Cirrhosis

Epidemiology

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Etiology

• Cardiac cirrhosis
  • A complication of right-sided heart failure characterized by cirrhosis due to chronic hepatic vein congestion.
  • Associated with “nutmeg liver” (diffuse mottling on imaging due to ischemia and fatty degeneration).

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Pathophysiology

• Cytokine‑mediated activation of hepatic stellate cells has been identified as a central element for developing fibrosis. t
  • A cell found in the perisinusoidal space of the liver
    • Quiescent phase: vitamin A storage
    • Activated phase: transform into myofibroblast to secrete collagen (primary cell involved in hepatic fibrosis)

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Clinical features

• Stigmata of hyperestrogenism: Spider angiomas, palmar erythema, gynecomastia, testicular atrophy.
• Portal HTN signs: Caput medusae, splenomegaly, ascites.
• Hepatic dysfunction: Scleral icterus, jaundice, asterixis (hepatic encephalopathy), pruritus.
• Dupuytren contracture, Muehrcke lines (dual white transverse bands on nails due to hypoalbuminemia).

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Diagnostics

Routine laboratory studies

• CMP
  • ↓ Albumin
  • Impaired hepatic protein synthesis leads to ↓ TBG, resulting in ↓ total T3 and T4 levels. c
    • However, the biologically active free T3 and T4 levels remain normal, which maintains a normal TSH (euthyroid state).
  • ↓ Total protein

CT abdomen

• Relative hypertrophy of the left lobe and caudate lobe
• Regenerative nodules
• Irregular liver surface
• Indirect findings: ascites, splenomegaly, portosystemic collaterals

Pathology

• Fibrosis (fibrous septa)
• Replacement of normal liver tissue with collagenous regenerative nodules

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Treatment

1. General Health Maintenance
   • Avoid all hepatotoxins (complete EtOH cessation, avoid NSAIDs due to renal failure/bleed risk).
   • Vaccinations: HAV, HBV, Pneumococcus, Influenza. (unless already immune) c
     • Acute HAV or HBV infection in unvaccinated/nonimmune patients with cirrhosis can cause severe acute or chronic liver failure.
   • HCC screening: RUQ US $\pm$ AFP every 6 months.
   • Varices screening: Esophagogastroduodenoscopy (EGD) at time of diagnosis.
2. Ascites Management:
   • First-line: Sodium restriction (<2g/day) + diuretics (Spironolactone + Furosemide in a 100:40 mg ratio).
   • Second-line: Large-volume paracentesis (LVP). Give IV albumin (6-8 g/L of fluid removed) if >5L removed to prevent circulatory dysfunction.
   • Refractory: TIPS (transjugular intrahepatic portosystemic shunt).
3. Variceal Management:
   • Primary Prophylaxis (small/medium varices): Non-selective beta-blockers (nadolol, propranolol) or endoscopic variceal ligation (EVL).
   • Acute Bleeding: IV Octreotide (splanchnic vasoconstriction) + Ceftriaxone (prophylaxis against SBP) + urgent EGD (within 12 hours) for EVL.
   • Refractory Bleeding: TIPS.
4. Hepatic Encephalopathy:
   • First-line: Lactulose (titrate to 2-3 soft stools/day to convert ammonia to non-absorbable ammonium).
   • Second-line (or add-on for recurrent episodes): Rifaximin (decreases ammonia-producing gut bacteria).
5. HCC Screening:
   • RUQ US +/- AFP every 6 months for all cirrhotic patients. c

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Complications

Complications screening

Hepatocellular Carcinoma (HCC) Surveillance

• Indication: All pts with Child-Pugh Class A or B cirrhosis. Pts with Child-Pugh Class C only if they are listed for liver transplantation (otherwise, surveillance does not improve survival).
• Modalities: Abdominal ultrasound (US) AND serum alpha-fetoprotein (AFP).
• Frequency: Every 6 months.
• Management of abnormal screen:
  • Nodule ≥ 1 cm: Order diagnostic multiphase contrast-enhanced CT or MRI of the liver (LI-RADS protocol showing arterial enhancement with venous washout).
  • Nodule < 1 cm: Repeat US and AFP in 3–6 months.
  • Elevated AFP with normal/inconclusive US: Order diagnostic multiphase CT or MRI.

Gastroesophageal Varices Screening

• Indication: All pts at the time of initial diagnosis of cirrhosis. c
• Primary Modality: Esophagogastroduodenoscopy (EGD).
• Alternative (Baveno Criteria): Screening EGD can be deferred if liver stiffness measurement (LSM) by transient elastography is < 20 kPa AND platelet count is > 150,000/µL.
• Surveillance Intervals (by EGD findings):
  • No varices: EGD every 2–3 years if compensated; annually if decompensated.
  • Small varices: EGD every 1–2 years if compensated; annually if decompensated. Start non-selective beta-blockers (NSBB) (e.g., carvedilol, nadolol, propranolol) if high risk of bleeding (e.g., red wale signs, Child-Pugh C).
  • Medium/Large varices: Do not repeat screening EGD. Initiate primary prophylaxis immediately with NSBB or endoscopic variceal ligation (EVL).

Osteoporosis Screening

• Rationale: Pts with cirrhosis have high risk of hepatic osteodystrophy (due to Vitamin D deficiency, malnutrition, and direct inflammatory bone resorption).
• Modality: Dual-energy X-ray absorptiometry (DXA) scan.
• Frequency: Baseline at diagnosis. Repeat every 2–3 years if normal.

Preventative Care & Vaccinations

• Immunizations:
  • Hepatitis A & B (if seronegative/non-immune).
  • Pneumococcal vaccine (PCV20 or PCV15 followed by PPSV23).
  • Annual influenza vaccine.
• Substance Avoidance:
  • NSAIDs: Absolutely contraindicated (inhibits renal prostaglandins, leading to renal vasoconstriction and precipitating AKI/hepatorenal syndrome).
  • Alcohol: Complete cessation.
  • Acetaminophen: Limit to < 2 g/day.

Portal hypertension

• Portal-Caval Anastomoses
  • These are connections between the portal venous system and the systemic (caval) venous system. In portal hypertension, these sites become engorged and dilated as blood is shunted away from the high-pressure liver.
  1. Esophageal:
     • Portal: Left Gastric Vein
     • Caval: Esophageal branches of the Azygos Vein (drains to SVC)
     • Clinical: Esophageal Varices (risk of life-threatening hematemesis).
  2. Anorectal: t
     • Portal: Superior Rectal Vein (from IMV)
     • Caval: Middle and Inferior Rectal Veins (drain to internal iliac vein → IVC)
     • Clinical: Anorectal Varices (often confused with hemorrhoids, can cause rectal bleeding).
  3. Paraumbilical:
     • Portal: Paraumbilical veins (travel with ligamentum teres)
     • Caval: Superficial Epigastric Veins of the anterior abdominal wall (drain to axillary/femoral veins → SVC/IVC)
     • Clinical: Caput Medusae (dilated, radiating periumbilical veins).
  4. Retroperitoneal:
     • Portal: Veins draining the ascending/descending colon, spleen, and liver.
     • Caval: Veins of the posterior abdominal/body wall (e.g., renal, lumbar veins).
     • Clinical: Usually asymptomatic, but can be a source of occult bleeding.
• Management/Treatment
  • Treatment is aimed at managing and preventing life-threatening complications.
  • Primary Prophylaxis of Variceal Bleeding:
    • Non-selective β-blockers (e.g., propranolol, nadolol): Decrease portal pressure by reducing cardiac output and causing splanchnic vasoconstriction. c
    • Endoscopic Variceal Ligation (EVL): Banding of varices to prevent rupture.
  • Acute Variceal Bleeding:
    • Medical Emergency: Secure airway, resuscitate with fluids/blood products.
    • Octreotide (somatostatin analog): Causes splanchnic vasoconstriction, reducing portal flow. c
    • Urgent EGD: For banding/ligation of bleeding varices. Perform within 12 hours of presentation once hemodynamically stable.
  • Refractory Bleeding/Ascites:
    • Transjugular Intrahepatic Portosystemic Shunt (TIPS): A stent placed between the portal vein and hepatic vein, shunting blood to decompress the portal system. Risk of worsening hepatic encephalopathy.
  • Ascites Management: Sodium restriction, diuretics (spironolactone, furosemide), and paracentesis for large volumes.
  • Definitive Treatment: Liver transplantation for end-stage liver disease.

Pulmonary complications of cirrhosis

Hepatic hydrothorax

• Definition: pleural effusions (typically one-sided; 70% right, 18% left) with transudate characteristics in the absence of any other cardiac, pulmonary, or pleural disease
• Pathophysiology: increased permeability of the diaphragm (small defects, increased abdominal pressure)
• Clinical presentation
  • May be asymptomatic
  • Signs and symptoms of pleural effusion: cough, dyspnea, hypoxia
• Diagnosis: Thoracocentesis shows transudate.