J Pathol Transl Med.  2025 Jan;59(1):1-10. 10.4132/jptm.2024.11.15.

Post-transplant liver biopsies: a concise and practical approach for beginners

• Ourfali MB
• Hirsch D
• Scranton M
• Jabbour TE

• KMID: 2563880
• DOI: http://doi.org/10.4132/jptm.2024.11.15

Abstract

Exposure to post-transplant liver biopsies varies among pathology residencies and largely depends on the institution's training program, particularly if the hospital has a liver transplant program. The interpretation of biopsies from transplanted livers presents its own set of challenges, even for those with a solid understanding of non-transplant medical liver biopsies. In this review, we aim to provide a succinct, step-by-step approach to help you interpret liver transplant biopsies. This article may be beneficial for residents interested in liver pathology, gastrointestinal and liver pathology fellows in the early stages of training, clinical gastroenterology and hepatology fellows, hepatologists and general pathologists who are curious about this niche.

Keyword

Liver transplantation; Graft rejection; Liver transplant biopsy; Viral hepatitis

Figure

• 

  Fig. 1. (A) Autoimmune hepatitis: plasma cell-rich infiltrate with periportal apoptotic hepatocytes (arrows). (B) Primary biliary cholangitis: lymphocyte-rich infiltrate with poorly formed granuloma (arrow). (C, D) Primary sclerosing cholangitis: concentric periductal fibrosis (arrow) (D, Trichrome).

• 

  Fig. 2. (A) Steatohepatitis: macrovesicular steatosis with ballooned hepatocytes (black arrows) and Mallory-Denk bodies (red arrow). (B) Alpha-1 antitrypsin deficiency: intrahepatocytic alpha-1 antitrypsin globules (arrow) (periodic acid–Schiff–diastase). (C) Hemochromatosis: intrahepatocytic iron accumulation (arrow) (Perl’s stain). (D) Wilson’s disease: intrahepatocytic copper accumulation (arrow) (Rhodanine stain).

• 

  Fig. 3. (A) Hepatitis B virus hepatitis: ground glass hepatocytic inclusion (arrows). (B) Hepatitis C virus hepatitis: lymphoid follicle formation in the portal tract (arrow).

• 

  Fig. 4. (A) Acute cellular rejection: endothelitis (arrows). (B) Plasma cell-rich rejection: centrilobular plasma cell-rich inflammatory infiltrate (arrow) (Courtesy of Maria Isabel Fiel MD). (C) Chronic rejection with foam cell arteriopathy: foam cell accumulation in the arterial wall (arrows) (Courtesy of Maria Isabel Fiel MD). (D) Chronic ductopenic rejection: absence of native bile duct in a portal tract.

• 

  Fig. 5. (A, B) Antibody-mediated rejection: C4d deposition in a hepatic arteriole (B, C4d immunostain).

• 

  Fig. 6. (A) Hepatic artery thrombosis: centrilobular (black arrow) and periportal coagulative necrosis (red arrow). (B) Hepatic vein thrombosis: centrilobular congestion and necrosis (arrow). (C) Portal vein thrombosis: dystrophic (dilated) portal vein (arrow).

• 

  Fig. 7. (A) Bile duct obstruction: portal edema neutrophils and bile ductular reaction (arrow). (B) Reperfusion injury: centrilobular cholestasis and hepatocyte ballooning (arrows).

• 

  Fig. 8. (A) Herpes simplex virus hepatitis: nuclear inclusion (arrow) (Courtesy of Hwa Jeong Lee, MD). (B) Cytomegalovirus: neutrophilic microabscess (arrows). (C) Epstein-Barr virus hepatitis: sinusoidal mildly atypical lymphocytic infiltrate (arrows).

• 

  Fig. 9. (A) Drug-induced liver injury: pseudo-ground-glass inclusion secondary to polypharmacy (arrows).

Reference

References

1. Wu F, Wang J, Pu C, Qiao L, Jiang C. Wilson's disease: a comprehensive review of the molecular mechanisms. Int J Mol Sci. 2015; 16:6419–31. DOI: 10.3390/ijms16036419. PMID: 25803104.

2. Catana AM, Medici V. Liver transplantation for Wilson disease. World J Hepatol. 2012; 4:5–10. DOI: 10.4254/wjh.v4.i1.5. PMID: 22312450.

3. Fromme M, Schneider CV, Trautwein C, Brunetti-Pierri N, Strnad P. Alpha-1 antitrypsin deficiency: a re-surfacing adult liver disorder. J Hepatol. 2022; 76:946–58. DOI: 10.1016/j.jhep.2021.11.022. PMID: 34848258.

4. Mitchell EL, Khan Z. Liver disease in alpha-1 antitrypsin deficiency: current approaches and future directions. Curr Pathobiol Rep. 2017; 5:243–52. DOI: 10.1007/s40139-017-0147-5. PMID: 29399420.

5. Dobrindt EM, Keshi E, Neulichedl J, et al. Long-term outcome of orthotopic liver transplantation in patients with hemochromatosis: a summary of a 30-year transplant program. Transplant Direct. 2020; 6:e560. DOI: 10.1097/txd.0000000000001007. PMID: 33062844.

6. Shubin AD, De Gregorio L, Hwang C, MacConmara M. Combined heart-liver transplantation in a case of haemochromatosis. BMJ Case Rep. 2021; 14:e241508. DOI: 10.1136/bcr-2020-241508. PMID: 34059542.

7. Schreibman I, Regev A. Recurrent primary biliary cirrhosis after liver transplantation: the disease and its management. MedGenMed. 2006; 8:30.

8. Visseren T, Erler NS, Polak WG, et al. Recurrence of primary sclerosing cholangitis after liver transplantation: analysing the European Liver Transplant Registry and beyond. Transpl Int. 2021; 34:1455–67. DOI: 10.1111/tri.13925. PMID: 34028110.

9. Harputluoglu M, Caliskan AR, Akbulut S. Autoimmune hepatitis and liver transplantation: Indications, and recurrent and de novo autoimmune hepatitis. World J Transplant. 2022; 12:59–64. DOI: 10.5500/wjt.v12.i3.59. PMID: 35433333.

10. Faisal N, Renner EL. Recurrence of autoimmune liver diseases after liver transplantation. World J Hepatol. 2015; 7:2896–905. DOI: 10.4254/wjh.v7.i29.2896. PMID: 26689244.

11. Shetty A, Giron F, Divatia MK, Ahmad MI, Kodali S, Victor D. Nonalcoholic fatty liver disease after liver transplant. J Clin Transl Hepatol. 2021; 9:428–35. DOI: 10.14218/JCTH.2020.00072. PMID: 34221929.

12. Jothimani D, Venugopal R, Vij M, Rela M. Post liver transplant recurrent and de novo viral infections. Best Pract Res Clin Gastroenterol. 2020; 46-47:101689. DOI: 10.1016/j.bpg.2020.101689. PMID: 33158469.

13. Salomao MA. Pathology of hepatic iron overload. Clin Liver Dis (Hoboken). 2021; 17:232–7. DOI: 10.1002/cld.1051. PMID: 33968381.

14. Mazhar A, Piper MS. Updates on Wilson disease. Clin Liver Dis (Hoboken). 2023; 22:117–21. DOI: 10.1097/cld.0000000000000079. PMID: 37908869.

15. Choudhary NS, Saigal S, Bansal RK, Saraf N, Gautam D, Soin AS. Acute and chronic rejection after liver transplantation: what a clinician needs to know. J Clin Exp Hepatol. 2017; 7:358–66. DOI: 10.1016/j.jceh.2017.10.003. PMID: 29234201.

16. Demetris AJ, Bellamy C, Hubscher SG, et al. 2016 Comprehensive update of the Banff Working Group on Liver Allograft Pathology: introduction of antibody-mediated rejection. Am J Transplant. 2016; 16:2816–35. DOI: 10.1111/ajt.13909. PMID: 27273869.

17. Lee BT, Fiel MI, Schiano TD. Antibody-mediated rejection of the liver allograft: an update and a clinico-pathological perspective. J Hepatol. 2021; 75:1203–16. DOI: 10.1016/j.jhep.2021.07.027. PMID: 34343613.

18. Rampes S, Ma D. Hepatic ischemia-reperfusion injury in liver transplant setting: mechanisms and protective strategies. J Biomed Res. 2019; 33:221–34. DOI: 10.7555/jbr.32.20180087. PMID: 32383437.

19. Lee M, Agostini-Vulaj D, Gonzalez RS. Evaluation of histologic changes in the livers of patients with early and late hepatic artery thrombosis. Hum Pathol. 2019; 90:8–13. DOI: 10.1016/j.humpath.2019.04.019. PMID: 31075300.

20. Gupta NB. Liver biopsy made easy. New Delhi: Jaypee Brothers Medical Publishers;2017.

21. Nakhleh RE. Pathology and differential diagnosis of hepatic venous outflow impairment. Clin Liver Dis (Hoboken). 2017; 10:49–52. DOI: 10.1002/cld.647. PMID: 30992759.

22. Terada T, Hoso M, Nakanuma Y. Microvasculature in the small portal tracts in idiopathic portal hypertension: a morphological comparison with other hepatic diseases. Virchows Arch A Pathol Anat Histopathol. 1989; 415:61–7. DOI: 10.1007/bf00718605. PMID: 2499979.

23. Geramizadeh B, Hassani M, Kazemi K, Shamsaifar AR, Malek-Hosseini SA. Value of histopathologic findings of post-reperfusion liver needle biopsies. Int J Organ Transplant Med. 2018; 9:168–72. PMID: 30863519.

24. Dancygier H. Viral infections by nonhepatotropic viruses. In: Dancygier H, ed. Clinical hepatology. Berlin: Springer;2010. p. 823–30.

25. Zheng N, Wang Y, Rong H, Wang K, Huang X. Human adenovirus associated hepatic injury. Front Public Health. 2022; 10:878161. DOI: 10.3389/fpubh.2022.878161. PMID: 35570934.

26. Lucey MR, Terrault N, Ojo L, et al. Long-term management of the successful adult liver transplant: 2012 practice guideline by the American Association for the Study of Liver Diseases and the American Society of Transplantation. Liver Transpl. 2013; 19:3–26. DOI: 10.1002/lt.23566. PMID: 23281277.

27. Livertox: clinical and research information on drug-induced liver injury [Internet]. Bethesda: National Institute of Diabetes and Digestive and Kidney Diseases;2012. [cited 2024 Jul 31]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK547852/.

28. Fischer AK, Baba H, Lainka E, et al. Rapid development of pseudo-ground-glass bodies in liver transplants. Histopathology. 2024; 85:190–2. DOI: 10.1111/his.15188. PMID: 38622086.