How should chronic liver disease be managed, including treatment of the underlying cause, supportive measures, diet and sodium restriction, vaccinations, monitoring, beta‑blockers for compensated cirrhosis, ascites and hepatic encephalopathy therapy, variceal bleeding treatment, hepatocellular carcinoma screening, TIPS considerations, and transplant referral?

Management of Chronic Liver Disease

Treat the underlying cause aggressively—alcohol abstinence improves 3-year survival from 0% to 75% in alcoholic cirrhosis, while antiviral therapy for hepatitis B reduces HCC rates, and weight loss of 7-10% improves both steatosis and fibrosis in NAFLD-related disease. 1, 2

Treat the Underlying Etiology

Alcoholic Liver Disease

• Alcohol abstinence is non-negotiable and represents the single most effective intervention, with complete cessation reversing the reversible component of disease and dramatically improving response to medical therapy even in advanced cirrhosis 2
• Avoid disulfiram due to hepatotoxicity; consider baclofen as a safe anti-craving medication in advanced liver disease 2
• Provide aggressive nutritional support with 1.2-1.5 g/kg/day protein intake, frequent interval feedings, emphasis on nighttime snacks, and consider enteral nutrition if oral intake is compromised 2

Viral Hepatitis

• Antiviral nucleoside analogues in hepatitis B cirrhosis decrease HCC rates and should be continued until HBV DNA negativity is achieved 1
• Hepatitis C therapy eradicates virus and resolves chronic liver disease in approximately 50% of patients 1
• Continue surveillance even after successful viral clearance if metabolic risk factors or advanced liver disease signs persist 3

NAFLD/NASH-Related Disease

• Target 7-10% weight loss through caloric restriction and increased physical activity as the cornerstone of treatment for all NAFLD patients regardless of fibrosis stage 3, 2
• Aggressively manage metabolic comorbidities: metformin decreases HCC incidence, and statins reduce HCC risk by 37% 2
• Reserve pharmacologic treatment for patients with NASH or hepatic fibrosis ≥F2, as these patients have worse long-term prognosis 2

Autoimmune Hepatitis

• Initiate immunosuppression with prednisone with or without azathioprine when the International Autoimmune Hepatitis Group scoring system supports probable or definite diagnosis 3

Dietary Management and Supportive Measures

Sodium and Fluid Restriction

• Restrict dietary sodium to 2000 mg per day (88 mmol/day) for all patients with ascites 1, 2
• Fluid restriction is unnecessary unless serum sodium falls below 120-125 mmol/L 1, 2
• More stringent sodium restriction can speed ascites mobilization, as fluid loss and weight change are directly related to sodium balance 1

Nutritional Support

• Provide adequate protein intake of 1.2-1.5 g/kg/day to favor positive nitrogen balance and increase muscle mass, as weight loss with sarcopenia worsens hepatic encephalopathy 1, 2
• Frequent interval feedings with emphasis on nighttime snacks and morning feeding are critical, as malnutrition affects up to 50% of alcoholic liver disease patients 2

Vaccinations

Recommended Vaccines

• Administer hepatitis B vaccine to all patients with chronic liver disease, with priority given to those with higher MELD scores 4
• Give inactivated influenza vaccine annually to all cirrhotic patients and household contacts 4
• Administer pneumococcal vaccines: PCV13 followed by PPSV23 at least 8 weeks later for patients ≥2 years old 4
• Provide COVID-19 vaccines (inactivated or mRNA) with priority for higher MELD scores 4
• Tetanus/diphtheria toxoid is safe per standard protocols, though antibody levels may be lower 4

Critical Timing

• Vaccinate early in chronic liver disease, ideally before cirrhosis develops, as immunogenicity decreases with advancing liver dysfunction 4
• Complete all indicated vaccines before transplantation for patients on waiting lists, including two doses of COVID-19 vaccine 4
• Postpone vaccination 3-6 months after liver transplantation when immunosuppression is lower 4

Contraindications

• Live-attenuated vaccines are absolutely contraindicated in cirrhotic patients, including live influenza vaccine, MMR, varicella, and oral polio vaccine 4

Monitoring and Surveillance

Fibrosis Assessment

• Use FIB-4 score as initial stratification tool, with values ≥1.30 warranting further evaluation 3
• Perform transient elastography (FibroScan) as second-line assessment to evaluate liver stiffness and guide prognosis 3
• Reassess fibrosis every 3 years using non-invasive tests in patients with ongoing risk factors; extend to 5 years in patients achieving weight loss goals without progression risk factors 3

Hepatocellular Carcinoma Screening

• Perform HCC surveillance in all cirrhotic patients regardless of etiology, as annual HCC incidence is approximately 2.6% in alcoholic cirrhosis 1, 2
• Use abdominal ultrasound as primary surveillance test, but switch to CT or MRI in overweight/obese patients where ultrasound is difficult 2
• Small HCC complicating cirrhosis (≤5 cm, ≤3 lesions) is an indication for transplantation 1

Ongoing Follow-Up

• Continue hepatology follow-up indefinitely in patients with compensated advanced chronic liver disease or cirrhosis, regardless of risk factor modification 3

Beta-Blockers for Compensated Cirrhosis

Non-selective β-blockers effectively prevent decompensation in patients with compensated cirrhosis and clinically significant portal hypertension (≥10 mmHg), mainly by reducing the risk of ascites. 5, 6

• Portal pressure ≥10 mmHg defines clinically significant portal hypertension as the threshold from which decompensating events may occur 5
• Use non-invasive tests to identify patients with clinically significant portal hypertension with reasonable confidence before initiating therapy 5
• Critical pitfall: Patients with refractory ascites taking propranolol have poorer outcomes than those not taking propranolol, so avoid in decompensated disease 7

Management of Ascites

Initial Therapy

• Start spironolactone 100 mg once daily and furosemide 40 mg once daily as single morning doses 1, 2
• Increase to maximum doses of 400 mg/day spironolactone and 160 mg/day furosemide if needed 2
• Approximately 50% of patients with compensated cirrhosis develop ascites during 10 years of observation, marking an important prognostic landmark 1

Large-Volume Paracentesis

• Perform large-volume paracentesis for tense ascites and administer intravenous albumin at 8g/L of fluid removed to prevent circulatory dysfunction 2
• Paracentesis complications occur in only 1% of patients (abdominal wall hematomas) despite 71% having abnormal prothrombin time 1
• Approximately 1,500 mL of fluid must be present before flank dullness is detected on physical examination 1

Critical Pitfalls

• Avoid NSAIDs as they reduce urinary sodium excretion and can convert diuretic-sensitive patients to refractory ascites 2
• Coagulopathy is not a contraindication to paracentesis 1

Hepatic Encephalopathy Management

Acute Episode

• Perform brain imaging in every patient with chronic liver disease and unexplained alteration of brain function to exclude structural lesions 1
• Identify and treat precipitating factors: infection, gastrointestinal bleeding, diuretics, constipation 1
• Start empiric treatment with lactulose or rifaximin to reduce serum ammonia levels 1, 2

Secondary Prevention

• Rifaximin leads to better maintenance of remission and decreased readmission rates in patients with cirrhosis and hepatic encephalopathy 7
• Pharmacological secondary prevention should be instituted after hospital discharge 1
• Hepatic encephalopathy has the highest mortality among decompensated cirrhosis complications 2

Post-Discharge Management

• Confirm neurological status before discharge and judge extent of deficits attributable to hepatic encephalopathy versus other comorbidities 1
• Plan outpatient consultations to adjust treatment and prevent reappearance of precipitating factors 1
• Educate patients and relatives on medication effects (lactulose, rifaximin), importance of adherence, early signs of recurring encephalopathy, and actions for recurrence 1
• Monitor neurological manifestations in patients with persisting encephalopathy to adjust treatment and assess for minimal hepatic encephalopathy 1

Variceal Bleeding Treatment

Primary Prophylaxis

• Carvedilol reduces the rate of initial bleeding compared with band ligation in primary prophylaxis 7
• Non-selective β-blockers are not generally recommended for primary prophylaxis in children 8
• For gastric varices, primary prophylaxis with cyanoacrylate may decrease probability of hemorrhage compared with non-selective β-blockers 7

Acute Bleeding Management

• Use stepwise approach from least to most invasive strategies for control of bleeding 8
• Early transjugular intrahepatic portosystemic shunts (TIPS) placed in highly selected patients with acute variceal bleeding and high risk of endoscopic failure decrease long-term mortality 7

Secondary Prevention

• Prevent re-bleeding using bypass operations, with particular enthusiasm for meso-Rex bypass in pediatric population 8
• Manage complications of cirrhosis (spontaneous bacterial peritonitis and gastrointestinal bleeding) according to available guidelines 1

TIPS Considerations

• Occlusion of dominant portosystemic shunt may improve hepatic encephalopathy in patients with recurring encephalopathy and good liver function, though current experience is limited and risks/benefits must be weighed 1
• TIPS is considered for highly selected patients with acute variceal bleeding at high risk of endoscopic failure 7

Transplant Referral

Timing of Referral

• Refer patients after development of ascites, as approximately 50% succumb within 2 years 1
• Development of fluid retention is an important landmark in natural history of chronic liver disease 1
• Patients who have developed overt hepatic encephalopathy often have advanced liver failure without hope for functional improvements and are potential transplant candidates 1

Specific Indications

• Decompensated cryptogenic cirrhosis warrants transplantation, with careful post-transplant monitoring as disease recurrence occurs in 22-33% of cases 3
• Pediatric patients with cryptogenic cirrhosis require expedited evaluation and early transplant referral, as disease course can be aggressive and progress rapidly to liver failure 3
• Hepatocellular carcinoma ≤5 cm or ≤3 lesions is an indication for transplantation 1
• Alcoholic liver disease in selected patients can improve outcome with transplantation; six-month supervised community abstinence is desirable but not mandatory 1
• Young patients with alcoholic liver disease on first medical presentation may not need stringent evaluation if illness is life-threatening 1

Pre-Transplant Optimization

• Patients must be HBV DNA negative before transplantation for hepatitis B-related disease 1
• Complete all indicated vaccinations before transplantation, including two doses of COVID-19 vaccine 4
• Long-term passive immunization with hepatitis B immunoglobulin is effective strategy to prevent reinfection post-transplant 1

Contraindications

• Local or systemic extrahepatic hepatocellular carcinoma disease is an absolute contraindication 1
• Extrahepatic metastatic disease from neuroendocrine tumors is a contraindication 1
• Cholangiocarcinoma is not an indication unless in conjunction with novel management strategy 1