What is the definition of chronic liver disease?

Definition of Chronic Liver Disease

Chronic liver disease is defined as cirrhosis (clinically suspected or histologically proved) or the presence of severe cholestatic liver disease with a serum bilirubin level more than three times the upper limit of normal for more than six months. 1

Core Characteristics of Chronic Liver Disease

• Chronic liver disease encompasses a variety of causes of chronic liver injury that can progress to hepatic fibrosis and cirrhosis, with associated complications of portal hypertension, gastrointestinal hemorrhage, refractory ascites, hepatic encephalopathy, and primary liver cancer 1

• The disease is characterized by diffuse chronic liver damage existing for at least 6 months, with cirrhosis being a potential sequel 2

• The progression of hepatic fibrosis to compensated cirrhosis to decompensated cirrhosis can be slow and clinically silent, often making early diagnosis challenging 1

Major Etiologies of Chronic Liver Disease

• Nonalcoholic fatty liver disease (NAFLD)/Metabolic dysfunction-associated steatotic liver disease (MASLD) - now the most common cause of chronic liver disease worldwide 1

• Viral hepatitis (hepatitis B, hepatitis C) 1, 2

• Alcohol-related liver disease 1

• Autoimmune liver diseases (autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis) 1, 2

• Drug-induced liver disease 2

Disease Spectrum and Progression

• Chronic liver disease represents a spectrum ranging from inflammation to fibrosis to cirrhosis 3

• In MASLD specifically, the spectrum includes steatosis, metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis, and MASH-related hepatocellular carcinoma 1

• Compensated cirrhosis may decompensate, causing ascites, hepatic encephalopathy, or variceal bleeding 3

• Acute-on-chronic liver failure (ACLF) represents a severe complication characterized by acute deterioration in clinical condition, liver failure (elevated bilirubin and INR), and at least one extrahepatic organ failure in patients with chronic liver disease 1

Diagnostic Approaches

• Diagnosis typically involves history, physical examination, laboratory tests, combination scoring indices, and imaging (ultrasonography, transient elastography) 3

• Liver biopsy remains the reference standard for diagnosis but is costly, subject to sampling errors, and not well accepted for longitudinal disease monitoring 1

• Non-invasive tests for monitoring chronic liver disease are increasingly being used to avoid the morbidity and mortality related to invasive procedures 4

Management Considerations

• Management focuses on treating the underlying cause, as chronic liver disease is potentially reversible through appropriate interventions 3

• Regular clinical assessment with laboratory tests and calculation of the Child-Pugh and Model for End-stage Liver Disease (MELD) scores should occur every 6 months 3

• Liver transplantation is indicated for patients with a MELD score of 15 or greater, complications of cirrhosis, or hepatocellular carcinoma 3

Important Clinical Considerations

• Patients with chronic liver disease are at risk for osteoporosis and should be evaluated with bone mineral density measurements 1

• Medications with potential for hepatotoxicity should be avoided in patients with chronic liver disease 3

• Recent advances in understanding the gut-liver axis and the role of gut dysbiosis in liver diseases may lead to new therapeutic approaches 4