What is Hepatitis C Virus (HCV)?

Hepatitis C Virus (HCV): Overview and Clinical Significance

Hepatitis C virus (HCV) is a major cause of chronic liver disease worldwide, with approximately 71 million chronically infected individuals, many of whom are unaware of their infection. 1

Definition and Epidemiology

• HCV is a hepatotropic RNA virus in the Flaviviridae family that causes acute and chronic hepatitis, with potential progression to severe liver damage 2
• Globally, an estimated 71 million people are chronically infected with HCV, representing approximately 2.35% of the world population 1
• In 2015, many infected individuals were unaware of their infection status, complicating public health control efforts 1
• HCV infection remains one of the main causes of chronic liver disease worldwide 1

Viral Characteristics and Pathophysiology

• HCV is both hepatotropic and lymphotropic, explaining the variety of hepatic and extrahepatic manifestations 1
• The virus is a positive-sense, single-stranded RNA virus that primarily targets liver cells 3
• HCV has high genetic variability, allowing it to escape the host's immune response, which contributes to its high rate of chronicity 4
• The virus is not directly cytopathic; liver damage is mainly related to immune-mediated mechanisms 4

Disease Progression and Clinical Impact

• The long-term natural history of HCV infection is highly variable, ranging from minimal changes to extensive fibrosis and cirrhosis with or without hepatocellular carcinoma (HCC) 1
• Chronic HCV infection can lead to progressive liver damage resulting in:
  • Chronic hepatitis
  • Liver fibrosis
  • Cirrhosis (compensated or decompensated)
  • Hepatocellular carcinoma 1, 2
• HCV is associated with numerous extrahepatic manifestations (HCV-EHDs) that can significantly impact patient outcomes 1
• HCV-related end-stage liver disease is a leading indication for liver transplantation in many countries 5

Transmission and Risk Factors

• HCV is primarily transmitted through blood exposure 1
• Major risk factors include:
  • Unsafe injection drug use
  • Unsterile medical procedures (iatrogenic infections), particularly in countries with high HCV prevalence
  • Blood transfusion (prior to screening implementation)
  • Other percutaneous exposures 2, 1

Diagnosis

• Diagnosis of HCV infection is based on:
  • Detection of HCV antibodies (anti-HCV) for initial screening
  • Confirmation with HCV RNA testing to identify active infection
  • Viral genotype and subtype determination to guide treatment decisions
  • Assessment of resistance-associated substitutions in some cases 2

Treatment Advances

• The primary goal of HCV therapy is to cure the infection by achieving a sustained virological response (SVR) 1
• Treatment has evolved dramatically from interferon-based regimens to direct-acting antivirals (DAAs) 1
• Modern DAA therapies target three key viral proteins:
  • NS3/4A protease
  • NS5A protein
  • RNA-dependent RNA polymerase NS5B protein 2
• Current DAA combinations can cure >90% of patients, including previously difficult-to-treat populations 2
• SVR is associated with normalization of liver enzymes, improvement in liver inflammation and fibrosis, and reduced risk of complications 1

Public Health Implications

• WHO has called for the elimination of HCV as a public health threat by 2030 6
• Despite therapeutic advances, challenges remain in screening, linkage to care, and treatment access globally 6
• In the absence of a preventive vaccine, control strategies focus on treatment-as-prevention, effective screening programs, and global treatment access 2

Monitoring and Follow-up

• Patients with cirrhosis who achieve SVR remain at risk for complications and require ongoing surveillance for hepatocellular carcinoma 1
• Testing for hepatitis B virus (HBV) coinfection is essential before initiating HCV treatment due to risk of HBV reactivation 7, 8