Liver, Gallbladder, Pancreas

alk phos, bilirubin, AST, ALT

LFTs

Not specific to liver - also assoc. with bone, intestine, placenta

alk phos

What enzyme is MOST sensitive in detecting long term liver damage associated with alcohol ingestion?

Gamma-Glutamyl Transpeptidase (GGT)

measure of liver detoxification function

ammonia level

measure of liver synthetic function

PT/INR

albumin

icterus

caused by accumulation of bilirubin the tissues

jaundice

bilirubin is a product of _______ metabolism

heme

normal serum bilirubin

.2-1.2 mg/dL

at what level is jaundice clinically evident

3 mg/dL

any condition in which substances normally excreted into bile are retained

cholestasis

also known as indirect hyperbilirubinemia

caused by overproduction of bilirubin (hemolysis), impaired uptake (drugs), or impaired glucuronidation

unconjugated hyperbilirubinemia

mild unconjugated hyperbilirubinemia due to decrease in glucuronyl transferase

gilbert syndrome

moderate unconjugated hyperbilirubinemia due to complete absence of glucuronyl transferase

crigler-najjar

elevated direct bilirubin caused by impaired excretion of bilirubin from liver

(hepatocellular disease, drugs, sepsis, hereditary defefct, extrahepatic obstruction)

conjugated hyperbilirubinemia

which type of jaundice is more likely to be sicker and more clinically evident?

conjugated hyperbilirubinemia

symptoms of conjugated hyperbilirubinemia

anorexia

RUQ discomfort

dark urine

icterus

palmar erythema

ascites

symptoms of unconjugated hyperbilirubinemia

mild jaundice

normal stool and urine

splenomegaly

a clinical syndrome characterized by severe impairment of liver function associated with hepatic encephalopathy

acute hepatic failure

hepatic encephalopathy within 8 weeks after the onset of acute liver disease. INR > 1.5

fulminant acute liver failure

hepatic encephalopathy 8 weeks - 6 months after the onset of acute liver disease. INR > 1.5

subfulminant acute liver failure

acute hepatic liver failure diagnostics

very high AST/ALT

INR > 1.5

most common cause of acute hepatic failure

acetaminophen

2nd is idiosyncratic drug reactions

acute encephalopathy and liver dysfunction

elevated ammonia

reye syndrome

acute hepatic failure s/sx

GI sx

hemorrhagic phenomena

jaundice

encephalopathy

what is the treatment for acute hepatic failure?

- correct metabolic abnormalities

- acetylcysteine (for acetaminophen toxicity)

- early transport to liver transplant center

mostly irreversible liver fibrosis with nodular regeneration secondary to hepatocellular injury

cirrhosis

what are the most common causes of cirrhosis?

chronic viral hepatitis infection and alcohol

cirrhosis s/sx

weakness, fatigue, disturbed sleep, muscle cramps, weight loss

appears chronically ill, anorexia, nausea (advanced dz)

ascites, hepatosplenomegaly (firm, nodular edge), gynecomastia, spider angioma, fever, palmar erythema, depuytren contracture, caput medusae, cheilosis

hepatic encephalopathy s/sx

day-night reversal, asterixis, tremor, delirium -> coma

what would you expect to see on the following labs for cirrhosis?

CBC:

PT/INR

LFTs:

albumin:

vit D

anemia (macrocytic, hemolytic), thrombocytopenia

prolonged

modest AST and alk phos elevation

low

low

cirrhosis diagnostic standard

biopsy

US can shpw liver size and ascites, CT/MRI further characterize nodules

what is the single most important step in the treatment of cirrhosis?

stopping alcohol

what is the treatment for cirrhosis?

diet (sodium restriction, protein restriction)

vitamin supplementation

vaccines

screening (for hepatocellular carcinoma)

transplant

what is the treatment for ascites/edema?

- sodium restriction

- diuretics (spironolactone + furosemide)

- large-volume paracentesis (if above fails)

complication of cirrhosis:

characterized by fever, progressive ascites and pain

spontaneous bacterial peritonitis

IV abx

complication of cirrhosis:

characterized by azotemia, oliguria, hyponatremia

hepatorenal syndrome

need liver transplant

complication of cirrhosis:

characterized by confusion, lethargy, asterixis

hepatic encephalopathy

complication of cirrhosis:

TRIAD: chronic liver disease, increased alveolar-

arterial gradient, right-to-left pulmonary shunt

Dyspnea worse when upright

Hepatopulmonary Syndrome

inciting factors of hepatic encephalopathy

sedation, intestinal bleed, constipation, infection

what is the treatment for hepatic encephalopathy?

protein restriction, lactulose, Abx

what is the treatment for hepatic coagulopathy?

vit K

FFP

prodrome of anorexia, fatigue, vomiting, malaise, abdominal pain, decreased desire to smoke

^^^ subsides over 2-3 weeks

exam: fever, jaundice, hepatomegaly

acute viral hepatitis

what lab abnormalities would you expect to see with acute viral hepatitis?

normal to low WBC

abnormal LFTs (elevated AST/ALT)

mild proteinuria and bilirubinuria

this type of hepatitis is transmitted via fecal-oral route

common source is contaminated food or water

30 day incubation period

hepatitis A

is there a chronic carrier state of hepatitis A?

no

this type of hepatitis is transmitted through infected blood or blood products or sexual contact

healthcare personnel are at risk

pregnant women may transmit to baby at delivery

incubation is 6 weeks - 6 months

hepatitis B

the positive lab is a good indicator of acute hep a

IgM anti-HAV

this positive lab finding is the 1st evidence of a hepatitis B infection

HBsAg (Hepatitis B surface antigen)

this lab test can be done to check for successful vaccination to hepatitis B

can also signify clearance of the antigen

anti-HBs (Hepatitis B Surface Antibody)

this lab test indicates acute infection of hepatitis B and can also be present during chronic flares

anti-HBV-IgM

HB core Ab _____ shows up early in hep B infection (acute) and can return during flares in chronic

HB core Ab ______ also shows up early, but will persist indefinitely (even if Hep B clears)

IgM

IgG

this type of hepatitis only occurs in association with HBV

percutaneous exposure (needle stick)

hepatitis D

this type of hepatitis is transmitted through blood/body fluids

>50% of cases transmitted by IV drug use; can also be mother to infant

incubation 6-7 weeks

illness is mild or even asx

hepatitis C

hepatitis _____ has waxing and waning AST/ALT elevations

C

this lab test is diagnostic for hepatitis C infection but does not indicate immunity

anti-HCV

this hepatitis is most likely to cause an acute infection presentation

hep A

this hepatitis is waterborne, rare in US, and self-limited with no carrier state

hep E

this hepatitis is percutaneously transmitted, does not cause major disease, and may be beneficial to patients with HIV

hep G

what is the recommendation for hepatitis A vaccination?

hepatitis B?

all children aged 1-2

all children, and adults at risk

what is the treatment for acute viral hepatitis?

avoid strenuous activity, alcohol, hepatotoxic agents

antiviral therapy (primarily for HCV)

chronic necroinflammation >3-6 months

persistently elevated AST/ALT

sxs absent to mild, non-specific

chronic hepatitis

MCC of chronic hepatitis

Hepatitis B & C

this lab test is the most precise marker of viral replication and infectivity of hepatitis B

HBV DNA

who is at risk for hepatitis B?

partners of people with hep B

injection drug users

MSM

from endemic regions

what is the treatment for chronic hepatitis B?

based on ALT and HBV DNA levels

antivirals (peginterferon, nucleoside/tide analogues)

goal of hepatitis B treatment

immunologic cure

which type of hepatitis causes the most chronic hepatitis cases?

hep C

how is hep C diagnosed?

antiHCV confirmed with HCV RNA

*antiHCV alone does not differentiate those who have cleared the virus from those with active infection

what is the screening recommendation for chronic hepatitis C?

annual for IV drug users and HIV+ homosexual men

and

1 time testing for US adults aged 18-79

what is the treatment for hep C infection?

ledipasivir and sofosbuvir x 8 to 24 weeks

direct acting antivirals, protease inhibitors, NS5A inhibitors

can be cured!

Liver inflammation due to immune system attack.

autoimmune hepatitis

who normally gets autoimmune hepatitis?

young to middle-aged women

autoimmune hepatitis s/sx?

diagnosis?

insidious onset, may follow viral illness

spider nevi, cutaneous striae, hirsutism, arthritis, thyroiditis (can be asx)

elevated aminotransferases, bilirubin

HLA antigens

what diagnostic can be done to establish a diagnosis, determine severity, and need for treatment for autoimmune hepatitis?

liver biopsy

what is the treatment for autoimmune hepatitis?

prednisone +- azathioprine

(high relapse rate)

a spectrum of liver disorders caused by chronic and excessive alcohol consumption

ranges from hepatic steatosis (fatty liver) to alcoholic hepatitis and cirrhosis

alcoholic liver disease

most common precursor of cirrhosis in the US

alcoholic liver disease

acute inflammation of the liver caused by excessive and prolonged alcohol consumption

alcoholic hepatitis

what are the s/sxs of alcoholic hepatitis?

fever, RUQ pain, tender hepatomegaly, jaundice

end-stage of alcoholic liver disease, characterized by irreversible fibrosis and nodular regeneration of the liver due to chronic alcohol consumption

alcoholic cirrhosis

alcoholic liver disease

hx

s/sx

diagnostics

Hx of: recent period of heavy drinking, anorexia, nausea

hepatomegaly, jaundice

elevated LFTs, GGT, alk phos, bilirubin, prolonged PT

anemia (macrocytic), folic acid deficiency

what is the treatment for alcoholic liver disease?

- stop alcohol consumption

- folic acid, thiamine

- methylprednisolone x 1 month

primary cause of liver disease world wide

nonalcoholic fatty liver disease (NAFLD)

a spectrum of liver disorders characterized by excessive fat accumulation in the liver (hepatic steatosis) in individuals who consume little to no alcohol

nonalcoholic fatty liver disease (NAFLD)

(2 types: nonalcoholic fatty liver (hepatic steatosis) and nonalcoholic steatohepatitis)

hepatic steatosis vs nonalcoholic steatohepatitis

• accumulation of fat in the liver, more common, more benign

• liver cell injury, inflammation, cirrhosis, hepatocellular CA, elevated LFTs

A more severe form of liver damage not from alcohol involving hepatic inflammation, ballooning degeneration, and fibrosis, which can progress to cirrhosis and hepatocellular carcinoma (HCC)

nonalcoholic steatohepatitis (NASH)

LFTs are _________ in NAFL and _______ in NASH

normal, elevated

what are some causes of NAFLD?

obesity, DM, high TG, endocrinopathies, OSA

what are the s/sxs of NAFLD?

asx or mild RUQ pain

hepatomegaly

what is the diagnostic test for NAFLD?

labs?

liver biopsy - can't always distinguish from alcoholic dz

mildly elevated AST/ALT, alk phos

ratio ALT to AST > 1

(can also do US, CT, MRI; would see macrovesicular fat)

what is the treatment for NAFLD?

- remove/modify causative factors

- weight loss

- TZDs, GLP-1s, statins

(refer to GI if high chance of NASH fibrosis)

steatosis (NAFL) can lead to __________ which can lead to ____________

steatohepatitis (NASH/MASH)

cirrhosis

autoimmune destruction of small intrahepatic bile ducts and cholestasis, middle aged women

marked by fatigue, itching, hepatospenomegaly, xanthelasma

primary biliary cirrhosis

primary biliary cirrhosis staging and treatment

biopsy

bile acid sequestrants for itching, modafinil for daytime somnolence, vit deficiencies

transplant

hereditary disorder with an excessive buildup of iron deposits in the body

hemochromatosis

drugs & toxins that can induce liver disease

NSAIDS

ABX

Acetaminophen

heavy metals

ketoconozole

niacin

mechanism of drug induced liver toxicity

direct liver damage

idiosyncratic

cholestatic reactions

hepatitis

fatty liver

Hx: pt >50 yo

early: fatigue, arthralgias

late: hepatomegaly, skin pigmentation (bronze), DM, arthropathy

elevated iron transferrin

hemachromatosis

testing for _____ mutations is required for confirmation of hemacrhomatosis

HFE

what is the treatment for hemachromatosis?

- avoid iron-rich foods, alcohol, vit C

- phlebotomy if sx and ferritin > 1000

- PPI

- chelation