Approximately 4 million people in the United States and an estimated 200 million people worldwide are infected with hepatitis C virus (HCV). New HCV infections averaged 230,000 per year during the 1980’s, according to the Centers for Disease Control and Prevention (CDC). By 1996, this number had declined to 36,000 new infections per year, a >80% reduction. This impressive reduction is due largely to screening of blood products, which has virtually eliminated HCV from the blood supply. Although blood transfusion accounted for a substantial proportion of infections acquired 10 years ago, injecting drug use currently accounts for 60% of HCV transmission in the U.S.
HCV is the most common chronic bloodborne infection in the U.S. and is responsible for 20% of acute hepatitis, 60% of chronic hepatitis, and 30% of liver cirrhosis cases. On average, it takes 14 years from infection to the first clinical manifestations of chronic HCV, 20 years to clinical evidence of cirrhosis, and >25 years to clinical presentation of hepatocellular carcinoma. Approximately 20% of infected persons develop cirrhosis within 20 years of infection. End-stage liver disease due to HCV infection is the most frequent indication for liver transplantation among adults. Chronic liver disease is the tenth leading cause of death among adults in the U. S. According to CDC data, HCV is the cause of 40% of chronic liver disease, with a resultant 8,000 to 10,000 deaths each year.
The average rate of HCV infection among infants born to HCV-infected women is 5-6%. The transmission rate increases to 14-17% when the mother is coinfected with HCV and HIV. The only factor consistently associated with transmission has been the presence of HCV RNA in the mother at the time of birth. Passively acquired maternal HCV antibody may persist for at least 12 months.
Since most HCV-infected persons are aged 30-49 years old, the number of deaths due to HCV-related chronic liver disease could increase substantially during the next 10-20 years. However, although it is accepted that 80% of infected persons develop chronic infection due to failure to clear the virus, long-term outcomes are less certain due to controversy over the natural history of hepatitis C. According to a recent review article, data from several retrospective and prospective outcomes studies suggest that 15-20% of persons with HCV infection will progress to end-stage liver disease preceded by cirrhosis. The rest are likely to die of causes other than liver disease. In these cases, the predisposing risk factor may itself be associated with decreased life expectancy, competing with HCV for morbidity and mortality.
The recommended initial test for hepatitis C infection is enzyme immunoassay for HCV antibody (HCV Ab). HCV Ab is reported as reactive when a specimen tests positive in triplicate. This test detects HCV Ab in ³97% of infected patients, but does not distinguish between acute, chronic, or resolved infection. In the event of a positive HCV Ab, supplemental testing by recombinant immunoblot assay (RIBA) or PCR for viral DNA is recommended because the specificity of the test is not 100%.
Recent publications have addressed the most cost-effective approach to confirmatory testing for a positive HCV Ab. The earliest testing protocol recommended RIBA initially followed by PCR when RIBA was positive or indeterminate. However, in 1998, the CDC suggested that PCR should be the initial confirmatory test of choice in clinical settings. The same publication suggested that RIBA should be used as a supplemental test when HCV PCR is negative to differentiate resolved infection from false positive HCV Ab. This approach proves to be the most efficient and cost-effective due to the greater sensitivity and specificity of the PCR assay compared to RIBA. For example, Saint Luke’s Regional Laboratories has recommended qualitative HCV PCR as the initial test of choice for confirmation since 1997. Based on test volumes, approximately $63,000 in patient charges has been saved since then by using HCV PCR initially for confirmation.
In patients at high risk for hepatitis C who test positive for HCV Ab, quantitative HCV PCR could be considered for initial confirmatory testing instead of qualitative PCR. The lower limit of detection is 100 copies/mL for qualitative HCV PCR and 200 copies/mL for ultraquantitative HCV PCR. Patients with low HCV-RNA levels tend to have a better response to therapy than those with high levels of virus, but high levels do not preclude the possibility of a response. Genotyping can be performed simultaneously with quantitative HCV PCR to better assess the patient’s likelihood of response to therapy. Genotypes 1a and 1b are the most common in the U. S., 1b is most prevalent in Japan, northern Europe, and South America, type 4 in Africa and the Middle East, type 5 in South Africa, and type 6 in Southeast Asia. Patients with genotypes 2 and 3 have a better response to interferon therapy alone than those with genotype 1. However, combination therapy with interferon and ribavirin may eliminate the virus in up to 50% of patients with genotype 1.
HCV Ab testing of infants born to infected women should be done no earlier than the age of 12 months, when passively transferred maternal HCV Ab declines below detectable levels. If earlier detection of HCV infection is necessary, qualitative HCV PCR may be performed. Umbilical cord blood should not be submitted for perinatal diagnosis due to the potential for contamination with maternal blood.
References:
Centers for Disease Control and Prevention. Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. MMWR 1998;47(No.RR-19)
Medical Laboratory Management Report. 1999;99-12
Liang, TJ, moderator. Pathogenesis, natural history, treatment, and prevention of hepatitis C. Ann Intern Med. 2000;132:296-305.
Epstein Barr Virus (EBV) PCR is now available at CMH. Two tests are offered, a Qualitative PCR and a Quantitative PCR.
The Qualitative PCR is done on Wednesdays. The specimen is whole blood in a purple top (EDTA) tube. This assay is appropriate for monitoring Post Transplant Lymphoproliferative Disease. The assay turns positive at very low viral copy numbers. If positive, the Quantitative PCR can provide more definitive information. Except in unusual circumstances, it is not recommended for Infectious Mononucleosis or EBV Hepatitis. In these rare cases clinical consultation is recommended.
The Quantitative PCR is done on Thursdays. This permits a quantitative follow-up on a positive qualitative test if desired. This follow-up can be done on the same specimen, EDTA whole blood. Serial testing provides the best information.