Hepatitis C Virus

Introduction

The Hepatitis C Virus (HCV) is a major cause of chronic liver disease worldwide. It is an enveloped RNA virus that belongs to the Flaviviridae family, specifically the Hepacivirus genus. HCV infects liver cells (hepatocytes) and can lead to chronic hepatitis, cirrhosis, or liver cancer if left untreated.
Although millions of people are affected globally, HCV is now curable with modern antiviral medicines — yet no vaccine exists to prevent it.

Key Facts

• Virus Type: Enveloped, single-stranded positive-sense RNA virus.
• Family: Flaviviridae.
• Genome Length: ~9.6 kb.
• Global Burden: About 50 million people live with chronic HCV.
• Transmission: Bloodborne, sexual, and perinatal routes.
• Chronicity: 70–85% of infections become chronic.
• Cure Rate: >95% with direct-acting antivirals (DAAs).
• Vaccine: None currently available.

Keywords

·         Hepatitis C Virus (HCV), Chronic Hepatitis, Flaviviridae, RNA Virus, Cirrhosis, Liver Cancer (HCC), Hepacivirus, Genetic Drift, Antiviral Therapy, Vaccine Prevention.

Characteristics of HCV

HCV is a spherical, enveloped virus with a positive-sense RNA genome approximately 9.6 kilobases long. After entering a host cell, the viral RNA is translated into a polyprotein, which is then broken down into structural and non-structural proteins, such as NS3, NS5A, and NS5B.
Replication occurs in endoplasmic reticulum–associated complexes through an RNA-dependent RNA polymerase, an enzyme prone to errors. This high mutation rate allows HCV to form quasispecies — slightly different viral strains that help it evade immune defenses and resist antiviral drugs.

Major Genotypes

There are at least six major genotypes (1–6), with subtypes such as 3a common in Pakistan and South Asia. Genotype testing is crucial because it helps determine the most effective treatment plan.

Epidemiology

Globally, about 1 million new HCV infections occur each year, and around 50 million people live with chronic infection.
The highest numbers are found in:

• Eastern Mediterranean Region: ~12 million cases
• South-East Asia: ~9 million
• Europe: ~9 million
• Western Pacific: ~7 million
• Africa: ~8 million
• The Americas: ~5 million

Countries such as Egypt, parts of Eastern Europe, and Central Asia report particularly high HCV prevalence. Each year, around 242,000 deaths are attributed to complications of chronic hepatitis C, including cirrhosis and liver cancer.

Transmission

HCV spreads mainly through blood-to-blood contact. Major transmission routes include:

• Unsafe injections or reuse of contaminated syringes
• Transfusions with unscreened blood or blood products
• Injection drug use and needle sharing
• Inadequate infection control in healthcare settings

Although sexual and mother-to-child (perinatal) transmission can occur, they are much less efficient than in hepatitis B. Preventive screening of blood donors and high-risk groups is critical to reduce transmission.

Pathogenesis: How HCV Affects the Liver

Unlike some other viruses, HCV does not directly kill liver cells. Instead, the immune system’s ongoing inflammatory response damages the liver over time.

• Chronic inflammation results from persistent viral replication.
• Cytokines released by immune cells (like CD8⁺ T-cells and macrophages) activate liver stellate cells, which lay down fibrous tissue.
• Over years, this process leads to fibrosis, cirrhosis, and possibly hepatocellular carcinoma (HCC).

Coexisting conditions such as alcohol abuse, HIV infection, and obesity can speed up this damage.

Genetic Drift and Viral Diversity

HCV’s RNA polymerase lacks proofreading ability, so mutations frequently occur during replication.
This genetic drift creates a diverse population of viral variants (called quasispecies) within each patient.

These mutations allow HCV to:

• Evade neutralizing antibodies
• Escape cytotoxic T-cell attack
• Develop drug resistance

Although genetic shift (as seen in influenza viruses) is rare in HCV because it has a non-segmented genome, occasional recombination between strains can lead to new genotypes or altered virulence.

Immunity and Chronic Infection

The immune system can sometimes clear HCV, but not always:

• About 15–30% of acute infections clear spontaneously due to a strong T-cell response.
• The remaining 70–85% progress to chronic infection.
  There is no lifelong immunity, so reinfection is possible even after recovery.
  Chronic HCV persists due to T-cell exhaustion, viral escape mutations, and the high variability of viral antigens.

Symptoms and Clinical Presentation

Acute Hepatitis C

Most people with acute infection have no symptoms.
If symptoms occur, they may include:

• Fatigue and malaise
• Mild fever and nausea
• Joint pain
• Jaundice (yellowing of skin and eyes)

Only about 20% of patients experience these signs during the early phase.

Chronic Hepatitis C

Chronic infection often remains silent for decades. Many patients discover it accidentally during blood tests.
Over time, chronic infection may cause:

• Persistent fatigue
• Right upper abdominal pain
• Signs of cirrhosis (ascites, swelling, confusion)
• Liver cancer (HCC) in advanced stages

Extrahepatic (outside the liver) symptoms can include skin disorders, kidney disease, and cryoglobulinemia.

Diagnosis

HCV testing involves two main steps:

1.     Antibody Test (Anti-HCV): Detects exposure to the virus.

2.     HCV RNA PCR: Confirms active infection and measures viral load.

Because up to 30% of infections clear naturally, PCR confirmation is necessary to detect active cases.
Additional tests include:

• Genotype testing to tailor therapy
• Liver function tests (ALT, AST)
• Fibrosis assessment using noninvasive tools such as FibroScan or APRI score.

Treatment

Modern therapy has revolutionized HCV management.

Acute HCV

Most acute cases are monitored for spontaneous clearance. If the infection persists beyond six months, treatment is initiated.

Chronic HCV

Today, chronic HCV is curable in over 95% of patients using direct-acting antivirals (DAAs).
Common regimens include:

• Sofosbuvir + Velpatasvir
• Glecaprevir + Pibrentasvir
• Sofosbuvir + Ledipasvir

Treatment duration is typically 8–12 weeks, with minimal side effects.
Older therapies like interferon and ribavirin are no longer standard due to poor tolerance and lower success rates.

Early treatment prevents cirrhosis, liver failure, and liver cancer.

Prevention

Currently, there is no approved vaccine for HCV, so prevention focuses on reducing blood exposure and infection control.

Key Preventive Measures:

1.     Screen blood and organ donors for HCV.

2.     Use sterile needles and syringes; promote safe injection practices.

3.     Implement infection control in hospitals and clinics.

4.     Educate injection drug users about needle exchange programs.

5.     Practice safe sex, especially in high-risk groups.

6.     Early diagnosis and treatment to reduce transmission.

Conclusion

Hepatitis C Virus (HCV) remains a global public health challenge, but the future is promising. Thanks to the advent of direct-acting antivirals, chronic HCV infection is now curable in most patients. However, screening, awareness, and prevention remain essential since no vaccine exists. With proper control measures and early treatment, the burden of HCV-related liver disease can be drastically reduced worldwide.