3.7 Cirrhosis & the Complications of Portal Hypertension

1. Cirrhosis & Complications of Portal Hypertension

Diagnostic Paracentesis & Ascites Evaluation

Every patient with new-onset ascites or cirrhosis admitted with clinical deterioration must undergo diagnostic paracentesis.

• Serum-Ascites Albumin Gradient (SAAG): $\text{SAAG} = \text{Serum Albumin (g/dL)} - \text{Ascitic Fluid Albumin (g/dL)}$
• SAAG $\ge 1.1\text{ g/dL}$ (High Gradient $\rightarrow$ Portal Hypertension Present):
  • Ascitic Protein $< 2.5\text{ g/dL}$: Cirrhosis (~80% of cases), late Budd-Chiari syndrome.
  • Ascitic Protein $\ge 2.5\text{ g/dL}$: Heart Failure (Cardiac Ascites), Constrictive Pericarditis, early Budd-Chiari, Sinusoidal Obstruction Syndrome.
• SAAG $< 1.1\text{ g/dL}$ (Low Gradient $\rightarrow$ Normal Portal Pressure / Peritoneal Disease):
  • Peritoneal Carcinomatosis (positive cytology), Peritoneal Tuberculosis (elevated Adenosine Deaminase [ADA]), Pancreatic Ascites (ascitic amylase $>1,000\text{ U/L}$), Nephrotic Syndrome.

Spontaneous Bacterial Peritonitis (SBP)

• Diagnostic Criterion: Ascitic fluid Absolute Polymorphonuclear (PMN) Count $\ge 250\text{ cells/mm}^3$ (calculated as $\text{Total WBC} \times %\text{ neutrophils}$).
• Bacteriology: Monomicrobial infection, most commonly enteric gram-negative bacilli (Escherichia coli, Klebsiella pneumoniae) or Streptococcus pneumoniae.
• Treatment Protocol:
  1. IV Antibiotic: Empiric IV 3rd-generation cephalosporin (Ceftriaxone 2 g IV daily or Cefotaxime 2 g IV q8h) for 5 to 7 days.
  2. IV Albumin Infusion (Mandatory): Proven to reduce the incidence of hepatorenal syndrome from 30% to 10% and significantly reduce in-hospital mortality. Administer $1.5\text{ g/kg}$ IV within 6 hours of diagnosis (Day 1), followed by $1.0\text{ g/kg}$ IV on Day 3.
  3. Secondary Prophylaxis: Indefinite oral antibiotic prophylaxis (Ciprofloxacin 500 mg daily or TMP-SMX 1 DS daily) following recovery from an index episode of SBP until liver transplantation.

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Gastroesophageal Variceal Hemorrhage

Screening EGD at Cirrhosis Diagnosis ➔ Small/Medium/Large Varices Identified
Primary Prophylaxis: Non-Selective Beta-Blocker (Nadolol / Propranolol / Carvedilol) OR Endoscopic Variceal Ligation (EVL)

Acute Variceal Bleed Emergency Protocol

1. Hemodynamic Resuscitation: Restrictive transfusion threshold targeting $\text{Hb } 7.0-8.0\text{ g/dL}$.
2. Vasoactive Infusion: IV Octreotide ($50;\mu\text{g}$ IV bolus followed by $50;\mu\text{g/hr}$ continuous IV infusion for 2 to 5 days) to induce selective splanchnic vasoconstriction and decrease portal inflow pressure.
3. Prophylactic Antibiotics (Mandatory): IV Ceftriaxone 1 g daily for up to 7 days (reduces bacteremia, rebleeding rates, and overall mortality).
4. Urgent Endoscopy: EGD within 12 hours of presentation with Endoscopic Variceal Ligation (EVL / Banding).
5. Refractory / High-Risk Bleeding: Preemptive Transjugular Intrahepatic Portosystemic Shunt (TIPS) within 72 hours for high-risk patients (Child-Pugh C score 10–13 or Child-Pugh B with active spurting bleeding). Balloon tamponade (Sengstaken-Blakemore tube) as temporary bridge ($<24\text{ hours}$) if uncontrollable.

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Hepatic Encephalopathy (HE)

• Pathophysiology: Neuropsychiatric syndrome caused by neurotoxin (ammonia) accumulation and portosystemic shunting.
• Precipitating Triggers (Must Identify and Treat):
  • Gastrointestinal bleeding (increased protein load in gut lumen).
  • Infection (SBP, UTI, pneumonia, bacteremia).
  • Electrolyte derangements (hypokalemia, metabolic alkalosis, hyponatremia; hypokalemia increases renal ammonia production).
  • Constipation, dehydration/overdiuresis, sedatives/opioids, or TIPS placement.
• Medical Therapy:
  • First-Line: Lactulose (non-absorbable disaccharide converted by gut flora into lactic/acetic acid, trapping ammonia as unabsorbable ammonium $\text{NH}_4^+$). Administer 20–30 g PO TID–QID, titrated to achieve 2 to 3 soft bowel movements per day.
  • Second-Line / Add-On: Rifaximin 550 mg PO BID (non-absorbable antibiotic targeting urease-producing gut bacteria; added after a second breakthrough episode of HE while on lactulose).

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Hepatorenal Syndrome (HRS-AKI)

• Pathophysiology: Extreme splanchnic arterial vasodilation mediated by nitric oxide, leading to profound renal arterial vasoconstriction, hypoperfusion, and functional renal failure.
• Diagnostic Criteria (ICA 2015):
  1. Cirrhosis with ascites.
  2. Acute Kidney Injury (KDIGO criteria: increase in $\text{Cr} \ge 0.3\text{ mg/dL}$ within 48h or $\ge 50%$ from baseline).
  3. No response after at least 48 hours of diuretic withdrawal and IV albumin volume expansion ($1\text{ g/kg/day}$, max 100 g/day).
  4. Absence of shock, nephrotoxic medications, and intrinsic renal parenchymal disease (proteinuria $<500\text{ mg/day}$, microhematuria $<50\text{ RBCs/HPF}$, normal renal ultrasound).
• First-Line Pharmacotherapy: Terlipressin (vasopressin V1a receptor agonist, 0.85–1.7 mg IV q6h) combined with IV Albumin (20–40 g/day). (Alternative: IV Norepinephrine infusion + Albumin in ICU, or oral Midodrine + subcutaneous Octreotide + Albumin).
• Definitive Treatment: Orthotopic Liver Transplantation (OLT).

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Hepatocellular Carcinoma (HCC) Surveillance & MELD-Na

• Surveillance Protocol: Abdominal Ultrasound with or without Alpha-Fetoprotein (AFP) every 6 months in all patients with cirrhosis (regardless of etiology) and in high-risk non-cirrhotic chronic HBV carriers.
• Diagnostic Imaging (LI-RADS Criteria): If a nodule $\ge 1\text{ cm}$ is detected on ultrasound, proceed to Multiphasic Contrast-Enhanced CT or MRI. The classic hallmark of HCC is Arterial Phase Hyperenhancement (APHE) followed by "washout" on portal venous/delayed phases with an enhancing capsule (LI-RADS 5). In a cirrhotic liver, classic imaging findings are diagnostic of HCC without requiring tissue biopsy.
• MELD-Na Score: Used to calculate 90-day mortality in cirrhosis and prioritize donor liver allocation (Scores 6–40). Incorporates Serum Bilirubin, Serum Creatinine, INR, and Serum Sodium.