Management of Cirrhosis

1. Treat the Underlying Etiology

2. General Measures

• Nutrition: High-protein diet (1.2–1.5 g/kg/day); avoid prolonged fasting; consider BCAA supplementation in sarcopenic patients.
• Vaccinations: HAV, HBV, influenza, pneumococcal, COVID-19.
• Avoid hepatotoxins: NSAIDs (risk of AKI/GI bleed), aminoglycosides, contrast nephropathy precautions.
• Alcohol: Complete abstinence regardless of etiology.
• Sedatives/opioids: Use with extreme caution — risk of precipitating hepatic encephalopathy.
• Statins: May be used for lipid control; associated with reduced portal pressure and HCC risk; use with caution in decompensated disease.

3. Management of Complications

A. Portal Hypertension & Varices

• Compensated cirrhosis: Upper GI endoscopy at diagnosis.
• If no varices: repeat every 2–3 years (compensated) or 1 year (decompensated).

• Small varices with high-risk features or medium/large varices: Non-selective beta-blockers (NSBBs) — propranolol 20–40 mg BD, nadolol, or carvedilol 6.25–12.5 mg OD (preferred — reduces HVPG more effectively).
• Medium/large varices: Endoscopic band ligation (EBL) is equally effective; preferred if NSBBs are contraindicated.
• Target: Resting HR ~55–60 bpm; or HVPG reduction to <12 mmHg.

1. Resuscitation: Restrictive transfusion strategy (Hb target 7–8 g/dL); avoid over-transfusion (raises portal pressure).
2. Vasoactive drugs (start immediately, before endoscopy): Terlipressin 2 mg IV q4h (or octreotide/somatostatin); continue for 3–5 days.
3. Antibiotics: Ceftriaxone 1 g/day IV for 7 days (reduces SBP and mortality).
4. Endoscopy within 12 hours: EBL (preferred) or sclerotherapy.
5. TIPS (transjugular intrahepatic portosystemic shunt): For refractory/uncontrolled bleeding or early rebleeding; also considered early (pre-emptive TIPS within 72 h) in high-risk patients (Child-Pugh C or B with active bleeding at endoscopy).

• Combination of NSBB + EBL (superior to either alone).
• TIPS if combination therapy fails.

B. Ascites

• Dietary sodium restriction: 88 mmol/day (~2 g/day).
• Spironolactone 100 mg/day (first-line; anti-aldosterone), up to 400 mg/day.
• Add furosemide 40 mg/day (maintain 100:40 ratio with spironolactone to preserve normokalemia), up to 160 mg/day.

• Drain all ascites in single session.
• Albumin replacement: 6–8 g per liter of ascites removed (if >5 L drained) to prevent post-paracentesis circulatory dysfunction (PPCD).

• Defined as lack of response to maximum diuretics OR diuretic-related complications.
• Options: Repeated LVP + albumin, TIPS (best evidence), or liver transplant evaluation.
• Tolvaptan: V2-receptor antagonist; can help hyponatremia-associated ascites.
• Discontinue NSBBs if refractory ascites + hypotension (SBP <90 mmHg) — worsens outcomes.

• Diagnose: Ascitic PMN >250 cells/mm³.
• Treat: Cefotaxime 2 g IV q8h × 5 days (or ceftriaxone 1 g/day).
• Add albumin 1.5 g/kg on day 1 and 1 g/kg on day 3 (reduces hepatorenal syndrome and mortality).
• SBP prophylaxis: Norfloxacin 400 mg/day OR trimethoprim-sulfamethoxazole; indicated after:
  • Prior episode of SBP
  • Ascitic protein <1.5 g/dL + Child-Pugh ≥9 or bilirubin ≥3 mg/dL or renal dysfunction
  • During acute variceal bleed (ceftriaxone preferred)

C. Hepatic Encephalopathy (HE)

• GI bleed, infection, constipation, dehydration, electrolyte disturbance, hepatotoxic drugs, AKI, porto-systemic shunt.

• Lactulose: 25–30 mL q1–2h until 2–3 soft stools/day; cornerstone of therapy.
• Rifaximin 550 mg BD: Added for recurrent or persistent HE; significantly reduces hospitalizations.
• Treat precipitant.
• Protein restriction is NOT recommended (worsens sarcopenia); maintain 1.2–1.5 g/kg/day.
• IV branched-chain amino acids (BCAAs) if unable to tolerate oral protein.

• Lactulose ± rifaximin (combination preferred after first overt episode).
• TIPS occlusion if HE is TIPS-induced and refractory.

D. Hepatorenal Syndrome (HRS)

• First-line: Terlipressin 1–2 mg IV q4–6h (or as CI infusion) + albumin 1 g/kg/day (max 100 g/day) for up to 14 days.
• Where terlipressin is unavailable: Norepinephrine + albumin (ICU setting); midodrine + octreotide + albumin (weaker evidence).
• Bridge to liver transplant.

E. Hepatopulmonary Syndrome (HPS) & Portopulmonary Hypertension (PoPH)

• HPS (PaO₂ <80 mmHg): Supplemental O₂; liver transplant is only definitive treatment.
• PoPH (mPAP >25 mmHg): Pulmonary vasodilators (sildenafil, bosentan, epoprostenol); transplant if controlled.

F. Hepatocellular Carcinoma (HCC) Surveillance

• All cirrhotic patients: Liver ultrasound ± AFP every 6 months.
• If nodule detected: CT/MRI with contrast for LI-RADS characterization.
• Curative options: Resection, ablation, liver transplant (Milan criteria: 1 lesion ≤5 cm or ≤3 lesions each ≤3 cm, no vascular invasion).

4. Liver Transplantation

• MELD-Na score ≥15 (benefits outweigh transplant risk).
• CTP score ≥7 (Child B/C).
• First episode of decompensation (ascites, HE, variceal bleed, HRS).
• HCC within Milan criteria.
• Hepatopulmonary syndrome.

5. Monitoring in Stable Cirrhosis

6. Compensated vs. Decompensated Cirrhosis

Quantitative PCR for Hepatitis

Hepatitis B — HBV DNA (Quantitative PCR)

Principle

• HBV DNA is measured by PCR-based amplification assays, which are far more sensitive than older hybridization assays (Harrison's, p. 9471).
• Results are expressed in IU/mL (International Units/mL) — the WHO-standardized unit — or copies/mL (1 IU/mL ≈ 5.6 copies/mL, but conversion varies by assay).
• Modern PCR assays detect as low as 10–20 IU/mL.

Clinical Interpretation

Indications for Testing

1. Diagnosis of active HBV infection (confirm HBsAg-positive result)
2. Staging: Determine phase of chronic infection (immune-tolerant, immune-active, inactive, reactivation)
3. Treatment decision: Determines who needs antiviral therapy
4. Monitoring on treatment: Goal is undetectable or very low HBV DNA
5. Reactivation screening: Before immunosuppression or chemotherapy
6. Occult HBV: HBsAg-negative but anti-HBc positive patients — qPCR can detect occult replication

Treatment Thresholds (EASL/AASLD Guidelines)

• HBV DNA >2,000 IU/mL + elevated ALT + significant fibrosis/necroinflammation (HBeAg-negative disease)
• HBV DNA >20,000 IU/mL + elevated ALT (HBeAg-positive disease)
• Any detectable HBV DNA in cirrhotic patients (regardless of ALT)
• HBV DNA >200 IU/mL in patients undergoing immunosuppression (prophylaxis indication)

Monitoring on Treatment

• Preferred first-line agents: Entecavir, Tenofovir disoproxil fumarate (TDF), Tenofovir alafenamide (TAF) (Harrison's, p. 9471)
• Primary non-response: <1 log₁₀ IU/mL decline at 12 weeks → check adherence, consider switch

Hepatitis C — HCV RNA (Quantitative PCR)

Principle

• HCV is an RNA virus; its genome is detected by reverse-transcriptase PCR (RT-PCR):
  • Viral RNA → complementary DNA (cDNA) → PCR amplification → quantification
• Sensitivity: Lower limit of detection ~10 IU/mL; lower limit of quantitation ~25 IU/mL; dynamic range 10–10⁷ IU/mL (Harrison's, p. 9407)
• Results expressed in IU/mL (log₁₀ scale commonly used: e.g., 6 log₁₀ = 1,000,000 IU/mL)

Clinical Interpretation

Important: HCV RNA level is not a reliable marker of disease severity or prognosis — a patient with low viral load can still have advanced fibrosis. Viral load predicts relative responsiveness to antiviral therapy but does not reflect liver damage (Harrison's, p. 9407).

Indications for Testing

1. Diagnosis: Confirm active HCV infection (anti-HCV antibody positive → reflex to HCV RNA)
   • Anti-HCV can be false-positive; positive HCV RNA confirms active infection
   • Anti-HCV negative + high suspicion (acute infection, immunocompromised) → HCV RNA directly
2. Baseline before treatment: Establishes viral load; guides regimen selection in some cases
3. On-treatment monitoring (mainly for pegIFN-based regimens — now largely obsolete with DAAs)
4. SVR assessment: The primary endpoint of HCV treatment

Sustained Virological Response (SVR)

• SVR12 = "functional cure" — equivalent to SVR24, with ~99% durability.
• After SVR12: Monitor HCV RNA at 24 weeks to confirm (some guidelines); annual LFTs; continue HCC surveillance if cirrhosis present.

Monitoring Algorithm with DAAs

Baseline HCV RNA
      ↓
Start DAA regimen (8–12 weeks)
      ↓
HCV RNA at end of treatment (optional with DAAs)
      ↓
HCV RNA at SVR12 (12 weeks post-treatment) ← PRIMARY ENDPOINT
      ↓
Undetectable = CURED
Detectable = Virological failure → check genotype/resistance, retreatment

Hepatitis D — HDV RNA (Quantitative PCR)

• HDV only infects HBsAg-positive patients (requires HBV co-infection).
• HDV RNA PCR confirms active HDV replication.
• Indication: Any HBsAg-positive patient with unexplained disease severity should be tested.
• Monitoring: HDV RNA monitored on treatment (Bulevirtide ± pegIFN); goal is undetectable or >2 log₁₀ decline.

Hepatitis E — HEV RNA (Quantitative PCR)

• Indicated in immunocompromised patients (solid organ transplant, HIV, hematologic malignancy) with acute hepatitis — chronic HEV can occur in these patients.
• Also used in acute severe hepatitis in endemic regions.
• Threshold for treatment (with ribavirin): Any detectable HEV RNA in chronic infection.

Comparative Summary