What is the medical treatment for cirrhosis?

Medical Treatment for Cirrhosis

The cornerstone of cirrhosis treatment is aggressive management of the underlying etiology—complete alcohol cessation for alcoholic cirrhosis, antiviral therapy for viral hepatitis, or immunosuppression for autoimmune hepatitis—combined with sodium restriction, diuretic therapy for ascites, and early referral for liver transplantation when decompensation occurs. 1, 2, 3

Primary Treatment Strategy: Address the Underlying Cause

Treating the underlying etiology is the single most important intervention that decreases risk of further decompensation and increases survival. 1, 4 The management paradigm has shifted from merely treating complications as they arise to preventing disease progression while patients remain compensated. 1

Alcoholic Cirrhosis

• Complete and permanent cessation of alcohol consumption is mandatory and can lead to dramatic improvement, with Child-Pugh class C patients who stop drinking having approximately 75% 3-year survival versus 0% survival in those who continue drinking. 3
• Some patients experience progressive "re-compensation" of cirrhosis with excellent long-term outcomes after alcohol cessation. 1

Viral Hepatitis-Related Cirrhosis

• For HBV-related cirrhosis, initiate antiviral therapy with entecavir or tenofovir as first-line agents due to their potent antiviral efficacy and high genetic barrier to resistance. 2
• All patients with decompensated cirrhosis should receive treatment regardless of HBV DNA level. 2
• Entecavir 1 mg/day demonstrates superior HBV DNA suppression (57% vs 20% undetectability at week 48 compared to adefovir) and improves Child-Pugh scores in almost half of treatment-naïve patients. 2
• Interferon-α is absolutely contraindicated in decompensated cirrhosis due to risk of serious complications including infection and hepatic failure. 2
• For HCV-related cirrhosis, direct antiviral agents improve liver function and portal hypertension, though effects are not universal. 1, 3

Autoimmune Hepatitis

• Immunosuppressive therapy shows beneficial effects in decompensated cirrhosis due to autoimmune hepatitis. 3

Management of Ascites

Initial Approach

• For Grade 1 ascites (detectable only by imaging): sodium restriction, treatment of underlying disease, and discontinuation of NSAIDs, ACE inhibitors, or angiotensin receptor blockers. 2
• For Grade 2 ascites (moderate, visible on inspection): add oral diuretics (spironolactone with or without furosemide) to sodium restriction. 1, 2
• For Grade 3 ascites (massive/tense): perform therapeutic paracentesis first, then initiate sodium restriction and diuretic therapy. 1, 2

Diuretic Therapy

• Start spironolactone 100 mg once daily as first-line monotherapy for a first episode of ascites. 1, 2, 5
• If weight loss is <2 kg/week, increase spironolactone by 100 mg every 72 hours up to a maximum of 400 mg/day. 1, 2
• Add furosemide 40 mg/day when spironolactone alone is insufficient or hyperkalemia develops; titrate by 40 mg increments to a maximum of 160 mg/day. 1, 2
• For recurrent or long-standing ascites, begin combination therapy (spironolactone + furosemide) from the outset to achieve faster natriuresis and lower hyperkalemia risk. 2
• Target weight loss of 0.5 kg/day without peripheral edema or 1 kg/day with edema. 2

Monitoring During Diuretic Therapy

• Check serum creatinine, sodium, and potassium at least weekly during the first month of diuretic treatment. 2
• Watch for diuretic-related complications: renal failure, worsening hepatic encephalopathy (via increased renal ammonia production), hypo- or hyperkalemia, and hypomagnesemia. 2

Sodium and Fluid Management

• Restrict dietary sodium to <5 g/day (≈88 mmol/day); more stringent restriction is not advised because it may worsen malnutrition. 1, 2, 3
• Fluid restriction is unnecessary unless serum sodium falls below 120–125 mmol/L. 1, 2, 4

Management of Hyponatremia

• Serum sodium 126–135 mmol/L with normal creatinine: continue diuretic therapy but observe electrolytes closely; do not water restrict. 1
• Serum sodium 121–125 mmol/L with normal creatinine: stop diuretics or adopt a more cautious approach. 1
• Serum sodium 121–125 mmol/L with elevated creatinine (>150 mmol/L or >120 mmol/L and rising): stop diuretics and give volume expansion. 1
• Serum sodium <120 mmol/L: stop diuretics and perform volume expansion with colloid (haemaccel, gelofusine, or voluven) or saline, but avoid increasing serum sodium by >12 mmol/L per 24 hours. 1

Refractory Ascites

• Options include serial large-volume paracentesis, transjugular intrahepatic portosystemic stent-shunt (TIPS), liver transplantation, or experimental medical therapy. 2
• For large volume paracentesis, use 8 g albumin per liter of ascites removed (approximately 100 ml of 20% albumin per 3 liters ascites) once paracentesis is complete. 1
• Paracentesis of <5 liters can be followed by synthetic plasma expander (150–200 ml of gelofusine or haemaccel) and does not require albumin. 1

Management of Hepatic Encephalopathy

Diagnosis and Assessment

• Diagnose hepatic encephalopathy clinically based on mental status, vigilance, attention, and spatial-temporal orientation; the Animal Naming Test (<20 animals in 1 minute) suggests covert hepatic encephalopathy. 1, 2
• Measure blood ammonia only when hepatic encephalopathy is uncertain; a normal value argues against hepatic encephalopathy, whereas an elevated value does not confirm it. 2
• Do not rely on ammonia levels to diagnose or monitor hepatic encephalopathy; it remains a clinical diagnosis of exclusion. 2

Treatment

• Identify and treat precipitating factors: GI bleeding, infection, dehydration, constipation, electrolyte disturbances. 1, 2
• Initiate lactulose as first-line therapy for hepatic encephalopathy; it reduces mortality and recurrent overt hepatic encephalopathy. 4
• Add rifaximin for persistent or recurrent hepatic encephalopathy episodes. 2
• Discontinue benzodiazepines immediately; they are contraindicated in decompensated cirrhosis. 2
• Limit proton-pump inhibitor use to validated indications only. 2

Management of Variceal Bleeding

Acute Management

• Initiate vasoactive drugs immediately upon suspicion of variceal bleeding, even before endoscopic confirmation. 2, 4
• Antibiotic prophylaxis is mandatory: use ceftriaxone 1 g/24h for up to 7 days in decompensated cirrhosis or quinolone-resistant settings; use oral norfloxacin 400 mg twice daily in remaining patients. 2, 4
• Use a restrictive transfusion strategy with a hemoglobin threshold of 7 g/dL and target 7-9 g/dL. 2
• Perform endoscopic band ligation within 12 hours of admission once hemodynamic stability is achieved. 2
• Use TIPS as rescue therapy for persistent bleeding or early rebleeding. 2

Prevention

• Consider non-selective beta blockers (propranolol) for prevention of variceal bleeding; in responders, propranolol decreases risk of ascites, hepatorenal syndrome, spontaneous bacterial peritonitis, and hepatic encephalopathy beyond variceal bleeding prevention. 1, 2, 4
• Use prophylactic band ligation as standard of care for varices. 2

Management of Spontaneous Bacterial Peritonitis (SBP)

Diagnosis

• Perform diagnostic paracentesis without delay in all cirrhotic patients with ascites on hospital admission. 1, 2
• Perform diagnostic paracentesis in all cirrhotic patients with ascites who have signs and symptoms of peritoneal infection, development of encephalopathy, renal impairment, or peripheral leucocytosis without a precipitating factor. 1, 2
• Inoculate ascitic fluid into blood culture bottles at the bedside. 1, 2
• Ascitic neutrophil count >250 cells/mm³ is the gold standard for diagnosis of SBP. 2

Treatment and Prophylaxis

• Initiate immediate empirical antibiotic therapy, determined by context, severity, and local resistance patterns. 2
• Patients recovering from one episode of SBP should receive prophylaxis with continuous oral norfloxacin 400 mg/day (or ciprofloxacin 500 mg once daily). 1
• All patients with SBP should be considered for referral for liver transplantation. 1

Medications to Avoid

NSAIDs are absolutely contraindicated in patients with cirrhosis; they reduce urinary sodium excretion, precipitate renal dysfunction, and convert diuretic-sensitive ascites to refractory ascites. 1, 2, 3

Discontinue ACE inhibitors and angiotensin receptor blockers. 2

Nutritional Management

• Nutritional intake should include: carbohydrate 2-3 g/kg/day, protein 1.2-1.5 g/kg/day, and caloric intake 35-40 kcal/kg/day. 3
• Perform rapid nutritional screening in all patients with cirrhosis, assuming high risk for malnutrition if BMI <18.5 kg/m² or Child-Pugh C. 2
• Assess sarcopenia using CT scan, anthropometry, DEXA, or BIA; evaluate muscle function with handgrip strength and/or short physical performance battery. 2
• Bed rest is not recommended; excessive bed rest may cause muscle atrophy. 1, 2

Liver Transplantation

All patients with decompensated cirrhosis should be evaluated for liver transplantation, which is the ultimate treatment of ascites and its complications. 1, 2, 4, 6

Early referral for liver transplantation evaluation is essential for appropriate candidates, as decompensation significantly worsens prognosis. 4, 6

Evaluation for liver transplantation is indicated for patients with a MELD score of 15 or greater, complications of cirrhosis, or hepatocellular carcinoma. 7

Mean pulmonary arterial pressure ≥45 mmHg is an absolute contraindication to liver transplantation. 4

Monitoring and Follow-up

• Clinical assessment with laboratory tests and calculation of Child-Pugh and MELD scores should occur every 6 months. 7
• Consider telemedicine and remote monitoring technologies (Bluetooth-linked weighing scales, smartphone apps) to enable early detection of complications and reduce hospital readmissions. 2, 3
• Hepatocellular carcinoma screening includes ultrasound screening every 6 months for patients with cirrhosis. 8

Common Pitfalls

• Do not impose routine fluid restriction; restrict fluids only when serum sodium is severely low (<120–125 mmol/L). 2
• Patients requiring paracenteses more frequently than every 2 weeks likely have poor dietary compliance. 2
• Serum sodium <130 mmol/L is an independent risk factor for hepatic encephalopathy and predicts poor response to lactulose. 2
• Extracorporeal liver support systems (MARS, Prometheus) do not improve survival in acute-on-chronic liver failure and should not be used routinely. 4