Reply to: “Is transient elastography inaccurate in chronic hepatitis B and non-alcoholic fatty liver disease?”

Abstract

Is transient elastography inaccurate in chronic hepatitis B and non-alcoholic fatty liver disease?Journal of HepatologyVol. 55Issue 2PreviewWe read with great interest the study by Gaia and colleagues on the accuracy of transient elastography (TE) in patients with chronic hepatitis B (CHB) and non-alcoholic fatty liver disease (NAFLD) [1]. The authors casted doubt on the reliability of TE based on two provocative observations: (i) the median liver stiffness measurement (LSM) was higher in CHB patients with severe fibrosis (F3) than in those with histological cirrhosis (F4); and (ii) NAFLD patients with advanced fibrosis (F3) and severe steatosis (>33%) had similar LSM to those with milder fibrosis (F0-1) but less steatosis. Full-Text PDF Open Access To the Editor:I appreciate the letter by Dr. Wong and colleagues on our manuscript “Reliability of transient elastography for the detection of fibrosis in non-alcoholic fatty liver disease and chronic viral hepatitis” [[1]Gaia S. Carenzi S. Barilli A.L. et al.Reliability of transient elastography for the detection of fibrosis in non-alcoholic fatty liver disease and chronic viral hepatitis.J Hepatol. 2011; 54: 64-71Abstract Full Text Full Text PDF PubMed Scopus (196) Google Scholar] because it allows me to comment more about our results.The manuscript aimed to describe possible factors influencing the estimation of fibrosis by transient elastography (TE) in patients with chronic liver damage.As is well known, elevation in serum alanine aminotransferase (ALT) is a major confounding factor for liver stiffness measurements (LSM) [2Arena U. Vizzutti F. Corti G. et al.Acute viral hepatitis increases liver stiffness values measured by transient elastography.Hepatology. 2008 Feb; 47: 380-384Crossref PubMed Scopus (595) Google Scholar, 3Coco B. Oliveri F. Maina A.M. et al.Transient elastography: a new surrogate marker of liver fibrosis influenced by major changes of transaminases.J Viral Hepat. 2007 May; 14: 360-369Crossref PubMed Scopus (553) Google Scholar, 4Chan H.L.Y. Wong G.L.H. Choi P.C.L. et al.Alanina aminotransferase-based algorithms of liver stiffness measurement by transient elastography (Fibroscan) for liver fibrosis in chronic hepatitis B.J Vir Hepat. 2008; 16: 36-44Crossref PubMed Scopus (345) Google Scholar]. In order to analyze the accuracy of TE in CHB and NAFLD in comparison with CHC, we excluded “a priori” factors known to affect TE measurement: patients with acute liver disease, acute reactivation upon chronic liver damage, and alcohol abuse were not included in order to avoid the influence of acute necro-inflammatory edema on stiffness measurements. Amongst 219 enrolled patients only 2 (0.9%) had ALT higher than 300 IU/L (1 CHC and 1 CHB) and 4 (0.18%) higher than 250 IU/L (1 NAFLD, 1 CHC, 2 CHB). A stratification of patients for ALT levels was not available because the studied population was too homogeneous regarding aminotransferases. For these reasons, as already reported in the discussion section of our manuscript, we considered the influence of ALT on liver stiffness measurement as not significant enough in our cohort of patients.On the other hand, our clinical observations showed that in our patients, steatosis was a confounding factor for LSM. Compared with CHC, TE was less accurate in detecting severe fibrosis in NAFLD patients, especially in those with a high degree of steatosis. Fig. 4 of the paper represents the distribution of patients with NAFLD according to fibrosis and to percentage of steatosis at biopsy vs. LSM. If we analyze this figure in detail and regroup patients with advanced liver disease (severe fibrosis/cirrhosis), we can see that hepatic steatosis is associated with a lower LSM within the same fibrosis stage (F3–F4). Moreover, in NAFLD patients, the stepwise multiple logistic regression analysis showed that LSM was not an independent predictor of severe fibrosis or cirrhosis, suggesting that, in our opinion, TE is not able to completely replace liver biopsy for the detection of fibrosis in NAFLD.Different results reported by Wong and others from Oriental areas [5Yoneda M. Yoneda M. Mawatari H. et al.Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with nonalcoholic fatty liver disease (NAFLD).Dig Liver Dis. 2008; 40: 371-378Abstract Full Text Full Text PDF PubMed Scopus (336) Google Scholar, 6Wong V.W. Vergniol J. Wong G.L. et al.Diagnosis of fibrosis and cirrhosis using liver stiffness measurement in nonalcoholic fatty liver disease.Hepatology. 2010; 51: 454-462Crossref PubMed Scopus (892) Google Scholar] have to be interpreted while considering that the features of the metabolic syndrome and the clinical correlates are different from European ones. However, these different results support the concept that different steatosis features may have significant influences on LSM.In conclusion our work confirmed the reliability of Fibroscan for evaluating liver fibrosis in CHB or NAFLD patients, but it also describes some limitations to be taken into account in such categories of patients. Although the correlation between LSM and fibrosis stage was demonstrated, its sensibility and specificity were lower in CHB and NAFLD with respect to CHC patients. This work helps the physician to interpret, in a proper manner, Fibroscan results in CHB and NAFLD patients with possible liver steatosis or other confounding factors such as high BMI, elder age or high ALT values.Conflict of interestThe author declared she does not have anything to disclose regarding funding or conflict of interest with respect to this manuscript. To the Editor: I appreciate the letter by Dr. Wong and colleagues on our manuscript “Reliability of transient elastography for the detection of fibrosis in non-alcoholic fatty liver disease and chronic viral hepatitis” [[1]Gaia S. Carenzi S. Barilli A.L. et al.Reliability of transient elastography for the detection of fibrosis in non-alcoholic fatty liver disease and chronic viral hepatitis.J Hepatol. 2011; 54: 64-71Abstract Full Text Full Text PDF PubMed Scopus (196) Google Scholar] because it allows me to comment more about our results. The manuscript aimed to describe possible factors influencing the estimation of fibrosis by transient elastography (TE) in patients with chronic liver damage. As is well known, elevation in serum alanine aminotransferase (ALT) is a major confounding factor for liver stiffness measurements (LSM) [2Arena U. Vizzutti F. Corti G. et al.Acute viral hepatitis increases liver stiffness values measured by transient elastography.Hepatology. 2008 Feb; 47: 380-384Crossref PubMed Scopus (595) Google Scholar, 3Coco B. Oliveri F. Maina A.M. et al.Transient elastography: a new surrogate marker of liver fibrosis influenced by major changes of transaminases.J Viral Hepat. 2007 May; 14: 360-369Crossref PubMed Scopus (553) Google Scholar, 4Chan H.L.Y. Wong G.L.H. Choi P.C.L. et al.Alanina aminotransferase-based algorithms of liver stiffness measurement by transient elastography (Fibroscan) for liver fibrosis in chronic hepatitis B.J Vir Hepat. 2008; 16: 36-44Crossref PubMed Scopus (345) Google Scholar]. In order to analyze the accuracy of TE in CHB and NAFLD in comparison with CHC, we excluded “a priori” factors known to affect TE measurement: patients with acute liver disease, acute reactivation upon chronic liver damage, and alcohol abuse were not included in order to avoid the influence of acute necro-inflammatory edema on stiffness measurements. Amongst 219 enrolled patients only 2 (0.9%) had ALT higher than 300 IU/L (1 CHC and 1 CHB) and 4 (0.18%) higher than 250 IU/L (1 NAFLD, 1 CHC, 2 CHB). A stratification of patients for ALT levels was not available because the studied population was too homogeneous regarding aminotransferases. For these reasons, as already reported in the discussion section of our manuscript, we considered the influence of ALT on liver stiffness measurement as not significant enough in our cohort of patients. On the other hand, our clinical observations showed that in our patients, steatosis was a confounding factor for LSM. Compared with CHC, TE was less accurate in detecting severe fibrosis in NAFLD patients, especially in those with a high degree of steatosis. Fig. 4 of the paper represents the distribution of patients with NAFLD according to fibrosis and to percentage of steatosis at biopsy vs. LSM. If we analyze this figure in detail and regroup patients with advanced liver disease (severe fibrosis/cirrhosis), we can see that hepatic steatosis is associated with a lower LSM within the same fibrosis stage (F3–F4). Moreover, in NAFLD patients, the stepwise multiple logistic regression analysis showed that LSM was not an independent predictor of severe fibrosis or cirrhosis, suggesting that, in our opinion, TE is not able to completely replace liver biopsy for the detection of fibrosis in NAFLD. Different results reported by Wong and others from Oriental areas [5Yoneda M. Yoneda M. Mawatari H. et al.Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with nonalcoholic fatty liver disease (NAFLD).Dig Liver Dis. 2008; 40: 371-378Abstract Full Text Full Text PDF PubMed Scopus (336) Google Scholar, 6Wong V.W. Vergniol J. Wong G.L. et al.Diagnosis of fibrosis and cirrhosis using liver stiffness measurement in nonalcoholic fatty liver disease.Hepatology. 2010; 51: 454-462Crossref PubMed Scopus (892) Google Scholar] have to be interpreted while considering that the features of the metabolic syndrome and the clinical correlates are different from European ones. However, these different results support the concept that different steatosis features may have significant influences on LSM. In conclusion our work confirmed the reliability of Fibroscan for evaluating liver fibrosis in CHB or NAFLD patients, but it also describes some limitations to be taken into account in such categories of patients. Although the correlation between LSM and fibrosis stage was demonstrated, its sensibility and specificity were lower in CHB and NAFLD with respect to CHC patients. This work helps the physician to interpret, in a proper manner, Fibroscan results in CHB and NAFLD patients with possible liver steatosis or other confounding factors such as high BMI, elder age or high ALT values. Conflict of interestThe author declared she does not have anything to disclose regarding funding or conflict of interest with respect to this manuscript. The author declared she does not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.