What are the current guidelines for managing adult patients with liver cirrhosis?

Current Guidelines for Managing Adult Patients with Liver Cirrhosis

The management of cirrhosis has fundamentally shifted from reactive treatment of complications to aggressive early intervention targeting the underlying disease cause, which directly prevents decompensation and improves survival more than any other single intervention. 1, 2

Core Management Principles

1. Treat the Underlying Etiology First

Addressing the root cause of cirrhosis is the cornerstone of management and must be initiated immediately, even while managing acute complications. 1, 3

• Alcoholic cirrhosis: Complete and permanent alcohol cessation is mandatory; this can lead to "re-compensation" with excellent long-term outcomes in selected patients 1, 4
• Hepatitis B: Start entecavir 1 mg daily (not 0.5 mg) or tenofovir immediately when HBV DNA is detectable by PCR, regardless of ALT level or viral load 1, 4; interferon-α is absolutely contraindicated in decompensated disease due to risk of hepatic failure and death 1
• Hepatitis C: Treat with direct-acting antivirals, which improve liver function and reduce portal hypertension 1, 4
• Autoimmune hepatitis: Immunosuppressive therapy yields clear benefits even in decompensated disease 1
• MASH (metabolic dysfunction-associated steatohepatitis): Aggressive treatment of metabolic dysfunction with weight reduction, high protein intake (1.2–1.5 g/kg/day), and physical activity 3

2. Hepatocellular Carcinoma Surveillance

• Perform abdominal ultrasound combined with serum AFP every 6 months in all patients with cirrhosis, regardless of etiology 4, 3
• HCC develops in 1–4% of cirrhotic patients annually; MASH-related cirrhosis may carry even higher risk (18–27%) than hepatitis C 3
• For lesions >2 cm with AFP >400 ng/mL, diagnosis can be made without biopsy 4

3. Variceal Bleeding Prevention

Non-selective beta-blockers (carvedilol or propranolol) are first-line prophylaxis and reduce not only bleeding risk but also ascites, hepatorenal syndrome, spontaneous bacterial peritonitis, and hepatic encephalopathy in responders. 1, 4, 3

• In patients with clinically significant portal hypertension (HVPG ≥10 mmHg) without high-risk varices, NSBBs reduce decompensation or death from 27% to 16% 1
• Perform screening endoscopy in all compensated cirrhosis patients to assess for varices requiring prophylaxis 1, 4
• Prophylactic band ligation is standard of care for varices 1, 4
• Use NSBBs with caution in refractory ascites: reduce or stop if mean arterial pressure falls <65 mmHg or acute renal dysfunction develops 1

Management of Specific Complications

Ascites Management

Grade ascites as 1 (detectable only by imaging), 2 (moderate, visible), or 3 (massive/tense) to guide therapy. 1

Grade 1 Ascites

• Sodium restriction to <5 g/day (≈88 mmol/day); stricter restriction worsens malnutrition 1, 4, 3
• Discontinue NSAIDs, ACE inhibitors, and angiotensin receptor blockers 1, 4
• Fluid restriction is unnecessary unless serum sodium falls below 120–125 mmol/L 1

Grade 2 Ascites

• Start spironolactone 100 mg once daily as first-line monotherapy 1
• If weight loss is <2 kg/week, increase spironolactone by 100 mg every 72 hours, up to maximum 400 mg/day 1
• Add furosemide 40 mg/day when spironolactone alone is insufficient or hyperkalemia (>5.5 mmol/L) develops; titrate in 40-mg increments to maximum 160 mg/day 1
• For recurrent or long-standing ascites, begin combination therapy (spironolactone + furosemide) from the outset to achieve faster natriuresis and lower hyperkalemia risk 1
• Check serum creatinine, sodium, and potassium at least weekly during the first month of diuretic therapy 1
• Target weight loss of 0.5 kg/day without peripheral edema or 1 kg/day with edema 1

Grade 3 (Tense) Ascites

• Perform therapeutic paracentesis first, then initiate sodium restriction and diuretic therapy 1, 4, 3
• Administer 8 g albumin per liter of ascites removed when >5 L are extracted (≈100 mL of 20% albumin for every 3 L) 1
• For <5 L, synthetic plasma expander (150–200 mL gelofusine or Haemaccel) is sufficient 1

Refractory Ascites

• Defined as ascites recurring ≥3 times within 12 months despite optimal sodium restriction and maximal tolerated diuretics 1
• Options include serial large-volume paracentesis, TIPS, or liver transplantation 1, 4
• Refer to gastroenterology immediately for TIPS evaluation or transplant assessment 1, 4
• Palliative care referral should be offered to non-transplant candidates 1

Spontaneous Bacterial Peritonitis (SBP)

• Perform diagnostic paracentesis without delay in any cirrhotic patient with ascites on hospital admission or showing clinical deterioration (fever, abdominal pain, encephalopathy, renal impairment, unexplained leukocytosis) 1, 3
• Inoculate ≥10 mL ascitic fluid into blood-culture bottles at bedside to improve detection 1
• Ascitic neutrophil count >250 cells/mm³ confirms SBP 1
• Administer albumin 1.5 g/kg within 6 hours of diagnosis, followed by 1 g/kg on day 3, especially when serum creatinine is rising 1
• Patients recovering from SBP should receive continuous oral norfloxacin 400 mg daily (or ciprofloxacin 500 mg daily) for secondary prophylaxis 1
• All patients with SBP should be evaluated for liver transplantation 1

Hepatic Encephalopathy (HE)

• Diagnose clinically (mental status, vigilance, attention, spatial-temporal orientation); Animal Naming Test (<20 animals in 1 minute) suggests covert HE 1
• Identify and treat precipitating factors: GI bleeding, infection, dehydration, constipation, electrolyte disturbances 1
• Serum sodium <130 mmol/L is an independent risk factor for HE and predicts poor response to lactulose 1
• Discontinue benzodiazepines immediately; they are contraindicated in decompensated cirrhosis 1
• Limit proton-pump inhibitor use to validated indications only 1
• Initiate lactulose as first-line therapy; add rifaximin for persistent or recurrent episodes 1
• Do not rely on ammonia levels to diagnose or monitor HE; HE remains a clinical diagnosis of exclusion 1
• Obtain brain imaging (CT or MRI) during the first HE episode to exclude intracranial hemorrhage 1

Acute Variceal Bleeding

• Start vasoactive drugs (terlipressin, octreotide) immediately upon suspicion, even before endoscopic confirmation 1
• All cirrhotic patients with GI bleeding require antibiotic prophylaxis (ceftriaxone 1 g daily for up to 7 days or norfloxacin 400 mg twice daily) 1
• Use restrictive transfusion strategy with hemoglobin threshold of 7 g/dL, target 7–9 g/dL 1
• Erythromycin 250 mg IV 30–120 minutes before endoscopy improves visibility unless QT prolongation is present 1
• Perform endoscopic band ligation within 12 hours of admission once hemodynamic stability is achieved 1
• TIPS should be used as rescue therapy for persistent bleeding or early rebleeding 1
• Terlipressin is contraindicated in patients with hypoxemia or active coronary, peripheral, or mesenteric ischemia 1

Pharmacologic Management of Comorbidities

Diabetes Management

Compensated Cirrhosis (Child-Pugh A)

• GLP-1 receptor agonists (semaglutide, liraglutide, dulaglutide) or coagonists (tirzepatide) are first-line agents 3
• SGLT2 inhibitors (empagliflozin, dapagliflozin) are appropriate 3
• Metformin may be used when eGFR >30 mL/min 5, 3

Child-Pugh B

• SGLT2 inhibitors may be used with close monitoring of renal function and volume status 5, 3

Decompensated Cirrhosis (Child-Pugh C)

• Insulin is the only evidence-based pharmacologic option for type 2 diabetes 1, 3
• Metformin is absolutely contraindicated due to lactic acidosis risk 5, 1, 3
• Sulfonylureas should be avoided due to severe hypoglycemia risk 5, 3
• HbA1c should not be used for diagnosis or monitoring glycemic control 3

Lipid Management

• Statins can and should be used in compensated cirrhosis according to cardiovascular risk guidelines; they may also lower portal pressure and improve survival 1, 3

Nutritional Management

• In sarcopenia, sarcopenic obesity, or decompensated cirrhosis, provide high-protein diet (1.2–1.5 g/kg/day) plus a late-evening snack 5, 3
• Supply at least 35 kcal/kg body weight per day 5, 3
• In compensated cirrhosis with obesity, aim for moderate weight reduction (5–10% body weight) with emphasis on high protein intake and physical activity to maintain muscle mass 5, 3
• Avoid excessive bed rest; it causes muscle atrophy and sarcopenia 1, 4
• Perform rapid nutritional screening in all patients, assuming high risk for malnutrition if BMI <18.5 kg/m² or Child-Pugh C 3
• Assess sarcopenia using CT scan, anthropometry, DEXA, or BIA; evaluate muscle function with handgrip strength and/or short physical performance battery 3

Bariatric Surgery in MASH Cirrhosis

• In non-cirrhotic MASH with approved indication, bariatric surgery should be considered because it induces long-term beneficial liver effects and is associated with remission of type 2 diabetes 5, 3
• In MASH-related compensated cirrhosis with approved indication, bariatric surgery can be considered but requires careful evaluation by a multidisciplinary team with experience in this population, particularly assessing for clinically significant portal hypertension 5, 3

Medications to Absolutely Avoid

NSAIDs are absolutely contraindicated in all patients with cirrhosis because they reduce urinary sodium excretion, precipitate renal dysfunction, and convert diuretic-responsive ascites to refractory ascites 1, 4, 3

Other contraindications:

• ACE inhibitors and angiotensin receptor blockers 1, 4, 3
• Metformin in decompensated cirrhosis or eGFR ≤30 mL/min 5, 1, 3
• Sulfonylureas in hepatic decompensation 5, 3
• Interferon-α in decompensated HBV cirrhosis 1
• Benzodiazepines in decompensated cirrhosis 1

Indications for Gastroenterology Referral

Refer immediately for:

• Any decompensation event (ascites, variceal bleeding, hepatic encephalopathy) 1, 4
• Refractory ascites not responding to maximum diuretic therapy 1, 4
• Need for TIPS evaluation 1, 4
• Liver transplantation evaluation (all patients with decompensated cirrhosis, MELD score ≥15, or HCC) 1

Liver Transplantation

• Liver transplant is first-line treatment for decompensated cirrhosis with HCC within Milan criteria (solitary ≤5 cm or up to three lesions ≤3 cm) 5, 3
• Tumour-related vascular invasion and extrahepatic metastases are absolute contraindications 5
• Mean pulmonary arterial pressure ≥45 mmHg is an absolute contraindication 3
• Patients listed for transplant should be considered for neoadjuvant locoregional therapy while on the waiting list 5

Emerging Technologies

• Remote monitoring technologies (Bluetooth-linked weighing scales, smartphone apps) and telemedicine can improve outcomes and reduce hospital readmissions 1, 4
• Heart rate variability monitoring may identify patients at risk of decompensation 1, 4

Common Pitfalls to Avoid

• Do not impose routine fluid restriction; restrict fluids only when serum sodium is severely low (<120–125 mmol/L) 1
• Do not use ammonia levels to diagnose or monitor HE; it remains a clinical diagnosis 1
• Do not prescribe NSAIDs under any circumstances in cirrhotic patients 1, 4, 3
• Do not delay diagnostic paracentesis in any cirrhotic patient with ascites showing clinical deterioration 1, 3
• Do not use metformin in decompensated cirrhosis regardless of renal function 5, 1, 3
• Do not recommend bed rest; encourage activity to prevent sarcopenia 1, 4