CMPP -- Cirrhosis and Hepatocellular Carcinoma

hepatic fibrosis

distortion of hepatic architecture

formation of regenerative nodules

cirrhosis is characterized by...

in early stages, maybe, but in late stages, it is not

is cirrhosis reversible?

chronic viral hepatitis (HCV/HBV)

alcoholic liver disease

MASLD (steatosis/steatohepatitis)

most common causes of cirrhosis

Hemochromatosis

genetic disorder of increased intestinal iron absorption resulting in inappropriate storage of iron in liver and other tissues

iron panel

how to screen for hemochromatosis

elevated serum iron, ferritin, percent saturation, and low total iron binding capacity

what would be seen in an iron panel for one with hemochromatosis

Hemochromatosis gene study

if the iron panel is elevated in one with suspected hemochromatosis, what is the next step?

liver biopsy

how to get definitive diagnosis of hemochromatosis

autoimmune hepatitis

primary biliary cholangitis

primary sclerosing cholangitis

atypical causes of cirrhosis

Wilson's disease

abnormal storage of copper in the liver and other body tissues

serum ceruloplasmin followed by 24 hour urine copper testing

how to assess for Wilson's disease

Copper rings around iris -- Keyser-Fleisher rings

classic finding in Wilson's disease

methotrexate or INH

what medications can cause cirrhosis

Alpha-1-antitrypsin deficiency

genetic disorder characterized by development of serious liver disease/cirrhosis and/or emphysema in a non-smoker; complications seen in YOUNG patients

Compensated cirrhosis

asymptomatic or non-specific symptoms such as anorexia, weight loss, generalized weakness, generalized fatigue

processing problems

portal HTN and its complications

Hormonal influence

three causes of decompensated cirrhosis

RBCs due, transported to spleen

step 1 of normal bilirubin physiology

macrophages break down heme into unconjugated/indirect bilirubin -- not water soluble

step 2 of normal bilirubin physiology

unconjugated bilirubin binds to albumin, making it water soluble

step 3 of normal bilirubin physiology

complex transported to liver where it combines with glucuronic acid to make conjugated/direct bilirubin

step 4 of normal bilirubin physiology

liver disease

hemolysis

Gilbert's syndrome

increased unconjugated bilirubin can indicate...

Gilbert's syndrome

a genetic disorder of bilirubin metabolism

hepatobiliary disease -- decreases rate of secretion of bilirubin into the bile or clearance of bile from the liver

increased conjugated bilirubin can indicate...

decreased albumin for transportation to the liver

liver cannot conjugate bilirubin

what issues with liver dysfunction can results in more serum unconjugated bilirubin?

liver cannot properly release it into the bile

what issues with liver dysfunction can results in more serum conjugated bilirubin?

jaundice

clinical result of too much bilirubin

under tongue

where is jaundice most noticeable first?

hepatic encephalopathy

problems with processing ammonia into urea can lead to...

ammonia passes BBB -- used by brain cells to convert glutamate to glutamine in the cell --> too much glutamine results in increased osmotic pressure in the brain cell --> cellular edema results in altered mental status

pathophysiology of hepatic encephalopathy

a precipitating factor can tip the nitrogen balance into excess

why do ammonia processing issues happen?

eating large amounts of protein

GI bleeding

medications

infection

electrolyte imbalance

what can tip the nitrogen balance into excess?

Lactulose laxative

first line management for hepatic encephalopathy

decreases ammonia production by gut bacteria

drawers ammonia from blood into colon

lower pH in gut converts Nh3 to NH4 -- traps it there

how does a Lactulose laxative treat hepatic encephalopathy?

Portal hypertension

the elevation of blood pressure within the portal venous system; occurs when there is resistance to portal blood flow

decreased blood vessel diameters

portal vascular resistance is caused by...

mechanical consequence (fibrosis)

decreased production of NO by portal system and endothelial cels

how does liver decrease vascular radius?

Caput medusae

Result of portal hypertension - dilation of abdominal veins. Increased pressure causing dilation of collateral veins radiating over abdomen

Ascites

acute fluid accumulation in the abdominal compartment

albumin levels fall -- lose osmotic pull of albumin to keep fluid in intravascular space -- fluid leads outside of vessels

how does liver disease cause ascites?

abdominal distension, + fluid wave/shifting dullness

weight gain, SOB, early satiety

presentation of ascites

AVOID alcohol

SALT RESTRICTION AND DIURETIC THERAPY

first line treatment for ascites

Spironolactone and Furosemide

what are the drugs of choice for treating ascites?

40:100mg

the ratio of Lasix:Aldactone should be maintained at...

paracentesis, then diuretic regimen

if a patient has a tense abdomen due to ascites, what can be done?

Spontaneous Bacterial Peritonitis (SBP)

infection of pre-existing ascitic fluid without an intra-abdominal source

patient with cirrhosis and ascites

fever with abdominal pain

+/- change inlmntal status

what signs/symptoms should make one suspicious of SBP?

paracentesis -- cell count (neutrophils)

how to diagnose SBP

empiric Abx with broad spectrum Abx (cefotaxime) until cultures return -- keep them on these even after diagnosis of SBP

if you suspect someone has SBP, what should you do to begin treating them?

Bactrim or Ciprofloxacin

what is the tx of choice for confirmed SBP?

decompensated

when bleeding occurs, the patients cirrhosis becomes...

differences between systemic and portal circulation pressure

what causes varices?

GEJ

most common location for esophageal varices?

EGD

it is recommended that all patients with cirrhosis have ___ to document existence of varices

ligation/banding during endoscopy

nonselective beta blockers (Nadolol and propanolol)

treatment for esophageal varices

Nadolol and propanolol

nonselective beta blockers of choice for esophageal varices

yearly

if a person with cirrhosis gets an EGD to look for varices, and it's positive, when should the next EGD be repeated?

Q2-3 years

if a person with cirrhosis gets an EGD to look for varices, and it's negative, when should the next EGD be repeated?

Hepatorenal syndrome

a syndrome that represents the end-stage of a sequence of reductions in renal perfusion induced by increasingly severe hepatic injury; liver failure that causes renal failure

moderate increase

* normal LFTs do not exclude cirrhosis

what are the AST/ALT levels associated with cirrhosis?

usually elevated but less than 3X ULN

what are the Alk phos levels associated with cirrhosis?

cholestatic liver disease

if Alk phos is higher than 3x ULN, what should you suspect?

normal in compensated cirrhosis

will rise as cirrhosis progresses

what are the bilirubin levels associated with cirrhosis?

levels fall as liver loses synthetic function, but it is not specific for liver disease

what are the albumin levels associated with cirrhosis?

higher INR -- more severe disease

how does clotting factors/clotting times indicate severity of cirrhosis?

HYPONATREMIA

what are the sodium levels associated with cirrhosis?

thrombocytopenia -- pooling of blood in spleen -- splenomegaly

what is the most common CBC finding associated with cirrhosis?

microcytic -- iron deficiency from acute/chronic GI blood loss

macrocytic -- folate/B12 deficiency

bone marrow suppression -- chronic iron/folate deficiency OR toxic effect of alcohol

what can cause anemia associated with cirrhosis?

abdominal ultrasound -- liver will look small and nodular in advanced disease

what is the best initial test to order when diagnosing cirrhosis?

liver biopsy (but not needed when clinical, lab, and radiology suggests cirrhosis and a biopsy would not change management)

what is considered the gold standard for diagnosing cirrhosis?

Child-Pugh classification system

MELD score

what are the two classification systems used to establish severity of cirrhosis?

Child-Pugh Score

classification system used to determine who should have hepatic dose adjustments for their medications

MELD score

prognostic model to help estimate disease severity, survival, and transplant; composed of serum bilirubin, serum creatinine, INR, sodium serum albumin, female sex, and change to Cr cutoff; used to predict short-term survival; increasing MELD score is associated with increasing severity of hepatic dysfunction and three-month mortality risk

Hepatocellular Carcinoma

primary cancer of the liver that occurs mostly in patients with underlying chronic liver disease and cirrhosis; can come beforehand though

HBV

hemochromatosis

HCV

MASLD/MASH

alcoholic cirrhosis

risk factors for HCC

Alpha-fetoprotein

protein that is given off by tumor cell or by regenerating hepatocyte; can be elevated for a variety or reasons

hepatomegaly

weight loss

abdominal pain

weakness

abdominal fullness/swelling

jaundice

nausea

presentation of HCC

abdominal ultrasound

initial test for HCC

biopsy -- but can be diagnosed based on characteristic CT/MRI findings with AFP

gold standard for diagnosis of HCC

TNM classification

staging for HCC

surgical resection, ablation/embolization, radiation, liver transplant

treatment for HCC