C4d immunopositivity is uncommon in ABO-compatible liver allografts, but correlates partially with lymphocytotoxic antibody status

AIMS: To determine whether C4d immunopositivity helps recognition of humoral rejection in dysfunctional liver allografts. METHODS AND RESULTS: C4d immunopositivity was retrospectively evaluated in liver allografts. There were three staining patterns: portal venular plexus, sinusoidal and hepatocellular. The latter was related to ischaemic necrosis and not scored as positive. C4d immunopositivity was not encountered in 10 preperfusion or 15 consecutive early protocol biopsies. However, three of 12 early protocol biopsy specimens from crossmatch-positive patients were C4d+, two showing repeated positivity on at least one further biopsy specimen, while others remained negative. C4d was also positive in 2/16 early moderate acute cellular rejections, 3/14 cases of centrilobular necroinflammation, 3/11 biliary obstructions, 3/13 chronic rejections and 1/10 primary non-functional allografts. CONCLUSION: C4d immunopositivity is uncommon in liver allografts. There is a weak positive correlation with a positive lymphocytotoxic crossmatch and some patterns of allograft dysfunction. The morphological associations resemble those reported in lymphocytotoxic crossmatch-positive patients, plus occasional sinusoidal and hepatocellular injury. Although the practical utility of C4d immunohistochemistry seems limited, it may identify a small subgroup of individuals in whom chronic humoral microvascular injury contributes to allograft dysfunction.     

Histological diagnosis of cytomegalovirus hepatitis in liver allografts.

AIMS--To determine the incidence of histologically documented cytomegalovirus (CMV) hepatitis following orthotopic liver transplantation (OLT) and to assess the effectiveness of immunohistochemistry and in situ hybridisation (ISH) in detecting CMV. To describe the histological pattern most frequently associated with CMV hepatitis in order to select the biopsy group in which these modern techniques are most effective. METHODS--A prospective histological study was carried out on 853 biopsy specimens, obtained from 191 liver allografts (160 patients). Specimens were stained with haematoxylin and eosin and immunohistochemically (avidin-biotin complex) using monoclonal antibodies directed against early and late CMV antigens. A retrospective selection was made of 23 specimens with viral inclusion bodies in cytomegalic cells (group A) to characterise the most frequently associated histological pattern, and of 34 other specimens without viral inclusion bodies (group B) but with the same microscopic features as group A. Re-cuts from both specimen groups were studied using immunohistochemistry and ISH with a CMV specific complementary DNA probe. RESULTS--CMV infection was confirmed in 35 specimens (29 by immunohistochemistry, 23 by presence of inclusion bodies in haematoxylin and eosin stained sections, 16 by ISH) from 27 patients (incidence 16.9%). CMV hepatitis was diagnosed within 46 +/- 19 (range 21-114) days posttransplant. Twenty on (91.3%) of the 23 biopsy specimens with inclusion bodies (group A) displayed heterogeneous inflammatory foci disseminated throughout the hepatic lobule. Nineteen specimens (82.6%) were positive by immunohistochemistry and 14 (60.9%) by ISH. In eight (23.5%) of the 34 group B specimens CMV infection was confirmed by immunohistochemistry (n = 6) or ISH (n = 2). Another 12 (35.3%) of the group B specimens negative on staining with haematoxylin and eosin, immunohistochemistry and ISH came from allografts in which previous or subsequent biopsy specimens were CMV positive. CONCLUSIONS--Demonstration of cytomegalic inclusion bodies in haematoxylin and eosin sections is sufficient for a diagnosis of CMV hepatitis. The routine use of immunohistochemistry in all allograft biopsy specimens in more sensitive than demonstration of inclusion bodies by staining with haematoxylin and eosin but may yield false negative results because of the focal distribution of positive cells. ISH was less sensitive than staining with haematoxylin and eosin and/or immunohistochemistry. A histological picture of "disseminated focal hepatitis" without viral inclusion bodies selects a group of allograft biopsy specimens in which immunohistochemistry and/or ISH may improve detection of CMV.     

Pathologic diagnosis of renal transplantation

Eighty-seven renal allografts were examined at our department between 1980 and 1989. In these specimens, 24 cases involved so-called "1 hour biopsy", including a case of donor carrying IgA nephropathy. Nine cases showed glomerulonephritis, of which three cases are suspected as de novo membranous nephropathy. Acute rejection, glomerular, tubular and vascular type were seen in 11 cases, and chronic rejection in 20 cases. Four cases showed tubular injury which may be associated with cyclosporine nephrotoxicity. At diagnosis of acute cellular rejection, immunohistological analysis was performed to characterize the composition of the micronuclear cells. In all cases we examined, T lymphocyte is dominant, and CD8+ (Leu 2) cells and CD4+ (Leu 3) cells were seen in various percentages. The Leu M1(+) macrophage was also seen in glomerular capillary lumen or peritubular space. Whether the expression of HLA-DR antigens is altered in renal transplants was examined. Expression of DR antigens increased considerably on renal tubular cells and glomerular capillary endothelial, and may be a markers of acute rejection.     

Histologic changes in liver allograft biopsies associated with elevated whole blood and tissue cyclosporine concentrations.

Cyclosporine is used in the postoperative management of rejection in liver allograft recipients. Despite its efficacy in the treatment of allograft rejection, the drug exhibits toxicity at elevated whole blood concentrations including nephrotoxicity with associated histologic changes, and evidence of hepatotoxicity as determined by liver function studies. To date, there have been few published reports describing histologic changes in liver biopsies from patients with elevated blood cyclosporine levels. In the present study, we retrospectively examined biopsies from 16 liver allograft recipients, seven patients with elevated whole blood cyclosporine levels (> 1000 ng/ml) and nine control patients who had whole blood cyclosporine levels in the therapeutic range (558 to 993 ng/ml). In each case, frozen liver biopsy tissue was available to measure tissue levels of cyclosporine and metabolites. The blood and tissue drug levels were then correlated with the histologic changes present in the biopsy specimens. Patients with increased cyclosporine levels displayed histologic changes consisting of hypertrophy of the bile ductal epithelium with cytoplasmic vacuoles and the presence of "foamy" material within the hepatic sinusoids that were either absent or occurred less frequently in the control group. The histologic changes correlated best with cyclosporine metabolite levels rather than tissue levels of native drug. When liver function studies were correlated with cyclosporine levels, only gamma glutamyl transpeptidase (GGT) demonstrated a significant positive correlation with the histologic changes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Histologic findings in protocol biopsies of transplanted kidneys

Fourty eight patients with cadaveric kidney allografts treated by cyclosporin A (CSA) or tacrolimus (FK506) underwent protocol graft biopsies at 1, 3 and 12 months after transplantation, and 110 biopsy specimens were obtained. Histologic diagnosis was made according to the Banff scheme. The main cause of the graft instability at 1 and 3 months was acute clinical rejection, these biopsies showed all known histological patterns of tubulointersticial and vascular rejection. Acute tubular nephropathy was found in 13% and borderline changes or nephrotoxicity in 8.7% of instable grafts. Specifically, we focused on the occurRence of subclinical rejection and toxic reactions in stable renal allografts. Of these, 36.1% showed histological patterns of acute tubulointersticial and vascular rejection. The Banff score of subclinical rejection was significantly lower than in clinically apparent rejection. CSA and tacrolimus nephrotoxicity were seen in 14.2%, 19.5% and 27.2% of specimens at 1, 3 and 12 months, respectively. In over one half of the identified cases of nephrotoxicity neither increased level of immunosuppression nor features of allograft dysfunction were found. At 12 months, 45.5% of specimens showed mild chronic transplant nephropathy and 18.1% moderate chronic transplant nephropathy. Normal morphology was found in 36.4% of biopsies. We found a high prevalence of subclinical rejection and nephrotoxicity in the studied cohort. We conclude that protocol biopsy is a reliable method in the diagnosis of clinically silent, as well as clinically apparent, disorders of the transplanted kidney.     

Beta-2-microglobulin expression in the liver after liver transplantation.

The distribution of major histocompatibility complex (MHC) class 1 antigens was studied in the liver after transplantation by immunoperoxidase staining for beta-2-microglobulin (beta 2m), a subunit of the class 1 antigen system. Paraffin wax sections were examined from 25 "time zero" biopsy specimens, taken immediately after insertion of the graft, and 87 biopsy specimens taken after transplantation in seven diagnostic categories: acute cellular rejection (n = 22); resolving acute rejection (n = 8); chronic rejection (n = 22); pure cholestasis (n = 14); ischaemia/infarction (n = 5); biliary obstruction (n = 8); massive haemorrhagic necrosis (n = 8). Staining was graded semiquantitatively on a scale of 0-3+ in bile ducts, hepatocytes, sinusoidal lining cells and vascular endothelium. Using the "time zero" biopsy specimens as a baseline for comparison, increased expression of beta 2m was seen in bile ducts, hepatocytes, and endothelial cells after transplantation. These changes were most pronounced in cases of rejection but also occurred in other graft conditions. The degree of hepatocyte and endothelial staining was significantly higher in cases of rejection and massive haemorrhagic necrosis than in the other categories. These findings may have implications for the pathogenesis and diagnosis of rejection of the transplanted liver.     

Apoptosis in acute pulmonary allograft rejection and cytomegalovirus infection.

Apoptosis is a form of programmed cell death, characterized by activation of endonucleases that cleave DNA into oligonucleosomal fragments, which can be identified by in situ terminal deoxyribonucleotide transferase-mediated dUTP nick-end labeling (TUNEL). This process has recently been implicated in cardiac and hepatic allograft rejection, and we investigated its contribution to acute pulmonary allograft rejection and cytomegalovirus (CMV) pneumonitis by in situ TUNEL of transbronchial biopsy specimens. In situ TUNEL was performed on 70 transbronchial biopsy samples collected from 25 pulmonary allograft recipients for diagnosis of acute rejection or CMV pneumonitis, and the number of apoptotic nuclei/mm2 was correlated with the rejection grade (International Society of Heart and Lung Transplantation classification). During acute pulmonary allograft rejection, apoptotic nuclei were demonstrated in pulmonary parenchymal cells and mononuclear infiltrating cells, and the number of apoptotic cells was positively correlated with the rejection grade. In addition, a marked increase in the density of apoptotic cells was found in pulmonary allografts with CMV pneumonitis. We conclude that apoptosis contributes to cell death during acute pulmonary allograft rejection and CMV infection.     

Fine-needle aspiration biopsy in transplantation pathology.

Invasive methods are the only reliable method for diagnosis of rejection and other intragraft complications. Needle biopsy (NB) histology is considered as the "gold standard," but because of potential complications, cannot be used for frequent monitoring of organ allografts. Fine-needle aspiration biopsy (FNAB) is an invasive, but less traumatic, diagnostic method for continuous monitoring of intragraft events. The FNAB method makes it possible to evaluate the onset, intensity, and duration of inflammatory episodes of acute rejection. Parenchymal changes in the FNAB specimens give additional information of the intragraft events. As FNAB can be repeated daily, it enables not only diagnosis of the presence or absence of acute rejection, but can also monitor the effect of immunosuppressive therapy and the response to antirejection treatment. However, the diagnosis of chronic rejection and other later complications is established only by biopsy histology.     

494例次移植肝穿刺活检病理组织学分析

目的 通过对354例(494例次)移植肝穿刺活检组织进行病理分析，观察移植肝的组织学变化，探讨其出现肝功能不全的原因。方法 移植肝穿刺活检组织经10％中性福尔马林固定，快速石蜡连续切片，常规HE染色。部分病例做VG、Masson、PAS、网状纤维组织化学和免疫组织化学染色，抗体为HBsAg、HBcAg、HcVAg、CMV、CD8、CD4、CK19。对排斥反应病例，依照国际统一的BANFF标准进行急性排斥反应分级，应用排斥活动指数(RAI)进行排斥反应程度评分。结果 急性细胞性排斥反应最常见，180例(50．85％)，慢性排斥反应11例(3．11％)，再灌注缺血损伤20例(5．65％)，胆汁淤滞及急慢性小胆管炎64例(18．08％)，药物性肝损害18例(5．08％)，移植肝无功1例(0．28％)，CMV感染24例(6．78％)，乙肝病毒再感染及乙肝复发27例(7．63％)，丙型肝炎复发2例(0．56％)，原发性硬化性胆管炎复发1例(0．28％)，难以诊断6例(1．69％)。结论 移植肝穿刺活检对移植术后并发症的诊断及选择治疗方案具有重要价值。     

Propagation of infiltrating lymphocytes and graft coronary disease in cardiac transplant recipients

The pattern of lymphocyte growth from endomyocardial biopsies in 55 heart transplant recipients was shown to be correlated with the subsequent development of graft coronary disease. Persistent lymphocyte growth was observed in 39 patients, and 15 of these growers (or 41%) developed graft coronary disease. In contrast, only 1 of 15 patients (or 6%) with nongrower biopsies showed subsequent graft coronary disease. Thus, biopsy growth was associated with a higher incidence of subsequent GCD (p = 0.02). A comparison between the group of 15 growers with subsequent graft coronary disease and the 24 growers without subsequent graft coronary disease did not show any differences with respect to patient age, presence of coronary artery disease in the native heart, biopsy histology, donor alloreactivity of biopsy grown lymphocytes, and immunosuppressive drug regimen. On the other hand, the number of treated rejection episodes was significantly lower in the grower group with subsequent graft coronary disease (p = 0.04). These data support the concept that graft coronary disease may involve rejection and that more immunosuppression may lower its incidence. This concept is strengthened by findings showing that alloreactive T cells can be propagated from coronary arteries of cardiac allografts with graft coronary disease.     

Clonal analysis of graft-infiltrating lymphocytes from renal and cardiac biopsies. Dominant rearrangements of TcR beta genes and persistence of dominant rearrangements in serial biopsies

Graft-infiltrating lymphocytes from both human renal and cardiac allografts were propagated in interleukin 2 in order to evaluate rearrangements in the T-cell receptor (TcR) beta-chain genes. Individual biopsies from renal allografts during episodes of cellular rejection were examined as well as multiple biopsies of heart transplant patients from whom endomyocardial samples were taken prior to, during, and after episodes of rejection. TcR beta-chain rearrangements were evaluated in Southern blots using DNA extracted from interleukin 2-propagated cells and digested with restriction endonucleases permitting assessment of rearrangements to both C beta 1 and C beta 2. Rearrangements shared among greater than 5% of the "bulk" culture appear as nongermline bands when hybridized with a C beta probe. Single-cell progeny were generated from limiting dilution, and the rearrangements among the cloned progeny compared to the "bulk" of the cultured progeny of graft-infiltrating lymphocytes. The results indicate that "dominant" rearrangements are a common feature of renal allograft-infiltrating lymphocytes (14 of 15 cases examined). Since the number of cells which can be recovered from a given cardiac biopsy may be limiting, evaluation of clonal dominance from these cultures is more difficult to evaluate. However, sharing of "dominant" rearrangements among multiple biopsies from the same cardiac allograft patient indicates an in vivo selection for T cells with the same receptor rearrangement. Analysis of individual clones showed 3/33 clones from a renal allograft sharing the "dominant" rearrangement noted in the bulk culture, but none of these "dominant" clones showed antidonor specificity.(ABSTRACT TRUNCATED AT 250 WORDS)     

The relationship of nodular endocardial infiltrates (Quilty lesions) to survival, patient age, anti-HLA antibodies, and coronary artery disease following heart transplantation.

BACKGROUND: Quilty lesions are mononuclear cell infiltrates identified in human heart transplant biopsies. The biologic significance of Quilty lesions remains undetermined. METHODS: We monitored acute rejection by biopsy and lymphocyte growth assay (LGA) as well as transplant-related coronary artery disease (TRCAD) by yearly angiogram in 285 recipients of primary heart allografts. Patients showing Quilty lesions on biopsies during the first year posttransplant were compared with patients without such lesions. Recipients' sera were obtained at the time of biopsy and tested for anti-HLA Class I and II antibodies. RESULTS: The actuarial survival of patients who developed Quilty lesions was significantly better than those who did not (P=.0074). Patients with Quilty lesions were younger and more likely to have a biopsy diagnosis of acute rejection (P=.002) and positive LGA (P<.0001) during the first posttransplant year. Among patients who do not form anti-HLA Class II antibodies, those with Quilty lesions were more likely than patients without Quilty lesions to develop TRCAD 5 years posttransplantation (P=.04). There was no correlation of Quilty status with the number of HLA donor-recipient mismatches or posttransplant development of anti-HLA antibodies. CONCLUSIONS: Quilty formers showed improved survival and are more likely to be diagnosed with acute rejection on biopsy and have positive LGAs. Allograft recipients who do not form anti-HLA Class II antibodies but do form Quilty lesions are more likely to develop TRCAD by 5 years posttransplantation than those who do not form Quilty lesions.     

肝脏微循环障碍在慢性乙型肝炎中的作用及其发生机制

目的 :探讨肝脏微循环障碍的发生机制及其在慢性乙型肝炎 (慢乙肝 )病情发展中的作用。方法 :40例慢乙肝患者均行肝活检 ,活检组织分别进行HE染色、免疫组化染色及电镜观察。同时常规检查肝脏功能。结果 :40例慢乙肝患者均存在不同程度的肝脏微循环障碍 ,其中 2 3例肝窦内皮细胞胞浆内可见WP小体。 40例中vWF沿肝窦壁呈阳性表达的有 2 5例 ,肝细胞内HBcAg阳性表达 17例。vWF与HBcAg同时表达者肝功能均不正常。 2 8例肝功异常者中有9例肝细胞内无HBcAg表达 ,但vWF为阳性表达。结论 :慢乙肝存在肝脏微循环障碍 ;肝脏微循环障碍可协同乙肝病毒对肝细胞的免疫损伤 ,从而影响肝脏功能 ;肝窦内皮细胞中WP小体的出现可能是导致肝脏微循环障碍的重要环节。     

Histologic features of the liver in insulin resistance-associated iron overload. A study of 139 patients

The aim of the present study was to describe histologic features of the liver in insulin resistance-associated hepatic iron overload (IR-HIO), defined as the association of metabolic disorders and hepatic iron overload. We included 139 patients in the study on the basis of one or more metabolic disorders and liver iron overload unrelated to usual causes. Liver biopsy specimens were reviewed, and histologic data were compared with those of a previously published, well-defined population with genetic hemochromatosis. Iron overload was characterized by a mixed pattern with iron deposits in hepatocytes and sinusoidal cells. Steatosis was present in 59.7% of patients with inflammation in 32.4% of cases. Periportal fibrosis was found in 67.4% of patients. These patients were older, had higher sinusoidal iron scores, and had a higher prevalence of steatosis and inflammation than patients without fibrosis. Iron overload in IR-HIO was histologically different from that in genetic hemochromatosis.     

人异体移植肾之闭塞性动脉病的病理学研究

目的对移植肾之闭塞性动脉病（ｏｂｌｉｔｅｒａｔｉｖｅａｒｔｅｒｉｏｐａｔｈｙ,ＯＢＡ）进行组织学观察;分析病变中细胞成分;探讨其发病机理。方法对７４例急性血管型和慢性型排斥反应的移植肾进行光镜,电镜和免疫组化ＬＳＡＢ法观察。结果ＯＢＡ病变主要累及所有７４例移植肾内叶间动脉,弓形动脉和小叶间动脉内膜。２９例（３９．２％）在肾移植术后３个月内就能形成ＯＢＡ。早期病变１９例（２５．７％）,表现为动脉内膜炎;晚期病变５５例（７４．３％）,以动脉内膜梭形平滑肌细胞增生,管壁纤维化为主。ＯＢＡ病变中的细胞成分,一方面来自宿主;另一方面来自移植肾动脉壁本身,包括Ｔ淋巴细胞、单核（巨噬）细胞、内皮细胞和不同表型———“收缩型”及“合成型”平滑肌细胞,后者分泌Ⅰ,Ⅲ型胶原。结论ＯＢＡ是发生于移植后肾内动脉壁的增殖性病变,是移植物血管壁本身的细胞成分与宿主免疫细胞间一系列相互作用的结果,是一种免疫反应。     

Preferential endocardial residence of B-cells in the "Quilty effect" of human heart allografts: immunohistochemical distinction from rejection.

Endocardial infiltrates (EI) are a common and often problematic observation in endomyocardial biopsy specimens (EMBs) from patients receiving cyclosporine immunosuppression following cardiac transplant. Histologic and immunohistologic findings in 23 EMBs from 19 patients and 15 autopsy or explanted allografts demonstrated EIs to be rich in B lymphocytes (871/mm2) compared to T-lymphocytes (803/mm2). Macrophages also demonstrated an endocardial preference over deeper myocardium. In contrast, T-lymphocytes outnumbered B-lymphocytes in deeper myocardium (mean 44/mm2 versus 22/mm2) especially when rejection was present. In allograft specimens, the overall number of typical nodular EIs or percent length of endocardial involvement by EI did not correlate with the presence or absence of myocardial rejection at autopsy or explant but were related to implant duration (r = +0.63, p less than 0.01) and number of previous rejection episodes. The number of thin, nondiscrete endocardial infiltrates was greater in hearts with any myocardial rejection or inflammation present. No relationship was observed between EIs present in either EMB or allografts and the cumulative or mean dose or mean serum level of cyclosporine. Thus, a distinct morphologic and immunohistologic profile distinguishes EIs from acute rejection.     

Immunopathology of organ transplantation

Immunopathology techniques are useful and sometimes indispensable tools to diagnose and/or define pathogenesis of disease processes in an organ allograft. Using immunostaining and/or in situ hybridization, cells and molecules can be identified and localized in organ grafts. Considered in this chapter are the "priming" of tissues by ischemia and infection, cell-mediated and antibody-mediated acute and chronic rejection in xenografts and allografts, graft infection, and recurrent or de novo immune disease in organ grafts. The chapter is designed to provide an overview, with illustrative examples of the contribution of immunopathology to analysis of solid organ allografts.     

Graft eosinophilia in lung transplantation.

Graft eosinophilia was observed in lung biopsies from nine patients who received lung allografts. Five cases were associated with moderate to severe acute cellular rejection and responded well to steroid therapy. In this group the eosinophilia occurred early after transplantation and was associated with an elevated white blood cell count and occasional peripheral blood (one of five cases) and bronchoalveolar lavage (one of five cases) eosinophilia. A second group of four patients had graft eosinophilia due to infectious agents. In these cases patients frequently had underlying bronchiolitis obliterans (two of four cases) and developed tissue eosinophilia late after transplantation. Bronchoalveolar lavage cell profiles often demonstrated dramatic eosinophilia. Histologically, the biopsy specimens displayed an acute eosinophilic pneumonia, which was attributed to Aspergillus sp (two cases), coxsackie A2 virus (one case), and Pseudomonas maltophilia (one case). Two patients in this group died from infection. While eosinophils are a frequent cellular component of acute rejection reactions, they also may be the dominant cellular component in graft infection.     

Re-examination of sinusoidal deposition of complement 4d in liver allografts: experience from a single institution

Complement 4d (C4d) is a marker of complement activation that has been used to evaluate humoral rejection in renal and heart allografts. Studies suggested a role for C4d detection in liver allografts in diagnosing acute cellular and humoral rejection but none correlated this with the pre-transplant liver disease. Our study analyzed the association of C4d deposition in liver allografts with the pre-transplant liver disease. C4d deposition was evaluated by indirect immunofluorescence and correlated with lymphocytotoxic crossmatch results, post-transplant clinicopathological diagnosis and type of pre-transplant liver disease. Allograft biopsies were classified by the native liver disease. After excluding 20 patients with rare liver diseases; C4d deposition was evaluated in 506 biopsies from 310 patients including 25 with PSC, 198 with viral hepatitis and 87 with other diseases. C4d immunereactivity distribution was not different among biopsies from patients with different lymphocytotoxic crossmatch results. Sinusoidal C4d deposition was noted in 11.9% of biopsies and 15.2% of patients (in one or more biopsies). 26% (9/35) of biopsies from patients with PSC had sinusoidal C4d deposition; more frequently than from patients with viral hepatitis 12% (43/348) (p=0.04) and other liver diseases 7% (8/123) (p=0.005). In conclusion, C4d deposition in liver allografts is independent of the crossmatch results. It occurs with a variety of pathologic abnormalities and underlying liver diseases; but is more frequent in patients with PSC. This suggests that mechanisms other than allo-immunity activate complement. The mechanisms and clinical significance of C4d deposition in liver allografts in patients with PSC remain to be determined.     

Morphologic features resembling transplant rejection in core biopsies of native livers from patients with Hepatitis C

Morphologic differentiation of recurrent Hepatitis C from transplant rejection is a major problem in posttransplant liver biopsies. Although biopsies of the native livers from patients with Hepatitis C are known to display bile duct damage, other morphologic features similar to those seen in rejection, such as endotheliitis, portal eosinophils, and pericentral fibrosis, are not generally acknowledged. To determine the frequency with which features morphologically similar to rejection might be present, we examined 50 cases of core-needle biopsy from the native livers of patients with Hepatitis C for the presence of the following: bile duct damage, portal eosinophils, portal or central vein endotheliitis, ductopenia, vascular obliteration, pericentral fibrosis, and pericentral mononuclear cell infiltrate. Biopsy specimens with other concurrent disease processes were excluded. The frequency of each morphologic feature was as follows: bile duct damage (30%), portal eosinophils (42%), portal endotheliitis (20%), central vein endotheliitis (0%), pericentral mononuclear cell infiltrate (14%), ductopenia (2%), atrophic-looking bile ducts (2%), vascular obliteration (0%), and pericentral fibrosis (10%). Bile duct damage and portal endotheliitis were both more common with higher grade hepatitis (Fisher exact test, P = .001). None of the morphologic parameters correlated with biopsy stage, viral genotype, or liver function tests. We conclude that features similar to those found in acute rejection are common in Hepatitis C, whereas features resembling chronic rejection are less frequent. This study provides quantitative data that supports the need to interpret these features with great caution in posttransplant liver biopsies from patients with recurrent Hepatitis C who are suspected of rejection.