Currently, the second-and third-generation enzyme immuinfection, assessment of the severity of liver disease, monitornoassays (EIA-2 and EIA-3) for hepatitis C virus antibody ing progress of liver disease, determination of the likelihood (anti-HCV) are the most practical screening tests for the diagof response to interferon therapy, and monitoring of response nosis of HCV infection. The need for and the choice of suppleto treatment. mentary or confirmatory tests depend on the clinical setting and the likelihood of a true-positive EIA result. Detection of DIAGNOSIS OF HEPATITIS C HCV RNA in serum by polymerase chain reaction (PCR) assay Anti-HCV Tests. Currently, the second-generation enzyme is the gold standard for the diagnosis of HCV infection. Howimmunoassays (EIA-2) for anti-HCV are the most practical ever, the lack of uniformity in current PCR assays has tarscreening tests for the diagnosis of HCV infection in the nished this standard. Confirmatory tests for the diagnosis of United States. 1,2 These assays detect antibodies to recombi-HCV infection are in general unnecessary in anti-HCV-posinant HCV antigens from the core (C22) and nonstructural tive patients who present with chronic liver disease. When regions 3 (C33) and 4 (C-100). They are easy to perform indicated, the most appropriate test in this setting is a qualitaand the results are highly reproducible. Recently, third-gentive PCR assay for HCV RNA. Confirmatory tests should al-
eration EIAs (EIA-3) have been approved by the Food and ways be performed in anti-HCV-positive blood donors and Drug Administration for blood donor screening. EIA-3 differs individuals with normal aminotransferase levels. The most from EIA-2 in that it incorporates additional recombinant appropriate approach is to retest for anti-HCV using recombi-HCV antigen from the nonstructural region 5 (NS5). EIA-3 is nant immunoblot assay (RIBA) and then test for HCV RNA slightly more sensitive than EIA-2, but most of the improved using PCR assay in those who are RIBA positive or indetermisensitivity appears to be attributable to increased detection nate. Liver histology is the gold standard in assessing severity of anti-C33 and not the addition of NS5. [3][4][5] The secondof liver disease. Quantitative tests for serum HCV RNA levels generation recombinant immunoblot assays (RIBA-2) permit do not help to determine the severity of liver disease. At the the detection of antibodies to individual recombinant HCV moment, HCV genotyping should be considered a research antigens: C22, C33, C-100, and 5-1-1 (overlaps with C-100).
tool and not a part of the diagnostic work-up in clinical prac-
Patients who react to two or more HCV antigens are considtice. The goals of treatment for chronic hepatitis C are susered to be RIBA positive, whereas those who react to one tained biochemical and virological response. Viral clearance HCV antigen only are considered to have indeterminate reshould be determined by qualitative PCR assay. Quantifying sults. 1,2 RIBAs are technically more demanding than EIAs, serum HCV RNA level can help in predicting response to but they are simpler, more standardized, and more reproducinterferon treatment, but further studies using more standardible than tests for HCV RNA. RIBAs confer increased specificized assays are needed to determine if these values can be ity compared with EIAs. Nevertheless, RIBA positivity is not used to select patients for treatment. (HEPATOLOGY 1997;26 always indicative of ongoing HCV infection because patients (Suppl 1):48S-56S.)
with recovered HCV infection may remain anti-HCV positive for many years. RIBA-3, which differs from RIBA-2 in having Diagnosis of hepatitis C involves confirmation of the presadditional recombinant proteins from NS5 and synthetic pepence of hepatitis C virus (HCV) infection and assessment of tides from the core and NS3 antigens, has helped to resolve the severity of liver disease. In addition, the diagnostic workmany of the RIBA-2 indeterminate samples, but only approxiup should include investigations that may help to predict mately 50% of the RIBA-3-positive blood donors are HCV prognosis and response to treatment. This review focuses on RNA positive by polymerase chain reaction (PCR) assays. 6,7 the application of tests for antibody to HCV (anti-HCV), EIA-3 and RIBA-3 have replaced EIA-2 and RIBA-2 in many HCV RNA, and HCV genotypes in the diagnosis of HCV European and Asian countries. HCV RNA Assays. Confirmation of the diagnosis of ongoing HCV infection relies on the detection of viremia. This may Abbreviations: HCV, hepatitis C virus; anti-HCV, antibody to HCV; EIA, enzyme be achieved by qualitative reverse-transcription PCR or immunoassay; RIBA, recombinant immunoblot assay; PCR, polymerase chain reaction; branched DNA (bDNA) assays. Although the bDNA assay is bDNA, branched DNA signal amplification assay; ALT, alanine aminotransferase. technically simpler and has a lower chance of cross-contami-From the Division of Gastroenterology, University of Michigan and VA Medical nation, PCR assays are preferred for the confirmation of HCV