What is the treatment approach for a patient with suspected cirrhosis (liver cirrhosis) or another liver condition?

Treatment Approach for Cirrhosis

The primary treatment strategy for cirrhosis is to aggressively treat the underlying etiology to prevent disease progression and potentially reverse early fibrosis, while simultaneously managing complications as they arise. 1

Initial Diagnostic and Etiological Assessment

When cirrhosis is suspected, immediately pursue:

• Viral hepatitis serologies (HBV, HCV), ferritin, transferrin saturation, complete blood count, liver function tests, prothrombin time/INR, and abdominal ultrasonography 2
• Calculate Child-Pugh and MELD scores every 6 months to assess disease severity and prognosis 3, 2
• Assess for decompensation (ascites, hepatic encephalopathy, variceal bleeding) which occurs in approximately 40% at diagnosis and dramatically worsens prognosis 4

Treatment Based on Underlying Etiology

Viral Hepatitis-Related Cirrhosis

For HBV-related compensated cirrhosis (Child-Pugh A):

• Initiate entecavir or tenofovir monotherapy if HBV DNA ≥2,000 IU/mL regardless of ALT levels 1, 5
• These agents are preferred due to potent antiviral efficacy and high genetic barrier to resistance 1
• Peginterferon alfa-2a may be used in well-compensated cirrhosis but carries decompensation risk 6, 5

For decompensated cirrhosis (Child-Pugh B or C):

• All patients require treatment regardless of HBV DNA level 6, 1
• Use entecavir or tenofovir monotherapy as first-line 6, 5
• Peginterferon alfa is absolutely contraindicated in decompensated cirrhosis due to risk of infection and hepatic failure 1, 5
• Child-Pugh C patients should not receive current antiviral regimens due to high risk of life-threatening complications 6

HCV-Related Cirrhosis

For compensated cirrhosis:

• Patients must be treated in the absence of contraindications to prevent short to mid-term complications 6
• Direct-acting antivirals improve liver function and reduce portal hypertension 1
• Assiduous monitoring and management of side effects, especially those linked to portal hypertension and hypersplenism, is required 6

Alcohol-Related Cirrhosis

• Complete and permanent alcohol cessation is essential and can result in dramatic improvement in the reversible component within months 1, 7, 5
• This may lead to "re-compensation" and improved outcomes in some patients 1

Nonalcoholic Steatohepatitis

• Address metabolic risk factors, including obesity through lifestyle modifications 5

Management of Ascites

Grade 1 (mild) ascites:

• Sodium restriction to 88 mmol/day (2000 mg/day, approximately 5g salt/day) 1, 7
• Discontinue NSAIDs, ACE inhibitors, and angiotensin receptor blockers 1, 7
• Treat underlying disease 1

Grade 2 (moderate) ascites:

• Initiate spironolactone 100 mg once daily as first-line diuretic 1, 7
• Add furosemide 40 mg once daily if needed 1, 7
• Increase doses simultaneously every 3-5 days (maintaining 100 mg:40 mg ratio) up to maximum 400 mg/160 mg daily 1, 7
• Fluid restriction is NOT necessary unless serum sodium <120-125 mmol/L 1, 7

Grade 3 (tense) ascites:

• Perform therapeutic paracentesis first, followed by sodium restriction and diuretic therapy 1, 7
• For large-volume paracentesis (>5L), give albumin 8g per liter of ascites removed 7

Refractory ascites:

• Serial therapeutic paracenteses every 2-3 weeks 7
• Consider TIPS in selected patients 7
• Evaluate for liver transplantation 7

Management of Hepatic Encephalopathy

First-line therapy:

• Lactulose reduces mortality and prevents recurrent overt hepatic encephalopathy 5, 8, 4
• Lactulose therapy reduces blood ammonia levels by 25-50% with clinical response in approximately 75% of patients 8
• Can be given orally or as enema in severe cases 5

Second-line therapy:

• Rifaximin combined with lactulose for refractory cases 5, 4
• In meta-analyses, lactulose reduced mortality (8.5% vs 14%) and recurrent hepatic encephalopathy (25.5% vs 46.8%) 4

Before initiating therapy, identify and treat precipitants:

• Constipation, infection, gastrointestinal bleeding, certain medications, electrolyte imbalances, and medication noncompliance 9

Management of Varices and Variceal Bleeding

Primary prophylaxis:

• Nonselective beta-blockers (carvedilol or propranolol) reduce risk of decompensation or death (16% vs 27% over 3 years) 1, 4
• Prophylactic band ligation as standard of care 1

Acute variceal bleeding:

• Initiate vasoactive drugs immediately upon suspicion, before endoscopic confirmation (terlipressin, somatostatin, or octreotide) 1, 5
• Antibiotic prophylaxis with ceftriaxone 1 g/24h for up to 7 days in decompensated cirrhosis 1, 5
• Restrictive transfusion strategy: hemoglobin threshold 7 g/dL, target 7-9 g/dL 1, 5
• Endoscopic band ligation within 12 hours once hemodynamically stable 1, 5
• TIPS as rescue therapy for uncontrolled bleeding or early rebleeding 1, 5

Management of Hepatorenal Syndrome

Initial management:

• Withdraw diuretics and treat precipitating factors 5
• Volume challenge with IV albumin 1 g/kg (maximum 100 g/day) for 48 hours 5

For Stage 2 or greater HRS-AKI:

• Terlipressin 0.5-2.0 mg IV every 6 hours (or continuous infusion) plus albumin 20-40 g/day 5
• Terlipressin improved reversal rate from 18% to 39% in randomized trials 4

Hepatocellular Carcinoma Surveillance

• Screen with imaging (preferably MRI, or CT, ultrasound) every 6 months 5, 3, 2
• Continue surveillance even after achieving sustained virologic response, as HCC risk persists 1, 5

Nutritional Management

• Protein intake: 1.2-1.5 g/kg/day to prevent sarcopenia 1, 7, 5
• Caloric intake: 35-40 kcal/kg/day 1, 7
• 4-6 small meals per day including late-evening snack (200 kcal) 1, 7, 5
• Never restrict protein long-term as it induces catabolism, hepatic dysfunction, and sarcopenia 5

Medications to Avoid

• NSAIDs: reduce urinary sodium excretion, can precipitate renal failure and convert diuretic-sensitive to refractory ascites 1, 7, 10
• ACE inhibitors and angiotensin receptor blockers 1, 7
• Proton pump inhibitors: linked to increased risk of spontaneous bacterial peritonitis, use cautiously 10
• Hepatotoxic drugs: particularly antituberculosis and antiretroviral agents 10

Indications for Gastroenterology Referral

• Any decompensation event (ascites, variceal bleeding, hepatic encephalopathy) 1
• Refractory ascites not responding to maximum diuretic therapy 1
• Need for TIPS placement 1
• MELD score ≥15 or complications requiring transplant evaluation 3

Liver Transplantation Evaluation

Indications include:

• MELD score ≥15 3
• Decompensated cirrhosis with small hepatocellular carcinoma 5
• Severe hepatic encephalopathy not responding to medical treatment 5
• Hepatorenal syndrome in appropriate candidates 5

Common Pitfalls to Avoid

• Do not prescribe bed rest: excessive bed rest causes muscle atrophy; manage outpatients unless complicated by bleeding, encephalopathy, infection, hypotension, or liver cancer 1
• Do not use HbA1c for diabetes diagnosis or monitoring in decompensated cirrhosis 1
• Metformin is contraindicated due to lactic acidosis risk 1
• Paracetamol is safe in doses ≤2-3 g/day for short durations and is first-line for pain 10