JH IM Board Review - Acute and Chronic Liver Disease III Flashcards
Liver diseases of pregnancy (6):
- Hyperemesis gravidarum.
- Intrahepatic cholestasis of pregnancy.
- Preeclampsia/eclampsia.
- HELLP syndrome (subset of severe preeclampsia).
- Acute fatty liver of pregnancy.
- Hepatic rupture.
Hyperemesis gravidarum - Symptoms/signs:
- Intractable N/V.
2. Dehydration in 1st trimester.
Hyperemesis gravidarum - Labs:
- Bil up to 5x normal.
2. AST/ALT rarely 20x normal.
Hyperemesis gravidarum - Tx:
- Antiemetics.
2. IV hydration.
Hyperemesis gravidarum - Mortality risk: Mother/fetus:
-/- (resolves spontaneously).
Intrahepatic cholestasis of pregnancy - Symptoms/signs:
- Pruritus.
- Jaundice.
- Steatorrhea in 2nd and 3rd trimester.
Intrahepatic cholestasis of pregnancy - Labs:
- Bil up to 5x normal.
- AST/ALT up to 20x normal.
- Bile acid up to 100x normal.
Intrahepatic cholestasis of pregnancy - Tx:
- UDCA.
- Dexamethasone.
==> Deliver if fetal distress.
Intrahepatic cholestasis of pregnancy - Mortality risk: Mother/fetus:
-/Low.
Preeclampsia/eclampsia - Symptoms/signs:
- HTN.
- Edema.
- Proteinuria.
- Seizures/coma in late 2nd or 3rd trimester.
Preeclampsia/eclampsia - Labs:
- Bil <5mg/dL.
2. AST/ALT up to 10 to 20x normal.
Preeclampsia/eclampsia - Tx:
- Tx HTN and edema.
- MgSO4.
- Deliver in severe cases.
Preeclampsia/eclampsia - Mortality risk: Mother/fetus:
+/Low.
HELLP syndrome - Symptoms/signs:
- RUQ pain.
- N/V.
- HTN.
- Edema.
- Proteinuria in late 2nd/3rd trimester or postpartum period.
HELLP syndrome - Labs:
- AST/ALT up to 10 to 20x normal.
- Low haptoglobin.
- LDH >600 U/L.
- Platelets <100K.
HELLP syndrome - Tx:
Delivery.
HELLP syndrome - Mortality risk: Mother/fetus:
+/+.
Acute fatty liver of pregnancy - Symptoms/signs:
- RUQ pain.
- N/V.
- Fatigue.
- Jaundice.
- Ascites.
- Encephalopathy.
- Renal failure in 3rd trimester.
Acute fatty liver of pregnancy - Labs:
- Bil commonly <5mg/dL, but HIGHER in severe disease.
- AST/ALT up to 1000.
- Hyperammonemia.
- Azotemia.
- Hypoglycemia.
- DIC can develop.
Acute fatty liver of pregancy - Tx:
Delivery.
Acute fatty liver of pregnancy - Mortality risk: Mother/fetus:
+/+.
Hepatic rupture - Symptoms/signs:
- Severe abdominal pain.
2. Shock in 3rd trimester.
Hepatic rupture - Labs:
Variable.
Hepatic rupture - Tx:
Immediate surgery.
Hepatic rupture - Mortality risk: Mother/fetus:
+/+.
HCV - Virus info:
Heterogeneous RNA virus with at least 6 major genotypes.
HCV - Genotypes vary with geographic distribution?
- Genotype 1 ==> North/South Americas, Australia, Europe.
- Genotype 4 ==> Middle East and Egypt.
- Genotype 5 ==> South Africa.
- Genotype 6 ==> Southeast Asia.
HCV - Overall global prevalence:
2-3%.
Highest in Africa (Eg Egypt), eastern Mediterranean region, and Southeast Asia.
==> Can reach 50% among IVDA.
MC hepatotropic infection in the USA:
HCV infection.
==> 4 million people estimated to be Anti-HCV positive.
HCV - Chronicity:
60-85% ==> Adults.
55-70% ==> Pediatric.
HCV - What may accelerate the progression of fibrosis?
- Heavy alcohol use.
- Older age at initial HCV infection.
- Obesity.
- Co-infection with HIV.
Risk factors for HCV infection include:
- Birthdate from 1945-1965.
- History of IVDA.
- Transfusions or organ transplants before 1992.
- Hx of long-term hemodialysis.
- HIV infection.
- Vietnam war era veterans.
- Known exposures to HCV (including being born to HCV-positive mothers).
HCV - Incubation:
2-12 weeks.
==> Acute infections are usually mild/asymptomatic.
HCV - Jaundice?
<20%.
==> MAY be associated with incr. spontaneous viral clearance.
Common symptoms of chronic HCV?
- Fatigue.
- Anorexia.
- Myalgias/Arthralgias.
HCV - Progression to cirrhosis?
Approx. 20% of pts progress to cirrhosis after 20yrs of chronic HCV.
HCV - Once cirrhotic …?
4% ANNUAL RISK OF CLINICAL DECOMPENSATION (eg ascites).
3% ANNUAL RISK OF HCC.
HCV - Extrahepatic manifestations:
- Mixed cryoglobulinemia.
- Leukocytoclastic vasculitis.
- Membranous GN.
- Porphyria cutanea tarda.
- Insulin resistance.
- NHL.
HCV - Dx - Screening:
Anti-HCV is the 1st line screening test.
==> It indicates past or chronic HCV infection, but does NOT imply immunity.
==> Anti-HCV becomes detectable within 2-3 months postinfection, so it may miss acute cases.
HCV - Dx - Check serum HCV RNA if:
- Anti-HCV positive.
- Considering antiviral Tx.
- Suspicion for infection remains despite negative anti-HCV.
HCV - Role of HCV RNA?
- Presence of HCV RNA suggests active viral replication.
- HCV RNA is detectable in serum within 2 weeks of infection.
- Persistence for more than 6 months defines chronic HCV infection.
- RNA titer does NOT correlate with disease activity or progression.
Why to obtain HCV genotyping?
To guide appropriate antiviral Tx.
HCV - Single-nucleotide polymorphism at the …?
IL28B gene on chr. 19 ==> Predicts SPONTANEOUS VIRAL CLEARANCE AND RESPONSE TO ANTIVIRAL Tx.
HCV - CC genotype?
Associated with the most favorable spontaneous and Tx-induced clearance rates.
HCV - TT genotype?
Least favorable.
HCV - Frequency of C allele?
Highest ==> East Asia.
Intermediate ==> Europe.
Lowest ==> Africa.
HCV - What is useful for prognosis to ascertain?
- Liver fibrotic stage + Degree of inflammatory activity.
- Liver Bx is gold standard but invasive.
- Non invasive options ==> Serum biomarkers + Imaging (MRI/US) with elastography.
HCV - Role of aminotransferases:
Do NOT help differentiate the presence or absence of disease.
==> 25-50% of chronic HCV pts may have persistently NORMAL levels.
Historical Tx for chronic HCV:
Pegylated IFN + Ribavirin +/- NS3/4A PI (ie telaprevir or boceprevir) for UP TO 12 MONTHS.
==> 30-70% EFFECTIVE with side effects.
In 2013, 2 new direct-acting antivirals (DAAs) were approved for Tx of chronic HCV:
- Simeprevir ==> NS3/4A PI.
- Sofosbuvir ==> NS5B POLYMERASE inhibitor.
==> Recommended regimens vary depending on HCV genotype and Hx of HCV Tx.
First-ever IFN-free regimen for chronic HCV?
Sofosbuvir and Ledipisvir.
==> >90% success rates after 12-24 WEEKS of Tx.
HCV - Use of IFN and ribavirin requires monitoring of …?
Routine lab tests + TSH.
Tx is generally recommended for acute HCV that …?
Does NOT spontaneously clear within 12 WEEKS.
ACUTE HCV Tx:
- Viral response to CONVENTION Tx is significantly better.
2. Peg-IFN MONOTHERAPY FOR AT LEAST 12 WEEKS results in viral clearance in 80-90% of acute HCV.
HDV - Requires?
Presence of HBsAg FOR INFECTION + REPLICATION.
HDV - Prevalence?
- Mediterranean countries.
- East Africa.
- Central and Northern Asia.
HDV - CO-INFECTION:
Biphasic aminotransferase elevations separated by a few weeks because of distinct acute effects of HBV and HDV.
==> Chronic HDV infection occurs in only 2% of cases.
HDV - Superinfection:
Hepatitis is more severe with higher rates of FULMINANT LIVER DISEASE (more common in HDV than other types of viral hep).
==> Progression to chronic infection in more than 90% of cases.
HDV - What MUST be present to diagnose HDV infection?
HBsAg.
HDV - Dx - CO-INFECTION:
- Positive anti-HDV IgM is preceded by the appearance of anti-HBc-IgM 1 to 2 weeks EARLIER.
- Anti-HDV IgM disappears after 1.5-3 months, and is followed by anti-HDV IgG positivity.
- HDAg appears early in serum but is short-lived (because of sequestration in antibody complexes), thus often escapes detection.
HDV - Dx - SUPERINFECTION:
- Rising titers of BOTH anti-HDV IgM + anti-HDV IgG.
- Early and short-lived presence of serum HDAg.
- Negative anti-HBc IgM + Positive anti-HBc IgG.
HDV - Tx:
NO effective antiviral therapies exists for acute HDV.
HDV - Tx - Role of IFN?
1y course of standard IFN-a or Peg-IFN offers modest efficacy for viral suppression in chronic HDV.
==> Peg-IFN tends to be better tolerated.
==> CONTRA IN DECOMPENSATED LIVER DISEASE.
HDV - Tx - Role of nucleos(t)ide analogues used against HBV?
NO effect on HDV replication.
HEV - Anti-HEV has seroprevalence of approx …% in the USA.
25%.
HEV - Incubation period?
2-8 week.
HEV - Chronicity?
RARE ==> In post-liver tranplant or HIV.
HEV - Dx - Role of HEV RNA?
Measure HEV RNA titer in immunocompromised or post-transplant individuals.
==> Anti-HEV testing can be unreliable in this cohort.
HEV - Tx:
- Often a mild disease course where supportive care is sufficient.
- Ribavirin 600 to 8000mg daily for 3 to 6 months associated with viral clearance in immunocompromised pts.
