Term
Which of the following gives you highest chance of progressing to chronic infection of HBV?
Being immunocompetent
Being born to an HbeAg + mother
Being infected between the ages of 1-5 |
|
Definition
Risk of chronic infection
The risk of progression to chronic HBV infection is inversely proportional to the age at infection. Up to 50 to 90% of neonates and infants born to HBeAg positive mothers become HBV carriers, as compared to 20 to 30 % among children infected between the age of 1-5 years, and less than 5% among immunocompetent adults. |
|
|
Term
| What's a key difference between HBV and HAV in children |
|
Definition
| Children with HAV are aSx |
|
|
Term
| T/F: The HBV directly destroys the liver in its progression to cirrhosis |
|
Definition
| F: virus not cause it, it’s immune mediated so there’s a constant shift! Sometimes it becomes quiescent… |
|
|
Term
| T/F: In both HBV and HCV, cirrhosis is a necessary precursor to the development of HCC. |
|
Definition
| F: Patients with chronic HBV infection are at risk of developing cirrhosis and hepatocellular carcinoma (HCC). Although the risk of cirrhosis and HCC is higher among those with chronic hepatitis, adverse clinical outcome may develop among inactive carriers. In addition, unlike hepatitis C, chronic hepatitis B patients without cirrhosis can also develop HCC. |
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
|
Definition
|
|
Term
HBsAg
Anti-HBc IgM
Anti-HBe
Anti-HBs |
|
Definition
Acute/Chronic infection
Recent infection
Low infectivity
Immunity |
|
|
Term
| What's a tricky thing we encounter when measuring serum HBV DNA levels? |
|
Definition
| Fluctuating levels <10 to >10 billion IU/mL [10 log], serial tests important for clinical assessment |
|
|
Term
| Because of this nature of HBV, what's a possible result esp in a patient with a previous infx but now recovered? |
|
Definition
Virus persists at low levels even after recovery
Reactivation can occur spontaneously and more often when immune system is suppressed
HBV DNA levels do not always correlate with ALT levels or histologic activity of liver disease
Persistently high serum HBV DNA levels are associated with increased risk of cirrhosis and HCC |
|
|
Term
| What's the molecular nature of HBV outside in circ and inside? How replication? |
|
Definition
Circulating is PARTIALLY DS…insdie then it becomes closed.
Makes RNA and then you have reverse transcription! A lot of drugs are similar for HIV! |
|
|
Term
| Why is it that HBeAg presence means low infectivity? |
|
Definition
| Virus continues to rep but e ag is repressed, but you'll still have antibodies to it |
|
|
Term
| What are goals of HBV treatments as far as the virus goes? |
|
Definition
Decrease in serum HBV DNA: preferably to undetectable by PCR
HBeAg loss / seroconversion: applicable to HBeAg+ patients only
HBsAg loss: Ultimate goal |
|
|
Term
| What are the Indications to Start Treatment? |
|
Definition
AASLD Practice Guidelines 2007
Evidence of liver disease – abnormal ALT (>2x ULN) in the presence of high serum HBV DNA (>20,000 IU/mL for HBeAg+ patients, and >2,000 IU/mL for HBeAg- patients)
Lower threshold if
Older age
Active inflammation or advanced fibrosis on biopsy
Clinical evidence of cirrhosis
Borderline ALT or HBV DNA – monitor, if persistent, consider biopsy
Others – monitor, treat later when indication arises or more effective treatment available |
|
|
Term
|
Definition
Interferon alpha 2b – 1992
Pegylated interferon alpha 2a – 2005
Lamivudine (Epivir) – 1998
Adefovir (Hepsera) – 2002
Entecavir (Baraclude) – 2005
Telbivudine (Tyzeka) – 2006
Tenofovir (Viread) - 2008 |
|
|
Term
| Most efficacious and safe drug with very little antiviral resistance? |
|
Definition
|
|
Term
| 1-2% resistance by yr 5, not really safe, but effective! |
|
Definition
|
|
Term
|
Definition
Genetically engineered hepatitis B surface antigen alone or in combination with hepatitis A vaccine
3 doses: month 0, 1, 6
Immune response: 50% after 1 dose 95% after 3 doses
Duration of protection: >15 years, dependent on initial antibody response |
|
|
Term
| Would you give an HBV vaccine to an infant of an HBsAg+ mother? |
|
Definition
|
|
Term
| A patient has a + HCV antibody what does this mean? |
|
Definition
Hepatitis C antibody
Indicator of exposure
60% - 80% of anti-HCV+ persons have ongoing HCV infection |
|
|
Term
| His HCV PCR test is positive but has low levels. T/F: this means his liver disease could be really high |
|
Definition
T: Hepatitis C virus RNA - PCR test
Direct test for presence of virus / ongoing infection
No correlation between virus count and severity of liver disease |
|
|
Term
| most common HCV genotypes |
|
Definition
At least 6 types: 1-6, a, b, c…
Genotype 1 (1a and 1b)
Most common in the US, ~70%
Lower rate of response to treatment
Not related to severity of liver disease
Genotypes 2 and 3
~25-30% of HCV infection in the U.S.
Better response to treatment |
|
|
Term
| HEPATITIS C Clinical Manifestations |
|
Definition
Most patients with acute hepatitis C have little or no symptoms.
Many patients with chronic hepatitis C have no symptoms until they develop complications of cirrhosis.
Common symptoms including fatigue, anorexia, itching and RUQ discomfort correlate poorly with severity of liver disease.
Quality of life frequently impaired, even in pre-cirrhotic patients, with improvement after sustained response to therapy.
Extrahepatic manifestations (renal, skin, neurologic) in 5 – 10% patients. |
|
|
Term
| T/F: although immune function and alcoholism/AFLD affect dz progression of HCV, NAFLD, obesity or steatosis does not accelerate progression. |
|
Definition
|
|
Term
| Lab tests Initial Evaluation of Patients with Hepatitis C |
|
Definition
HCV RNA, HCV Genotype
Tests to r/o HBV, HIV, other causes of liver disease
Tests to assess liver disease severity – liver chemistry, CBC+P, PT
+/- Tests to detect HCC
PLATELET COUNT IS VERY IMPORTANT! |
|
|
Term
| Pegylated interferon (Peg IFN) + Ribavirin (RBV) has what affect on SVR in Genotypes 1 and 2/3 |
|
Definition
|
|
Term
|
Definition
| Sustained virologic response (SVR) = HCV RNA undetectable during treatment and at 6 months post-treatment |
|
|
Term
Put the following in order of predictive value for SVR:
cEVR, pEVR, RVR |
|
Definition
RVR, cEVR, pEVR
RVR = rapid VR, HCV RNA undetectable by wk 4
cEVR = complete early VR, HCV RNA undetectable by wk 12
pEVR = partial early VR or slow response, >2 log decrease in HCV RNA by wk 12, undetectable by wk 24
Null response = <2 log decrease in HCV RNA by wk 24 |
|
|
Term
| An obese, older, and diabetic black dude with IL28B polymorphism and HCV comes to you for treatment. What is he unlikely to be responsive to (tx)? |
|
Definition
|
|
Term
|
Definition
Flu-like symptoms - fever, chills, headache, muscle ache
Fatigue
Mood changes - anxiety, irritability, depression MAIN EFFECT!!!!
Sleep disturbance
Hair loss
Decrease in white cell and platelet, more common with peg-IFN
Retinal hemorrhage, rarely decrease and even loss of vision
Unmasking or exacerbation of autoimmune diseases |
|
|
Term
| Pregnant woman wants HCV tx. What can't you give her? |
|
Definition
|
|
Term
| T/F: you should treat all 2/3 and 1 genotype patients unless CIs or comorbidities. |
|
Definition
F: Genotype 2/3 –
All patients unless contraindications or serious co-morbidities
Genotype 1 -
Patients who are likely to develop progressive liver disease
Patients with no significant co-morbid medical illness
Patients with no contraindications to treatment |
|
|
Term
| NS3/4 protease inhibitors |
|
Definition
|
|
Term
| You give monotherapy of DAA drugs for HCV Genotype I only. What happens and in what timeframe? What should you have given? |
|
Definition
Drug-resistance mutations emerge within 2 weeks in patients receiving monotherapy
Boceprevir (BOC) and Telaprevir (TVR) – protease inhibitors, phase III trials completed
BOC or TVR + peginterferon and ribavirin – triple therapy results in higher SVR rates than peginterferon and ribavirin |
|
|
Term
| Though that IL28B polymorphism black dude w/ HCV was unresponsive to IFN, what's his outcome likely to be? |
|
Definition
IL28B polymorphisms associated with
Higher SVR rates[1]
Higher RVR rates[2]
Higher rate of spontaneous viral clearance[3]
Favorable genotype, rs12979860 CC, most common among Asians, followed by Caucasians, Hispanics and Blacks
New HCV treatments involving direct antiviral agents continue to rely on IFN / RBV |
|
|
Term
| T/F: a px with active liver disease but a low HBV DNA does not need to be tested for HDV. |
|
Definition
F:
Acute hepatitis
HBsAg+ and IgM anti-HBc+
Severe course
Risk factors
Chronic liver disease
HBsAg+
Active liver disease despite low HBV DNA
Risk factors – injection drug use, immigrants from countries where HDV infection is common, former Soviet Union, Eastern European countries, central America, Amazon basin |
|
|
Term
|
Definition
HBV vaccination prevents hepatitis D
Interferon – only treatment that is effective
Long duration of treatment needed
High relapse rate
Oral nucleos(t)ide analogs for HBV not effective |
|
|
Term
|
Definition
Similar to hepatitis A
Risk factors:
Travel to endemic areas: Asia (India-Pakistan), Mexico
Contact with animals such as pigs
Ingestion of undercooked meat
Rare cases of chronic infection in immunosuppressed patients
Up to 20% mortality among pregnant women (esp. third trimester) |
|
|
