Cirrhosis learning objectives (Riche)

is a severe, chronic, and potentially irreversible disease

Cirrhosis

- Fibrosis (scarring)

- Nodular regeneration

- Loss of normal liver architecture

what is cirrhosis characterized by

- Portal hypertension (increased pressure in portal circulation)

- Liver insufficiency (inability to perform normal functions)

structural damage leads to

- Liver injury → activation of hepatic stellate cells

- hepatic stellate cells lose bit A and produce TGF-β1, causing fibrosis

- Creates a vicious cycle: hepatocyte death → more fibrosis → worsening damage

Pathophysiology

- Metabolism of nutrients, vitamins, hormones

- Drug metabolism (CYP450)

- Synthesis of Albumin and Clotting factors

- Immune function (Kupffer cells)

Normal Liver Functions

- Impaired metabolism & detoxification

- Decreased protein synthesis → ↓ albumin, ↓ clotting factors

- Altered drug handling

Cirrhotic Liver

- decrease first-pass metabolism

- decrease CYP450 activity

- increase drug concentrations

- increase volume of distribution

- low albumin (ceftriaxone doesn't work bc highly protein bound)

Altered drug handling

- Chronic alcohol use

- Chronic Hepatitis C

- MASLD (formerly NAFLD)

cirrhosis common causes

- Obesity

- Diabetes

- Hypertension / hyperlipidemia

- Hemochromatosis (iron overload)

- Wilson disease (copper accumulation)

Metabolic & Medical Conditions

iron accumulation

Hemochromatosis

copper accumulation

Wilson disease

- Autoimmune hepatitis

- Acetaminophen

- Amiodarone

- Methotrexate

- Nitrofurantoin

- Isoniazid

cirrhosis other causes

- Portal hypertension

- Esophageal varices

- Ascites

- Systemic shunting

Hemodynamic / Structural

- Hypoalbuminemia

- Coagulopathy

- Thrombocytopenia

Metabolic / Functional

- Hepatic encephalopathy

- Spontaneous bacterial peritonitis (SBP)

- Hepatorenal syndrome

Major Clinical Complications

- Nonselective beta blockers (preferred: carvedilol)

- decrease cardiac output

- decrease splanchnic blood flow

- Endoscopic variceal ligation (EVL)

Portal Hypertension / Varices primary prophylaxis

- Octreotide (drug of choice)

- Antibiotics (ceftriaxone)

- Balloon tamponade (temporary)

- TIPS (definitive)

Portal Hypertension / Varices acute bleeding

- Lifelong beta-blocker therapy

- target HR reduction of 55-60 bpm while maintaining SPB > 90 mmHg

Portal Hypertension / Varices secondary prophylaxis

- Sodium restriction (<2 g/day)

- ± Fluid restriction (if Na <125)

- Diuretics Spironolactone ± furosemide

- Paracentesis Give albumin if >5 L removed

Ascites Management

Ceftriaxone or cefotaxime (5 days)

Spontaneous Bacterial Peritonitis (SBP) Treatment

Ciprofloxacin or TMP/SMX

Spontaneous Bacterial Peritonitis (SBP) Prophylaxis

increase ammonia (NH₃)

Hepatic Encephalopathy cause

- Lactulose (first-line): Converts NH₃ → NH₄ and Increases excretion

- Rifaximin add-on

- Protein restriction 1.2-1.5 g/kg/day

Hepatic Encephalopathy treatment

- Avoid NSAIDs (↓ renal perfusion)

- Manage hyponatremia with fluid restriction

- Monitor for bleeding/clotting abnormalities

Other Management Points

mortality risk

Child-Pugh Score

transplant priority

MELD Score

liver transplant

only cure for cirrhosis

due to bilirubin accumulation, irritating skin

pruritus

usually esophagus, but can also include all other veins and vessels along the GI tract

variceal bleeding

causes confusion, drowsiness, slurred speech, coma in severe cases

encephalopathy

- bilirubin

- AST and ALT

- PT/INR

- Alk phos

common lab abnormalities elevated

- platlets

- albumin

- hemoglobin

- WBC

common lab abnormalities decrease

- early stage with some fibrosis

- liver still functions

- asymptomatic or nonspecific symptoms (weight loss, weakness, fatigue)

compensated

- late stage with extensive fibrosis

- liver can't function

- symptomatic

- jaundice and pruritus

- ascites

- hepatic encephalopathy

- bruise easily (decrease platelets)

decompensated

- hepatic venous pressure gradient > 10 mmHh

- increased risk of esophageal varices

portal hypertension

upper GI endoscopy

screen all patients with cirrhosis using an

endoscopy every 2 years

small varices without risk factors

primary prophylaxis

small varices with risk factors

primary prophylaxis

medium to large varices

endoscopic variceal ligation

what is more effective than sclerotherapy

- starting dose 6.25 mg daily

- usual dose 6.25 mg BID

- max dose per day 12.5 mg

carvedilol

- octreotide

- prevents/stops vasodilation of splanchnic blood vessels to slow/stop esophageal bleeding

- 50 mcg bolus, then continuous infusion of 50 mcg/hour x 2-5 days

acute vatical hemorrhage treatment DOC

- inflated within the esophagus or stomach to apply pressure on bleeding blood vessels and stop the bleeding

- temporary until TIPS can be preformed

balloon tamponade

surgically create a new vein that bypasses the liver to relieve portal pressure

Trandjugular intrahepatic portosystemic shunt (TIPS)

- ceftriaxone 2g IVPB daily until hemorrhage is resolved and vasoactive drugs are discontinued (max 7 day treatment)

antibiotic therapy for acute vatical hemorrhage treatment

- fever +/- chills

- abdominal tenderness/pain

- rebound encephalopathy

- renal failure

- acidosis

- peripheral leukocytosis

- altered mental status

spontaneous bacterial peritonitis S/S

- klebsiella pneumoniae

- streptococcus pneumoniae

- viridans group streptococci (most common)

spontaneous bacterial peritonitis causative organisms