Hepatitis C: A Brief Review
Based on recent guidance from the Food and Drug Ad-ministration, the blood services community is implementing a targeted lookback for transfusion recipients who may have received blood components from donors suspected, because of subsequent testing, of being infected with the hepatitis C virus (HCV). The strategy is analogous to traditional contact tracing efforts for other infectious diseases. HCV lookback will coincide with a campaign by the Public Health Service to educate physicians and the public about HCV in general. Although identification of HCV-positive blood donors has been possible since the early 1990s, significant improvements in our understanding of the natural history of HCV, the availability of excellent diagnostic testing, and improvements in antiviral treatment are recent developments that justify proceeding with HCV lookback now. These advances underscore the importance of notifying HCV-infected individuals in a lookback investigation so that they might have the opportunity to be tested and evaluated for treatment.
In a lookback investigation, hospital transfusion services are provided with a list of blood components supplied in the past and required to make good-faith attempts to identify
recipients and arrange for their notification, counseling and testing. The following overview of current knowledge of HCV provides information fundamental to such a process.
Non-A, non-B hepatitis was described clinically and epidemiologically in the 1970s after the recognition of hepatitis A (HAV) and hepatitis B (HBV) viruses. HCV was partially cloned in 1988 and blood screening assays developed and implemented in 1990. Because 80% of people infected with HCV remain persistently infected, HCV is the most common cause of chronic viral hepatitis in the United States. The Centers for Disease Control and Prevention (CDC) estimate that almost 4 million Americans are chronically infected with HCV. Sequelae of chronic HCV infection include cirrhosis, liver failure, hepatocellular carcinoma, and several extrahepatic syndromes. Eight to ten thousand deaths a year are related to chronic hepatitis C in the US. Chronic hepatitis C is the most frequent single indication for liver transplantation in this country, accounting for 15-20% of the operations (as many as 800) annually.
New hepatitis C infections in the United States peaked at 175,000 cases/year in 1989 and have declined to about 30,000 cases per year. Injection drug use accounts directly or indirectly for about 60% of new infections. Injection drug users acquire infection very rapidly after they initiate drug use, with 60-90% becoming infected in the first year.
Recipients of clotting factor concentrates manufactured before 1987 have very high prevalences of infection, and chronic dialysis patients have intermediate prevalences. HCV infection was commonly acquired from transfusion of blood products before donor screening began in 1990; however, the current risk is less than 1 infection/100,000 products transfused. Less than 5% of new HCV infections have been related to transfusion during the past decade.
Relatively weak risk associations for acquisition of HCV include sex with an infected person, high risk sexual behaviors, low socioeconomic status, imprisonment, and occupational exposure among health-care workers. The risk associated with a single sexual encounter is negligible, and the cumulative risk to an uninfected partner in a monogamous relationship for 10 to 20 years is 5%. The rate of acquisition of HCV infection among nonsexual household contacts is very small, and no cases of nonsexual direct transmission are documented.
The risk of vertical transmission is about 5%, and there are no recommendations against pregnancy for infected women. HCV is not transmitted through breast feeding. The risk of infection from an accidental needlestick in the hospital is about 0.1%. When the patient is known to be HCV infected, the risk is 2-3%, about 10 times higher than the risk for HIV transmission and tenfold lower than that for HBV. Infected health-care workers do not appear to pose a material risk to patients.
Testing for HCV infection is indicated in members of groups with a high prevalence of
HCV, as defined by CDC.
HCV is a single-stranded RNA virus in the genus
Flavivirus. At least six main genotypes (species) and multiple
subtypes of HCV exist. HCV mutates rapidly, and exists in the host as a population of different genetic variants called "quasispecies." This diversity may result in an ineffective immune response and explain the high rate of chronic HCV infection.
Less than a third of patients have acute symptoms (malaise, loss of appetite, and jaundice). HCV rarely causes fulminant liver failure, although recent data suggest that hepatitis A virus superinfection of patients with chronic HCV infection may be associated with a high rate of fulminant liver failure.
During the chronic phase, 30% of patients are carriers with no symptoms and normal liver enzymes, half have no symptoms with increased liver enzymes, and 20% have clinical liver disease. It is debated what proportion of patients surviving with chronic hepatitis C will develop clinical liver disease. A case-control study of post-transfusion hepatitis demonstrates no difference in mortality between infected and uninfected patients after two decades. Liver-related mortality was 3% versus 2% in controls after this long interval (p=.033).
The risk of serious HCV associated liver disease is
increased by heavy alcohol consumption, with acquisition beyond age 40, and male gender. Hepatocellular carcinoma is seen with
HCV-associated cirrhosis after a mean of about 30 years.
Treatment is offered to selected patients to prevent progression to clinical liver disease. The primary goal is virus eradication. Interferons and interferon in combination with ribavirin are licensed in the US. Maximal reported rates of sustained viral disappearance after treatment approach 50% in the context of randomized trials using the combination.
Treatment is recommended for patients whose disease is most likely to progress to
cirrhosis—those with persistently increased serum ALT levels, presence of HCV RNA in the blood, and a biopsy specimen showing moderately severe hepatitis or some degree of fibrosis (or both). Benefit is less clear in patients with mild hepatitis or established cirrhosis, and in children or those older than 60 years of age and thus must be judged individually. Adverse effects of interferon and interferon with ribavirin are nearly universal and are
responsible for discontinuation of treatment in about 10% of appropriately selected and managed patients.
Patients with chronic hepatitis C should abstain from using alcohol because no level of use is known to be safe.
Vaccination against hepatitis A and B should be considered if the
patient is not immune. Patients with chronic hepatitis should be evaluated by clinicians who are familiar with indications for liver biopsy and antiviral therapy. Patients with cirrhosis may be considered for evaluation at liver transplant centers.
Prophylaxis with immune serum globulin after a patient has been exposed to HCV infection is not effective and should not be used. Interferon administered during acute HCV may reduce the rate of chronic infection. Development of a vaccine has been difficult, mainly because of the genetic variation of the virus.
The following measures, recommended by the Public Health Service, will reduce transmission from infected people.
Selected Additional Reading on HCV Infection