Pathology and Disorders of the Liver (Fatty Liver/Acute Liver Failure/Cirrhosis/HCC

Non Alcoholic Fatty Liver Disease

PP: insulin resistance→fat deposit in liver

E: metabolic sydnrome
obesity
diabetes
hypertriglyceridemia
insulin resistance

CM: asymptomatic
RUQ discomfort
hepatomegaly

DX:
transaminases increased
alkaline phosphate increased
AST/ALT increased

ultrasound: echogenecity

CT: no hepatic attenuation

MRI: fat signal

img: hepatic steatosis

MR elastography/fibroscan: assess fibrosis

liver biopsy: steatosis+inflammation without hepatocyte ballooning
determines if NAFLD or NASH

fibrosis assessment

TX:

NP: weight loss
diet
exercise
avoid alcohol
control blood glucose (metformin+thiazolidinediones)
don’t stop statins

MX: obeticholic acid
glucagon-like protein-1 analogs

Jaundice Review

E:
prehepatic→excessive RBC hemolysis: high indirect bilirubin

intrahepatic→liver dysfxn: high direct+indirect bilirubin

posthepatic/extrahepatic→obstructed bile flow: high direct bilirubin

CM: yellow skin/tissues
dark urine
clay-colored stool

DX: serum bilirubin over 2.5-3mg/dL

Nonalcoholic Steatohepatitis (NASH)

PP: hepatic steatosis+inflammation
2nd hit: oxidative stressors

E: 3-5% US
old age
female
not black
diabetes
obesity

CM: hepatomegaly
asymptomatic
fatigue
malaise
vague RUQ discomfort

DX:
NAFLD over 1.5x normal
serum ferritin over 1.5x normal

liver biopsy: steatosis+inflammation with hepatocyte ballooning

TX:
NP: abstinence from alcohol
tx underlying conditions
BMI over 35→bariatric surgery

MX:
biopsy proven+non diabetic→IU vitamin E
vitamin E+ursodeoxycholic acid
semaglutide
liraglutide
pioglitazone

Acute Liver Failure

PP: hepatocytes get edema→patchy necrosis+inflammatory infiltrates→disrupt liver parenchyma→hepatic necrosis (irreversible)

E: acetaminophen (Tylenol) overdose

CM: anorexia/vomiting/abdominal pain→jaundice/ascites/GI bleeding
hepatic encephalopathy→asterixis/flapping tremor

Tx:
sx management
prevent infections
nutritional support
liver transplant

Gonadal Hormone Dysfxn

Men: testicular atrophy
gynecomastia
loss of libido
impotence

Women: dysmennorrhea (no periods)
loss of libido
sterility

Cirrhosis

PP: long term liver injury→regenerative nodules→hepatocyte dysfxn→portal HTN=>portosystemic shunting

E: alcohol
viral hepatitis
NAFLD/NASH
hereditary hemochromatosis
celiac disease

CM:
compensated: weight loss
fatigue
insomnia

muscle loss
dupuytren’s contracture
spider telangectasias on chest+face
palmar erythema
etc.

decompensated

DX: low WBC
macrocytic anemia
thrombocytopenia
elevated PT/INR
decreased albumin
etc.

ultrasound: nodular/heterogeneous liver

doppler

mass/nodule/confirmed cirrhosis→MRI/CT+MRE

liver/laparoscopic/transjugular biopsy

MELD score

child-pugh score

TX: none

Portal Hypertension

PP: liver damage→blood backs up→raising pressure→ascites/splenomegaly/esophageal varices/gastic varices/portosystemic shunts

Splenomegaly Pathophysiology

portal HTN→blood goes to splenic vein→spleen becomes enlarged→increased risk of bleeding

Hypersplenism PP

decreased lifespan of blood cells→pancytopenia

Portosystemic Shunts PP

collateral channels: develop between portal and systemic veins
compensate for increased portal pressure

caput medusa: around umbilicus

hemorrhoids+esophageal/gastric varices: increased pressure→hemorrhage
intestine ammonia+neurotoxins into general circulation→mental status changes/confusion/coma

Hepatorenal Syndrome (HRS)

PP: changes in general+splanchic circulations→severe renal constriction→renal failure

CM: HTN
oliguira (low urine)
peripheral vasodilation
structural kidney injury
shock

DX: increased serum creatine over 0.3mg/dL within 48 hrs
OR
increased serum creatine 50% in 7 days

no improvement in kidney fxn 2 days after diuretic withdrawal+albumin

TX:

ideal: liver transplant

stop diuretics
OR
add midodrine PO TID with diuretics

IV albumin+midrodrine PO+octreotide x 7-14 days

Hepatopulmonary Syndrome

CM:
chronic liver disease
intrapulmonary vasodilation
gas exchange abnormality

DX: lung perfusion scan

TX: long-term O2 therapy
TIPS→liver transplant

Esophageal Varices

PP: cirrhoses→high blood pressure in portal vein→forces blood into smaller veins in the esophagus→enlarge and bleed

E: 2/3 cirrhosis pts

CM: coughing
retching
dyspepsia

hypotension
tachycardia
portal HTN→varicose esophageal veins→hemorrhage

DX/TX: endoscopic variceal ligation+cauterization

Decompensated Cirrhosis CM

hepatic encepalopathy
bleeding esophageal varices
ascites
spontaneous bacterial peritonitis
hepatocellular carcinoma (HCC)

Ascites

PP: increased hydrostatic pressure (pushes fluid out)+ serum oncotic pressure (pulls fluid in)→fluid in peritoneal cavity

CM: abdominal distention
weight gain
dyspnea

DX: abdominal ultrasound
SAAG gradient calculation over 1.1 g/dL→portal HTN

CBC
paracentesis
albumin
protein
SBP culture

TX:
NP: alcohol abstinence
low sodium diet
paracentesis

MX: spironolactone
furosemide

Spontaneous Bacterial Peritonitis (SBP)

E: GI bleeding
proton pump inhibitor (PPI)

CM: fever
abdominal pain
progressive encephalopathy

DX: WBC over 500
PMN over 250
protein over 1
culture: ecoli
streptococcus sppp

Tx: IV/PO cefotaxime Q8-12 hrs x 5 days
prophylaxis→ciprofloxacin x daily

Esophageal Vericeal Bleeding

PP: portal hypertension→varices in esophagus rupture+bleed

Tx: fluid resuscitation
transfusion

INR elevated→vitamin K

hepatic encephalopathy→lactulose

bleeding control→upper endoscopy+epinephrine injections

last resort→TIPS

Hepatic Encephalopathy

PP: liver dysfxn+portal systemic shunting→can’t detoxify→toxins go to brain→disrupted CNS fxn

E: GI bleeding
constipation

CM: mild fatigue
insomnia
lethargy
stupor
coma
asterixis

DX: elevated ammonia

TX: lactulose
rifaximin BID
avoid opioids+sedatives

Hepatocellular Carcinoma (HCC)

RF: cirrhosis
hepatitis b
hepatitis c
NAFLD+adenomas
obesity+adenomas

decreased risk: coffee
vegetables
fish
white meat
aspirin
diabetes→statins/metformin

CM: cachexia
cirrhosis
ascites
hepatomegaly

DX: leukocytosis
anemia
elevated alkaline phosphatase
AFP

MRI: washout pattern
CT: washout pattern
abdomen ultrasound
liver biopsy

TX: radiofrequency ablation
transarterial chemoembolization (TACE)

Liver Transplant

I: acute liver failure
decompensated cirrhosis+high MELD score
HCC+met milan criteria

CI:
absolute: malignancy
advanced cardiopulmonary disease

relative: alcohol/drugs
over 70 y/o
morbidly obese

donor needs to be 18-55 y/o and perfectly healthy

Metastatic Liver Disease

PP: malignant tumor from another fever

CM: anorexia
weight loss
dark urine
hepatomegaly

DX: elevated serum AFP
abdomen CT

TX: chemotherapy
radiation therapy
RFA