For professionals:

• General:
  • Hepatitis C virus (HCV) infection is the most common chronic bloodborne infection in the United States. In the US, 3.9 million of people are infected with HCV, and 8,000 ~ 10,000 of people in the US die of HCV infection yearly. HCV is the leading cause of liver transplantation in the US.

  • Most risk factors associated with transmission of HCV in the United States were identified in case-control studies conducted during 1978-1986. These risk factors included blood transfusion, injecting-drug use, employment in patient care or clinical laboratory work, exposure to a sex partner or household member who has had a history of hepatitis, exposure to multiple sex partners, and low socioeconomic level. No data exist in the U.S. indicating that persons with exposures to tattooing and body piercing alone are at increased risk of HCV infection.

• Etiology:
  • RNA virus: 30 ~ 50 nm Hepacavirus (flaviviridae family)
  • Incubation period: 1 ~ 5 months (average: 1.5 ~ 2.0 months).
  • In the US, current risk for transfusion-associated hepatitis C is 1/100,000 per unit transfused. Injecting-drug use currently accounts for most HCV transmission in the United States, and has accounted for a substantial proportion of HCV infections during the past decades.

  • A low prevalence of HCV infection has been reported by studies of long-term spouses of patients with chronic HCV infection who had no other risk factors for infection. Although considerable inconsistencies exist among studies, data indicate overall that sexual transmission of HCV appears to occur, but that the virus is inefficiently spread through this manner. More data are needed to determine the risk for, and factors related to, transmission of HCV between long-term steady partners as well as among persons with high-risk sexual practices.

  • Transmission of HCV within a household is uncommon.

  • The only consistent factor found to be associated with HCV transmission during birth is the presence of HCV in the mother at the time of birth.

  • The transmission of HCV infection through breast milk has not been documented.

• Dianosis:
  • Before 1989: diagnosis was made only by "exclusion diagnosis" --- non-A, non-B hepatitis.
  • Diagnostic tests for HCV infection:
    • Serological test:
      • EIA: for screening test
        • 1989: first generation reagent for detection of anti-HCV was developed, containig recombinant and synthetic antigens --- C100-3 (NS3 and NS4, NS: non-structure)
        • 1991: second generation reagent --- C22(core), C33c(NS3), and C200(NS3+NS4) .
        • 1995: third generation reagent --- C22(core), C33c(NS3), C200(NS3+NS4), and NS5.

      • RIBA (recombinent immunoblot assay): for confirmatory supplementary test
        • RIBA-1
        • RIBA-2
        • RIBA-3
    • Molecular assay for HCV-RNA:
      • Qulitative assay
      • Quantitative assay
      • Genotyping
    • Antibody subclass tests (IgM-, IgG-):
      • current available data --- conflicting and no consistent results

• Acute infection:
  • 20% might have jaundice; 60% might have no symptoms; 10% might have non-specific symptoms.
  • Average time period from exposure to onset of symptom is 6 weeks.
  • Average time period from exposure to seroconversion is 8 weeks.
  • Anti-HCV can be detected in 80% of patients within 15 weeks after exposure.
  • Elevated serum ALT levels, often in a fluctuating pattern, are the most characteristic feature.
  • Fulminant hepatic failure is rare.
• Chronic hepatitis:
  • After acute infection, 15% of patients appear to resolve their infection without sequelae.
  • Chronic HCV infection develops in around 75% of patients (different from HBV: below 10 %).
  • around 60% of chronic hepatitis patients are with persistent or fluctuating ALT elevations indicating active liver disease.
  • ALT levels are normal in around 30% of chronic hepatitis cases.
  • No clinical or epidemiologic features among patients with acute infection have been found to be predictive of either persistent infection or chronic liver disease.
  • Various ALT patterns have been observed in chronic hepatitis patients, and patients might have prolonged periods of normal ALT activity even though they have histologic-confirmed chronic hepatitis. Thus, a single ALT determination cannot be used to exclude ongoing hepatic injury.
  • The course of chronic liver disease is usually insidious, without any apparent clinical symptom, and progressing at a slow rate in many patients during the first two or more decades after infection.
  • Thus, chronic hepatitis patients are frequently discovered by occasion such as in routine physical check-up.
  • Intake of alcohol in HCV infected cases enhance the severity and progression of liver condition.
• Superinfection of hepatitis viruses --- (Vento et al.) --- Although most patients with chronic hepatitis B who acquired HAV infection had an uncomplicated course, patients with chronic hepatitis C had a substantial risk of fulminant hepatitis and death associated with HAV superinfection. Our data suggest that patients with chronic hepatitis C should be vaccinated against hepatitis A. (N Engl J Med 1998;338:286-90.)
• Extrahepatic manifestations of chronic HCV infection are considered to be of immunologic origin and include cryoglobulinemia, membranoproliferative glomerulonephritis, and porphyria cutanea tarda.

• Quasispecies naure of HCV
  • The genetic heterogeneity of viral population within an infected individual is referred to as a quasispecies nature
  • Many important biological features of a virus are attributable to its quasispecies nature, such as persistent infection, resistent to antiviral agents and failure of vaccination
  • The HCV genome having a HVR (hypervariable region) in the E2/NS1 region causes the characteristics of quasispecies nature
• Genotypes of HCV:
  • Simmonds:(1994)
    suggested classification system: major groupings (Arabic numericals in order of discovery), subtypes designated by lower-case letters
  • previopus classification:
    
    • Enomoto (1990): HCV-K1-PT, HCV-K2a, HCV-K2b
    • Houghton (1992): HCV-I, HCV-II, HCV-III
    • Okamoto (1992): I, II, III, IV
  • 9 major groups, and 30+ subtypes
• Implications of viral factors and host factors:
  • Both host and virus-specific factors affect the outcome of hepatitis C infection.
    • Host factors: underlying immune status, age, disease duration, body mass index, and comorbid alcoholism
    • Virus-specific factors: level of viremia, viral genotype, quasispecies nature.
  • and also affect the severity of liver damages, response to interferon therapy, and transmission from mother to infant.
• Influence of mode of infection on outcome:
  • The mode of viral acquisition does seem to influence the histopathologic and clinical outcome of hepatitis C,
  • but an intricate balance between the source of infection and the host's initial immunologic response to the virus is decisive.
• In Taiwan:
  • 15% of chronic liver diseases patients are non-B hepatitis, of them 30 ~ 50 % are HCV infection.
  • thus 90 ~ 95% of chronic liver disease are associated with either HBV or HCV infection.
  • Over 90% of post-transfusion hepatitis in Taiwan was HCV hepatitis during the period after the application of screening test for HBV and before the start of the screeing test for HCV for blood to be used for transfusion in1990.
  • Prevalence rate (before blood screening test became available): (with 2nd generation reagent)
  • in general population: adult --- 0.6 ~ 1.2 %,
  • children of 5-yrs old and under --- 0.1 %.
  • IVDU (intravenous drug abuser) --- 95 %
  • female prostitute --- 20.7 %

  • The prevalence rate differs little in dfferent regions or countries worldwide. New infections rate has dropped since after the blood screening test for HCV became available.