Is transient elastography inaccurate in chronic hepatitis B and non-alcoholic fatty liver disease? (2011)

Reliability of transient elastography for the detection of fibrosis in Non-Alcoholic Fatty Liver Disease and chronic viral hepatitisJournal of HepatologyVol. 54Issue 1PreviewTransient elastography (TE) is validated in chronic hepatitis C (CHC) to evaluate hepatic fibrosis; however, limited data are available in chronic hepatitis B (CHB) and Non-Alcoholic Fatty Liver Disease (NAFLD). This prospective study is aimed to assess the accuracy and the efficacy of TE for the detection of fibrosis in patients with chronic liver disease of different etiology and to evaluate the effect of steatosis on the liver stiffness measurement (LSM). Full-Text PDF Reply to: “Is transient elastography inaccurate in chronic hepatitis B and non-alcoholic fatty liver disease?”Journal of HepatologyVol. 55Issue 2PreviewTo the Editor: Full-Text PDF Open Access We 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]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 (199) Google Scholar]. 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. We believe that these observations should be interpreted carefully. Based on the previous validation studies of larger sample sizes, serum alanine aminotransferase (ALT) level is one of the major confounding factors of LSM [2Wong G.L. Wong V.W. Choi P.C. et al.Assessment of fibrosis by transient elastography compared with liver biopsy and morphometry in chronic liver diseases.Clin Gastroenterol Hepatol. 2008; 6: 1027-1035Abstract Full Text Full Text PDF PubMed Scopus (127) Google Scholar, 3Chan H.L. Wong G.L. Choi P.C. et al.Alanine aminotransferase-based algorithms of liver stiffness measurement by transient elastography (Fibroscan) for liver fibrosis in chronic hepatitis B.J Viral Hepat. 2009; 16: 36-44Crossref PubMed Scopus (347) Google Scholar]. Patients with high ALT will have increased LSM independent of the fibrosis stage, and LSM might be deceivingly high to even a cirrhotic range in patients of severe acute exacerbation of CHB [[4]Wong G.L. Wong V.W. Choi P.C. et al.Increased liver stiffness measurement by transient elastography in severe acute exacerbation of chronic hepatitis B.J Gastroenterol Hepatol. 2009; 24: 1002-1007Crossref PubMed Scopus (96) Google Scholar]. Therefore, LSM should be interpreted in the context of ALT level. In the current study, the median ALT level was 70 IU/L among 70 CHB patients, and it was as high as 464 IU/L in one patient. If patients with F3 fibrosis have higher ALT levels than those with F4 fibrosis, the LSM might have been misinterpreted. To prove the accuracy of LSM, the influence of ALT should be taken into consideration. One could present the box plots of LSM versus Metavir fibrosis stage in CHB patients after stratifying into normal ALT, ALT 1-5x upper limit of normal (ULN) and ALT >5× ULN. Contrary to previous reports on NAFLD and chronic hepatitis C, the authors observed an underestimation of LSM in patients with steatosis >33% [[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 (199) Google Scholar]. However, it was based on an over-simplified statistical analysis, because the real relationship between steatosis and LSM could not be demonstrated by mean LSM values only. Instead, upon detailed assessment of the effect of steatosis on LSM in patients with different fibrosis stages (Fig. 4 in the paper), there was no evidence that hepatic steatosis was associated with lower LSM in patients within the same fibrosis stage [[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 (199) Google Scholar]. In our previous study including 246 NAFLD patients, the mean LSM for F0, F1, F2, F3, and F4 fibrosis was 5.7, 6.8, 7.8, 11.8, and 25.1 kPa, respectively [[5]Wong 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 (903) Google Scholar]. Again, the groups with higher hepatic steatosis did not have lower LSM (Fig. 1). Grace L.H. Wong has served as a speaker for Echosens. Vincent W.S. Wong has served as a speaker for Roche, Novartis Pharmaceuticals and Abbott Diagnostic. Henry L.Y. Chan has served as an advisory board member for Bristol-Myers Squibb, F. Hoffmann La Roche, Novartis Pharmaceutical and Abbott Diagnostic.