To Evaluate Efficacy of Non-Invasive Markers of Fibrosis in Determining Liver Fibrosis vis-à-vis Liver Biopsy, in Patients of Nonalcoholic Fatty Liver Disease

  • Dr. Parveen Malhotra, Malhotra V, Malhotra N, Dahiya H, Jeetender, Chugh A

Abstract

Background & Purpose: Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease & liver transplantation and its incidence is increasing even in Asian countries. The gold standard for
assessing hepatic fibrosis is liver histology but due to its limitations, noninvasive tests to assess hepatic fibrosis which can be used as alternative to liver biopsy have been developed, such the AST-to-platelet ratio
index (APRI), Forns test, FibroTest, transient elastography, fibrometer and hepascore.
Methods: In a cross-sectional study, 25 diagnosed NAFLD patients underwent detailed laboratory investigations including the specific non-invasive markers of fibrosis namely, haptoglobin, alpha-2 macroglobulin,
apolipoprotein- A1 levels and insulin resistance was calculated by homoeostasis model assessment (HOMA), then patients were subjected to liver biopsy.
Results. Out of 25 patients, 19(76%) were male and 6(24%) were females. Nine patients (36%) were diabetic and 21 (84%) were dyslipidaemic. Metabolic syndrome was present in 18(72%), body mass index was increased
in 22 patients and waist hip ratio was altered in 22 patients (88%). Using SPSS 10, p value was significant (p = 0.04) for correlation between steatosis and waist/hip ratio and HOMA-IR with inflammation and
fibrosis (p = 0.03) but non-invasive markers were not significant in predicting hepatic fibrosis on histology.
Conclusion. The non-invasive markers were not significant in predicting hepatic fibrosis on histology in present study. The limitation of the study was small sample size and majority of patients had steatosis only.

References

1. Liver disease. NASH and related disorders. Blackwell Publishing Oxford (U.K.) 2005: 23-37.
2. Ludwig J, Uiggiano T, McGill DB. Non-alcoholic steatohepatitis. Mayo Clinic experiences with a hither to unnamed disease. Mayo Clin Proc 1980; 55: 434-8.
3. Falck YY, Yornoss ZM, Marchesini G. clinical features and natural history of nonalcoholic steatosis syndrome. Semin Liver Dis 2001; 21: 17-26.
4. Matteoni CA, Youno ZM, Glremr T. Non alcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology 1999; 116: 1413-9.
5. McCullough AJ. Pathophysiology of nonalcoholic hepatitis. J Clin Gastroenterol 2005; 39: 1-13.
6. Duseja A, Nanda M, Das A, Das R, Bhansali A, Chawla Y. Recurrence of obesity, diabetes mellitus and hyperlipidemia in patient’s with cryptogenic liver cirrhosis. Trop Gastroenterol 2004; 25: 15-7.
7. Duseja A, Muralijhar R, Bhansali A, Sharma S, Das A, Das R, et al. Assessment of insulin resistance and effect of metformin in nonalcoholic steatohepatitis – a preliminary report. Indian J Gastroenterol 2004; 23: 12-5.
8. Brown JD, Szczepaniak LS, Dobbins R. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 2004; 30: 1387- 95.
9. Hui JM, Kench JG, Chittuli S. Survival, liver failure and hepatocellular carcinoma in obesity related cryptogenic cirrhosis. Hepatology 2002; 35: 1485-93.
10. Pratzivu N, Banhay L, DiMartino V. Cryptogenic cirrhosis: clinical characterization and risk factors for underlying liver disease. Hepatology 1999; 32: 689- 692.
11. Caldwell SH, Gelgnee DH, Jezzoni JC. Cryptogenic cirrhosis: clinical characterization and risk factors for underlying disease. Hepatology 1999; 32: 689-92.
12. Caldwell SV, Hespenhire EE. Subacute liver failure in obese women. Am J Gastroenterology 2002; 97: 2058- 67.
13. Bugiones E, Leone A, Vanni E. Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular cancer. Gastroenterology 2002; 123: 134-40.
14. Ong J, Younossi ZM, Reddy V. Cryptogenic cirrhosis and post transplantation non alcoholic fatty liver disease. Liver Transplant 2001; 707-801.
15. Harisson SA, Torgerson S, Hayashi PH. The natural history of nonalcoholic fatty liver disease: a clinical histopathological study. Am J Gastroenterol 2003; 98: 2024-49.
16. Teli MR, James OFW, Burt AD. The natural history of nonalcoholic fatty liver: a follow up study. Hepatology 1995; 22: 1714-9.
17. Dom LS, Franzman M, Anderson IB. Long term roghosis of fatty liver disease and death. Gut 2002; 53: 750-55.
18. Flegal KM, Calore MD, Ogden CL. Prevalence and trends in obesity among US adults. 1999-2000.
19. Edmisson J, McCullough AJ. Pathogenesis of nonalcoholic steatohepatitis: human data. Clin Liv Dis 2007; 11(1).
20. Kahn CR. Insulin resistance, insulin sensitivity and insulin unresponsiveness: a necessary distinction. Metabolism 1978; 27: 1893-1902.
21. Pham T, Cornea A, Brick KE, Jenkins A, Scofiees RHMD. Oral glucosamine in doses uses to treat osteoarthritis insulin resistance. Am J Med Sci 2007; 333(6): 33-9.
22. Neuschwander TBA, Caldwell SH. Non alcoholic steatohepatitis: summary of an AASLD single topic conference. Hepatology 2003; 37: 1202-19.
23. Chitturi S, Farrell GC, Hashimoto E. Nonalcoholic fatty liver disease in the Asia – Pacific region: definitions and overview of proposed guidelines. J Gastroenterol Hepatol 2007; 22: 778-87.
24. Saadeh S, Younoss ZM, Remer EM. The utility of radiological imaging in non alcoholic fatty liver disease. Gastroenterology 2002; 123: 745-50.
25. Sanyal AJ. AGA technical review on nonalcoholic fatty liver disease. Gastroenterology 2002; 123: 1205-25.
26. James CH, Lindol KD. Outcome of patients admitted with complications after outpatient liver biopsies. Ann Intern Med 1993; 118: 96-8.
27. Regev A, Beerno M, Jeffees LJ. Sampling error and intraobserver variation in liver biopsy in patients with chronic HCU infection. A J Gastroenterol 2002; 99: 2614-8.
28. Renou C, Muller P, Jouve E. Relevance of moderate isolated thrombocytopenia as a strong predictive marker of cirrhosis in patients with chronic hepatitis C. Am J Gastroenterol 2001; 96: 1657-9.
29. Poynard T, Inbert BF, Munteanu M. Overview of diagnostic value of biochemical markers of liver fibrosis and necrosis in patients with chronic hepatitis C. Hepatol 2004;3:8.
30. Forns X, Ampurdanes S, Llovet JM, et al. Identification of chronic hepatitis C patients without hepatic fibrosis by a simple predictive model. Hepatology 2002; 36:986-92
31. Rosenberg WM, Voelker M, Theil R, and et al. Serum markers detect the presence of liver fibrosis: a cohort study. Gastroenterology 2004; 127:1704-13
32. Adams LA, Bulsara M, and Rossi E, et al. Hepascore: an accurate validated predictor of liver fibrosis in chronic hepatitis C infection. Clin Chem 2005; 51:1867-73)
33. Cales P, Oberti F, Michalak S, et al. A novel panel of blood markers to assess the degree of liver fibrosis. Hepatology 2005; 42:1373
34. Westwater J, Fainer D. Liver impairment in the obese. Gastroenterology 1958; 34:686-93.
35. Uygun A, Kadayifci A, Isik AT, et al. Metformin in the treatment of patients with non-alcoholic steatohepatitis. Aliment Pharmacol Ther.2004; 19:537-44
36. Arun J, Clements RH, Lazenby AJ, Leeth RR, Abrams GA. The prevalence of nonalcoholic steatohepatitis is greater in morbidly obese men compared to women. Obes Surg.2006; 16:1351-1358
37. Madan K, Batra Y, Gupta SD, et al. Nonalcoholic fatty liver disease may not be a severe disease at presentation among Asian Indians. World J Gastroenterol 2006; 12: 3400-5
38. Ioannov GN, Weiss NS, Kowdley KV, et al. is obesity a risk for cirrhosis-related death or hospitalization? A population based cohort study. Gastroenterology 2003:125(4): 1053-9
39. Sabir N, Semez Y, Kazil S, et al. Correlation of abdominal fat accumulation and liver steatosis: importance of ultrasonographic and anthropometric measurements. Eur J Ultrasound 2001:14(2-3):121-8
40. Expert panel on Detection Evaluation and Treatment of high blood cholestrol in adults. Executive summary of third report of the National Cholestrol Education Program (NCEP), expert panel on detection, evaluation
and treatment of high blood cholestrol in adults (Adult Treatment Panel 111). JAMA2001; 285(19): 2486-97
41. Carr DB, Utzschneider KM, Hull RL, et al. Intra ab- dominal fat is a major determinant of the insulin resistance. National Cholestrol Education Program Adult Treatment Panel 111 criterion for the metabolic syndrome. Diabetes 2004; 53 (8): 2087-94
42. Duseja A, Nanda M, Das A, Das R, Bhansali A, Chawla Y. Prevalence of, diabetes mellitus and hyperlipidemia in patients with cryptogenic liver cirrhosis. Trop Gastroenterol. 2004; 25:52-58
43. Assy N, Kaita K, Mymin D, et al. Fatty infiltration of liver in hyper lipidemia patients. Dig Dis Sci 2004; 45(10): 1929-34
44. Bellentani S, Saccoccio G, Masutti F, Croce S, Brandi G, Sasso F, et al. Prevalence of and risk factors for hepatic steatosis in Northern Italy. Ann Intern Med 2000; 132: 112-7
45. Gupte P, Amarpurkar D, Agal S, Baijal R, Kulshrestha P, Pramanik S, et al. Non-alcoholic steatohepatitis in type 2 diabetes mellitus. J Gastroenterol Hepatol 2004; 19: 854-8
46. Angulo P. GI Epidemiology: nonalcoholic fatty liver disease. Aliment Pharmacol Ther 2007; 25: 883-9.
47. Misra A, Misra R, Wijesuriya M, Banerjee D. The metabolic syndrome in South Asians: continuing escalation & possible solutions. Indian J Med Res 2007; 125: 345-54
48. Naevau S, Ray nard B, Ratziu V, Abella A, Imbert- Bismut F, Messous D, Beuzen F, Capron F, Thabut D, Munteanu M, Chaput JC, Poynard T: Biomarkers for the prediction of liver fibrosis in patients with chronic
alcoholic liver disease. Clin Gastroenterol Hepatol 2005, 3:167-74.)
49. Poynard T, McHutchinson J, Manns M, and Myers RP, Albrecht J: Biochemical surrogate markers of liver fibrosis and activity in a randomized trial of peginterferon alfa-2b and ribaviron. Hepatology 2003, 38:481- 92.
50. Halfon P, Bourliere M, Deydier R, Portal I, Renou R, Bertrand J, Trana A, Rosenthal A, Rotily M, Sattonet A, D O: Independent prospective multicenter validation of biochemical markers (Fibrotest-Actitest) for the prediction of liver fibrosis and activity in patients with chronic hepatitis C. Am J Gastro 2006)
51. Zahnd GR, Scheidegger JJ: Role of alpha-2-macroglobulin of human serum in the fixation in vitro of iodine- 131 labeled bovine insulin. Helv Med Acta 1963, 30:506-11
52. Castera 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; 128:343-50
53. Cales P, Oberti F, Michalak S, et al. A novel panel of blood markers to assess the degree of liver fibrosis. Hepatology 2005; 42:1373-81
54. Mofrad J, Haque M, Sargeant C, Fisher RA, Luketic VA, Sterling RK, Shiffman ML, Stravitz RT, Sanyal AJ. Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values. Hepatology 2003; 37:1286-92
55. Marchesini G, Brizi M, Morselli-Labate AM, Bianchi G, Bugianesi E, McCullough AJ, et al. Association of nonalcoholic fatty liver disease with insulin resistance. Am J Med 1999; 107: 450-5).
56. Duseja A, Das A, Das R, Dhiman RK, Chawla Y, Bhansali A, et al. The clinicopathological profile of Indian patients with nonalcoholic fatty liver disease (NAFLD) is different from that in the West. Dig Dis
Sci 2007; 52: 2368-74.)
57. Garg A, Misra A. Hepatic steatosis, insulin resistance and adipose tissue disorders. J Clin Endocrinol Metab 2002; 87: 3019-22.).
58. Duseja A, Das A, Das R, Dhiman RK, Chawla Y, Bhansali A, et al. The clinicopathological profile of Indian patients with nonalcoholic fatty liver disease (NAFLD) is different from that in the West. Dig Dis Sci 2007; 52: 2368-74.)
59. Forns X, Ampurdanes S, Llovet JM, et al. Identification of chronic hepatitis C patients without hepatic fibrosis by a simple predictive model. Hepatology 2002; 36:986-992
60. Lee JY, Kim KM, Lee SG, et al. Prevalence and risk factors of non-alcoholic fatty liver disease in potential living liver donors in Korea: A review of 589 consecutive liver biopsies in a single centre. J Hepatol 2006: pp S256
61. Amarpurkar D. Prevalence of non-alcoholic fatty liver disease: population based study. Annals of Hepatology 6(3) 2007: 161-163
62. Brunt EM. Nonalcoholic steatohepatitis. Semin Liver Dis 2004; 24:3-20
63. Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, AJ. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology 1999; 116:1413-1419.
Published
2019-09-25
How to Cite
Dr. Parveen Malhotra, Malhotra V, Malhotra N, Dahiya H, Jeetender, Chugh A. (2019). To Evaluate Efficacy of Non-Invasive Markers of Fibrosis in Determining Liver Fibrosis vis-à-vis Liver Biopsy, in Patients of Nonalcoholic Fatty Liver Disease. The Indian Practitioner, 67(5), 298-306. Retrieved from https://articles.theindianpractitioner.com/index.php/tip/article/view/827