What is the number one cause of liver inflammation?

Number One Cause of Liver Inflammation

Hepatitis C virus (HCV) infection is the number one cause of chronic liver inflammation worldwide, with approximately 71 million chronically infected individuals globally. 1

Epidemiology and Impact

• HCV infection affects approximately 71 million people worldwide 1
• Represents one of the main causes of chronic liver disease globally 1
• The long-term natural history is highly variable, ranging from minimal inflammation to extensive fibrosis, cirrhosis, and hepatocellular carcinoma (HCC) 1
• Many infected individuals are unaware of their infection, complicating public health efforts 1

Pathophysiology of HCV-Induced Inflammation

HCV causes liver inflammation through multiple mechanisms:

1. Direct viral effects - The virus itself triggers inflammatory responses in hepatocytes 2
2. Immune-mediated mechanisms:
   • Activation of innate and adaptive immune responses 3
   • Inflammasome activation 4
   • Cytokine and chemokine cascades 4
3. Oxidative stress - Leads to hepatocyte damage and perpetuates inflammation 2
4. Steatosis induction - Contributes to ongoing inflammatory processes 2

Clinical Manifestations of HCV-Related Inflammation

The inflammatory response in chronic hepatitis C is linked to:

• Liver-limited injury:

  • Progressive fibrosis
  • Cirrhosis development
  • Hepatocellular carcinoma 2

• Extrahepatic manifestations:

  • Lymphoproliferative disorders
  • Cardiovascular disease
  • Neurological complications 2

Diagnostic Markers of Inflammation

• Elevated liver enzymes (ALT/AST) - Though correlation between ALT and actual inflammation is imperfect 1
• Approximately 30% of patients with normal ALT may still have significant inflammation 1
• 24% of patients with elevated ALT and no significant fibrosis may not have significant inflammation 1

Treatment Implications

• The primary goal of HCV therapy is to cure the infection and achieve sustained virological response (SVR) 1
• SVR is generally associated with normalization of liver enzymes and improvement or regression of liver necroinflammation and fibrosis 1
• Direct-acting antivirals (DAAs) effectively eliminate HCV but may not be sufficient to completely resolve inflammation in all cases 4
• Some patients who achieve SVR may still be at long-term risk for progression to cirrhosis and HCC 4

Other Common Causes of Liver Inflammation

While HCV is the leading cause globally, other significant causes include:

1. Hepatitis B virus (HBV) - Another major viral cause of chronic hepatitis 1
2. Alcohol-related liver disease - Typically shows AST:ALT ratio >2 1
3. Non-alcoholic fatty liver disease (NAFLD) - Most common liver disease in developed countries 1
4. Autoimmune hepatitis - Characterized by interface hepatitis, hypergammaglobulinemia, and autoantibodies 1
5. Drug-induced liver injury - From prescription medications, over-the-counter drugs, and supplements 5

Clinical Approach to Liver Inflammation

When evaluating liver inflammation:

1. Obtain thorough history including risk factors for viral hepatitis
2. Test for viral hepatitis markers (HBV surface antigen, HCV antibody)
3. Assess alcohol consumption and metabolic risk factors
4. Consider autoimmune markers if viral causes are negative
5. Evaluate for drug-induced causes

HCV-induced inflammation represents a significant global health burden that requires prompt diagnosis and treatment to prevent progression to advanced liver disease and its complications.