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External Validation of P2/MS and Comparison with Other Simple Non-invasive Indices for Predicting Liver Fibrosis in HBV-Infected Patients

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Abstract

Background

To optimize management strategies and predict the long-term clinical course in patients with chronic hepatitis B (CHB), non-invasive tests to determine the degree of hepatic fibrosis have been developed.

Aims

We aimed to conduct a large-scale external validation of a simple, non-invasive test called P2/MS using CHB patients and to compare it to other non-invasive tests for the prediction of histological cirrhosis.

Methods

From 2006 to 2009, we enrolled a total of 521 consecutive CHB patients who underwent liver biopsy. Fibrosis stage was assessed according to the Metavir scoring system by a single pathologist who was unaware of the patients’ histories.

Results

For predictions of significant (p ≥ 2) and severe (p ≥ 3) fibrosis and cirrhosis (p = 4), the areas under the receiver operating characteristic curves were 0.801, 0.856, and 0.906, respectively. In predicting cirrhosis, we found that diagnostic values were comparable to age-spleen platelet ratio index (0.931, p = 0.063), spleen-platelet ratio index (0.923, p = 0.145), age-platelet index (0.914, p = 0.670), and FIB-4 (0.898. p = 0.597) and had better outcomes than the aspartate aminotransferase (AST)-platelet ratio index (0.780, p < 0.001), and AST-alanine aminotransferase ratio index (0.729, p < 0.001). The cut-off points of P2/MS >83 and P2/MS <30 provided 91.1% of negative predictive value and 91.3% of positive predictive value, respectively. Based on these results, liver biopsies could be avoided in 67.0% of the population. These cut-offs were validated internally using bootstrap resampling methods, which showed good agreement.

Conclusions

P2/MS is a simple, accurate, and inexpensive method with comparable outcomes to other non-invasive tests and may reduce the need for liver biopsy in the majority of CHB patients.

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References

  1. Lok AS, Mcmahon BJ. Chronic hepatitis B. Hepatology. 2007;45:507–539.

    Article  CAS  PubMed  Google Scholar 

  2. De Franchis R. Non-invasive (and minimally invasive) diagnosis of oesophageal varices. J Hepatol. 2008;49:520–527.

    Article  PubMed  Google Scholar 

  3. Spinzi G, Terruzzi V, Minoli G. Liver biopsy. N Engl J Med. 2001;344:2030.

    CAS  PubMed  Google Scholar 

  4. Poynard T, Halfon P, Castera L, et al. Variability of the area under the receiver operating characteristic curves in the diagnostic evaluation of liver fibrosis markers: impact of biopsy length and fragmentation. Aliment Pharmacol Ther. 2007;25:733–739.

    Article  CAS  PubMed  Google Scholar 

  5. Wai CT, Greenson JK, Fontana RJ, et al. A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C. Hepatology. 2003;38:518–526.

    Article  PubMed  Google Scholar 

  6. Forns X, Ampurdan SS, Llovet JM, et al. Identification of chronic hepatitis C patients without hepatic fibrosis by a simple predictive model. Hepatology. 2002;36:986–992.

    PubMed  Google Scholar 

  7. Imbert-Bismut F, Ratziu V, Pieroni L, et al. Biochemical markers of liver fibrosis in patients with hepatitis C virus infection: a prospective study. Lancet. 2001;357:1069–1075.

    Article  CAS  PubMed  Google Scholar 

  8. Han KH, Yoon KT. New diagnostic method for liver fibrosis and cirrhosis. Intervirology. 2008;51(1):11–16.

    Article  PubMed  Google Scholar 

  9. Lackner C, Struber G, Liegl B, et al. Comparison and validation of simple noninvasive tests for prediction of fibrosis in chronic hepatitis C. Hepatology. 2005;41:1376–1382.

    Article  PubMed  Google Scholar 

  10. Wai C, Cheng CL, Wee A, et al. Non-invasive models for predicting histology in patients with chronic hepatitis B. Liver Int. 2006;26:666–672.

    Article  PubMed  Google Scholar 

  11. Cast Ra L, Vergniol J, Foucher J, et al. Prospective comparison of transient elastography, FibroTest, APRI, and liver biopsy for the assessment of fibrosis in chronic hepatitis C. Gastroenterology. 2005;128:343–350.

    Article  Google Scholar 

  12. Friedrich-Rust M, Ong MF, Martens S, et al. Performance of transient elastography for the staging of liver fibrosis: a meta-analysis. Gastroenterology. 2008;134:960–974.

    Article  PubMed  Google Scholar 

  13. Ziol M, Handra-Luca A, Kettaneh A, et al. Noninvasive assessment of liver fibrosis by measurement of stiffness in patients with chronic hepatitis C. Hepatology. 2005;41:48–54.

    Article  PubMed  Google Scholar 

  14. Vallet-Pichard A, Mallet V, Nalpas B, et al. FIB-4: an inexpensive and accurate marker of fibrosis in HCV infection. Comparison with liver biopsy and FibroTest. Hepatology. 2007;46:32–36.

    Article  CAS  PubMed  Google Scholar 

  15. Cal SP, Oberti F, Michalak S, et al. A novel panel of blood markers to assess the degree of liver fibrosis. Hepatology. 2005;42:1373–1381.

    Article  Google Scholar 

  16. Lee JH, Yoon JH, Lee CH, et al. Complete blood count reflects the degree of oesophageal varices and liver fibrosis in virus-related chronic liver disease patients. J Viral Hepat. 2009;16:444–452.

    Article  PubMed  Google Scholar 

  17. Sheth SG, Flamm SL, Gordon FD, et al. AST/ALT ratio predicts cirrhosis in patients with chronic hepatitis C virus infection. Am J Gastroenterol. 1998;93:44–48.

    Article  CAS  PubMed  Google Scholar 

  18. Poynard T, Bedossa P. Age and platelet count: a simple index for predicting the presence of histological lesions in patients with antibodies to hepatitis C virus. METAVIR and CLINIVIR Cooperative Study Groups. J Viral Hepat. 1997;4:199–208.

    Article  CAS  PubMed  Google Scholar 

  19. Kim BK, Kim SA, Park YN, et al. Noninvasive models to predict liver cirrhosis in patients with chronic hepatitis B. Liver Int. 2007;27:969–976.

    Article  CAS  PubMed  Google Scholar 

  20. Vallet-Pichard A, Mallet V, Pol S. FIB-4: a simple, inexpensive and accurate marker of fibrosis in HCV-infected patients. Hepatology. 2006;44:769–770.

    Article  PubMed  Google Scholar 

  21. Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group. Hepatology. 1996;24:289–293.

    Article  CAS  PubMed  Google Scholar 

  22. Hanley JA, Mcneil BJ. A method of comparing the areas under receiver operating characteristic curves derived from the same cases. Radiology. 1983;148:839–843.

    CAS  PubMed  Google Scholar 

  23. Sterling RK, Lissen E, Clumeck N, et al. Development of a simple noninvasive index to predict significant fibrosis in patients with HIV/HCV coinfection. Hepatology. 2006;43:1317–1325.

    Article  CAS  PubMed  Google Scholar 

  24. Taylor-Robinson SD, Goldin RD, Hajnal JV, et al. The relationship of in vivo 31P MR spectroscopy to histology in chronic hepatitis C. Hepatology. 2003;37:788–794.

    Article  PubMed  CAS  Google Scholar 

  25. Chen D, Kao J, Chen J, et al. Noninvasive diagnosis of hepatic fibrosis in patients with chronic hepatitis C by splenic Doppler impedance index. Clin Gastroenterol Hepatol. 2007;5:1199–1206.e1.

    Article  PubMed  Google Scholar 

  26. Ehman RL, Fidler JL, Rossman PJ, et al. Assessment of hepatic fibrosis with magnetic resonance elastography. Clin Gastroenterol Hepatol. 2007;5:1207–1213.e2.

    Article  PubMed  Google Scholar 

  27. Chang PE, Lui HF, Chau YP, et al. Prospective evaluation of transient elastography for the diagnosis of hepatic fibrosis in Asians: comparison with liver biopsy and aspartate transaminase platelet ratio index. Aliment Pharmacol Ther. 2008;28:51–61.

    Article  CAS  PubMed  Google Scholar 

  28. Afdhal NH, Nunes D. Evaluation of liver fibrosis: a concise review. Am J Gastroenterol. 2004;99:1160–1174.

    Article  PubMed  Google Scholar 

  29. Giannini EG. Review article: thrombocytopenia in chronic liver disease and pharmacologic treatment options. Aliment Pharmacol Ther. 2006;23:1055–1065.

    Article  CAS  PubMed  Google Scholar 

  30. Cioni G, Tincani E, D’Alimonte P, et al. Relevance of reduced portal flow velocity, low platelet count and enlarged spleen diameter in the non-invasive diagnosis of compensated liver cirrhosis. Eur J Med. 1993;2:408–410.

    CAS  PubMed  Google Scholar 

  31. Wognum AW, Westerman Y, Visser TP, et al. Distribution of receptors for granulocyte-macrophage colony-stimulating factor on immature CD34 + bone marrow cells, differentiating monomyeloid progenitors, and mature blood cell subsets. Blood. 1994;84:764–774.

    CAS  PubMed  Google Scholar 

  32. Kubota A, Okamura S, Omori F, et al. High serum levels of granulocyte-macrophage colony-stimulating factor in patients with liver cirrhosis and granulocytopenia. Clin Lab Haematol. 1995;17:61–63.

    Article  CAS  PubMed  Google Scholar 

  33. Blackstone EH. Breaking down barriers: helpful breakthrough statistical methods you need to understand better. J Thorac Cardiovasc Surg. 2001;122:430–439.

    Article  CAS  PubMed  Google Scholar 

  34. Grunkemeier GL, Wu Y. Bootstrap resampling methods: something for nothing? Ann Thorac Surg. 2004;77:1142–1144.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The author thanks Eun Hee Choi, PhD (Department of Biostatistics, Yonsei University College of Medicine, Seoul, Republic of Korea) and Hae Ryoung Song, PhD (Department of Research Affairs, Yonsei University College of Medicine, Seoul, Republic of Korea) for critical comments on statistics. This study was supported by the Liver Cirrhosis Clinical Research Center, in part by a grant from the Brain Korea 21 Project for Medical Science, and by a grant from Ministry for Health, Welfare and Family Affairs, Republic of Korea (no. A050021).

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Correspondence to Do Young Kim.

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Kim, B.K., Han, K.H., Park, J.Y. et al. External Validation of P2/MS and Comparison with Other Simple Non-invasive Indices for Predicting Liver Fibrosis in HBV-Infected Patients. Dig Dis Sci 55, 2636–2643 (2010). https://doi.org/10.1007/s10620-009-1070-3

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