Can cirrhosis regress?

Cirrhosis Regression: Possibility and Clinical Implications

Yes, cirrhosis can regress in certain situations, particularly when the underlying cause of liver damage is effectively treated or eliminated, though this is not possible in all cases or at all stages of cirrhosis. 1

Evidence for Cirrhosis Regression

Pathophysiological Basis

Cirrhosis regression involves:

• Suppression of inflammation
• Fibrosis regression
• Regularization of portal and arterial circulation
• Normalization of cell number and function 1

Disease-Specific Evidence

Hepatitis C

• A study of 38 HCV patients with cirrhosis showed regression (decrease >1 METAVIR stage) in 61% of patients after sustained virological response (SVR) with interferon-based therapies 1
• With direct-acting antivirals (DAAs), fibrosis regression is becoming more common due to higher SVR rates 1
• Successful HCV treatment leads to improved liver function, reduced portal hypertension, and in some cases, avoidance of liver transplantation 2

Hepatitis B

• Spontaneous reversal of cirrhosis has been documented after loss of HBV viremia, even in patients who developed cirrhosis as children 3

Alcoholic Liver Disease

• In some patients with decompensated alcoholic cirrhosis, suppression of alcohol consumption is associated with progressive "re-compensation" and excellent long-term outcomes 1
• However, in other patients, alcoholic cirrhosis progresses despite stopping alcohol intake 1

Limitations and Caveats

Stage of Cirrhosis Matters

• Early cirrhosis has better chances of regression than advanced cirrhosis 3
• It remains unclear if all histological transformations in cirrhosis are reversible 4
• Decompensated cirrhosis is less likely to regress than compensated cirrhosis 5

Assessment Challenges

• Non-invasive tests like liver stiffness measurement (LSM) by transient elastography are not accurate in detecting fibrosis regression 1
• LSM decreases after successful treatment may reflect resolution of inflammation rather than true fibrosis regression 1
• Cut-offs used for untreated liver disease should not be used to stage fibrosis after treatment 1

Clinical Implications

• Patients with cirrhosis who achieve regression have:
  • Reduced risk of liver failure
  • Reduced risk of hepatocellular carcinoma
  • Improved survival 4
• However, patients with cirrhosis remain at risk of life-threatening complications even after achieving SVR 1
• Continued surveillance for hepatocellular carcinoma is necessary even after apparent regression 1

Management Approach

1. Identify and treat the underlying cause:

   • This is the most effective approach for promoting regression 1, 4
   • Examples: antiviral therapy for viral hepatitis, alcohol cessation for alcoholic liver disease

2. Monitor for regression:

   • Liver biopsy remains the gold standard but has limitations 1
   • Non-invasive methods should be interpreted cautiously 1

3. Continue surveillance:

   • Even with apparent regression, continue monitoring for complications
   • Hepatocellular carcinoma risk persists 1

4. Consider emerging therapies:

   • Anti-fibrotic agents are being developed that may potentially halt or reverse progression of cirrhosis 6

Future Directions

Research is ongoing for:

• Development of accurate non-invasive methods to detect fibrosis regression
• Antifibrotic therapies that directly target the fibrotic process
• Better understanding of the point of "no return" in cirrhosis progression 2

Cirrhosis is now recognized as a dynamic disease that can progress and regress between compensated and decompensated stages, rather than an irreversible end-stage condition 5.