Hepatology Digest: You have mentioned the area of fibrosis as a reflection of fibrosis quantity as a future academic reference. Would you like to tell us about the difference between staging and quantity (area) and how it will improve the study of non-invasive detection for fibrosis?
Dr Cales: Measuring fibrosis relies on a reference which is liver biopsy but in clinical practice, the evaluation of liver fibrosis is limited by inter-observer variability. We have performed several studies that clearly show that when you consider a pathologist as first-line you have a poor reproducibility. This is due to the pathologist classifying liver fibrosis according to a semiquantitative classification called staging. On the other hand, when you measure liver fibrosis on a liver slide with an automated device called morphometry, you can standardize the measurement of liver fibrosis. So several experts now think that the future best reference could be the measurement of the area of fibrosis or % of fibrosis.
Hepatology Digest: Different etiologies will cause different liver fibrosis progression. What is the difference between fibrosis progression induced by HBV and HCV infection? Are there differences in the results of FibroScan studies in chronic hepatitis B and hepatitis C?
Dr Cales: Most of the studies performed with non-invasive tests have been conducted with hepatitis C because it has a linear progression so it is easy to perform studies on the progression of liver fibrosis in hepatitis C. On the contrary, in hepatitis B there are several different stages and the progression is not linear. For example, you can have a flare up in chronic hepatitis B and the increase in fibrosis is probably not linear. Therefore we can compare only stable chronic hepatitis B with hepatitis C. I have recent data performed in Africa in hepatitis B which shows there is the same trend as with HCV. We have two main results. Firstly, the degree of fibrosis in the liver is lower in the beginning in females compared to men but in post-menopausal women with hepatitis B there is an acceleration of fibrosis progression so that in our experience, the level of fibrosis is similar in men and women by the age of around 70. For FibroScan, studies have shown that it is possible to follow the progression of hepatitis B with FibroScan.
Hepatology Digest: Why is the accuracy of significant fibrosis diagnosis (especially F2) so poor using any of the non-invasive fibrosis detection techniques? What is the clinical significance of F2 staging being correctly diagnosed? How can we improve the accuracy of F2 significant fibrosis diagnosis?
Dr Cales: I disagree a little with the first part of your question. In hepatitis C, we have some tests that are considered to be accurate in detecting significant fibrosis. In HBV for example, with our Fibrometer test, we have five studies in the world, one of them was performed in China, and the results for significant fibrosis were satisfactory.
Dr Cales: In fact, there is perhaps a misunderstanding because when you compare the AUROC (area under the receiving operator characteristic curve) for significant fibrosis and cirrhosis, the AUROC for significant fibrosis for most liver disease tests is lower than for cirrhosis. This is not due only to the test but also to the prevalence of the diagnostic target. When you have an AUROC of 0.94 for cirrhosis for example with FibroScan, many people think that the percentage of well-classified patients with cirrhosis is 94% but in fact this is the overall rate of well-classified patients. So when you consider a diagnostic target like significant fibrosis or cirrhosis, the rate of well-classified patients is similar between the two diagnostic targets. In some respects, your question is somewhat right because, for example, with FibroScan the performance for significant fibrosis is less than for cirrhosis.
Dr Cales: Regarding the final part of your question, we can improve the accuracy for significant fibrosis by combining a blood test and FibroScan. This year we have developed a test combining both tests and we have had excellent accuracy of around 91% in all fibrosis stages, i.e. in patients with cirrhosis and with less severe fibrosis. You also asked what the clinical significance of accurate diagnosis was. Ten years ago, the meaning of significant fibrosis was in fact not known. Only cirrhosis was thought to alter or impact on the prognosis, for example for overall mortality. But in recent years, we now know that in hepatitis C and even fatty liver disease, the presence of significant fibrosis decreases the prognosis concerning overall mortality by five to ten years. Significant fibrosis is a clinical condition and is included in most guidelines to recommend a treatment.
Dr Cales: For example, in HBV, this is one of the criteria for treating patients and in HCV, this is also the limit by which we can treat the patient with genotype 1. So we can improve diagnosis but for me, the question is somewhat old-fashioned because at the beginning of the implementation of non-invasive tests the main diagnostic target was clinically significant fibrosis but we have developed a method that can show the patient and the doctor the detailed classification. With a combination of Fibrometer and FibroScan we have an eight stage classification so we can precisely give a diagnosis to the patient or doctor.
