infected

    If the HBsAg is negative, the anti-HBc is positive, and the anti-HBs is negative, the interpretation is unclear. Most likely a resolved infection, but could be susceptible, low level chronic infx, or resolving acute infx.
  9. How is chronic infection defined? What does the timeline look like graphically?
    • Defined as presence of detectable HBsAg, HBeAg, and HBV DNA for > 6 months.
    • The HBsAg peaks around 2 weeks post exposure and then levels out and stays high.
    • The total anti-HBc and IgM anti-HBc begin to rise around 6 weeks and peak around 16 weeks. The IgM then drops off while the total anti-HBc remains high and levels off.
  10. What are the phases of chronic hepatitis infection? Describe each.
    Immune tolerant (4-10 weeks) - viral replication is active, but little or no evidence of disease. HBsAg are produced and IgM anti-HBc are produced before sx onset

    Immune active - symptomatic - flares of hepatitis and increased ALT. Presence of HBeAg. Development of cirrhosis and hepatocellular carcinoma occurs in this phase. Repetitive cycle of inflammation, damage, healing, inflammation, damage, healing, etc.

    Inactive carrier - levels of HBV DNA are present in liver, but undetectable. Seroconversion - anti-HBe develop and clear HBeAg.
  11. Treatment of HBA
    • No drugs therapies
    • Supportive tx only - bed rest, anti-nausea meds (avoid chlorpromazine d/t cholestasis), correct fluid imbalance, pain control with APAP, cholestyramine for pruritis
  12. Treatment of HBV
    • Acute - just supportive tx
    • Chronic - interferons, lamivudine, adefovir, entecavir, tenofovir, telbivudine
    • Only interferons have a defined duration of teatment - the rest are for at least 6 months after appearance of anti-HBe
  13. When is treatment indicated for HBV?
    • infants born to infected mothers
    • decompensated cirrhosis
    • compensated cirrhosis
    • cirrhosis or advanced fibrosis and HBV in serum
    • reactivation following immunosuppression
    • acute liver failure
  14. What indicates the presence of decompensated cirrhosis?
    • acites
    • hepatic encephalopathy
    • hemorrhage d/t portal HTN
  15. What are positive indicators of compensated liver disease?
    • Bilirubin </= 2
    • Albumin stable and WNL
    • PTT < 3 sec (prolonged)
    • WBC >/= 3,000
    • Platelets >/= 70,000
  16. In order to use interferons, patients must have which - compensated or decompensated liver disease?
    • compensated
    • cannot use interferons if decompensated d/t incr risk of liver failure
  17. Treatment goals for HCV & when indicated
    • goal = complete resolution of s/s and eradication of HCV
    • tx indicated for previously untreated pts with chronic HCV, circulating HCV DNA, increased ALT, and histologic evidence of moderate to severe hepatitis and fibrosis
  18. Symptoms of all types of viral hepatitis
    • fever
    • fatigue
    • loss of appetite
    • nausea
    • vomiting
    • abdominal pain
    • clay-colored stool
    • joint pain
    • jaundice
  19. MOA of peginterferon-alpha2b, peginterferon-alpha2a, interferon-alpha2b
    • inhibit viral replication and cell proliferation
    • immunomodulation
  20. Indication for peginterferon alpha 2 b
    alone or in combo with ribavirin for chronic HCV
  21. indication for peginterferon alpha 2 a
    • alone or in combo with ribavirin for chronic HCV
    • chronic HBV with compensated liver disease
  22. indication for interferon alpha 2 b
    • alone or in combo with ribavirin for chronic HCV in pts > 3 years with compensated liver disease
    • chronic HBV in pts > 1 year with compensated liver disease
  23. Adverse reactions with interferons
    Depression, flu-like sx, insomnia, bone marrow suppression - neutropenia, irritability, alopecia
  24. MOA of lamivudine and indications and AEs
    • nucleoside analogue inhibits reverse transcriptase of HBV
    • indicated for treatment of chronic HBV
    • AEs - lactic acidosis and severe hepatomegaly with steatosis, malaise, fatigue, GI

    Resistance may develop
  25. Nucleotide/nucleoside analogues used to treat HBV and their MOA
    • lamivudine
    • adefovir
    • entecavir
    • tenofovir
    • telbivudine
    • They inhibit reverse transcriptase of HBV
  26. AEs of nucleoside/nucleotide analogs used to treat HBV
    lactic acidosis and severe hepatomegaly with steatosis
  27. MOA of ribavirin, indication, and AEs
    • nucleoside analogue - MOA vs. HCV unknown
    • indicated in combo with peginterferon alpha2a or alpha2b to treat chronic HCV infx
    • AE - hemolytic anemia within 1-2 weeks of initiation of tx
    • Pregnancy category X
  28. Appropriate antiviral agent dosing for HBV and HCV
    • peginterferon-alpha2b: 1mcg/kg/wk x 52 wk
    • peginterferon-alpha2a: 180mcg/wk SQ x 48 wk
    • interferon-alpha2b: for HBV, 30-35 million IU SQ TIW; for HCV, 3 million IU SQ TIW
    • Lamivudine: 100 mg PO QD
    • Adefovir: 10 mg PO QD
    • Entecavir: 0.5 - 1 mg PO QD (depend on if tx naive or not)
    • Tenofovir: 300 mg PO QD
    • Telbivudine: 600 mg PO QD
    • Ribavirin: genotypes 2,3 give 800 mg po qd; genotypes 1,4 give 1000 mg po qd if , 75 kg or 1200 mg po qd if 75 kg +
Card Set
Viral Hepatitis
Exam 6 Therapeutics Viral Hepatitis Klepser