9.3 Hepatic Disorders, Cirrhosis & Portal Hypertension

9.3 Hepatic Disorders, Cirrhosis & Portal Hypertension

High-Yield Overview: Hepatic pathology centers on evaluating parenchymal liver injury, cholestatic patterns, metabolic liver diseases, and the systemic consequences of cirrhosis. Management revolves around risk-stratifying ascites via the SAAG score, identifying spontaneous bacterial peritonitis, preventing variceal hemorrhage, and maintaining strict semi-annual HCC surveillance.

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Viral Hepatitis & Hereditary Metabolic Liver Diseases

Viral Hepatitis Summary

Hereditary Metabolic Liver Pathology

• Hereditary Hemochromatosis: Autosomal recessive HFE gene mutation (C282Y). Iron overload deposits in liver, pancreas, heart, joints, and pituitary gland ("Bronze Diabetes": skin hyperpigmentation, diabetes mellitus, cirrhosis, restrictive/dilated cardiomyopathy, hypogonadism, MCP joint arthropathy).
  • Screening: Transferrin saturation >45% and serum ferritin >200 ng/mL (female) or >300 ng/mL (male).
  • Treatment: Weekly therapeutic phlebotomy (target ferritin 50-100 ng/mL).
• Wilson Disease (Hepatolenticular Degeneration): Autosomal recessive mutation in ATP7B (chromosome 13), impairing biliary copper excretion and ceruloplasmin binding.
  • Presentation: Hepatic dysfunction (cirrhosis, acute liver failure), neuropsychiatric symptoms (resting tremor, parkinsonism, dysarthria, psychosis), and Kayser-Fleischer rings (copper deposition in Descemet membrane of cornea).
  • Diagnostics: Decreased serum ceruloplasmin (<20 mg/dL), elevated 24-hour urinary copper excretion (>100 mcg/24h), and elevated hepatic copper on biopsy (>250 mcg/g dry weight).
  • Treatment: Copper chelators (D-penicillamine, trientine) and oral zinc.
• Alpha-1 Antitrypsin Deficiency: Autosomal codominant mutation in SERPINA1 (PiZZ allele). Accumulation of misfolded AAT protein in hepatocytes (PAS-positive, diastase-resistant globules) leads to cirrhosis and panacinar emphysema in young non-smokers.

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Autoimmune & Cholestatic Liver Disorders

Primary Biliary Cholangitis (PBC)

Autoimmune destruction of intrahepatic small interlobular bile ducts occurring primarily in middle-aged women (9:1 female ratio).

• Clinical Presentation: Severe fatigue, generalized pruritus (often preceding jaundice), hyperpigmentation, and xanthelasmas.
• Diagnostics: Elevated alkaline phosphatase, elevated IgM, and highly specific Anti-Mitochondrial Antibodies (AMA positive >95%).
• Histology: Florid duct lesions with granulomatous duct destruction.
• First-Line Therapy: Ursodeoxycholic acid (UDCA) slows histological progression and delays liver transplantation.

Primary Sclerosing Cholangitis (PSC)

Fibrosing inflammation and obliteration of both intrahepatic AND extrahepatic bile ducts.

• Association: 80% associated with Ulcerative Colitis.
• Diagnostics: p-ANCA positive. MRCP or ERCP demonstrates multifocal strictures and segmental dilations forming a "beaded" appearance.
• Complications: High risk of developing cholangiocarcinoma (10-15% lifetime risk) and gallbladder carcinoma.

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Ascites Evaluation & SAAG Diagnostic Algorithm

Diagnostic paracentesis is indicated for all patients with new-onset ascites or hospital admission for cirrhotic decompensation.

$$\text{SAAG} = \text{Serum Albumin (g/dL)} - \text{Ascitic Fluid Albumin (g/dL)}$$

                         Paracentesis Performed
                                   |
                     Calculate SAAG & Total Protein
                                   |
         +-------------------------+-------------------------+
         |                                                   |
   SAAG >= 1.1 g/dL                                   SAAG < 1.1 g/dL
 (Portal Hypertension)                             (Non-Portal Cause)
         |                                                   |
  +------+------+                                     +------+------+
  |             |                                     |             |
Protein       Protein                               Peritoneal     Tuberculous
>=2.5 g/dL    <2.5 g/dL                             Carcinomatosis  Peritonitis /
(Cardiac      (Cirrhosis /                          / Nephrotic    Pancreatitis
 Heart Failure) Budd-Chiari)                        Syndrome

• High SAAG (>=1.1 g/dL) = Portal Hypertension Present:
  • Ascitic Protein <2.5 g/dL: Cirrhosis, Budd-Chiari syndrome, Sinusoidal Obstruction Syndrome.
  • Ascitic Protein >=2.5 g/dL: Congestive heart failure, constrictive pericarditis.
• Low SAAG (<1.1 g/dL) = No Portal Hypertension:
  • Peritoneal carcinomatosis, tuberculous peritonitis, nephrotic syndrome, acute pancreatitis.

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Decompensated Cirrhosis Complications

Spontaneous Bacterial Peritonitis (SBP)

Monomicrobial infection of ascitic fluid without an intra-abdominal surgical source.

• Diagnostic Criteria: Paracentesis fluid Absolute Neutrophil Count (ANC) >=250/mm^3 (WBC x % neutrophils).
• Treatment: Empiric IV 3rd generation cephalosporin (Cefotaxime or Ceftriaxone) PLUS IV Albumin (1.5 g/kg on day 1, 1.0 g/kg on day 3) to prevent hepatorenal syndrome.
• Prophylaxis: Daily oral fluoroquinolone (ciprofloxacin) or TMP-SMX for secondary prevention or high-risk primary prevention (ascitic protein <1.5 g/dL).

Acute Esophageal Variceal Hemorrhage

• Screening: Screening EGD for all newly diagnosed cirrhosis patients.
• Primary Prophylaxis: Non-selective beta-blockers (nadolol, propranolol) or endoscopic band ligation (EBL).
• Acute Hemorrhage Management:
  1. Restrictive blood transfusion strategy (target hemoglobin 7–8 g/dL).
  2. IV Octreotide bolus and infusion (somatostatin analog to decrease splanchnic blood flow).
  3. Prophylactic IV Ceftriaxone for 7 days (reduces re-bleeding and mortality).
  4. Emergent upper endoscopy within 12 hours for endoscopic band ligation.
  5. Refractory bleeding: Transjugular Intrahepatic Portosystemic Shunt (TIPS).

Hepatic Encephalopathy

Neuropsychiatric impairment driven by systemic accumulation of neurotoxins (ammonia) due to portosystemic shunting.

• Features: Flapping tremor (asterixis), altered sleep-wake cycle, disorientation, somnolence, fetor hepaticus.
• Common Triggers: GI bleeding, infection (SBP), constipation, hypokalemia, hypovolemia, sedatives.
• First-Line Therapy: Lactulose (converted by colonic bacteria to $NH_4^+$, trapping ammonia in stool; titrated to 2-3 soft bowel movements/day). Second-line add-on: Rifaximin.

Hepatocellular Carcinoma (HCC) Surveillance

All patients with cirrhosis of any etiology (or chronic HBV carriers with high-risk features) require screening with abdominal ultrasound +/- serum alpha-fetoprotein (AFP) every 6 months.