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Is liver stiffness equal to liver fibrosis?

We read with interest the article by Koehler and colleagues. The elaborate study provides important information on the prevalence of increased liver stiffness in a suburban population in the Netherlands. By systematically investigating 3,041 participants, the authors conclude that 5.6% of the general population over 45 years of age has increased liver stiffness above 8 kPa, suggestive of clinically relevant fibrosis. Diabetes and ultrasound-assessed steatosis in combination was a particularly strong predictor of increased liver stiffness. We commend the authors for their large-scale, thorough work, which is an important step toward early detection of chronic liver disease in the general population. With increasing availability of noninvasive markers of liver fibrosis, it is likely that more studies similar to the Rotterdam Study will be conducted. We therefore wish to use the opportunity to discuss the pitfalls of equating liver stiffness with liver fibrosis in a population with a low prevalence of chronic liver disease. The authors chose 8 kPa as a cutoff for clinically relevant fibrosis ( F3). The biopsy-controlled study used for reference assessed transient elastography in 246 nonalcoholic fatty liver disease patients referred for investigations at a hospital liver clinic, where 23% of patients had severe fibrosis. When this result is extrapolated to the general population, one should consider the problem of spectrum bias—that disease prevalence affects test performance. In an unsorted background population, the prevalence of severe fibrosis is most likely lower than the 5.6% with elevated liver stiffness reported in the Rotterdam Study. An “optimistic” estimate is 5%. Given this prevalence and assuming that transient elastography has the same accuracy as in the index study— a sensitivity of 91% and a specificity of 75% for detecting severe fibrosis—the positive predictive value is only 16%. As an example of spectrum bias, in a recent screening study of type 2 diabetics, 18% had elevated liver stiffness, whereas only half of those with elevated liver stiffness undergoing liver biopsy had severe fibrosis. Consequently, we need strategies to increase the positive predictive value when screening for chronic liver diseases in the general population or in groups with low prevalence such as those with diabetes or alcoholism. We suggest considering pretest probabilities or disease prevalence before interpreting the result of a diagnostic test. Only in high-prevalence populations can liver stiffness with certainty be equated with liver fibrosis.