Hepatic Steatosis: Issues in Hepatic Transplantation
Linda Ferrell, MD
University of California San Francisco
San Francisco, California
One of the important issues in liver transplantation is to avoid primary nonfunction or initial poor
function of the donor graft. Such dysfunction can be due to preservation injury, operative technical
complications, and hyperacute rejection. Moderate to severe degrees of macrovesicular steatosis has also
been shown to be a risk factor for nonfunction or prolonged dysfunction of the graft.1,2,3
Significant macrovesicular steatosis can be identified grossly by the surgeon. This is most often done by
noting a yellowish discoloration on finger pressure, and/or hepatomegaly or rounded borders of the organ.
However, accuracy of this determination, especially in questionable cases, can be improved by routine
Hematoxylin and Eosin (H&E) staining done on frozen sections. Oil red O staining can be misleading as it
can result in overinterpretation of the amount of fat present (especially the presence of microvesicular
fat), leading to the discard of usable organs.4
Grading of macrovesicular fat on frozen sections. In general, organs with more than 40-50% of the
parenchyma involved by macrovesicular fatty change on routine frozen section would be discarded, and those
organs with less than 30% would be usable if no other significant injury (such as ischemic necrosis) was
noted as well.5 Organs with borderline amounts of fate (30-50% macrovesicular fat) have been used in
various situations as needed with some success (personal observation).
In contrast, microvesicular steatosis that consists of single to few small droplets of fat within the
hepatocyte probably has no effect on outcome of the graft.6,7 Here, the definition of the microvesicular
fat is important as this does not include the type of microvesicular fat that completely fills and replaces
the cell cytoplasm without displacement of the nucleus. This type of fat is not well-demonstrated on
routine frozen sections stained with H&E, but will be stained discreetly by Oil red O. Thus, ORO is not
recommended for routine frozen sections so that the amount of fat in the liver is not overestimated due to
the presence of microvesicular fat droplets.
Due to the difference in outcome depending on the size of the fat droplets, one can report the amount of
macrovesicular and microvesicular steatosis as separate amounts in the determination of the fat content of a
donor liver on frozen section, or only comment on the amount of macrovesicular steatosis.
Outcome of Transplanted Organs Containing Steatosis
Steatotic donor livers have been shown to be associated with higher peaks of transaminases and lower bile
output in the first three days after transplantation proportional to the degree of fat present.8
Microscopically, this fat can often be seen in association with preservation injury (or reperfusion-injury,
thought to be due to ischemia to the graft before transplantation that leads to the histologic
manifestations of the ischemic injury after transplantation). In the mildest forms of injury, one may only
note a few foci of apoptotic hepatocytes and centrilobular cholestasis. In moderate degrees of injury, the
cholestasis is typically associated with hepatocyte swelling and/or dropout predominantly in the central
zone. In severe injury, the hepatocyte damage can be panlobular, and ductular injury is also present. The
ductular injury manifests as bile ductular (cholangiolar) cholestasis and proliferation, mimicking the
lesion of cholangitis lenta seen in sepsis.9
Lipopeliosis (Pseudopeliotic Steatosis)
When variable degrees of fatty change are present in the transplanted liver that has undergone moderate to
severe preservation injury with hepatocyte dropout (typically occurring in the central zone), then the
lesion of lipopeliosis (pseudopeliotic steatosis) can occur. Necrosis of fat-containing hepatocytes results
in the release of fat that becomes sequestered in large globules which, in turn, distend the hepatic plates
to give the appearance of dilated sinusoidal spaces. This lesion was first described as a dilation of the
sinusoids by the large fat globules that superficially mimicked the lesion of peliosis hepatitis;10,11
thus, we coined the term lipopeliosis to describe this lesion. However, since then, we have noted that the
fat is not truly present within sinusoids, but rather remains outside the sinusoidal space. Thus, we are
now recommending that a better terminology for this lesion would be pseudopeliotic steatosis since the
sinusoids are not truly dilated.12
Progression of the lesion. Within a few days after release of the fat, macrophages and other inflammatory
cells accumulate and surround the fat, which is gradually resorbed over the period of days to weeks without
long-term sequelae. These later lesions are essentially the same as lipogranulomata.11
Occasionally, with severe damage to the endothelial cells lining the sinusoids, fat can escape into the
sinusoids and result in fat embolism to the lung.12
Tillery W, et al. Pathologic recognition of preservation injury in hepatic allografts with six months
follow-up. Transplantation Proc 21:1330-1, 1989.
Todo S, et al. Primary nonfunction of hepatic allografts with preexisting fatty infiltration.
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D'Allessandro AM, et al. The predictive value of donor liver biopsies on the development of primary
nonfunction after orthotopic liver transplantation. Transplantation Proc 23:1536-7, 1991.
Strasberg, et al. Selecting the donor liver: risk factors for poor function after orthotopic liver
transplantation. Hepatol 20:829-38, 1994.
Markin RS, et al. Frozen section evaluation of donor livers before transplantation. Transplantation
Vartanian RK, et al. Microvesicular vs. macrovesicular fatty change in donor livers: relationship to
preservation injury. Modern Pathol 7:136A, 1994.
Sheiner P, et al. Use of donor livers with moderate-to-severe microvesicular fat. Hepatol 22 (4, pt
Adam R, et al. The outcome of steatotic grafts in liver transplantation. Transplantation Proc
Jones KD and Ferrell LD. Interpretation of biopsy findings in the transplant liver. Sem Diag Pathol
Ferrell LD, et al. Lipopeliosis: fat-induced sinusoidal dilatation in transplanted liver mimicking
peliosis hepatitis. J Clin Pathol 45: 1109-10, 1992.
Cha I, Bass N, and Ferrell LD. Lipopeliosis: an immunohistochemical and clinicopathologic study of
five cases. Amer J Surg Pathol 18:789-95, 1994.
Bioulac-Sage P, Balabaud C, Ferrell L. Lipopeliosis revisited: should we keep the term? Amer J Surg
Pathol, in press.