4.2 Acute & Chronic Liver Disease

Acute & Chronic Liver Disease

Viral & Metabolic Hepatitis

Liver disease presents across a continuum from acute injury to chronic inflammation, fibrosis, and end-stage cirrhosis.

Hepatitis B Serology Interpretation

Understanding Hepatitis B virus (HBV) serological markers is essential for evaluating clinical phase, infectivity, and vaccination status.

• Treatment Indications: Antiviral therapy (Tenofovir disoproxil fumarate, Tenofovir alafenamide, or Entecavir) is indicated for HBV DNA >2,000 IU/mL, elevated ALT, and evidence of moderate-to-severe necroinflammation or liver fibrosis (F2 or greater).

Hepatitis C Virus (HCV)

• Diagnosis: Initial screening with anti-HCV antibody. Active infection confirmed by quantitative HCV RNA PCR.
• Direct-Acting Antivirals (DAAs): All-oral, pangenotypic DAA combinations (e.g., Sofosbuvir/Velpatasvir for 12 weeks or Glecaprevir/Pibrentasvir for 8 weeks) achieve Sustained Virologic Response at 12 weeks (SVR12) in >95% of patients.

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Formerly termed NAFLD, MASLD is defined by hepatic steatosis accompanied by at least one cardiometabolic risk factor (BMI ≥25 kg/m², type 2 diabetes, hypertension, or dyslipidemia) in the absence of significant alcohol consumption (≥30 g/day for men, ≥20 g/day for women).

• Risk Stratification: Non-invasive fibrosis scoring systems are critical to identify MASH (steatohepatitis) with advanced fibrosis:
  • FIB-4 Index: Uses Age, AST, ALT, and Platelet count.
    • Low Risk (<1.30): High negative predictive value (>90%) for advanced fibrosis; manage in primary care.
    • High Risk (>2.67): High risk of advanced fibrosis (F3-F4); refer to hepatology.
  • Transient Elastography (FibroScan): Liver stiffness measurement (LSM) <8 kPa rules out advanced fibrosis; LSM ≥12–15 kPa indicates cirrhosis.

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Autoimmune & Inherited Liver Diseases

Diagnostic differentiation of non-viral chronic liver diseases relies on autoantibody panels, biochemical profiles, and genetic testing.

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Cirrhosis & Portal Hypertension

Cirrhosis represents end-stage liver fibrosis characterized by regenerative nodule formation surrounded by fibrous bands.

Scoring Tools in Cirrhosis

Child-Pugh Classification

Assesses severity and 1-year survival in cirrhosis based on 5 variables (Bilirubin, Albumin, INR, Ascites, Encephalopathy):

• Class A (5–6 points): Well-compensated (1-year survival 100%).
• Class B (7–9 points): Significant functional compromise (1-year survival 80%).
• Class C (10–15 points): Decompensated cirrhosis (1-year survival 45%).

Model for End-Stage Liver Disease (MELD)

Predicts 3-month mortality in end-stage liver disease and is used to prioritize liver transplantation allocation. Calculated using: Serum Bilirubin, Serum Creatinine, INR, and Serum Sodium (MELD-Na).

Complications of Decompensated Cirrhosis

1. Ascites & Spontaneous Bacterial Peritonitis (SBP)

• Paracentesis Evaluation: Diagnostic tap is mandatory for all new-onset ascites or hospital admissions with cirrhosis.
  • Serum-Ascites Albumin Gradient (SAAG) = Serum Albumin − Ascitic Fluid Albumin.
    • SAAG ≥11 g/L (High Gradient): Indicates Portal Hypertension (cirrhosis, heart failure, Budd-Chiari).
    • SAAG <11 g/L (Low Gradient): Non-portal cause (peritoneal carcinomatosis, tuberculous peritonitis, nephrotic syndrome).
• Spontaneous Bacterial Peritonitis (SBP): Infection of ascitic fluid without an intra-abdominal surgically treatable source.
  • Diagnostic Benchmark: Ascitic fluid absolute polymorphonuclear (PMN) neutrophil count ≥250 cells/mm³ (0.25 × 10⁹/L).
  • Immediate Protocol: Empiric IV Cefotaxime 2 g TDS (or Ceftriaxone 2 g OD) PLUS IV Human Albumin (1.5 g/kg body weight within 6 hours of admission, followed by 1.0 g/kg on day 3). Albumin reduces renal impairment from 30% to 10% and significantly improves survival.
  • Secondary Prophylaxis: Oral Ciprofloxacin 500 mg OD or Norfloxacin 400 mg OD long-term.

2. Hepatic Encephalopathy (HE)

HE results from neurotoxic substances (primarily ammonia) crossing the blood-brain barrier due to portosystemic shunting and impaired hepatic clearance.

• West Haven Criteria:
  • Grade 1: Mild confusion, altered mood, asterixis (flapping tremor) present.
  • Grade 2: Lethargy, disorientation to time, inappropriate behavior.
  • Grade 3: Somnolence, stupor, disorientation to place.
  • Grade 4: Coma.
• Precipitating Factors: Constipation, GI bleeding, infection (SBP, UTI), hypokalemic alkalosis, dehydration, sedatives.
• Management: Identify and treat precipitants. First-line therapy is oral Lactulose (titrated to achieve 2–3 soft bowel movements daily; metabolizes to lactic acid, trapping NH₄⁺ in bowel). Second-line add-on is Rifaximin 550 mg BD (non-absorbable antibiotic reducing urease-producing gut flora).

3. Hepatorenal Syndrome (HRS-AKI)

HRS-AKI is functional renal failure caused by severe renal vasoconstriction secondary to splanchnic arterial vasodilation in portal hypertension.

• Diagnostic Criteria:
  1. Diagnosis of cirrhosis with ascites.
  2. Acute Kidney Injury (AKI) per KDIGO criteria (increase in serum creatinine ≥26.5 µmol/L within 48 hours or ≥50% increase from baseline).
  3. No response after at least 48 hours of withdrawal of diuretics and volume expansion with IV albumin (1 g/kg/day).
  4. Absence of shock, structural kidney disease (proteinuria <0.5 g/day, microhematuria <50 RBCs/hpf), and nephrotoxic drug exposure.
• Treatment: First-line medical therapy is IV Terlipressin (0.5–2 mg IV every 4–6 hours or continuous IV infusion 2–12 mg/day) combined with IV Human Albumin (20–40 g/day). Transjugular Intrahepatic Portosystemic Shunt (TIPS) or liver transplantation is definitive.