The National Academy of Clinical Biochemistry
Laboratory Medicine Practice Guidelines
Laboratory Guidelines for Screening, Diagnosis and Monitoring of Hepatic Injury
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These guidelines represent a carefully crafted consensus statement of published evidence on testing for liver disease in literature published through early 2000. The editors and reviewers spent countless hours assuring that the information contained in this guideline were as up to date and accurate as possible. Since these guidelines were written almost 2 years ago, it appears appropriate to review what has changed in terms of consensus information or guidelines in the field of laboratory testing for hepatic injury.
In the area of chemical tests for hepatic injury, there have been no major changes in evidence from what is reflected in the guidelines. Recent guidelines for recognition and management of hepatic encephalopathy do not indicate a use for ammonia measurements (1), confirming our guidelines on the limited utility of this test.
Tests for hepatitis B virus have not changed appreciably, but use of PCR as a method for measuring HBV DNA has expanded over the past two years. This has led to the recognition of low-level viremia in many patients who have no apparent liver injury. A recent NIH conference on hepatitis B has suggested that viral loads over 105 copies/mL be considered "clinically significant" viremia, while lower viral loads represent an "inactive carrier state" (2). A WHO standard for reporting HBV viral loads, similar to that developed for HCV, has now been developed (3) but has not been adopted by North American manufacturers. In guidelines on chronic hepatitis B, it is now recommended that individuals with isolated anti-HBc now be considered to be HBV immune (4).
Tests for HCV have evolved slightly since the guidelines were published. New CDC guidelines for laboratories performing anti-HCV testing are in the process of finalization, and will recommend that laboratories report anti-HCV results along with the signal:cutoff ratio. It is becoming clear that those with "low positive" anti-HCV (defined as signal:cutoff ratio < 3.8 using the two most widely used EIA assays) indicates results that are found to be false positive 85-90% of the time. While the guidelines are not yet finalized, it is likely that they will suggest routine confirmatory testing of low positive results by laboratories before reporting them, as is done with HIV antibody tests. HCV RNA assays have now become more or less standardized by use of the WHO standard. Newer quantitative assays have lower limits of detection similar to those of qualitative assays, but our recommendation to use the assay with the lowest limit of detection seems to still be valid.
In monitoring of treatment for hepatitis C, a new term has been introduced and recommended for use at a recent NIH consensus conference (in press). The term is early virologic response, and is defined as a fall of > 2 logs (or to undetectable) at 12 weeks after initiation of treatment. Persons who fail to show an early virologic response have less than a 2% likelihood of sustaining a virologic response after treatment is concluded, and should be considered for discontinuation of treatment. Other findings discussed in the guidelines for combination interferon-ribavirin treatment appear to still be valid for treatment with pegylated interferon-ribavirin combinations.
As editor, I believe you will find most of the rest of the information contained in these guidelines to still be timely and relevant to practice. I welcome any comments or suggestions for revisions to future editions of the guidelines or this introductory material.
D. Robert Dufour, John A. Lott, Frederick S. Nolte,
David R. Gretch, Raymond S. Koff, Leonard B. Seeff (Editors)
1. Ferenci P, Lockwood A, Mullen K, Tarter R, Weissenborn K, Blei AT: Hepatic encephalopathy - definition, nomenclature, diagnosis, and quantification: final report of the working party at the 11th World Congresses of Gastroenterology, Vienna, 1998. Hepatology 2002;35:716-21.
2. Lok AS, Heathcote EJ, Hoofnagle JH: Management of hepatitis B: 2000 - summary of a workshop. Gastroenterology 2001;120:1858-1853.
3. Saldanha J, Gerlich W, Lelie N, Dawson P, Heermann K, Heath A: An international collaborative study to establish a World Health Organization international standard for hepatitis B virus DNA nucleic acid amplification techniques. Vox Sang 2001;80:63-71.
4. Lok AS, McMahon BJ: Chronic hepatitis B. Hepatology 2001;34:1225-1241.