11-30 Treatment of Hepatitis DSA - Phys & Tx Guidelines Flashcards

1
Q

What is the case definition of acute viral hepatitis?

A
  1. Discrete onset of symptoms – nausea, anorexia, fever, malaise, or abdominal pain;
  2. PLUS jaundice or elevation in serum aminotransferase levels.
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2
Q

How do you confirm Dx of hepatitis?

A

serological testing, clinical characteristics similar

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3
Q

What can untreated acute viral hepatitis lead to?

A

Untreated, hepatitis B and C infections may cause significant disease leading to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). These infections are associated with high morbidity and mortality.

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4
Q

Compare Hepatitis A, B, and C viruses in regards to:

RNA or DNA

A

A - RNA

B - DNA

C - RNA

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5
Q

Compare Hepatitis A, B, and C viruses in regards to:

Transmission

A

A - fecal oral

B - sexual, parenteral, perinatal

C - sexual, parenteral, perinatal

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6
Q

Compare Hepatitis A, B, and C viruses in regards to:

Incubation period

A

A - 28 (15-50 days)

B - 90 days (60-150 days)

C - 4-12 weeks (2-24 weeks)

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7
Q

Who is at risk in catching Hepatitis A?

A

Travelers to countries with high/intermediate prevalence of HAV

Children, household, or personal contacts

Men who have sex with men

Injection drug users

Persons with clotting factor disorders

Low socioeconomic status (poor sanitation/overcrowding)

Persons working with nonhuman primates

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8
Q

Who is at risk in catching Hepatitis B?

A

Sex partners of infected persons

Infants born to infected mothers

Men who have sex with men

Injection drug users

Household contacts of persons with chronic HBV

Healthcare workers at risk for occupational exposure

Hemodialysis patients

Travelers to countries with high/intermediate prevalence of HBV

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9
Q

Who is at risk for catching Hepatitis C?

A

Current or former injection drug users

Recipients of clotting factor concentrates before 1987

Recipients of blood transfusions or solid organ transplants before July 1992

Chronic hemodialysis patients

Persons with known exposure to HCV

Persons with HIV

Children born to HCV-positive mothers

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10
Q

What does Hepatitis A cause, in terms of SSXs?

A

Acute, self-limiting illness which confers lifelong immunity once exposed.

Adults – symptoms usually last < 2 months; most common sign is jaundice (70%).

Children < 6 years – no jaundice occurs; majority asymptomatic but viral shedding can last for months (serve as a highly infectious reservoir).

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11
Q

What is the incidence of Hepatitis A?

A

Incidence of acute HAV has dropped 95% (1995-2013), likely due to vaccination recommendations.

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12
Q

What is the testing for Hepatitis A?

A

Serologic test: immunoglobulin M (IgM) antibody to HAV.

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13
Q

What is the treatment for Hepatitis A?

A

Treatment: supportive care; nearly all patients will have clinical resolution within 6 months of infection (majority will experience clinical resolution earlier, within 2 months).

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14
Q

What is the prevention and prophylaxis of Hepatitis A?

A

Prevention and prophylaxis – good hand hygiene; vaccination.

Immunoglobulin (Ig) for pre-exposure and post-exposure prophylaxis (passive immunity).

Vaccination preferred (active immunity) but Ig used when vaccine not an option (i.e., allergy).

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15
Q

How infectious is Hepatitis B? Is it curable?

A

Highly infectious (50-100x more than Human Immunodeficiency Virus); infection is not curable.

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16
Q

How has the incidence of Hepatitis B changed?

A

Incidence of acute HBV has dropped ~82% (1991-2013); the greatest decline has occurred among children born since 1991 (routine vaccination recommendations implemented).

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17
Q

What are the SSXs of Hepatitis B infection?

A

Symptoms: fever, anorexia, nausea, vomiting, jaundice, dark urine, pale stools, abdominal pain, fatigue, joint pain.

Many neonates, children, and adults have no clinical symptoms.

Children (perinatal exposure) pose a special problem as viral replication may last decades while patient is asymptomatic, undiagnosed, and highly infectious.

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18
Q

In testing for Hep B, when does HBsAg occur?

A

Hepatitis B surface antigen (HBsAg) – HBV surface protein; high levels occur during acute or chronic infection. If HBsAg found, patient is infectious. Normal immune response produces antibodies to this antigen (HBsAg used to make HBV vaccine).

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19
Q

In testing for Hep B, when does anti-HBs occur?

A

Hepatitis B surface antibody (anti-HBs) – identification of surface antibodies may be interpreted as recovery or immunity from HBV. These antibodies will also arise after successful vaccination.

20
Q

In testing for Hep B, when does anti-HBc occur?

A

Total hepatitis B core antibody (anti-HBc) – appears at onset of infection (will persist for life) and indicates previous or ongoing infection.

21
Q

In testing for Hep B infection, when does IgM anti-HBc occur?

A

IgM antibody to hepatitis B core antigen (IgM anti-HBc) – delineates recent (acute) infection with HBV within the previous 6 months.

22
Q

In testing for Hep B, when does HBeAg occur?

A

Hepatitis B e antigen (HBeAg) – indicates high levels of HBV. Found during acute and chronic infection and indicates viral replication.

23
Q

In testing for Hep B, when does HBeAb occur?

A

Hepatitis B e antibody (HBeAb) – indicates lower levels of HBV. Immune system may produce these antibodies after acute infection or after a burst in viral replication. Spontaneous antigen to antibody conversion (aka “seroconversion”) is a good predictor of viral clearance in those receiving treatment.

24
Q

Describe interpreting serological tests for HBV in someone who is:

Susceptible

Immune: natural infection

Immune: HBV vaccination

Acutely infected

Chronically infected

Unclear

A

Interpretation:

Test Performed

HBsAg

Anti-HBc

IgM Anti-HBc

Anti-HBs

Susceptible

-

-

-

Immune: natural infection

-

+

+

Immune: HBV vaccination

-

-

+

Acutely infected

+

+

+

-

Chronically infected

+

+

-

-

Unclear*

-

+

-

* Four possibilities: 1. Resolved infection; 2. False-positive anti-HBc, thus susceptible; 3. “Low-level” chronic infection; 4. Resolving acute infection

25
Q

What is the most effective strategy to prevent HBV infection? Why is this strategy unique?

A

HBV vaccine is the first vaccine against a major human cancer (hepatocellular carcinoma; HCC).

Vaccination is the most effective strategy to prevent infection.

Passive immunity via hepatitis B Ig used in conjunction with vaccine for post-exposure prophylaxis.

26
Q

What is the goal of HBV therapy?

A

Decrease morbidity (progressive liver disease, cirrhosis, HCC, hepatic failure) and mortality.

Sustained suppression of HBV replication has been associated with normalization of serum ALT, loss of HBeAg with or without detection of anti-HBe, and improvement in liver histology.

27
Q

What are the indications for undergoing treatment for HBV infection?

A

Indications for undergoing treatment (not recommended for all chronic HBV patients):

Treat if risk of liver related morbidity and mortality is within foreseeable future and likelihood of achieving a sustained virologic response is high.

Certain patients are best monitored for disease progression. These patients have a low chance of therapeutic response which does not outweigh the risks/costs associated with treatment.

28
Q

What is the non-pharmacological management of HBV infection?

A

Non-pharmacologic management:

Vaccinate sexual and household contacts

Avoid alcohol

Vaccinate against HAV to prevent further liver damage

Currently there is insufficient data to support use of herbal remedies

29
Q

What is the most common blood-borne pathogen? When is this pathogen Dx’ed?

A

Most common blood borne pathogen. Disease course is insidious; many will not be diagnosed until there has been significant disease progression.

30
Q

What is the largest risk factor for HCV infection?

A

Single largest risk factor for infection – injection drug abuse.

31
Q

What are the SSXs of HCV?

A

Mild/non-specific symptoms (33%): fatigue, anorexia, weakness, jaundice, abdominal pain, dark urine.

Acute infections rarely progress to fulminant hepatitis, but 85% will go on to develop chronic HCV;

Increases risk of cirrhosis, end-stage liver disease, HCC.

Chronic symptoms: few if any; persistent fatigue, right upper quadrant pain, nausea, poor appetite.

32
Q

What is the goal of treatment for HCV?

A

Viral eradication, called a sustained viral response (SVR), which is defined as the absence of HCV RNA by polymerase chain reaction for 12-weeks (traditionally defined as undetectable at 24-weeks post-treatment) after completion of therapy.

Clinical trial endpoints typically include SVR.

SVR associated with improved liver histology, decreased HCC, sometimes cirrhosis regression.

HCV clearance without therapy ~15-30%.

33
Q

What are the indications for treatment for HCV?

A
  1. ALL patients with virologic evidence of chronic HCV infection (detectable HCV viral level over a 6 month period), except for those with short life expectancies.
  2. Prioritize patients based on highest risk of morbidity and mortality from untreated HCV:
    1. Advanced fibrosis or compensated fibrosis, transplant recipients, extrahepatic manifestations
    2. Symptomatic HCV and potential for transmission
34
Q

What is the likelihood of achieving an SVR in HCV Tx?

A
  1. The likelihood of achieving an SVR is generally > 90% with use of the new, highly effective HCV regimens among:
    1. Adherent
    2. Immunologically competent
    3. Treatment-naïve patients with compensated liver disease
35
Q

Why is a basic understanding of the HCV lifecycle helpful?

A
  1. To better understand the mechanism of the new, direct-acting antivirals it may be useful to discuss key processes in the viral lifecycle of HCV. (Drug targets are bolded in the following discussion)
36
Q

What does HCV do after it enters the cell?

A
  1. After the virus enters the cell, viral RNA is translated (via host machinery) into a polyprotein precursor.
37
Q

What happens to HCV after translation?

A
  1. After the virus enters the cell, viral RNA is translated (via host machinery) into a polyprotein precursor.
  2. This polyprotein is cleaved (via host and viral-encoded proteases) into mature proteins, including a number of nonstructural (NS) proteins.
38
Q

How does HCV do post-translation processing?

A
  1. This polyprotein is cleaved (via host and viral-encoded proteases) into mature proteins, including a number of nonstructural (NS) proteins.
  2. Viral protease involved in post-translational processing = complex of NS3 and NS4A proteins (NS3/NS4A).
39
Q

What is the complex responsible for new HCV RNA synthesis?

A
  1. Viral protease involved in post-translational processing = complex of NS3 and NS4A proteins (NS3/NS4A).
  2. Complex responsible for new viral RNA synthesis consists of NS3, NS4A, NS4B, NS5A, and NS5B.
40
Q

What organizes the replication complex for HCV?

A
  1. NS5A may be involved in the organization of the replication complex, regulating replication, and assembly of the viral particle.
41
Q

What is NS5B?

A

NS5B is an RNA-dependent RNA polymerase essential for viral replication.

42
Q

What are all the drug targets in the HCV life cycle?

A

viral protease - (Ns3/NS4A)

NS3

NS4A

NS5A

NS5B

43
Q

Describe the entire HCV lifecycle.

A
  1. After the virus enters the cell, viral RNA is translated (via host machinery) into a polyprotein precursor.
  2. This polyprotein is cleaved (via host and viral-encoded proteases) into mature proteins, including a number of nonstructural (NS) proteins.
  3. Viral protease involved in post-translational processing = complex of NS3 and NS4A proteins (NS3/NS4A).
  4. Complex responsible for new viral RNA synthesis consists of NS3, NS4A, NS4B, NS5A, and NS5B.
  5. NS5A may be involved in the organization of the replication complex, regulating replication, and assembly of the viral particle.
  6. NS5B is an RNA-dependent RNA polymerase essential for viral replication.
44
Q

What do current therapies do to ‘cure’ HBV?

A

They don’t cure it:

  1. Current therapies suppress HBV replication without eradicating the virus; viral DNA exists indefinitely within the infected cell (would allow the virus to reactivate).
45
Q

What do the AASLD (American Association for the Study of Liver Diseases) recommend for Tx of HBV?

A

AASLD Guidelines for Treatment of Chronic Hepatitis B recommend:

Peg-IFN, entecavir, and tenofovir as preferred therapies.

Patient specific factors to consider in choosing between therapies:

desire for finite therapy (NA duration of therapy is variable), tolerability of side effects, comorbidities (see Peg-IFN CIs), history of resistance, family planning, medication cost

46
Q
A