Therapeutics ID Bergman Flashcard

Hepatitis A: Transmission

  • Fecal-Oral mainly
  • Rarely sexual or parenteral (IVDU)

Hepatitis E: Transmission

  • Fecal-Oral mainly
  • Rarely sexual or parenteral (IVDU)

Hepatitis B: Transmission

Blood and bodily fluids

  • Parenteral, both IVDU and healthcare workers
  • Perinatal, mother to child = high risk
  • Sexual contact and mucous membranes less common

Hepatitis C: Transmission

Blood and bodily fluids

  • Parenteral, both IVDU and healthcare workers
  • Perinatal, mother to child = high risk
  • Sexual contact and mucous membranes less common

Hepatitis A: Clinical Course

  • Acute only
  • No chance of cirrhosis or hepatocellular carcinoma
  • You get sick and it goes away

 

Hepatitis E: Clinical Course

  • Acute only
  • No chance of cirrhosis or hepatocellular carcinoma
  • You get sick and it goes away

Hepatitis B: Clinical Course

  • Chronic disease and hepatocellular carcinoma possible, but uncommon in adults (body develops antibodies against it)
  • Most likely to become chronic when acquired as newborn –> if mother develops Hep B, that means she hasn’t developed antibodies against, which means the baby doesn’t have antibodies against it either

Hepatitis C: Clinical Course

  • Very likely to become chronic in adults
  • Takes many years (~20) for cirrhosis to develop –> that is when symptoms start to appear
  • Hepatocellular carcinoma possible

Hepatitis A: Sources of Infection

  • Person to person contact, fecal contamination and oral ingestion
  • Contaminated water and food: raw, unwashed fruits, vegetables, or inadequately cooked shellfish
  • Associated with unsanitary conditions and hygiene practices

Hepatitis A: Persons at risk in US

  • International Travelers
  • Associated with food-borne outbreaks
  • Homosexual men
  • IV drug abusers (rare)

Hepatitis A: Clinical Features

  • Mild, self-limiting disease — lasts only a few weeks, but can take up to 6 months to fully resolve
  • Children

 Mild flu-like symptoms

No jaundice

  • Adults

 Mild flu-like symptoms (malaise, fever, headache, RUQ pain)

Abrupt onset of anorexia, N/V/D
Jaundice from increased total bilirubin -> scleral icterus

Elevated LFTs = hepatic transaminase, GGTP, Alkaline Phosphatase

  • Fulminant hepatitis or death (from dehydration usually) can occur rarely
  • No cases of chronic hepatitis or carrier state

Hepatitis A: Treatment

  • Prevention: Hep A vaccine — good handwashing and hygiene will help
  • Post-exposure prophylaxis: vaccine or IV immunoglobulin
  • Avoid alcohol and hepatoxic drugs
  • Eat a healthy diet and rest

Hepatitis B: Transmission

Blood and bodily fluid

  • saliva, vaginal fluids, or semen
  • post-transfusion infection now rare

Hepatitis B: High-Risks Groups

  • IV Drug Abusers
  • Multi-transfused patients
  • Health care workers through needlesticks, etc.
  • Male homosexuals
  • Heterosexual partners of HBV infected persons and partners of HIV infected patients

Hepatitis B: Clinical Features

  • First, an asymptomatic incubation period

THEN

  • Symptomatic Prodromal Phase

Malaise, fatigue, weakness, anorexia, myalgias, and arthralgias

Jaundice occurs in 1/3 of patients and may persist for several weeks

  • Symptoms are age dependent (range from no signs to developing liver failure)
  • Newborns: generally asymptomatic, but can’t clear the virus and can develop a chronic or persistent infection –> vaccination critical at birth
  • Adults: most adults develop antibodies against virus and have a subclinical infection — the others have symptomatic illness with jaundice and can develop:

 fulminant hepatic failure

chronic or persistent infection

chronic aggressive hepatitis

cirrhosis, ascites

  • Chronic infection can lead to cirrhosis or Hepatocellular Carcinoma

Hepatitis B: Treatment

FIRST LINE ORAL NRTIs

  1. Entecavir (HepB only)
  2. Tenofovir (HepB and HIV)

OTHER ORAL NRTIs

  1. Telbivudine (resistance developed quickly)
  2. Lamivudine (resistance developed quickly)
  3. Adefovir (no cross resistance with the above two)

ALT.

  • Interferon α-2 SQ injection

Hepatitis B: Monitoring

Disease:

  • Loss of antigen and viral DNA
  • Decrease symptoms (flu-like, etc.)
  • Normalize LFTs
  • Reduce rate of cirrhosis, liver failure, and death

Treatment Side Effects:

  • NRTIs: Lactic Acidosis, peripheral neuropathy/paresthias
  • Tenofovir and Adefovir: Renal function/SCr
  • Telbivudine: Myopathies
  • Interferon: bone marrow suppression, etc.

NRTIs: Side Effects

  • Lactic Acidosis
  • Peripheral neuropathy/paresthias
  • Pancreatitis
  • Myopathy
  • Bone Marrow Toxicity
  • Hepatic Toxicity

Tenofovir: Monitoring
Renal Function/SCr
Adefovir: Monitoring
Renal function/SCr
Telbivudine: Monitoring
Myopathies
Interferon α-2: Monitoring
Bone marrow suppression, etc.
Hepatitis B: Pre-Exposure Prophylaxis
Vaccine recommended for all children and at risk adults
Hepatitis B: Post-Exposure Prophylaxis
IV Immunoglobulin (HBIG)
Hepatitis C: Risk Groups

Blood and Bodily Fluids

  • IV drug users
  • Sexual contact with infected persons
  • Persons with multiple sex partners
  • Recipient of transfusion before July 1992
  • Recipient of clotting factors made before 1987
  • Infants born to infected women
  • Intranasal cocaine use
  • Tattooing/body piercing
  • Shared razors
  • Hemodialysis patients
  • Health care workers

Hepatitis C: Clinical Features

  • Physical symptoms do not correlate well with severity of liver injury
  • Little evidence that disease is progressing in patient
  • Serum enzymes can be normal or elevated
  • Symptoms: fatigue, malaise, anorexia, weight loss — NO N/V/D
  • Some patients develop jaundice
  • Mild but persistent elevations of LFTs
  • Ongoing viral replication is the most important factor in evaluating disease progression
  • Can progress to cirrhosis, then liver failure, and/or HCC

 

Hepatitis C: Treatment

ALWAYS USE COMBINATION IF POSSIBLE


Interferon-α 2a or 2b SQ infection — once weekly pegylated formulation

+

Ribavirin PO BID with food for GI upset

 

Vaccinate against Hep A and B

 

 

 

Hepatitis C: Duration of Treatment for Genotype 1 or 4
1 year treatment = poor cure rates
Hepatitis C: Duration of Treatment for Genotype 2 or 3
6 months of treatment = cure rates good
Hepatitis C: Monitoring

Viral Load: by halfway point of therapy, it must decrease by 2 log or else therapy is very unlikely to work

 

Drug Side Effects

  • Injection site reactions plus rash and dry skin
  • Flu-like symptoms and fatigue
  • Psychiatric events: depression and suicidal ideation
  • CBC: hemoglobin, neutrophils, platelets and TSH
  • Birth defects with ribavirin, pregnancy test monthly

Hepatitis D: Treatment

  • Virus is similar to Hep B
  • It can only be acquired in presence of HBV
  • Therefore, vaccinate against Hep B to prevent it!

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