Viral HEP-Table 1 Flashcards
Which hep infections can be chronic?
B,C, D
How long can Hep A live in an environment? How can you disinfect it?
Up to 1 mo
—Requires disinfection with 1:100 dilution of bleach in tap water
—Minimum of one minute at 85 degrees Celsius
What is the infectious cycle of Hep A?
Ingest HAV Absorption in stomach or small intestine Entry into circulation Uptake into liver Replication Released into blood and secreted into bile by liver Excreted in stool
Take away points about Hep A?
Acute, self limiting, confers lifelong immunity
What is the clinical presentation of HepA?
Non-specific –HA, anorexia, N/V etc
What pt population is generally asymptomatic if infected with HepA?
Children under 6 yr old
What are the rare complications associated with HepA?
—Relapsing hepatitis —Cholestatic hepatitis —Fulminant hepatitis More likely in patients with chronic liver disease High fatality rate —Fatalities More likely > 50 years of age More likely if pre-existing liver disease
How is Hep A tx?
Supportive- liver transplant if pt has liver failure
How can Hep A be prevented?
HAV vaccine part of childhood vaccination schedule at 1 year
Good hand hygiene
When is the HAV immunoglobulin most effective? What pts wouldn’t need this?
Most effective if given during incubation period (within 2 weeks of infection)
Patients with at least 1 dose of HAV vaccine at least 1 month prior do not need
When is the HAV immunoglobulin recommended?
Close personal contacts of HAV infected person
Staff and attendees of day care center when HAV occurrence is documented
Common source outbreak
Schools, hospitals, work settings with close contact of infected person
How is HepB transmitted?
Sexual —Homosexual —Heterosexual Parenteral —Injection Drug Use Perinatal —Most common in areas of high HBV prevalence Other —Contact with infected body fluid —Can survive 7 days in environment
What are the potential stages of Hep B?
Incubation, clinical illness, acute case fatality, chronic infection, premature mortality from liver dz
What is the average length of the incubation period?
60-90 days but can range from 45-180
What is the clinical presentation of Hep B?
Up to half of all adults will have jaundice Fever Anorexia Nausea Vomiting Dark urine Clay colored or pale stools Abdominal pain kids can be asymptomatic
When is the HBsAg present?
onset of clinical symptoms
If the HBsAg is persistent past 6mo, what does this indicate?
Chronic infection
If HBsAg is present, Is your pt infectious?
YES
When does the antibody to HBsAg indicate?
Immunity to virus and that HBsAg has been cleared
What serologic marker will be found in vaccinated pts?
Antibody to HBsAg
When is HBeAG present?
Acute phase of infection
What is the role of HBeAG ?
Unclear but assumed to be a marker of viral replication/inefectivity
When does the antibody to HBeAG (HBeAB or anti-HBe) develop?
Once the infection resolves
What is seroconversion and what does it predict/indicate?
Spontaneous conversion from antigen to antibody and predicts long term clearance of HBV and indicates lower levels of HBV
When does the hep B core antigen (HBcAg )appear? Where is it expressed?
Appears early and persists for life- it is expressed on hepatocytes and promotes immune mediated cell death
Which serologic marker is used to diagnose fulminant acute hep?
Immune globulin M Antibody (IgM anti-HBc)
When are IgM anti-HBc at high levels?
During acute infections
What does the Total Hepatitis B core Antibody (anti-HBc) indicate?
previous or recent infection
Chronically infected HBV patients may experience recurring flares of what?
Serum ALT levels
What factors are associated with HBV cirrhosis and dz progression?
Persistence of HBV serum DNA Infection with genotype C Co-infection with delta hepatitis Co-infection with HIV Age at diagnosis Severity of liver disease at diagnosis Male sex Frequency of severe hepatic flares Alcohol use Laboratory/ physical findings of abnormal liver function
What is HBV a known risk factor for?
Hepatocellular carcinoma
What factors are predicative of hepatocellular carcinoma development?
—Persistently elevated HBV DNA levels (> 10,000 copies/mL) —Males —Older age —Coinfection with HCV or delta hepatitis —Preexisting cirrhosis —Continued alcohol ingestion
What factors are predictors of survival in hepatocellular carcinoma?
—HBsAg seroclearance
—Younger age
—Maintenance of liver function
What is the dose series for the Hep B vaccine?
3 dose series
0, 1-2, 4-6 months
What is considered a non-repsonder to HepB vaccine?
If
What should you do if your pt is a nonresponder?
revaccinated with > 1 dose of HepB vaccine
What can be given as a post exposure prophylaxis?
Hepatits B immunoglobulin (HBIG)
What does Hepatits B immunoglobulin (HBIG) provide?
passive and temporary (3-6 month) protection.
What combo tx should be given if perinatal transmission is a possibility?
HBIG Hep B series combo is 85-95% effective in preventing infection
What is the tx for chronic HBV pts with HBV DNA = 2000 with normal ALT and no histologic disease?
No tx
What is the tx for chronic HBV pts with HBV DNA = 2000 with normal ALT and histologic disease is evident?
Consider tx
What is the tx for chronic HBV pts with HBV DNA >2000?
TX
tenofovir, entecavir or Peg-IFN alpha 2a
What was thr first approved therapy for tx of HBV?
Pegylated interferon
What is the MOA of pegylated interferon (INF)?
—Acts as host cytokine
Antiviral
Antiproliferative
Immunomodulatory
Pts with a response to INF typically have more what?
—more permanent seroconversion
Rates 30-40%
What factors are associated withimproved response to INF?
- Increased ALT
- High histological score at biopsy
- Non-Asian Patient
What are the ADRs of INF?
- Fatigue
- Fever
- Headahce
- Nausea
- Anorexia
- Rigors
- Myalgai
- Arthralgia
- Musculoskeletal pain
- Alopecia
- Injection Site reactions
- Risk of Infection
- Anxiety
- Insomnia
- Depression
- Suicidal/homicidal ideation
When is INF not indicated?
For pts with decompensated cirrhosis
Lamivudine has profound antiviral activity, why is it no longer the preferred agent for chronic therapy?
Resistance rates
How long does it take Lamivudine to normalize ALT levels?
3-6 months
How is the antiviral acvitivity of Lamivudine?
weak
How is Lamivudine administered?
Daily for 1 year
What is Lamivudine effective against?
wild type and lamivudine resistant HBV
When should entecavir not be used?
In HIV co-infected pts
Can use in lamivudine resistance but there is a higher chance of developing resistance
What is Telbivudine?
An HBV specific nucleoside analogue that has no other viral activity
What are the ADRs of Telbivudine?
Myopathy, peripheral neuropathy
When is tenovir used?
Used in HIV co-infection and useful for lamivudine resistant HBV
What drugs are used in compensated HBV cirrhosis?
Tenofovir or Entecavir
What is the tx from de-compensated HBV cirrhosis?
—Liver transplant
—Lamivudine and Adefovir or Entecavir or Tenofovir
What panel should be considered in pts with prior exposure to lamivudine/emtricitabine ?
Baseline HBV resistance panel
If pts have HBV and HIV coinfection with a CrCl >50, what is the preferred tx?
—Tenofovir, this is first line in HIV and effective with HBV including lamuvidine resistant
If pts have HBV and HIV coinfection with a CrCl
entecavir regimen is preferred since tenofovir can cause proximal tubular injury and worsen kidney disease
Where does Hep C replicate?
Within the hepatocytes
What can Hep C lead to?
—chronic liver disease
—Hepatocellular carcinoma
—deaths
What is the most frequent indication for liver transplant?
Hep C
In an acute Hep C infection, when do symptoms typically begin and what are they?
within weeks of exposure, symptoms of jaundice, fatigue, anorexia, weakness, abdominal pain
When are the serum labs elevated in acute hep C infections?
HCV RNA within 1-3 weeks exposure
Elevated ALT within 4-12 weeks
What are the initial symptoms in chronic Hep C infection?
mild; fatigue, nausea, right upper quadrant discomfort
As the dz progressively causes damage in chronic hep c, what are the symptoms?
fluid retention, muscle weakness, jaundice, weight loss
What are determinants of the dz progression of hep C?
Excessive alcohol intake Excessive marijuana smoking Concomitant disease associated with liver injury HIV Advanced histological grade Persistently elevated aminotransferases Male sex Older age Obesity Hepatic steatosis Immune suppression
Can Hep C be transmitted perinatal?
Transmission only from women HCV-RNA positive at delivery, this is a pretty low rate and the method of delivery and feeding has no association to transmission
What are the goals of HepC therapy?
CURE and prevention of complications
What is sofosbuvir?
Nucleotide inhibitor of HCV indicated for genotypes 1-4 as part of combination therapy
What is the duration of therapy for sofosbuvir?
12 weeks for tpe 1,2,4 or 24 weeks for type 3… once daily tablet
What is simepravir and what type is it effective against?
oral HCV protease inhibitor used as a component of combo antiviral tx
effective against genotype I
What are the ADRs of SImepravir?
—Photosensitivity —Rash, pruritus —Nausea —Myalgia Dyspnea
What are the drug interaction with simepravir?
—Carbamazepine —Phenytoin —Rifamycins —Clarithromycin —St. Johns wort —Milk thistle —Most antiretrovirals
What lab abnormalities will simepravir cause?
—Hyperbilirubinemia
—Anemia
What is the MOA of Ledipasvir?
Inhibits HCV NS5A protein needed for viral replication
What drug is ledipasvir always given in combo with?
Sofosbuvir- also effective against genotype I
What are the ADRs of ledipasvir?
Fatigue, headache
What lab abnormalities are seen with ledipasvir therapy?
Hyperbilirubinemia
How is ledipasvir dosed?
Once daily
What drugs comprise the Veikira Pak?
Paritaprevir/Ombitasvir/Dasabuvir/ Ritonavir
What is the MOA of Paritaprevir?
Protease inhibitor
What is the MOA of Ombitasvir?
HCV NS5A inhibitor
What is the MOA of Dasabuvir?
HCV virus nonnucleoside polymerase inhibitor
Why is Paritaprevir given with Ritonavir?
It’s the “boost”, CYP 3A inhib
What are the ADRs of the Pak?
Fatigue, diarrhea, nausea, decreased Hg
What are the drug interactions with the Pak?
P450
When tx HCV with a HIV co-infection, sofosbuvir should NOT be used with what?
tipranavir
When tx HCV with a HIV co-infection, ledipasvir-sofosbuvir should NOT be used with what?
elvitegravir, cobicistat, tenofovir, and emtricitabine
When tx HCV with a HIV co-infection, simeprevir should NOT be used with what?
protease inhibitors or non-nucleoside reverse transcriptase inhibitors
When tx HCV with a HIV co-infection, ribavirin should NOT be used with what?
didanosine
