Diagnosis and monitoring of hepatic injury. II. Recommendations for use of laboratory tests in screening, diagnosis, and monitoring

Abstract

Purpose: To review information on the use of laboratory tests in screening, diagnosis, and monitoring of acute and chronic hepatic injury.

Data sources and study selection: A MEDLINE search was performed for key words related to hepatic diseases, including acute hepatitis, chronic hepatitis, alcoholic hepatitis, cirrhosis, hepatocellular carcinoma, and etiologic causes. Abstracts were reviewed, and articles discussing use of laboratory tests selected for review. Additional articles were selected from the references. Guideline Preparation and Review: Drafts of the guidelines were posted on the Internet, presented at the AACC Annual Meeting in 1999, and reviewed by experts. Areas requiring further amplification or literature review were identified for further analysis. Specific recommendations were made based on analysis of published data and evaluated for strength of evidence and clinical impact.

Recommendations: Although many specific recommendations are made in the guidelines, only some summary recommendations are listed here. In acute hepatic injury, prothrombin time and, to a lesser extent, total bilirubin are the best indicators of severity of disease. Although ALT is useful for detecting acute and chronic hepatic injury, it is not related to severity of acute hepatic injury and only weakly related to severity of chronic hepatic injury. Specific tests of viral markers should be the initial differential tests in both acute and chronic hepatic injury; when positive, they are also useful for monitoring recovery from hepatitis B and C.

Figure 1.

Evaluation of suspected acute hepatic injury. Initial evaluation of patients with signs and symptoms such as jaundice, fever, and right upper quadrant abdominal pain should be by measurement of aminotransferases. Marked increases (>3000 U/L) of either enzyme are usually attributable to ischemic or toxic liver injury; if history is negative for either, then the diagnostic workup should continue as in persons with smaller increases. Viral serologies are the principal tests for evaluation of acute hepatic injury, although the falling incidence of viral diseases has made other causes proportionally more common. Because both prescription and nonprescription drugs can cause acute injury, a detailed drug history is critical, particularly in those with increased ALP. In those with coexistent increases in ALP, obstruction and other viruses such as EBV and CMV must be considered as well. ALK, alkaline phosphatase; Nl, normal.

Figure 2.

Management of therapy in chronic hepatitis C: laboratory testing depends on type of treatment given. At present, combined ribavirin-interferon is recommended for all patients without contraindications. HCV RNA should be measured at 24 weeks of treatment; if positive, treatment should be discontinued. If negative, duration of treatment is based on number of favorable risk factors present (see Table 5 ). If four or more factors are favorable (and genotype is 2 or 3), treatment is stopped; in other cases, treatment is continued for 48 weeks. If −70 °C storage is available, specimens for HCV genotype and viral load can be obtained before treatment and frozen until after the 24-week testing is performed; if not, testing should be performed before therapy. In those patients who cannot tolerate ribavirin, monotherapy with interferon is used. ALT and qualitative HCV RNA should be checked after 12 weeks of therapy; if ALT remains increased or HCV RNA is detectable, treatment should be discontinued. There is no benefit to determination of quantitative HCV RNA or genotype when interferon monotherapy is used.