Viral, Toxic, and Immune-Mediated Liver Diseases Flashcards
ddx for abnormal ASTs and ALTs (viral, toxic, and immune causes)
*viruses
*meds
*autoimmune hepatitis
ddx for abnormal alkaline phosphatase (viral, toxic, and immune causes)
*medication-induced cholestasis
*primary biliary cholangitis
*primary sclerosing cholangitis
hepatitis A virus - overview
*HAV is an RNA virus
*transmission: fecal-oral
*no treatment
*no chronic phase
*elevated IgM anti-HAV
*typically questions have a traveler returning to America from an endemic area
clinical presentation of all hepatitis viruses
*episodes of fever, jaundice
*elevated ALT and AST
risk factors for hepatitis B
- heterosexual activity
- injecting drug use
hep B is a DNA virus
acute HBV infection
*IgM anti-HBc is the diagnostic serology tool
acute HBV serology panel
*HBSAg = +
*HBcAb IgM = +
*HBcAb IgG = -
*HBSAb = -
resolved HBV serology panel (natural immunity)
*HBSAg = -
*HBcAb IgM = -
*HBcAb IgG = +
*HBSAb = +
chronic HBV serology panel
*HBSAg = +
*HBcAb IgM = -
*HBcAb IgG = +
*HBSAb = -
HBV vaccinated serology panel
*HBSAg = -
*HBcAb IgM = -
*HBcAb IgG = -
*HBSAb = +
risk factor for hepatitis C
*IV drug use
acute hepatitis panel
*HAV antibody (IgG + IgM) - if positive, lab will proceed to test for IgM
*HBSAg
*HBcAb (IgG + IgM) - if positive, the lab will proceed to test for IgM
*HCV Ab - if negative, test HCV RNA!!
treatment for chronic hepatitis C
there IS a very effective treatment (a cure) for HCV [direct-acting antiviral therapy]
hepatitis D - overview
*RNA virus
*requires the presence of HBV for complete virion assembly and secretion
*clinical presentation: SUPERINFECTION IS WORSE than coinfection
*diagnosis - serum testing for HDV RNA (PCR) [but only in the setting of HBSAg +]
hepatitis E and pregnancy
*clinical course: fulminant hepatitis in pregnant patients
*risk maternal mortality, worse in 3rd trimester
*pregnant women should avoid travel to endemic areas
*dx:
-HEV RNA in serum or stool
-serum HEV IgM Ab
drug-induced liver disease (DILI)
*most common cause of acute liver failure in the United States (acetaminophen is the most common drug but it is usually considered separately)
3 mechanisms of drug toxicity for drug-induced liver disease
- direct hepatotoxicity
- hepatic conversion of the drug to an active toxin
- immune-mediated liver injury, in which the drug or a metabolite act as a hapten, converting a cellular protein into an immunogen
making the diagnosis of drug-induced liver injury (DILI)
*history is key:
-careful medication history with start date (avg onset within 2 weeks)
-also consider other meds
*serologic evaluation for viral, autoimmune, and metabolic liver diseases
*correlate clinical features and LFT pattern “signature” (google “livertox”)
*consider liver biopsy for histologic differentiation
acetaminophen hepatotoxicity - doses
danger dosages (70 kg patient):
-toxicity possible > 10 gm
-severe toxicity certain > 25 gm
-lower doses potentially hepatotoxic in: chronic alcoholism, malnutrition or fasting, dilantan, tegretol, etc
*NOT in acute EtOH ingestion and NOT in non-alcoholic chronic liver disease
acetaminophen hepatotoxicity - timeline
*day 1: nausea, vomiting, malaise, or asymptomatic
*day 2-3:
-initial symptoms resolve
-AST and ALT begin to rise by 36 hours
-RUQ pain, tender enlarged liver on exam
*day 4:
-AST and ALT peak > 3000
-liver dysfunction: INR, encephalopathy, jaundice
-acute kidney injury: acute tubular necrosis
acetaminophen hepatotoxicity - treatment
*if < 4 hours from ingestion: activated charcoal
*IV N-acetylcysteine (NAC) !!!
*use the nomogram to determine probability of hepatic toxicity
what do we use N-acetylcysteine to treat
acetaminophen hepatotoxicity (N-acetylcysteine regenerates glutathione)
acetaminophen toxicity - pathogenesis
*acetaminophen metabolite (NAPQI) depletes glutathione and forms toxic tissue byproducts in liver
*N-acetylcysteine (treatment of choice) regenerates glutathione
Reye’s Syndrome
*mitochondrial dysfunction in liver and brain
*seen predominantly in children
*associated with ASPIRIN given for fever
*typically presents with vomiting, confusion, seizures, and coma
*liver biopsy shows microvesicular steatosis
test pearls for acute hepatitis
*ALT > AST and levels > 1000
*ddx: viral, toxic, ischemic
*lab evaluation:
-viral hepatitis panel: HAV IgM, HBSAg, HBcAb IgM, HCV RNA
-acetaminophen level
acute liver failure - definition
rapid development of hepatic dysfunction
*hepatic encephalopathy
INR > 1.5
*no prior history of liver disease
2 requirements for acute liver failure
- hepatic encephalopathy
- INR > 1.5
acute liver failure - most common causes
*acetaminophen
*unknown
*drug-induced liver injury
*acute viral hepatitis
autoimmune hepatitis - overview
*widely variable clinical presentations:
-asymptomatic LFT abnormality (ALT & AST)
-severe hepatitis with jaundice
-cirrhosis and complications of portal HTN
*FEMALE:male ratio 4:1
*often associated with other autoimmune diseases
gender prevalence in autoimmune hepatitis
FEMALE > male (4:1)
autoimmune hepatitis - diagnosis and treatment
*diagnosis:
-abnormal LFTs, primarily ALT and AST
-ANA or ASMA with titer 1:80 or greater
-IgG > 1.1 upper limits of normal
-liver biopsy: portal lymphocytes + plasma cells
*treatment: prednisone + azothioprine
primary biliary cholangitis
*cholestatic liver disease (ALP):
-immune attack on MICROSCOPIC bile ducts (intrahepatic)
-most common sx: pruritis + fatigue
*FEMALE:male ratio 9:1
*diagnosis:
-AMA titer 1:80 or greater (95% sens/spec)
-abnormal LFTs, primarily ALP
-liver biopsy (bile duct destruction)
*treatment: UDCA (ursodeoxycholic acid)
gender prevalence of primary biliary cholangitis
FEMALE > male (9:1)
primary sclerosing cholangitis
*cholestatic liver disease (ALP elevation)
*immune attack on LARGE BILE DUCTS (intra and extra-hepatic)
*90% associated with IBD (ulcerative colitis)
*diagnosis: MRCP & p-ANCA
*cholangiocarcinoma risk
*treatment = liver transplant
periportal liver fibrosis
*most causes of liver inflammation and fibrosis
*HBV, HCV, AIH, PBC, PSC, HH, A1AT, WD
*liver injury from toxins and viruses
centrizonal fibrosis
*ASH, NASH
*congestive hepatopathies: Budd-Chiaria, cor pulmonale, CHF, etc
*liver injury from oxidative stress (alcohol, non-alcohol fatty liver diseases, etc)
