Gastroenterology

Gastroenterology

Volume 134, Issue 6, May 2008, Pages 1670-1681
Gastroenterology

Introduction
Diagnosis and Quantitation of Fibrosis

https://doi.org/10.1053/j.gastro.2008.03.001Get rights and content

Hepatic fibrosis is the final common pathway for many different liver insults. Originally considered to be irreversible, hepatic fibrosis is now known to be a dynamic process with a significant potential for resolution. The diagnosis and quantitation of fibrosis have traditionally relied on liver biopsy. However, there are a number of drawbacks including the invasive nature of the procedure, sampling error, and interobserver variability. This article reviews the current role of liver biopsy in the assessment of hepatic fibrosis and discusses the role of the newer noninvasive methods including serum markers and radiologic tests.

Section snippets

Liver Biopsy

Liver biopsy has long remained the gold standard for the assessment of hepatic fibrosis. However, because it is an invasive test with the potential for serious, albeit rare, complications, it is not undertaken lightly. The first percutaneous liver biopsy was performed in 1923, but only in the last 50 years has it become a standard test following Menghini's description in 1958.9 Significant complications, defined as requiring hospital admission or prolonged hospital stay, occur in 1% to 5% of

Serum Markers of Fibrosis

A large number of putative serum markers have been evaluated for the assessment of hepatic fibrosis. Despite the dynamic nature of hepatic fibrogenesis, most of the presumed tests are suitable for the cross-sectional diagnosis of fibrosis stage rather than determining the rate of fibrosis progression or regression. No true serum marker that would act as a surrogate marker of hepatic fibrosis has been validated to date. It is almost certain that combinations of biomarkers will probably have to

Indirect Markers

A number of indirect markers of liver fibrosis have been used in clinical practice over the years, including serum aminotransferase levels, presence of coagulopathy, and platelet counts. A number of indices involving combinations of markers have also been evaluated. These indices incorporate a number of different markers and apply a score to the patient. Most of the studies on indirect markers have concentrated on the diagnosis of cirrhosis, but more recent studies have found them to be useful

FibroTest and FibroSure

FibroTest and FibroSure (Labcorp, Burlington, NC) are identical groups of biochemical markers, which are marketed under different names in Europe and the United States. The test was first developed by Imbert-Bismut et al3 and involves measurement of α2 macroglobulin, α2 globulin, γ globulin, apolipoprotein A1, γGT, and total bilirubin. The results from the test are formulated to determine 3 different categories of fibrosis: (1) mild (METAVIR F0–F1), (2) significant fibrosis (METAVIR F2–F4), (3)

Direct Markers

Direct markers of liver fibrosis include a number of serum or urinary markers, which have been shown to be or are thought to be involved in the deposition of ECM. Liver fibrosis involves both quantitative and qualitative changes in ECM markers. Because some of the markers reflect fibrosis progression and others fibrosis regression, it is thought that a dynamic evaluation of ECM activity should be possible. Potential markers of fibrosis include products of collagen synthesis or degradation,

SHASTA Index

The SHASTA index consists of measurements of serum HA, AST, and albumin and was developed in a cohort of 95 patients with HCV/HIV infection. It was capable of classifying mild fibrosis and advanced fibrosis and had similar accuracy to FibroTest and performed significantly better than APRI.57

FibroSpect

The FibroSpect (Prometheus Laboratories, San Diego, CA) assay involves 3 parameters: HA, TIMP-1, and α2-macroglobulin. All patients were able to be evaluated by FibroSpect, a major advantage. In clinical

Radiologic Imaging

Radiologic assessment of hepatic fibrosis has really been limited to patients with cirrhosis and its associated complications. Resolution of the hepatic parenchyma with ultrasound, computed tomography, or MRI is inadequate to assess earlier stages of fibrosis. A reduction in the size of the right lobe of the liver with relative enlargement of the left and caudate lobes is a reliable indicator of cirrhosis.5, 125, 126 The specificities in these studies are high, but have lower sensitivities

Transient Elastography

Elastography is an evaluation of the liver based on the fact that, as the liver becomes progressively more fibrotic, it becomes harder and less elastic. This technique easily and noninvasively measures the mean liver stiffness. Using a probe (Fibroscan; Echosens, Paris, France), which includes an ultrasonic transducer, a vibration of low frequency (50 MHz) and amplitude is transmitted into the liver. This vibration wave induces an elastic shear wave, which propagates through the liver. The

Clinical Utilization of Biomarkers

The number of choices of biomarkers for clinical practice is expanding, and commercialization of the FibroSure, FibroSpect, and Hepascore has occurred in the United States. The imaging modalities are not yet widely available but are expected to move rapidly into clinical practice. There are no definitive guidelines on the utilization of biomarkers, but we have suggested 2 general approaches to using them in practice. One is to combine them with liver biopsy at the initial evaluation, and the

Conclusion

Liver biopsy remains the gold standard for assessment of liver fibrosis. Although it remains an essentially safe procedure, complications do arise in a small number of cases. Bigger problems with liver biopsy are those of sampling error and interobserver variability. Understanding the limitations of liver biopsy has major clinical implications. Fibroscan and the currently available serologic tests can make the differentiation between early and advanced disease, which means that they could be

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    Conflicts of interest: Diarmuid S. Manning: None. Nezam H. Afdhal: 1. Quest, consultant, grant support; 2. EchoSens, consultant, grant support; 3. Prometheus, consultant, grant support.

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