Viral, Toxic, and Immune-Mediated Liver Diseases

Question 1

ddx for abnormal ASTs and ALTs (viral, toxic, and immune causes)

Answer 1

*viruses
*meds
*autoimmune hepatitis

Question 2

ddx for abnormal alkaline phosphatase (viral, toxic, and immune causes)

Answer 2

*medication-induced cholestasis
*primary biliary cholangitis
*primary sclerosing cholangitis

Question 3

hepatitis A virus - overview

Answer 3

*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

Question 4

clinical presentation of all hepatitis viruses

Answer 4

*episodes of fever, jaundice
*elevated ALT and AST

Question 5

risk factors for hepatitis B

Answer 5

1. heterosexual activity
2. injecting drug use

hep B is a DNA virus

Question 6

acute HBV infection

Answer 6

*IgM anti-HBc is the diagnostic serology tool

Question 7

acute HBV serology panel

Answer 7

*HBSAg = +
*HBcAb IgM = +
*HBcAb IgG = -
*HBSAb = -

Question 8

resolved HBV serology panel (natural immunity)

Answer 8

*HBSAg = -
*HBcAb IgM = -
*HBcAb IgG = +
*HBSAb = +

Question 9

chronic HBV serology panel

Answer 9

*HBSAg = +
*HBcAb IgM = -
*HBcAb IgG = +
*HBSAb = -

Question 10

HBV vaccinated serology panel

Answer 10

*HBSAg = -
*HBcAb IgM = -
*HBcAb IgG = -
*HBSAb = +

Question 11

risk factor for hepatitis C

Answer 11

*IV drug use

Question 12

acute hepatitis panel

Answer 12

*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!!

Question 13

treatment for chronic hepatitis C

Answer 13

there IS a very effective treatment (a cure) for HCV [direct-acting antiviral therapy]

Question 14

hepatitis D - overview

Answer 14

*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 +]

Question 15

hepatitis E and pregnancy

Answer 15

*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

Question 16

drug-induced liver disease (DILI)

Answer 16

*most common cause of acute liver failure in the United States (acetaminophen is the most common drug but it is usually considered separately)

Question 17

3 mechanisms of drug toxicity for drug-induced liver disease

Answer 17

1. direct hepatotoxicity
2. hepatic conversion of the drug to an active toxin
3. immune-mediated liver injury, in which the drug or a metabolite act as a hapten, converting a cellular protein into an immunogen

Question 18

making the diagnosis of drug-induced liver injury (DILI)

Answer 18

*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

Question 19

acetaminophen hepatotoxicity - doses

Answer 19

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

Question 20

acetaminophen hepatotoxicity - timeline

Answer 20

*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

Question 21

acetaminophen hepatotoxicity - treatment

Answer 21

*if < 4 hours from ingestion: activated charcoal
*IV N-acetylcysteine (NAC) !!!
*use the nomogram to determine probability of hepatic toxicity

Question 22

what do we use N-acetylcysteine to treat

Answer 22

acetaminophen hepatotoxicity (N-acetylcysteine regenerates glutathione)

Question 23

acetaminophen toxicity - pathogenesis

Answer 23

*acetaminophen metabolite (NAPQI) depletes glutathione and forms toxic tissue byproducts in liver
*N-acetylcysteine (treatment of choice) regenerates glutathione

Question 24

Reye’s Syndrome

Answer 24

*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

Question 25

test pearls for acute hepatitis

Answer 25

*ALT > AST and levels > 1000 *ddx: viral, toxic, ischemic *lab evaluation: -viral hepatitis panel: HAV IgM, HBSAg, HBcAb IgM, HCV RNA -acetaminophen level

Question 26

acute liver failure - definition

Answer 26

*rapid development of hepatic dysfunction ***hepatic encephalopathy*** ***INR > 1.5*** *no prior history of liver disease

Question 27

2 requirements for acute liver failure

Answer 27

1. hepatic encephalopathy 2. INR > 1.5

Question 28

acute liver failure - most common causes

Answer 28

*acetaminophen *unknown *drug-induced liver injury *acute viral hepatitis

Question 29

autoimmune hepatitis - overview

Answer 29

*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

Question 30

gender prevalence in autoimmune hepatitis

Answer 30

FEMALE > male (4:1)

Question 31

autoimmune hepatitis - diagnosis and treatment

Answer 31

*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

Question 32

primary biliary cholangitis

Answer 32

*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)**

Question 33

gender prevalence of primary biliary cholangitis

Answer 33

FEMALE > male (9:1)

Question 34

primary sclerosing cholangitis

Answer 34

***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

Question 35

periportal liver fibrosis

Answer 35

*most causes of liver inflammation and fibrosis *HBV, HCV, AIH, PBC, PSC, HH, A1AT, WD *liver injury from toxins and viruses

Question 36

centrizonal fibrosis

Answer 36

*ASH, NASH *congestive hepatopathies: Budd-Chiaria, cor pulmonale, CHF, etc *liver injury from oxidative stress (alcohol, non-alcohol fatty liver diseases, etc)