What are the implications of F4 (fibrosis grade 4) cirrhosis?

From the Guidelines

F4 cirrhosis patients should undergo regular medical follow-up every 3-6 months, including liver function tests, complete blood counts, and ultrasound screening for liver cancer every 6 months, as the risk of hepatocellular carcinoma (HCC) remains significant even after achieving sustained virologic response (SVR) 1.

Management of F4 Cirrhosis

The management of F4 cirrhosis focuses on preventing further liver damage, treating complications, and monitoring for HCC. Patients should completely abstain from alcohol and avoid hepatotoxic medications.

• Regular medical follow-up is essential to monitor liver function and detect potential complications early.
• Treatment often includes non-selective beta-blockers like propranolol (starting at 20mg twice daily) or nadolol (20-40mg daily) to reduce portal hypertension and prevent variceal bleeding.
• Diuretics such as spironolactone (starting at 100mg daily) and furosemide (starting at 40mg daily) may be needed to manage ascites.
• Lactulose (15-30ml two to three times daily) is commonly prescribed for hepatic encephalopathy.
• Nutritional support is crucial, with a moderate protein diet (1-1.5g/kg/day) and sodium restriction (<2g/day).
• Vaccination against hepatitis A, hepatitis B, pneumococcal disease, and annual influenza is recommended.

Surveillance for HCC

The risk of HCC remains significant even after achieving SVR, and surveillance should be continued indefinitely 1.

• Ultrasound screening for liver cancer every 6 months is recommended.
• There is no reliable elastography score below which clinicians can confirm an absence of HCC risk with sufficient confidence to warrant discontinuation of surveillance 1.
• Noninvasive blood or serum markers that assess fibrosis often improve after SVR, but studies have correlated with risk of HCC in some cases, including a study in which the Forns index, but not FIB-4 index or aspartate aminotransferase to platelet ratio, was associated with HCC risk 1.

Liver Stiffness Measurement

Liver stiffness measurement (LSM) by transient elastography (TE) can be used to assess liver fibrosis, but its role in monitoring fibrosis regression after SVR is limited 1.

• A cutoff of 9.5 kPa can be used to rule out advanced liver fibrosis, but this cutoff has a sensitivity of 0.78 and specificity of 0.86, and may misclassify some patients 1.
• LSM scores <12 kPa do not exclude the risk of HCC, and surveillance should be continued even in patients with low LSM scores 1.

From the Research

Definition and Diagnosis of Cirrhosis

• Cirrhosis is a significant cause of death in the U.S., with approximately 2.2 million adults affected 2.
• The most common causes of cirrhosis include viral hepatitis, alcoholic liver disease, and nonalcoholic steatohepatitis 3.
• Diagnosis of cirrhosis can be made through liver biopsy or noninvasive tests such as elastography, which measures liver stiffness 2.
• Noninvasive tests, including the Fibrosis 4 score, are useful in identifying patients with no to minimal fibrosis or advanced fibrosis 3.

Complications of Cirrhosis

• Complications of cirrhosis include variceal hemorrhage, ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, and hepatorenal syndrome 4.
• The median survival time following onset of hepatic encephalopathy and ascites is 0.92 and 1.1 years, respectively 2.
• Approximately 1% to 4% of patients with cirrhosis develop hepatocellular carcinoma each year, which is associated with a 5-year survival of approximately 20% 2.

Management and Treatment of Cirrhosis

• Treatment goals for cirrhosis include preventing decompensation, variceal bleeding, and hepatocellular carcinoma 3.
• Nonselective beta blockers, such as carvedilol or propranolol, can reduce the risk of decompensation or death in patients with portal hypertension 2.
• Lactulose is associated with reduced mortality and risk of recurrent overt hepatic encephalopathy in patients with cirrhosis 2.
• Terlipressin can improve the rate of reversal of hepatorenal syndrome in patients with cirrhosis 2.

Symptom Management in Cirrhosis

• Symptom management in cirrhosis can be challenging due to altered metabolism of drugs and complex medication regimens 5.
• Practical guidance is available for managing liver-specific symptoms such as ascites, hepatic encephalopathy, pruritus, and muscle cramping 5.
• Strategies for managing generalized symptoms such as pain, depression/anxiety, appetite, and fatigue in patients with cirrhosis are also available 5.