Study of Liver Biopsy in Chronic Liver Diseases

  • Pavan Kulkarni S Nijalingappa Medical College
  • Sheela Devi C S JSS Medical College, Mysuru, Karnataka, India
Keywords: Chronic liver diseases, histopathology, grading, staging, etiology


Background Chronic liver disease (CLD) represents liver disorders of varying causes and severity in which hepatic inflammation and necrosis continue for at least 6 months. The treatment of cause leads to regression of fibrosis and parenchymal recovery. Liver biopsy is often used to establish the diagnosis, assess the severity of disease in CLD and its role is evolving with advances in medical technology. To study the histopathological pattern of injury in patients with CLD and thereby establish a possible etiologic diagnosis in correlation with clinical, biochemical and serologic findings. Methods Thirty five cases of CLD with histopathological features of necroinflammation/fibrosis were studied for a period of five years. Along with demographics and laboratory parameters, sections were studied for the pattern and degree of injury. Grading and staging were done using standard systems. Results Nonalcoholic fatty liver disease (31.42%) and alcoholic liver disease (25.71%) were the most common causes followed by viral hepatitis (11.42%) and drug induced liver injury (8.58%). One case each of autoimmune hepatitis and primary biliary cirrhosis were seen. A definitive diagnosis was not possible in six patients, and only a probable etiology was considered. Conclusion The natural history of CLD is changing and is important to establish an etiological diagnosis.  Despite the advances in diagnostic techniques, liver biopsy remains a valuable tool to establish the etiology and traditional descriptive reports still hold importance for the treatment and prognosis. However, it remains challenging and should be interpreted in the setting of clinical, biochemical, serological and radiological findings. 

Author Biography

Sheela Devi C S, JSS Medical College, Mysuru, Karnataka, India
Department of Pathology


1. Quaglia A, Alves VA, Balabaud C, Bhathal PS, Bioulac-Sage P, Crawford JM et al. Role of aetiology in the progression, regression and parenchymal remodelling of liver disease: implications for liver biopsy interpretation. Histopathology. 2016;68(7):953-67.
2. Goodman ZD. Grading and staging systems for inflammation and fibrosis in chronic liver diseases. J Hepatol. 2007;47(4):598-607.
3. Bateman AC. Patterns of histological change in liver disease: my approach to ‘medical’ liver biopsy reporting. Histopathology 2007;51(5):585-96.
4. Brunt EM, Ramrakhaini S, Cordes BG, Neuschwander-Tetri BA, Janney CG, Bacon BR et al. Concurrence of histologic features of steatohepatitis with other forms of chronic liver diseases. Mod Pathol. 2003;16(1):49-56.
5. Rockey DC, Caldwell SH, Goodman ZD, Nelson RC, Smith AD. Liver Biopsy. Hepatology. 2009;49(3):1017-44.
6. Saracco GM, Evangelista A, Fagoonee S, Ciccone G, Bugianesi E, Caviglia GP et al. Etiology of chronic liver diseases in the Northwest of Italy, 1998 through 2014. World J Gastroenterol. 2016;22(36):8187-93.
7. Pinzani M, Romanelli RG, Magli S. Progression of fibrosis in chronic liver diseases: time to tally score. Journal of Hepatology 2001; 34: 764-767.
8. Singh DK, Rastogi A, Sakhuja P, Gondal R, Sarin SK. Comparison of clinical, biochemical and histological features of alcoholic steatohepatitis and non alcoholic steatohepatitis in Asian Indian patients. Indian J Pathol Microbiol. 2010;53(3):408-413.
9. Kazemi-Shirazi L, Veloso MP, Frommlet F, Steindl-Munda P, Wrba F, Zehetmayer S et al. Differentiation of non alcoholic from alcoholic steatohepatitis: are routine laboratory markers useful?. Wien Klin Wochenschr. 2008;120(1-2):25-30.
10. Adams A, Sanderson S, Lindor KD, Angulo P. The histological course of non alcoholic fatty liver disease: a longitudinal study of 103 patients with sequential liver biopsies. J Hepatol. 2005;42:132-138.
11. Michitaka K, Nishiguchi S, Aoyagi Y, Hiasa Y, Tokumoto Y, Onji M; Japan Etiology of Liver Cirrhosis Study Group. Etiology of liver cirrhosis in Japan: a nation wide survey. J Gastroenterol. 2010;45(1):86-94.
12. Bell BP, Manos MM, Zaman A, Terrault N, Thomas A, Navarro VJ et al. The epidemiology of newly diagnosed chronic liver diseases in gastroenterology practices in the United States: results from population-based surveillance. Am J Gastroenterol. 2008;103(11):2727-36.
13. Sagnelli E, Stroffolini T, Sagnelli C, Smidile A, Morisco F, Furlan C et al. epidemiological and clinical scenario of chronic liver diseases in Italy: Data from a multicenter nationwide survey. Dig Liver Dis. 2016;48(9):1066-71.
14. Wang X, Lin SX, Tao J, Wei XQ, Liu YT, Chen YM et al. Study of liver cirrhosis over ten consecutive years in Southern china. World J Gastroenterol. 2014;20(37):13546-55.
15. Giannousis IP, Papatheodoridis GV, Deutsch MJ, Manolakopoulos SG, Manesis EK, Koskinas JS et al. The burden and recent epidemiological changes of the main chronic liver diseases in the Greek referral tertiary center. Eur J Gastroenterol Hepatol. 2010;22(2):172-9.
16. Fung KT, Fung J, Lai CL, Yuen MF. Etiologies of chronic liver diseases in Hong Kong. Eur J Gastroenterol Hepatol. 2007;19(8):659-64.
17. Nayak NC, Jain D, Vasdev N, Gulwani H, Saigal S, Soin A. Etiologic types of end-stage chronic liver disease in adults: analysis of prevalence and their temporal changes from a study on native liver explants. Eur J Gastroenterol Hepatol. 2012;24(10):1199-208.
18. Kim YS, Jung ES, Hur W, Bae SH, Choi JY, Song MJ et al.Non invasive predictors of non alcoholicsteatohepatitis in Korean patients with histologically proven non alcoholic fatty liver disease.ClinMolHepatol. 2013;19(2):120-30.
19. Singh DK, Sakhuja P, Malhotra V, Gondal R, Sarin SK. Independent predictors of steatohepatitis and fibrosis in Asian Indian patients with non-alcoholic steatohepatitis. Dig Dis Sci. 2008;53(7):1967-76.
20. Ekstedt M, Hagström H, Nasr P, Fredrikson M, Stål P, Kechagias S et al. Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after upto 33 years follow-up. Hepatology. 2015;61(5):1547-54.
21. Yang JD, Abdelmalek MF, Pang H, Guy CD, Smith AD, Diehl AM et al. Gender and menopause impact severity of fibrosis among patients with non alcoholic steatohepatitis. Hepatology. 2014;59(4):1406-14.
22. Bruha R, Dvorak K, Petrtyl J. Alcoholic liver disease. World J Hepatol. 2012;4(3):81-90.
23. Yip WW, Burt AD. Alcoholic liver disease. Semin Diagn Pathol. 2006;23(3-4):149-160.
24. Sakhuja P. Pathology of alcoholic liver disease, can it be differentiated from non alcoholic steatohepatitis?. World J Gastroenterol. 2014;20(44):16474-16479.
25. Rakha EA, Adamson L, Bell E, Neal K, Ryder SD, Kaye PV et al. Portal inflammation is associated with advanced histological changes in alcoholic and non-alcoholic fatty liver disease. J Clin Pathol. 2010 ;63(9):790-5.
26. Testino G, Burra P, Bonino F, Piani F, Sumberaz A, Peressutti R et al. acute alcoholic hepatitis, end stage alcoholic liver disease and liver transplantation: an Italian position statement. World J Gastroenterol. 2014;20(40):14642-51.
27. Sahlman P, Nissinen M, Pukkala E, Färkkilä M. Cancer incidence among alcoholic liver disease patients in Finland: A retrospective registry study during years 1996-2013. Int J Cancer. 2016;138(11):2616-21.
28. Rastogi A, Sakhuja P, Kumar A, Hissar S, Jain A, Gondal R et al. Steatosis in chronic hepatitis B: prevalence and correlation with biochemical, histologic, viral and metabolic parameters. Indian J Pathol Microbiol. 2011;54(3):454-9.
29. Shafaei S, Soleimani Amiri S, Hajiahmadi M, Sadeghi-Haddad-Zavareh M, Bayani M. Histological grading and staging of liver and its relation to viral loads in chronic anti-HBe positive hepatitis. Caspian J Intern Med. 2013;4(3):681-5.
30. Biazar T, Yahyapour Y, Hasanjani Roushan MR, Rajabnia R, Sadeghi M, Taheri H et al. Relationship between hepatitis B DNA viral load in the liver and its histology in patients with chronic hepatitis B. Caspian J Intern Med. 2015;6(4):209-12.
31. Nabuco LC, Villela-Nogueira CA, Perez RM, Ceci L, Pannain VL, Nogueira CM et al. HBV-DNA levels in HBsAg-positive blood donors and its relationship with liver histology. J Clin Gastroenterol. 2007;41(2):194-8.
32. Bayram A, Erkilic S, Ozkur A, Bayram M, Sari I. Quantification of intrahepatic total hepatitis B virus DNA in chronic hepatitis B patients and its relationship with liver histology. J Clin Pathol. 2008;61(3):338-42.
33. Mannan R, Misra V, Misra SP, Singh PA, Dwivedi M. A comparative evaluation of scoring systems for assessing necro-inflammatory activity and fibrosis in liver biopsies of patients with chronic viral hepatitis. J Clin Diagn Res. 2014;8(8):FC08-12.
34. Mohamadnejad M, Tavangar SM, Sotoudeh M, Kosari F, Khosravi M, Geramizadeh B et al. Histopathological Study of Chronic Hepatitis B: A Comparative Study of Ishak and METAVIR Scoring systems. Int J Organ Transplant Med. 2010;1(4):171-6.
35. Kumar S, Subhadra S, Singh B, Panda BK. Hepatitis E virus: the current scenario. Int J Infect Dis. 2013;17(4):e228-33.
36. Goyal R, Kumar A, Panda SK, Paul SB, Acharya SK. Ribavarin therapy for hepatitis E virus-induced acute on chronic liver failure: aprelimnary report. Antivir Ther. 2012;17(6):1091-6.
37. Kakuda Y, Harada K, Sawada-Kitamura S, Ikeda H, Sato Y, Sasaki M et al. evaluation of a new histologic staging and grading system for primary biliary cirrhosis in comparison with classical systems. Hum Pathol. 2013;44(6):1107-17.
38. Chan AW, Chan RC, Wong GL, Wong VW, Choi PC, Chan HL et al. Evaluation of histological staging systems for primary biliary cirrhosis: correlation with clinical and biochemical factors and significance of pathological parameters in prognostication. Histopathology. 2014;65(2):174-86.
39. Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa NV, Heathcote EJ; American Association for Study of Liver Diseases. Primary biliary cirrhosis. Hepatology. 2009;50(1):291-308.
40. Weinmann A, Sattler T, Unold HP, Grambihler A, Teufel A, Koch S et al. Predictive scores in primary biliary cirrhosis a retrospective single center analysis of 204 patients. J Clin Gastroenterol. 2015;49(5):438-47.
41. Joshi M, Khettry U. Approach to management of autoimmune hepatitis. Indian J Pathol Microbiol. 2009;52(3):297-303.
42. Manns MP, Czaja AJ, Gorham JD, Krawitt EL, Mieli-Vergani G, Vergani D, Vierling JM; American Association for the Study of Liver Diseases. Diagnosis and management of autoimmune hepatitis. Hepatology. 2010;51(6):2193-213.
43. de Boer YS, van Nieuwkerk CM, Witte BI, Mulder CJ, Bouma G, Bloemena E. Assessment of the histopathological key features in autoimmune hepatitis. Histopathology. 2015;66(3):351-62.
44. Mehendiratta V, Mitroo P, Bombonati A, Navarro VJ, Rossi S, Rubin R et al. Serologic markers do not predict histologic severity or response to treatment in patients with autoimmune hepatitis. Clin Gastroenterol Hepatol. 2009;7(1):98-103.
45. Miao Q, Bian Z, Tang R, Zhang H, Wang Q, Huang S et al. Emperipolesis mediated by CD8 T cells is a characteristic histopathologic feature of autoimmune hepatitis. Clin Rev Allergy Immunol. 2015;48(2-3):226-35.
46. Tucker SM, Jonas MM, Perez-Atayde AR. Hyaline droplets in Kupfer cells: A novel diagnostic clue for autoimmune hepatitis. Am J Surg Pathol. 2015;39(6):772-8.
47. Kleiner DE, Chalasani NP, Lee WM, Fontana RJ, Bonkovsky HL, Watkins PB et al. Hepatic histological findings in suspected drug-induced liver injury: systematic evaluation and clinical associations. Hepatology. 2014;59(2):661-70.
48. Ramachandran R, Kakar S. Histological patterns in drug-induced liver disease. J Clin Pathol. 2009;62(6)481-92.
49. Chalasani N, Fontana RJ, Bonkovsky HL, Watkins PB, Davern T, Serrano J et al. Causes, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States. Gastroenterology. 2008;135(6):1924-34.
50. Abboud G, Kaplowitz N. Drug-induced liver injury. Drug Saf. 2007;30(4):277-94.
51. Suzuki A, Brunt EM, Kleiner DE, Miquel R, Smyrk TC, Andrade RJ et al. The use of liver biopsy evaluation in discrimination of idiopathic autoimmune hepatitis vs. drug-induced liver injury. Hepatology. 2011;54(3):931-39.
52. Gossard AA, Talwalkar JA. Cholestatic liver disease. Med Clin North Am. 2014;98(1):73-85.
53. Clark JM, Diehl AM. Non alcoholic fatty liver disease: an underrecognized cause of cryptogenic cirrhosis. JAMA. 2003;289(22):3000-4.
54. Mercado-irizarry M, Torres EA. Crptogenic cirrhosis: current knowledge and future directions. Clinical liver disease. 2016;7(4):69-72.
55. Gaya DR, Thorburn D, Oien KA, Morris AJ, Stanley AJ. Hepatic granulomas: a 10 year single centre experience. J Clin Pathol. 2003;56(11):850-3.
Original Article