Alanine aminotransferase-based algorithms of liver stiffness measurement by transient elastography (Fibroscan) for liver fibrosis in chronic hepatitis B

The aim of this study is to know the liver stiffness measurement (LSM) cutoffs for different stages of liver fibrosis in chronic hepatitis B (CHB) and to investigate the effect of alanine aminotransferase (ALT) on LSM. We prospectively studied consecutive CHB patients undergoing liver biopsy and tra...

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Published inJournal of viral hepatitis Vol. 16; no. 1; pp. 36 - 44
Main Authors Chan, H. L.-Y., Wong, G. L.-H., Choi, P. C.-L., Chan, A. W.-H., Chim, A. M.-L., Yiu, K. K.-L., Chan, F. K.-L., Sung, J. J.-Y., Wong, V. W.-S.
Format Journal Article
LanguageEnglish
Published Oxford, UK Blackwell Publishing Ltd 01.01.2009
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Abstract The aim of this study is to know the liver stiffness measurement (LSM) cutoffs for different stages of liver fibrosis in chronic hepatitis B (CHB) and to investigate the effect of alanine aminotransferase (ALT) on LSM. We prospectively studied consecutive CHB patients undergoing liver biopsy and transient elastography examinations. Diagnostic performance of LSM for different degrees of liver fibrosis was evaluated. One hundred and sixty‐one CHB patients with adequate liver biopsy sample size were studied. Area under receiver operating characteristics curves of LSM for no fibrosis (F0 vs F1–4), bridging fibrosis (F0–2 vs F3–4) and liver cirrhosis (F0–3 vs F4) was 0.80 (95% CI: 0.68–0.92), 0.87 (95% CI: 0.82–0.93) and 0.93 (95% CI: 0.89–0.97) respectively. For liver cirrhosis, these optimal cutoff values were 8.4 kPa (98% sensitivity), 9.0 kPa (maximum sum of sensitivity and specificity), 13.4 kPa (94% specificity) and 13.4 kPa (maximum diagnostic accuracy, 85%) respectively. Patients with the same fibrosis staging but higher ALT levels tend to have higher LSM, and the diagnostic performance for low stage fibrosis was most seriously affected when ALT was elevated. Different LSM cutoff values and algorithms were derived for normal and elevated ALT levels. Based on these algorithms, liver biopsy can be avoided in 62% and 58% of patients with normal and elevated ALT respectively. In conclusion, transient elastography is a reasonable noninvasive tool to substitute liver biopsy among the lowest and highest risk patients for the assessment of liver fibrosis.
AbstractList The aim of this study is to know the liver stiffness measurement (LSM) cutoffs for different stages of liver fibrosis in chronic hepatitis B (CHB) and to investigate the effect of alanine aminotransferase (ALT) on LSM. We prospectively studied consecutive CHB patients undergoing liver biopsy and transient elastography examinations. Diagnostic performance of LSM for different degrees of liver fibrosis was evaluated. One hundred and sixty-one CHB patients with adequate liver biopsy sample size were studied. Area under receiver operating characteristics curves of LSM for no fibrosis (F0 vs F1-4), bridging fibrosis (F0-2 vs F3-4) and liver cirrhosis (F0-3 vs F4) was 0.80 (95% CI: 0.68-0.92), 0.87 (95% CI: 0.82-0.93) and 0.93 (95% CI: 0.89-0.97) respectively. For liver cirrhosis, these optimal cutoff values were 8.4 kPa (98% sensitivity), 9.0 kPa (maximum sum of sensitivity and specificity), 13.4 kPa (94% specificity) and 13.4 kPa (maximum diagnostic accuracy, 85%) respectively. Patients with the same fibrosis staging but higher ALT levels tend to have higher LSM, and the diagnostic performance for low stage fibrosis was most seriously affected when ALT was elevated. Different LSM cutoff values and algorithms were derived for normal and elevated ALT levels. Based on these algorithms, liver biopsy can be avoided in 62% and 58% of patients with normal and elevated ALT respectively. In conclusion, transient elastography is a reasonable noninvasive tool to substitute liver biopsy among the lowest and highest risk patients for the assessment of liver fibrosis.The aim of this study is to know the liver stiffness measurement (LSM) cutoffs for different stages of liver fibrosis in chronic hepatitis B (CHB) and to investigate the effect of alanine aminotransferase (ALT) on LSM. We prospectively studied consecutive CHB patients undergoing liver biopsy and transient elastography examinations. Diagnostic performance of LSM for different degrees of liver fibrosis was evaluated. One hundred and sixty-one CHB patients with adequate liver biopsy sample size were studied. Area under receiver operating characteristics curves of LSM for no fibrosis (F0 vs F1-4), bridging fibrosis (F0-2 vs F3-4) and liver cirrhosis (F0-3 vs F4) was 0.80 (95% CI: 0.68-0.92), 0.87 (95% CI: 0.82-0.93) and 0.93 (95% CI: 0.89-0.97) respectively. For liver cirrhosis, these optimal cutoff values were 8.4 kPa (98% sensitivity), 9.0 kPa (maximum sum of sensitivity and specificity), 13.4 kPa (94% specificity) and 13.4 kPa (maximum diagnostic accuracy, 85%) respectively. Patients with the same fibrosis staging but higher ALT levels tend to have higher LSM, and the diagnostic performance for low stage fibrosis was most seriously affected when ALT was elevated. Different LSM cutoff values and algorithms were derived for normal and elevated ALT levels. Based on these algorithms, liver biopsy can be avoided in 62% and 58% of patients with normal and elevated ALT respectively. In conclusion, transient elastography is a reasonable noninvasive tool to substitute liver biopsy among the lowest and highest risk patients for the assessment of liver fibrosis.
The aim of this study is to know the liver stiffness measurement (LSM) cutoffs for different stages of liver fibrosis in chronic hepatitis B (CHB) and to investigate the effect of alanine aminotransferase (ALT) on LSM. We prospectively studied consecutive CHB patients undergoing liver biopsy and transient elastography examinations. Diagnostic performance of LSM for different degrees of liver fibrosis was evaluated. One hundred and sixty-one CHB patients with adequate liver biopsy sample size were studied. Area under receiver operating characteristics curves of LSM for no fibrosis (F0 vs F1-4), bridging fibrosis (F0-2 vs F3-4) and liver cirrhosis (F0-3 vs F4) was 0.80 (95% CI: 0.68-0.92), 0.87 (95% CI: 0.82-0.93) and 0.93 (95% CI: 0.89-0.97) respectively. For liver cirrhosis, these optimal cutoff values were 8.4 kPa (98% sensitivity), 9.0 kPa (maximum sum of sensitivity and specificity), 13.4 kPa (94% specificity) and 13.4 kPa (maximum diagnostic accuracy, 85%) respectively. Patients with the same fibrosis staging but higher ALT levels tend to have higher LSM, and the diagnostic performance for low stage fibrosis was most seriously affected when ALT was elevated. Different LSM cutoff values and algorithms were derived for normal and elevated ALT levels. Based on these algorithms, liver biopsy can be avoided in 62% and 58% of patients with normal and elevated ALT respectively. In conclusion, transient elastography is a reasonable noninvasive tool to substitute liver biopsy among the lowest and highest risk patients for the assessment of liver fibrosis.
The aim of this study is to know the liver stiffness measurement (LSM) cutoffs for different stages of liver fibrosis in chronic hepatitis B (CHB) and to investigate the effect of alanine aminotransferase (ALT) on LSM. We prospectively studied consecutive CHB patients undergoing liver biopsy and transient elastography examinations. Diagnostic performance of LSM for different degrees of liver fibrosis was evaluated. One hundred and sixty-one CHB patients with adequate liver biopsy sample size were studied. Area under receiver operating characteristics curves of LSM for no fibrosis (F0 vs F1-4), bridging fibrosis (F0-2 vs F3-4) and liver cirrhosis (F0-3 vs F4) was 0.80 (95% CI: 0.68-0.92), 0.87 (95% CI: 0.82-0.93) and 0.93 (95% CI: 0.89-0.97) respectively. For liver cirrhosis, these optimal cutoff values were 8.4kPa (98% sensitivity), 9.0kPa (maximum sum of sensitivity and specificity), 13.4kPa (94% specificity) and 13.4kPa (maximum diagnostic accuracy, 85%) respectively. Patients with the same fibrosis staging but higher ALT levels tend to have higher LSM, and the diagnostic performance for low stage fibrosis was most seriously affected when ALT was elevated. Different LSM cutoff values and algorithms were derived for normal and elevated ALT levels. Based on these algorithms, liver biopsy can be avoided in 62% and 58% of patients with normal and elevated ALT respectively. In conclusion, transient elastography is a reasonable noninvasive tool to substitute liver biopsy among the lowest and highest risk patients for the assessment of liver fibrosis.
The aim of this study is to know the liver stiffness measurement (LSM) cutoffs for different stages of liver fibrosis in chronic hepatitis B (CHB) and to investigate the effect of alanine aminotransferase (ALT) on LSM. We prospectively studied consecutive CHB patients undergoing liver biopsy and transient elastography examinations. Diagnostic performance of LSM for different degrees of liver fibrosis was evaluated. One hundred and sixty‐one CHB patients with adequate liver biopsy sample size were studied. Area under receiver operating characteristics curves of LSM for no fibrosis (F0 vs F1–4), bridging fibrosis (F0–2 vs F3–4) and liver cirrhosis (F0–3 vs F4) was 0.80 (95% CI: 0.68–0.92), 0.87 (95% CI: 0.82–0.93) and 0.93 (95% CI: 0.89–0.97) respectively. For liver cirrhosis, these optimal cutoff values were 8.4 kPa (98% sensitivity), 9.0 kPa (maximum sum of sensitivity and specificity), 13.4 kPa (94% specificity) and 13.4 kPa (maximum diagnostic accuracy, 85%) respectively. Patients with the same fibrosis staging but higher ALT levels tend to have higher LSM, and the diagnostic performance for low stage fibrosis was most seriously affected when ALT was elevated. Different LSM cutoff values and algorithms were derived for normal and elevated ALT levels. Based on these algorithms, liver biopsy can be avoided in 62% and 58% of patients with normal and elevated ALT respectively. In conclusion, transient elastography is a reasonable noninvasive tool to substitute liver biopsy among the lowest and highest risk patients for the assessment of liver fibrosis.
Author Choi, P. C.-L.
Chan, F. K.-L.
Chim, A. M.-L.
Chan, A. W.-H.
Chan, H. L.-Y.
Sung, J. J.-Y.
Wong, G. L.-H.
Wong, V. W.-S.
Yiu, K. K.-L.
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  surname: Chan
  fullname: Chan, H. L.-Y.
  organization: Institute of Digestive Disease
– sequence: 2
  givenname: G. L.-H.
  surname: Wong
  fullname: Wong, G. L.-H.
  organization: Institute of Digestive Disease
– sequence: 3
  givenname: P. C.-L.
  surname: Choi
  fullname: Choi, P. C.-L.
  organization: Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, China
– sequence: 4
  givenname: A. W.-H.
  surname: Chan
  fullname: Chan, A. W.-H.
  organization: Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong, China
– sequence: 5
  givenname: A. M.-L.
  surname: Chim
  fullname: Chim, A. M.-L.
  organization: Institute of Digestive Disease
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  givenname: K. K.-L.
  surname: Yiu
  fullname: Yiu, K. K.-L.
  organization: Institute of Digestive Disease
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  givenname: F. K.-L.
  surname: Chan
  fullname: Chan, F. K.-L.
  organization: Institute of Digestive Disease
– sequence: 8
  givenname: J. J.-Y.
  surname: Sung
  fullname: Sung, J. J.-Y.
  organization: Institute of Digestive Disease
– sequence: 9
  givenname: V. W.-S.
  surname: Wong
  fullname: Wong, V. W.-S.
  organization: Institute of Digestive Disease
BackLink https://www.ncbi.nlm.nih.gov/pubmed/18673426$$D View this record in MEDLINE/PubMed
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References Marcellin P, De Ledinghen B, Dhumeaux D et al. Non-invasive assessment of liver fibrosis in chronic hepatitis B using Fibroscan. Hepatology 2005; 42 (Suppl. 1): 715A-716A.
Sandrin L, Fourquet B, Hasquenoph JM et al. Transient elastography: a new noninvasive method for assessment of hepatic fibrosis. Ultrasound Med Biol 2003; 29: 1705-1713.
Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology 2007; 45: 507-539.
Sagir A, Erhardt A, Schmitt M et al. Transient elastography is unreliable for detection of cirrhosis in patients with acute liver damage. Hepatology 2008; 47: 592-595.
Chan HL, Tse CH, Mo F et al. High viral load and hepatitis B virus subgenotype ce are associated with increased risk of hepatocellular carcinoma. J Clin Oncol 2008; 26: 177-182.
Chan HL, Chui AK, Lau WY et al. Factors associated with viral breakthrough in lamivudine monoprophylaxis of hepatitis B virus recurrence after liver transplantation. J Med Virol 2002; 68: 182-187.
Hui AY, Chan HL, Wong VW et al. Identification of chronic hepatitis B patients without significant liver fibrosis by a simple noninvasive predictive model. Am J Gastroenterol 2005; 100: 616-623.
Bravo AA, Sheth SG, Chopra S. Liver biopsy. N Engl J Med 2001; 344: 495-500.
Foucher J, Chanteloup E, Vergniol J et al. Diagnosis of cirrhosis by transient elastography (Fibroscan): a prospective study. Gut 2006; 55: 403-408.
Talwalkar JA, Kurtz DM, Schoenleber SJ et al. Ultrasound-based treatment transient elastography for the detection of hepatic fibrosis: systemic review and meta-analysis. Clin Gastroenterol Hepatol 2007; 5: 1214-1220.
Poynard T, Zoulim F, Ratziu V et al. Longitudinal assessment of histology surrogate markers (FibroTest-ActiTest) during lamivudine therapy in patients with chronic hepatitis B infection. Am J Gastroenterol 2005; 100: 1970-1980.
Castera L, Negre I, Samii K et al. Pain experienced during percutaneous liver biopsy. Hepatology 1999; 30: 1529-1530.
Afdhal NH, Curry M. Technology evaluation: a critical step in the clinical utilization of novel diagnostic tests for liver fibrosis. J Hepatol 2007; 46: 543-545.
Bedossa P, Dargère D, Paradise V. Sampling variability of liver fibrosis in chronic hepatitis C. Hepatology 2003; 38: 1449-1457.
Chen CJ, Yang HI, Su J et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA 2006; 295: 65-73.
Sebastiani G, Vario A, Guido M, Alberti A. Sequential algorithms combining non-invasive markers and biopsy for the assessment of liver fibrosis in chronic hepatitis B. World J Gastroenterol 2007; 13: 525-531.
Arena U, Vizzutti F, Corti G et al. Acute viral hepatitis increases liver stiffness values measured by transient elastography. Hepatology 2008; 47: 380-384.
Coco B, Oliveri F, Maina AM et al. Transient elastography: a new surrogate marker of liver fibrosis influenced by major changes of transaminases. J Viral Hepat 2007; 14: 360-369.
Liaw YF, Leung N, Guan R et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2005 update. Liver Int 2005; 25: 472-489.
Wong GL, Wong VW, Choi PC et al. Assessment of fibrosis by transient elastography compared with liver biopsy and morphometry in chronic liver diseases. Clin Gastroenterol Hepatol 2008, Epub ahead of print.
Bedossa P, Poynard T. An algorithm for grading of activity in chronic hepatitis C. Hepatology 1996; 24: 289-293.
Poon TC, Hui AY, Chan HL et al. Prediction of liver fibrosis and cirrhosis in chronic hepatitis B infection by serum proteomic fingerprinting - a pilot study. Clin Chem 2005; 51: 328-335.
Fraquelli M, Rigamonti C, Casazza G et al. Reproducibility of transient elastography in the evaluation of liver fibrosis in patients with chronic liver disease. Gut 2007; 56: 968-973.
Ganne-Carrié N, Ziol M, De Ledinghen V et al. Accuracy of liver stiffness measurement for the diagnosis of cirrhosis in patients with chronic liver diseases. Hepatology 2006; 44: 1511-1517.
DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a non-parametric approach. Biometrics 1988; 44: 837-845.
Liaw YF, Sung JJ, Chow WC et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med 2004; 351: 1521-1531.
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References_xml – reference: Ganne-Carrié N, Ziol M, De Ledinghen V et al. Accuracy of liver stiffness measurement for the diagnosis of cirrhosis in patients with chronic liver diseases. Hepatology 2006; 44: 1511-1517.
– reference: Talwalkar JA, Kurtz DM, Schoenleber SJ et al. Ultrasound-based treatment transient elastography for the detection of hepatic fibrosis: systemic review and meta-analysis. Clin Gastroenterol Hepatol 2007; 5: 1214-1220.
– reference: Arena U, Vizzutti F, Corti G et al. Acute viral hepatitis increases liver stiffness values measured by transient elastography. Hepatology 2008; 47: 380-384.
– reference: Sagir A, Erhardt A, Schmitt M et al. Transient elastography is unreliable for detection of cirrhosis in patients with acute liver damage. Hepatology 2008; 47: 592-595.
– reference: Chan HL, Chui AK, Lau WY et al. Factors associated with viral breakthrough in lamivudine monoprophylaxis of hepatitis B virus recurrence after liver transplantation. J Med Virol 2002; 68: 182-187.
– reference: Afdhal NH, Curry M. Technology evaluation: a critical step in the clinical utilization of novel diagnostic tests for liver fibrosis. J Hepatol 2007; 46: 543-545.
– reference: Lok AS, McMahon BJ. Chronic hepatitis B. Hepatology 2007; 45: 507-539.
– reference: Castera L, Negre I, Samii K et al. Pain experienced during percutaneous liver biopsy. Hepatology 1999; 30: 1529-1530.
– reference: Sebastiani G, Vario A, Guido M, Alberti A. Sequential algorithms combining non-invasive markers and biopsy for the assessment of liver fibrosis in chronic hepatitis B. World J Gastroenterol 2007; 13: 525-531.
– reference: Sandrin L, Fourquet B, Hasquenoph JM et al. Transient elastography: a new noninvasive method for assessment of hepatic fibrosis. Ultrasound Med Biol 2003; 29: 1705-1713.
– reference: Hui AY, Chan HL, Wong VW et al. Identification of chronic hepatitis B patients without significant liver fibrosis by a simple noninvasive predictive model. Am J Gastroenterol 2005; 100: 616-623.
– reference: Liaw YF, Sung JJ, Chow WC et al. Lamivudine for patients with chronic hepatitis B and advanced liver disease. N Engl J Med 2004; 351: 1521-1531.
– reference: Wong GL, Wong VW, Choi PC et al. Assessment of fibrosis by transient elastography compared with liver biopsy and morphometry in chronic liver diseases. Clin Gastroenterol Hepatol 2008, Epub ahead of print.
– reference: Chen CJ, Yang HI, Su J et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA 2006; 295: 65-73.
– reference: DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a non-parametric approach. Biometrics 1988; 44: 837-845.
– reference: Bedossa P, Dargère D, Paradise V. Sampling variability of liver fibrosis in chronic hepatitis C. Hepatology 2003; 38: 1449-1457.
– reference: Bravo AA, Sheth SG, Chopra S. Liver biopsy. N Engl J Med 2001; 344: 495-500.
– reference: Poynard T, Zoulim F, Ratziu V et al. Longitudinal assessment of histology surrogate markers (FibroTest-ActiTest) during lamivudine therapy in patients with chronic hepatitis B infection. Am J Gastroenterol 2005; 100: 1970-1980.
– reference: Marcellin P, De Ledinghen B, Dhumeaux D et al. Non-invasive assessment of liver fibrosis in chronic hepatitis B using Fibroscan. Hepatology 2005; 42 (Suppl. 1): 715A-716A.
– reference: Coco B, Oliveri F, Maina AM et al. Transient elastography: a new surrogate marker of liver fibrosis influenced by major changes of transaminases. J Viral Hepat 2007; 14: 360-369.
– reference: Poon TC, Hui AY, Chan HL et al. Prediction of liver fibrosis and cirrhosis in chronic hepatitis B infection by serum proteomic fingerprinting - a pilot study. Clin Chem 2005; 51: 328-335.
– reference: Chan HL, Tse CH, Mo F et al. High viral load and hepatitis B virus subgenotype ce are associated with increased risk of hepatocellular carcinoma. J Clin Oncol 2008; 26: 177-182.
– reference: Fraquelli M, Rigamonti C, Casazza G et al. Reproducibility of transient elastography in the evaluation of liver fibrosis in patients with chronic liver disease. Gut 2007; 56: 968-973.
– reference: Liaw YF, Leung N, Guan R et al. Asian-Pacific consensus statement on the management of chronic hepatitis B: a 2005 update. Liver Int 2005; 25: 472-489.
– reference: Foucher J, Chanteloup E, Vergniol J et al. Diagnosis of cirrhosis by transient elastography (Fibroscan): a prospective study. Gut 2006; 55: 403-408.
– reference: Bedossa P, Poynard T. An algorithm for grading of activity in chronic hepatitis C. Hepatology 1996; 24: 289-293.
– volume: 44
  start-page: 837
  year: 1988
  end-page: 845
  article-title: Comparing the areas under two or more correlated receiver operating characteristic curves: a non‐parametric approach
  publication-title: Biometrics
– volume: 51
  start-page: 328
  year: 2005
  end-page: 335
  article-title: Prediction of liver fibrosis and cirrhosis in chronic hepatitis B infection by serum proteomic fingerprinting – a pilot study
  publication-title: Clin Chem
– volume: 100
  start-page: 1970
  year: 2005
  end-page: 1980
  article-title: Longitudinal assessment of histology surrogate markers (FibroTest–ActiTest) during lamivudine therapy in patients with chronic hepatitis B infection
  publication-title: Am J Gastroenterol
– volume: 47
  start-page: 380
  year: 2008
  end-page: 384
  article-title: Acute viral hepatitis increases liver stiffness values measured by transient elastography
  publication-title: Hepatology
– volume: 24
  start-page: 289
  year: 1996
  end-page: 293
  article-title: An algorithm for grading of activity in chronic hepatitis C
  publication-title: Hepatology
– volume: 46
  start-page: 543
  year: 2007
  end-page: 545
  article-title: Technology evaluation: a critical step in the clinical utilization of novel diagnostic tests for liver fibrosis
  publication-title: J Hepatol
– volume: 42
  start-page: 715A
  issue: Suppl. 1
  year: 2005
  end-page: 716A
  article-title: Non‐invasive assessment of liver fibrosis in chronic hepatitis B using Fibroscan
  publication-title: Hepatology
– volume: 45
  start-page: 507
  year: 2007
  end-page: 539
  article-title: Chronic hepatitis B
  publication-title: Hepatology
– volume: 55
  start-page: 403
  year: 2006
  end-page: 408
  article-title: Diagnosis of cirrhosis by transient elastography (Fibroscan): a prospective study
  publication-title: Gut
– volume: 30
  start-page: 1529
  year: 1999
  end-page: 1530
  article-title: Pain experienced during percutaneous liver biopsy
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Snippet The aim of this study is to know the liver stiffness measurement (LSM) cutoffs for different stages of liver fibrosis in chronic hepatitis B (CHB) and to...
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SubjectTerms Adult
Alanine Transaminase - blood
Elasticity Imaging Techniques
Female
hepatitis B virus
Hepatitis B, Chronic - pathology
histology
Humans
Liver - pathology
liver biopsy
liver cirrhosis
Liver Cirrhosis - diagnosis
Male
Middle Aged
Retrospective Studies
ROC Curve
Severity of Illness Index
Title Alanine aminotransferase-based algorithms of liver stiffness measurement by transient elastography (Fibroscan) for liver fibrosis in chronic hepatitis B
URI https://api.istex.fr/ark:/67375/WNG-013P1K6S-J/fulltext.pdf
https://onlinelibrary.wiley.com/doi/abs/10.1111%2Fj.1365-2893.2008.01037.x
https://www.ncbi.nlm.nih.gov/pubmed/18673426
https://www.proquest.com/docview/20274715
https://www.proquest.com/docview/66891196
Volume 16
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