Chronic Viral Hepatitis Flashcards
What are the two types of hepatitis that most commonly transition from acute to chronic?
Hepatitis B
Hepatitis C
What differentiates acute vs chronic hepatitis infection?
Presence of virus in the blood 6 months after infection
What biomarkers confirm chronic hepatitis B and hepatitis C infection?
Hepatitis B:
HBsAg
Hepatitis C:
Both anti-HCV and HCV RNA
What is the consequence of untreated chronic viral hepatitis?
Development of cirrhosis, hepatocellular carcinoma and decompensation with end-stage liver disease
Chronic hepatitis D is uncommon, but if patient is co-infected with B and D, the liver disease is typically _______ severe and has ________ clinical outcomes.
More
Worse
Goal of therapy for hepatitis B is to __________.
Goal of therapy for hepatitis C is to __________.
Control viral replication
Cure
What is defined as sustained viral suppression of hep B?
- Undetectable serum HBV DNA (<10-15 units/mL)
- Normalization of ALT
___________ cure of hep B is the most desirable goal of therapy but is rare and not the goal for most treatments
Functional
What is defined as functional cure of hep B?
HBsAg loss with or without appearance of anti-HBs
What does it mean when patient develop anti-HBs following loss of HBsAg?
They become immune to hepatitis B. This is rare though.
The goal of hep C is to cure. How do we define cure?
Sustained virologic response (SVR) which is defined as undetectable serum HCV RNA (<10-15 units/mL) 12 weeks after end of treatment
Following Hep C cure, can you be re-infected?
Yes
If patient is suspected to have chronic hepatitis B, how do we manage close contacts?
Test all household members and sexual contacts:
- HBsAg
- Anti-HBs
If contacts are negative for both, offer then hep B vaccine. Retest for anti-HBs 1 month after last dose to ensure response
If HBV is confirmed, what other viruses should we test for? Why?
HCV and HIV
They have the same transmission route.
How often should you monitor liver aminotransferases (ALT, AST) and liver function test (total bilirubin, serum albumin, INR) for chronic hep B?
Every 6-12 months
Is liver biopsy recommended for hepatitis B patients?
No, not recommended.
Non-invasive testing like FibroScan is available.
When is liver biopsy recommended?
Coexisting liver disease
Discrepancies from FibroScan, imaging and laboratory testing.
What parameters would warrant treatment?
- If there is HBeAg
- HBV DNA levels
- Persistent elevation of ALT >1 x ULN
- Any indication of severe liver disease (biopsy, noninvasive fibrosis markers, imaging and lab tests
What are some non-pharm we can recommend for patients with chronic hep B?
- Advise against alcohol
- Encourage smoking cessation
- Recommend weight reduction if BMI >30
- Blood sugar control if diabetic
What is the goal of therapy with hepatitis B? Can Hep B be cured?
No cure for hep B.
Control disease by complete suppression of HBV DNA
How do we avoid HBV reactivation once disease is resolved?
Oral antiviral therapy prophylactically
What are the three classes of medication for treatment of hepatitis B?
Peginterferon alfa-2a
Nucleoside Analogues
Nucleotide Analogues
What is the mechanism of action of peginterferon alfa-2a?
Antiviral and immunomodulatory effects promote seroconversion from HBeAg positive to anti-HBe positive
When do we use peginterferon alfa-2a as treatment?
Chronic hep B patients who are HBeAG positive.
- Have persistently lower HBV DNA levels and elevated serum aminotransferase values
Who should we avoid peginterferon alfa-2a in?
Acute episodes of Hep B (decompensated cirrhosis)
- Increased risk of life threatening infection and worsening hepatic decompensation
Immunosuppressed patients with chronic hep B
HIV+
What drugs are in the nucleoside analogue drug class?
Lamivudine
Entecavir
What drugs are in the nucleotide analogue drug class?
Tenofovir disoproxil fumarate (TDF)
Tenofovir alafenamide (TAF)
Adefovir
Which nucleos(t)ide analogues are first line?
TDF, TAF, and entecavir
What is the mechanism of action of nucleos(t)ide analogues?
Inhibit replication of HBV in patients who are HBeAg positive or negative
Resistance to therapy was a concern. Which nucleos(t)ide no longer has a concern with resistance?
TDF, TAF, entecavir
Why is lamivudine not a first-line therapy?
Low potency in reducing HBV DNA and high resistance rate.
What is lamivudine’s role in chronic hepatitis B?
Prophylaxis to prevent disease reactivation in patients who are on immunosuppressive therapy who are HBsAg negative but anti-HBc positive
______ is a prodrug of _______ meaning it is inactive until metabolized into it’s active form.
TAF is a prodrug of TDF
What is TDF active against?
HBV (including lamivudine-resistant HBV)
HIV
Is TDF approved for monotherapy of chronic hep B?
Yes
What is TDF active against?
HBV (including lamivudine-resistant HBV)
HIV
Is TAF approved for monotherapy of chronic hep B?
Yes
What makes TAF different from TDF, besides the fact that it is a prodrug?
TAF produces higher levels tenofovir diphosphate than TDF and therefore can be given at lower doses (lower toxicity potential).
What is the preferred management for the following patient with chronic hep B?
What would you categorize this patient as?
HBsAg -
Anti- HBc +
Anti- HBe +/-
ALT status normal
HBV DNA -
Immune from past exposure
No antiviral therapy indicated.
Assess for need of prophylaxis if patient receiving immunosuppressive therapy.
What is the preferred management for the following patient with chronic hep B?
What would you categorize this patient as?
HBsAg -
Anti- HBc -
Anti- HBe +/-
ALT status normal
HBV DNA -
Resolved infection
No antiviral therapy. Monitor ALT and HBV DNA q 3-6 months.
Assess for need of antiviral prophylaxis if patient undergoing immunosuppression
What is the preferred management for the following patient with chronic hep B?
What would you categorize this patient as?
HBsAg +
Anti- HBc -
Anti- HBe +/-
ALT status normal
HBV DNA often <2000
HBeAg- negative chronic infection
No antiviral therapy. Monitor ALT and HBV DNA q3-6 months.
Assess for need of prophylaxis therapy if patient is undergoing immunosuppression.
What is the preferred management for the following patient with chronic hep B?
What would you categorize this patient as?
HBsAg +
Anti- HBc -
Anti- HBe -
ALT status normal
HBV DNA often > 10 000 000
HBe-Ag positive chronic infection
No antiviral therapy. Monitor ALT and HBV DNA q6 months
Assess liver fibrosis. Treat only if severe disease suspected.
What is the preferred management for the following patient with chronic hep B?
What would you categorize this patient as?
HBsAg +
Anti- HBc -
Anti- HBe -
ALT status elevated
HBV DNA 10 000-10 000 000
HBeAg positive chronic hepatitis
Consider therapy with peginterferon or nucelos(t)ide analogues (entecavir, TDF, TAF) if:
- ALT is ≥1 × ULN and
- viral load is >2000
What is the preferred management for the following patient with chronic hep B?
What would you categorize this patient as?
HBsAg +
Anti- HBc -
Anti- HBe +
ALT status elevated fluctuates
HBV DNA 1000 -10 000 000
HBeAg- negative chronic hepatitis
Consider long-term therapy with nucleos(t)ide analogues (entecavir, TDF, TAF) if:
- ALT is ≥1 × ULN and
- viral load is >2000
What is the preferred management for the following patient with chronic hep B?
What would you categorize this patient as?
HBsAg +
Anti- HBc -
Anti- HBe +/-
ALT status elevated
HBV DNA >100
Decompensated cirrhosis
Nucleos(t)ide analogue therapy lifelong
What is the preferred management for the following patient with chronic hep B?
What would you categorize this patient as?
HBsAg +
Anti- HBc -
Anti- HBe +/-
ALT status elevated
HBV DNA +
Post- liver transplant
Nucleos(t)ide analogues plus HBIg
About ___to ___% of acute HCV infections in adults become chronic.
75-85
How is HCV most frequently acquired?
Illicit drug use (snorting cocaine, injecting drugs)
Blood transfusions
Tattooing
Needle-stick injuries
What are risk factors for progressive fibrosis and cirrhosis in patients with chronic hepatitis C?
- Male gender
- Being >40 years of age
- Duration of infection
- Alcohol consumption >50g daily
- Co-infection with HIB
- Immune suppression
- Diabetes
- Higher BMI
What makes the hepatitis C antibody (anti-HCV) different from antibodies in Hep A and B?
It’s a marker for exposure, not immunity.
Therefore an anti-HCV test is used for initial HCV testing
How do we confirm with there is an active infection?
HCV RNA detection by PCR
If patient receives negative anti-HCV test, what is the follow-up procedure?
HCV RNA or follow-up anti-HCV testing should be done if HCV exposure occurred within past 6 months or if patient is immunocompromised
Which patients should be screened for Hep C regardless of risk factors due to their 5x baseline risk?
Patients born between 1945-1975
Following Hep C treatment completion, patient must return ____-____ weeks after for HCV RNA test to determine sustained virologic response (SVR) status.
12-24
What are non-pharms for hepatitis C patients?
- Advise minimal alcohol use
- Advise weight loss if patient is obese
- Advise glycemic control if patient is diabetic
- Avoid herbal products and non prescription liver protective agents
What exams or scans are usually done prior to the start of treatment of HCV?
RNA viral load
Genotyping
Hepatic fibrosis staging (liver biopsy or FibroScan)
What are the drug of choice for treatment of HCV?
DAA (direct-acting antiviral)
What are the three classes of DAAs?
- NS5B polymerase inhibitors
- NS5A inhibitors
- NS3/4A protease inhibitors
What drug is under the NS5B polymerase inhibitor class?
Sofosbuvir
Is sofosbuvir usually used as monotherapy?
No, often used in combo with other antiviral agents.
What are the combo products of sofosbuvir?
- Sofosbuvir/Ledipasvir= Harvoni
- Sofosbuvir/Velpatasvir= Epclusa
- Sofosbuvir/Velpatasivr/Voxilaprevir= Vosevi
Is sofosbuvir a prodrug?
Yes
What are two drug interaction we need to watch out for with sofosbuvir?
Rifampin and sofosbuvir
- decreases sofosbuvir concentrations
Sofosbuvir, NS5A inhibitor and amiodarone
- severe bradycardia
What drugs are part of the NS5A inhibitor drug classes?
Ledispasvir
Pibrentasvir
Velpatasvir
Are NS5A drugs usually used as monotherapy?
No, typically utilized in combo with other drugs like with the NS5B polymerase inhibitors mentioned prior.
What are NS5A inhibitors all susbtrates of?
CYP3A4
Does that mean they have drug interactions with statins, antituberculosis medications and HIV regimens?
Minimal drug interaction
What is a drug interaction that we do have to watch out for with NS5A inhibitors? Is there specific NS5A inhibitors that are more at risk of this interaction?
Use of PPIs or antacids
Ledipasvir
Velpatasvir
What drugs are part of the protease inhibitors or NS3 inhibitors drug class?
Glecaprevir
Voxilaprevir
Are these protease inhibitors used as monotherapy?
No, typically used in combo with polymerase and NS5A inhibitors.
What is a common drug interaction with protease inhibitors?
Moderate or strong inducers or inhibitors of CYP3A4
Where does ribavirin come into play for Hep C chronic infection?
Only used in combo with other agents for the treatment of HCV
What is an example of immunosuppression in Hep B patients?
Use of immunosuppressive drugs like prednisone
- many Hep B carriers experience flare up in later course of tx or withdrawal of immunosuppressive drug
Nucleos(t)ide analogue therapy is usually used as monotherapy for HBV patients. When should we not use monotherapy?
In HBV patients who are also HIV positive patients.
- Increased risk of developing resistant HIV strains
Which of the hepatitis viruses is most likely be transmitted in daycare setting?
HAV and HEV, as they’re both fecal-oral
What does Epclusa include?
Sofosbuvir and Velpatasvir
What genotypes does Epclusa cover?
1, 2 3, 4, 5, 6
What drugs are in Harvoni?
Ledipasvir and Sofosbuvir
What genotypes does Harvoni cover?
1, 3, 4, 5, 6 (not 2)
What drugs are in Holkira Pak?
Ombitasvir, pariteprevir, ritonavir, dasabuvir
What genotypes does Holkira Pak cover?
1a, 1b, 4
What drugs are in maviret?
Glecaprevir and pibrentasvir
What genotypes does maviret cover?
1, 2, 3, 4, 5, 6
What drugs are in Technivie?
Ombitasvir, paritaprevir, and ritonavir
What genotype does technivie cover?
4
What drugs are in Vosevi?
Sofosbuvir, velpatasvir, voxilaprevir
What genotypes does vosevi cover?
1, 2, 3, 4, 5, 6
What drugs are in zepatier?
Elbasvir, grazoprevir
What genotypes does zepatier cover?
1a if with ribavirin
1b
3 with sofosbuvir
4
Which of the hepatitis C drugs need to be taken with food?
Vosevi
Technivie
Holkira
