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We read with interest the detailed comments made by Boursier and Cales1 on our article2 describing a large-scale, multicenter study of sequential algorithms combining noninvasive markers for liver fibrosis. Some comments are necessary. To date, our study represents the largest independent, international study about serum noninvasive markers for liver fibrosis. This study was intended to both validate and optimize our previously described stepwise algorithms for liver fibrosis.3 Boursier and Cales mention the positive predictive value of sequential algorithm for fibrosis evaluation (SAFE) biopsy. We have to underline that SAFE biopsy algorithms have been modeled to answer specific clinical issues. Indeed, the algorithms have been designed to reach a very high negative predictive value for both significant fibrosis and cirrhosis (ranging from 99% to 100%), so that no patient with an indication for antiviral therapy or a specific follow-up can be underdiagnosed. Boursier and Cales refer to a synchronous algorithm combining Fibrometer and FibroTest. It must be emphasized that both FibroTest and Fibrometer are patented tests, with an average cost of 100 euros per test. SAFE biopsy algorithms are based on the aspartate aminotransferase-to-platelet ratio index, which has virtually no cost and global availability, and on FibroTest, which is used as a second-line test only in a subgroup of patients. Indeed, SAFE biopsy algorithms are practical and cost-effective, and the sequential combination approach has been applied by others with excellent performance.4 Another important issue is that SAFE biopsy algorithms adopt widely available and validated tests.5, 6 Although Fibrometer has shown good performance in studies coming from the patenting group, it has been poorly evaluated externally. Moreover, Fibrometer is not widely available in all clinical settings and is not licensed in as many countries as FibroTest.

In conclusion, on the basis of the results of our multicenter, large-scale, independent study, SAFE biopsy seems a useful method in clinical practice for large-scale screening of liver fibrosis in patients with hepatitis C.

Giada Sebastiani*, Alfredo Alberti* †, * Venetian Institute of Molecular Medicine, Padua, Italy, † Histology, Microbiology and Medical Biotechnologies, University of Padua, Padua, Italy.

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