Donor Liver Biopsy

Evaluation of Donor Liver Biopsy for Transplant

Who You Gonna Call?

Please contact Dr. Hart first, followed by Dr. Alpert. If neither Liver pathologist is available, then contact the Surg Path Attending on call.

Preparation of the Slides

The biopsy should be blotted dry before rapid freezing to reduce ice crystal artifact. Standard 4-5 micron sections and H&E staining is all that is required. Oil red O stains are not necessary and in fact are often misleading, leading to overestimation of degree of steatosis. Slides should be prepared from ALL samples, since the harvesting team often takes one slide with them to show to their own pathologist at a later date.

Evaluation of the Histology

Macrovesicular Steatosis

The degree of macrovesicular steatosis is estimated by the pathologist as the percentage of hepatocytes throughout the biopsy that contain a large lipid droplet. The percentage should reflect the entire biopsy (not the worst area). Ice crystal artifact can produce uniform medium sized vacuoles within hepatocytes can that resemble large droplet fat vacuoles. One clue to the recognition of this artifact is the uniformity of this change through the biopsy (or a part of the biopsy).

Microvesicular Steatosis

Microvesicular steatosis is quite difficult to recognize on frozen section, and there is no convincing data that indicate that it significantly impacts post-transplant graft function. If the surgeon insists on a percent microvesicular steatosis is is best to record 0%.

Other Donor Biopsy Pathology

The presence of hepatocyte necrosis should be evaluated and reported if present. Centrilobular necrosis may be subtle if it is recent. It causes slight shrinkage and smudginess of hepatocytes with condensation of the cytoplasm and mild nuclear hyperchromasia. It most often occurs as a consequence of hepatic ischemia related to the use of a high dose of pressor agents and/or the development of hypernatremia and other metabolic derangements preceding the development of brain death. At an earlier stage there may be random individual apoptotic hepatocytes (acidophil bodies), but this degree of hepatocyte injury probably won’t cause significant post-transplant graft dysfunction.

A mild degree of portal mononuclear cell infiltration is acceptable, and the cause is generally never learned (donors are screened for HBV and HCV hepatitis). It is possible that chronic intermittent biliary obstruction, celiac disease, or prior resolved episodes of HBV or HCV hepatitis are responsible for these infiltrates in some donor organs. Unexplained heavy portal or lobular inflammatory cell infiltrates should be mentioned to the surgeon and likely will lead to rejection of the organ.

Significant portal and/or centrilobular fibrosis (stage 2 or worse) is generally unacceptable, except for recipients in fulminant hepatic failure. Remember that more abundant portal fibrous tissue is expected in the portal tracts that are quite close to the hepatic capsule.

Lobular inflation is generally not a contraindication to transplant unless it is quite florid or if an actual abscess is present. Scattered neutrophils in the sinusoids generally represents so-called “surgical hepatitis” and is not a pathologic process that prevents use of the donor organ.

Mass Lesions in Donor Organs

On rare occasions small mass lesions may be identified by the transplant surgeon at the time or organ harvest. Bile duct hamartomas (von Meyenberg complexes) even if numerous, are not a contraindication to the use of an organ. Likewise, bile duct adenomas are regarded as completely benign lesions that pose no risk to the recipient. These two lesions are often recognized by the surgeon as small well circumscribed subcapsular nodules are often ignored. Walled off hyalinized granulomas are also regarded as innocuous lesions, but the presence of caseating or necrotizing granulomas should probably lead to rejection of the donor organ. Small cavernous hemangiomas are common incidental findings (approximately 1% of livers at autopsy) and are usually easily recognized by both surgeons and surgical pathologists.

The presence of focal nodular hyperplasia is also not a contraindication to the use of a donor organ, as these lesions have no malignant potential. Small lesions often do not exhibit a central scar with an obvious abnormal vessel, so the diagnosis rests upon recognition of the “focal cirrhosis” pattern of fibrous septa containing proliferating bile ductules. Although not well studied, organs containing hepatic adenomas have also been utilized after complete excision of the mass. Naturally, confident exclusion of a well differentiated hepatocellular carcinoma must be assured, and this can be problematic by frozen section examination. Thus, many of these organs end up not be used.

The Bottom Line

  • There is no universally accepted threshold for the degree of macrovesicular steatosis that makes a cadaveric donor organ unusable.
  • Microvesicular steatosis cannot be reliably recognized in routine frozen sections and there is no convincing data to suggest that it’s presence adversely affects donor organ function.
  • Other histologic features that should be assessed include the degree of hepatocyte necrosis and fibrosis.
  • The presence of mild non-specific chronic portal inflammation is acceptable for transplantation.

References

Donor Biopsy Evaluation

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  • Markin RS et al. Frozen section evaluation of donor livers before transplantation Transplantation 1993; 56:1403-9.
  • Dabkowski PL et al. Site of principal metabolic defect in idiopathic hemochromatosis: insights from transplantation of an affected organ. Br Med J 1993; 306:1726-8.
  • Abraham S, Furth EE. Quantitative evaluation of histological features in “time-zero” liver allograft biopsies as predictors of rejection or graft failure: receiver-operating characteristic analysis application. Human Pathol 1996; 27:1077-84.
  • Velidedeoglu E et al. The outcome of liver grafts procured from hepatitis C-positive donors. Transplantation 2002; 73: 582-7.
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  • Renz JF et al. Utilization of extended donor criteria liver allografts maximizes donor use and patient access to liver transplantation. Ann Surg 2005; 242: 556-565.
  • Guarrera JV et al. Discovery of diffuse biliary microhamartomas during liver procurement. Liver Transpl 2007; 13:1470-1.
  • Deshpande R, Heaton N. Can non-heart-beating donors replace cadaveric heart-beating liver donors? J Hepatol 2006; 45:499-502.
  • Pungpapong S et al. Clinicopathologic findings and outcomes of liver transplantation using grafts from donors with unrecognized and unusual diseases. Liver Transnpl 2006; 12:310-15.
  • Lo IJ et al. Utility of liver allograft biopsy obtained at procurement. Liver Transpl 2008; 14:639-46.
  • Alkofer B et al. Extended-donor criteria liver allografts. Semin Liver Dis 2006; 26: 221-33.
  • Deshpande R, Heaton N. Can non-heart-beating donors replace cadaveric heart-beating liver donors? J Hepatol 2006; 45:499-502.
  • Pungpapong S et al. Clinicopathologic findings and outcomes of liver transplantation using grafts from donors with unrecognized and unusual diseases. Liver Transpl 2006; 12:310-15.
  • Feng S., et al., Characteristics associated with liver graft failure: the concept of a donor risk index. Am J Transplant, 2006; 6: 783-90.
  • Dodson SF et al. Infectivity of hepatic allografts with antibodies to hepatitis B virus. Transplantation 1997; 64: 1582-4.
  • Kocbiyik A et al. Role of postreperfusion subcapsular wedge biopsies in predicting initially poor graft function after liver transplantation. Transpl Proc 2009; 41:2747-8.
  • Melin C et al. Approach to intraoperative consultation for donor liver biopsies. [Review] Arch Pathol Lab Med 2013; 137:270-4.

Macrovesicular Steatosis in Donor Liver Biopsies

  • Todo S et al. Primary nonfunction of hepatic allografts with preexisting fatty infiltration. Transplantation, 1989; 47: 903-5.
  • Adams R et al. The outcome of steatotic grafts in liver transplantation. Transpl Proc 1991 23:1538.
  • Zamboni, F et al., Effect of macrovesicular steatosis and other donor and recipient characteristics on the outcome of liver transplantation. Clin Transplant, 2001; 15:53-7.
  • D’Alessandro AM et al. The predictive value of donor liver biopsies for the development of primary non-function after orthotopic liver transplantation. Transplantation 1991; 51:157-63.
  • Crowley H et al. Steatosis in donor and transplant liver biopsies. Human Pathol 2000; 31:1209-13.
  • Fiorini RN et al. Development of an unbiased method for the estimation of liver steatosis. Clin Transpl 2004; 18:700-6.
  • Rerez-Dega JA et al. Influence of degree of hepatic steatosis on graft function and postoperative complications of liver transplantation. Trans Proc 2006; 38:2468-70.
  • Nocito A et al When is steatosis too much for transplantation. J Hepatol 2006; 45:494-8.
  • Nikeghbalain S. Does donor’s fatty liver change impact on early mortality and outcome of liver transplantation. Transpl Proc 2007; 39:1181-3.
  • McCormack L et al. Use of severely steatotic grafts in liver transplantation: a matched case-control study. Ann Surg 2007; 246:940-46.
  • Fiorentino M et al. Predictive value of frozen-section analysis in the histological assessment of steatosis before liver transplantation. Liver Transpl 2009; 15:1821-1825.
  • Spitzer AL et all. The biopsied donor liver: incorporating macrosteatosis into high-risk donor assessment. Liver Transpl 2010; 16:874-84.
  • McCormack L et al. Liver transplantation using fatty livers: always feasible? J Hepatol 2011; 54:1055-62.
  • Gabrielli M et al. Steatotic livers. Can we use them in OLTX? Outcome data from a prospective baseline liver biopsy study. Ann Hepatol 2012; 11:891-8.
  • de Graaf EL et al. Grade of deceased donor liver macrovesicular steatosis impacts graft and recipient outcomes more than the donor risk index. J Gastroenterol Hepatol 2012; 27:540-46.
  • Sharkey FE et al. High-grade microsteatosis and delay in hepatic function after orthotopic liver transplantation. Human Pathol 2011; 42:1337-42.
  • Brunt EM. Surgical assessment of significant steatosis in donor livers: the beginning of the end for frozen-section analysis? Liver Transpl 2013; 19:360-1.
  • Holowko W et al. Reliability of frozen section in the assessment of allograft steatosis in liver transplantation. Transpl Proc 2014; 46:2755-7.
  • Chavin KD et al. Safe use of highly steatotic livers by utilizing a donor/recipient clinical algorithm. Clin Transpl 2013; 27:732-41.
  • Yersiz H et al. Assessment of hepatic steatosis by transplant surgeon and expert pathologist: a prospective, double-blind evaluation of 201 donor livers. Liver Transplant 2013; 19:437-49.
  • Jun MJ et al. Clinical implications of preoperative and intraoperative liver biopsies for evaluating donor steatosis in living related liver transplantation. Liver Transpl 2014; 20:437-45.

Microvesicular Steatosis in Donor Biopsies

  • Fishbein TM et al. Use of livers with microvesicular fat safely expands the donor pool. Transplantation 1997; 64:248-51.
  • Andert A et al. Grade of donor liver microvesicular steatosis does not affect the postoperative outcome after liver transplantation. Hepatobiliary Pancreat Dis Int 2017;16:617-23.
  • Doyle MB, Vachharajani N, Wellen JR, et al. Short- and long-term outcomes after steatotic liver transplantation. Arch Surg. 2010;145:653–60.
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