What are the characteristics of Hepatitis C (HCV)?

Characteristics of Hepatitis C Virus (HCV)

Hepatitis C virus (HCV) is both a hepatotropic and lymphotropic virus that causes progressive liver disease and various extrahepatic manifestations, with a significant proportion of infected individuals developing cirrhosis over 20-30 years and facing increased risk of hepatocellular carcinoma. 1

Virology and Transmission

• HCV is an RNA virus discovered in 1989 as the major agent of non-A/non-B chronic hepatitis 1
• Multiple genotypes exist, with genotype 1 (especially 1b) associated with more rapidly progressive disease 1
• Transmission occurs primarily through:
  • Blood transfusion (associated with more histologically active disease)
  • Injection drug use
  • Other parenteral exposures

Clinical Course and Natural History

Acute Infection

• Mean incubation period: 7 weeks (range 4-20 weeks) 1, 2
• Only one-third of acute infections are symptomatic and icteric 2
• Symptoms, when present, last 2-12 weeks 1
• 55-85% of infected individuals fail to clear the virus and develop chronic infection 1, 2

Chronic Infection

• Often asymptomatic or with nonspecific symptoms:
  • Fatigue
  • Muscle aches
  • Anorexia
  • Right upper quadrant pain
  • Nausea 1
• Progression to cirrhosis:
  • 5-20% develop cirrhosis over 20-25 years 1
  • Median time from infection to cirrhosis: approximately 30 years (range 13-42 years) 1
  • Risk factors for faster progression:
    • Age at infection >40 years
    • Male sex
    • Alcohol consumption >50g/day
    • High viral load
    • Obesity/hepatic steatosis
    • Coinfection with HBV or HIV 1

Advanced Disease

• Compensated cirrhosis: 5-year survival >90%, 10-year survival 80% 1
• Decompensated cirrhosis: 50% 5-year survival 1
• Hepatocellular carcinoma (HCC):
  • 1-7% annual risk in patients with established cirrhosis 1
  • HCV may promote HCC through chronic inflammation or direct viral effects 3, 4
  • Most HCV-associated HCC occurs in patients with established cirrhosis 1

Extrahepatic Manifestations (HCV-EHDs)

HCV is associated with numerous extrahepatic disorders due to its lymphotropism and immune system dysregulation 1:

• Mixed cryoglobulinemia syndrome (MCs) - strongest association 1
• B-cell non-Hodgkin's lymphoma (B-NHL) 1
• Autoimmune disorders:
  • Autoimmune hepatitis
  • Sjögren's syndrome
  • Lichen planus
  • Thyroiditis
  • Membranous glomerulonephritis
  • Polyarteritis nodosa 1
• Idiopathic thrombocytopenic purpura 1

Diagnostic Approach

Serological Testing

• Third-generation ELISA tests (ELISA-3) have 97% sensitivity 1
• Positive ELISA tests require confirmation due to false positives, especially in low-prevalence settings 1

Virological Testing

• HCV RNA testing confirms active infection
• Appears early in incubation period and peaks at symptom onset 2
• Persists in chronic infection 2

Clinical Implications and Management Considerations

• All HCV-infected patients should undergo comprehensive assessment for both hepatic and extrahepatic manifestations 1
• The presence of symptoms is a poor marker of disease severity - asymptomatic patients may have advanced liver disease 1
• Alcohol abstinence is critical as consumption >50g/day significantly accelerates fibrosis progression 1
• Regular HCC surveillance is necessary for patients with cirrhosis (1-7% annual risk) 1
• Recognition of extrahepatic manifestations may guide treatment decisions 1

Pitfalls in HCV Management

• Relying on symptoms to assess disease severity (many patients with cirrhosis remain asymptomatic) 1
• Underestimating the importance of alcohol abstinence in disease progression 1
• Failing to screen for and monitor extrahepatic manifestations 1
• Overlooking the risk of HCC in patients with established cirrhosis 1
• Assuming that disease progression is uniform (significant variability exists between individuals) 1

Despite advances in direct-acting antiviral treatments, HCV remains a significant global health problem with substantial morbidity and mortality related to both hepatic and extrahepatic manifestations.