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Purpose: To describe the vascular and tissue histopathological changes in seven sequential experimental liver transplantations in pigs., Methods: Fourteen female pigs, Sus domesticus species, with body mass between 5 and 8 kg were utilized. After the end of all anastomoses of the graft implantation in the receptor, the animal was monitored for 30 minutes, and at its end one of the biopsies was collected for histological analysis. The histological criteria utilized were: lytic hepatocyte necrosis, density of septal and portal inflammatory infiltrated, sinusoidal congestion and hemorrhage. The analysis was performed separately for the portal region in zone 1, 2 and 3., Results: Among the structural changes undergone by the graft, those with greater frequency and intensity were vascular congestion and steatosis, which stood out in transplantations 5, 6 and 7., Conclusions: The technique demonstrated vascular alterations represented by vasocongestion, edema and minimum inflammatory reaction. In relation to the parenchyma, was observed macrovacuolar pan-acinar steatosis, focal lytic and occasional hemorrhages, beyond the accumulation of hemosiderin in Kuppfer's cells.

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.

Background: The small-for-size (SFS) syndrome is caused by excessive portal inflow into a small-sized liver graft. Various approaches for portal decompression have been used, but details of their impact on liver regeneration in SFS graft remain unclear. We examined the effect of prophylactic splenic artery modulation (SAM)., Methods: We conducted a retrospective cohort study. The study group was 39 consecutive adult-to-adult living liver transplantation recipients, with a graft-to-recipient body weight ratio of less than 0.8. Patients were assigned into the non-SAM group (n=18, without any portal inflow attenuation) or SAM group (n=21, preoperative embolization in 15 patients and intraoperative ligation in 6 patients). Hepatic hemodynamics, graft function, liver regeneration, and outcome were evaluated., Results: In the SAM group, the excessive portal flow was significantly reduced (P<0.01) and the effect of embolization on portal decompression was equivalent to that of ligation. In the acute postoperative phase, serum transaminases, interleukin-6, and tumor necrosis factor-alpha, were lower in the SAM group than in non-SAM group. In both groups, a negative correlation was observed between graft-to-recipient body weight ratio and liver regeneration rate at 2 weeks after living donor liver transplantation. Splenic artery modulation was advantageous for liver regeneration, and significantly improved clinical features, hyperbilirubinemia, and prolonged ascites. Small-for-size syndrome occurred in five patients of the non-SAM group, and only one of SAM group (P=0.038)., Conclusion: In SFS graft with severe portal hypertension, prophylactic splenic embolization/ligation seems to relieve portal overperfusion injury and contributes in improvement of posttransplantation prognosis through liver regeneration.

Hepatoportal sclerosis (HPS) is one of the causes of noncirrhotic portal hypertension. In general, hepatic synthetic function is preserved and treatment is aimed at relief of the portal hypertension. In this study, we present the clinical and pathologic features of HPS cases who underwent liver transplantation (LT). LT cases with confirmed gross and microscopic diagnosis of HPS are included. Weight of the explanted liver, presence of thrombi in the main blood vessels, and gross and microscopic characteristics were assessed. Clinical information was gathered from chart review. From 1995 to 2004, 8 LT patients were diagnosed with HPS. Cirrhosis resulting from alcohol (2), autoimmune hepatitis (2), and hepatitis B (1), or cryptogenic cirrhosis (3) was the presumed diagnoses pre-LT. Seven patients presented with bleeding varices and 5 had concomitant ascites. At the time of LT, mean values were: prothrombin time of 15.2 seconds, serum albumin 3.2 g/dL, serum bilirubin 3.5 mg/dL, alkaline phosphatase 140 IU/L, aspartate aminotransferase 39.4 IU/L, and alanine aminotransferase 34.7 IU/L. Explanted livers were shrunken, with weights ranging from 715 to 1199 g (mean 934). Nonocclusive portal vein thrombosis was present in 2 patients. On histologic examination, there was dense portal fibrosis, marked phlebosclerosis, and presence of variable degrees of megasinusoid formation. Four livers also had features of incomplete septal cirrhosis. None showed histologic features of the presumed underlying liver disease. In conclusion, HPS can cause hepatic synthetic dysfunction that may necessitate LT. Small liver volume, significant portal fibrosis, and phlebosclerosis may contribute to hepatic parenchymal loss and subsequent synthetic compromise.

Endotheliitis is an important histologic feature of acute cellular rejection (ACR) in the liver allograft. This change is not specific, however, and has been suggested to be associated with various liver diseases. End-stage liver disease owing to chronic hepatitis C is the leading indication for transplantation in North America, and its recurrence in allograft recipients is common. Because the presence of endotheliitis remains a diagnostic and therapeutic dilemma in transplant pathology, we investigated the prevalence and severity of endotheliitis in chronic liver diseases including hepatitis C. Endotheliitis was evaluated in 128 nontransplant liver biopsies of chronic liver diseases before therapy, including hepatitis C (HCV, n=62), hepatitis B (HBV, n=17), and nonalcoholic steatohepatitis (NASH, n=49). Eighty posttransplant biopsies with ACR were also reviewed. Subendothelial and supraendothelial endotheliitis were separately scored in the portal and central regions using a semiquantitative scoring system from 0 to 4. Pathologists were blinded to the clinical histories, and each biopsy was independently scored by 2 pathologists. Histologic activity index was also scored subsequently for cases of chronic HCV and HBV, using the modified Knodell (Ishak) score. Mean endotheliitis scores>1 were seen in 60%, 35%, and 6% of HCV, HBV, and NASH patients, respectively. The scores for portal subendotheliitis and supraendotheliitis were significantly higher in the viral hepatitis group than in the NASH group (P<0.01). There was no significant difference in the scores of endotheliitis comparing HCV to HBV. ACR group showed significantly higher scores in both portal and central subendotheliitis than any other group (P<0.00005). In the HBV and HCV groups with mean scores of portal subendotheliitis>1 (n=44), mean Ishak scores for portal inflammation and periportal injury were 2.43 and 2.34, respectively; whereas in those with less severe portal subendotheliitis (

Abnormal portal vessels in small portal tracts can be seen in association with various causes of portal hypertension, such as noncirrhotic portal hypertension (NCPH) and cirrhosis. Very little has been reported about the presence of abnormal portal vessels in livers with normal portal pressure. Little attention has also been given to the presence of abnormal vessels in liver allografts outside the setting of transplant vasculopathy/chronic rejection. This study reports on the portal vasculature abnormalities, many similar to those described in NCPH, encountered in routine native liver biopsies (n = 46) and allograft liver biopsies (n = 48). A classification scheme for the abnormal portal vasculature was adapted from the literature, and the portal vessels were divided into five groups (types 0-IV). Abnormal vessels were present in greater than 25% of the portal tracts in 88% of all the biopsies studied; there was no significant difference between the native and allograft biopsies. In the allograft biopsy group, there were correlations between vascular abnormalities and severity of a concurrent acute cellular rejection episode, the presence of prior rejection episodes, and length of time after transplant. Biopsies from patients with viral hepatitis C infection (HCV) showed more type IV lesions (absent or sclerosed portal vessels) with fragmentation when compared with biopsies obtained for other reasons. The number of portal tracts with abnormal portal veins and fragmented vessels correlated positively with increasing fibrosis. This is the first study to demonstrate the presence of abnormal portal vessels, some of the type seen in NCPH, in a significant number of both native and allograft liver biopsies in patients without evidence of portal hypertension. Abnormal portal vasculature tends to be associated with HCV and increased fibrosis, and, within the transplant group, with the severity of rejection, presence of prior rejection episodes, and increased time posttransplantation.

Almost no data exist concerning the role of antibody-mediated mechanisms in human acute cellular liver allograft rejection (ACR). Therefore, the aim of this study was to determine whether ACR is associated with depositions of complement split products and increased infiltration by B-lymphocytes, plasma cells and macrophages. A total of 35 liver biopsy specimens (ACR n=22, controls n=13) were analyzed by immunohistochemical single and double staining. The average numbers of CD 20(+), CD 38(+) and CD 68(+) cells per portal tract were established while the presence of C4d and C3d deposits was evaluated semiquantitatively. Significantly greater numbers of CD 20(+) (P=0.029) and CD 38(+) (P=0.014) cells were found in the ACR specimens than in the control specimens. Additionally, 50% of patients diagnosed with ACR showed C4d deposits along portal capillaries, which was associated with a significantly increased portal infiltration by macrophages (P=0.007). Taken together these results support the involvement of humorally mediated mechanisms in some cases of ACR.

Humoral rejection caused by antidonor blood group A/B antibodies is one of the most important obstacles for successful ABO-incompatible liver transplantation. However, no specific morphologic features of liver biopsies to distinguish humoral rejection from other conditions such as ischemia or sepsis have been satisfactorily documented. To histologically clarify the early changes in humoral rejection, we studied 41 cases of living donor ABO-incompatible liver transplantation whose allograft biopsies during the first episode of suspected acute rejection were available within the first postoperative month. Postoperative isohemagglutinin IgM titers were x64 or more in 21 patients (51%; high-titer group) and less than x64 in 20 cases (49%; low-titer group). In the high-titer group, elevation of postoperative titers x64 or more occurred within postoperative days 5.7 +/- 4.1 (range: 1-17). An increase in the incidence of cholangitis was observed in the high-titer group (90% vs. 30%, P <.0001), as well as poorer overall graft survival than in the low-titer group (38% vs. 70%, P <.05). Seven biopsies obtained from the high-titer group within 3 days after the onset of elevation of the antibody titers and one biopsy obtained at the peak of the antibody titers demonstrated periportal edema and necrosis, neither of which was found in the low-titer group. All grafts of these patients caused massive hepatocyte necrosis or severe biliary complications. In conclusion, a high morbidity rate of ABO-incompatible liver transplantation is associated with high postoperative levels of antibody titers. Periportal edema and necrosis observed during elevation of antibody titers can be regarded as histological indications of early changes in severe humoral rejection.

Hepatic parenchymal changes associated with Budd-Chiari syndrome (BCS) have been tentatively explained by combined arterial and portal perfusion disturbances in addition to the complete occlusion of hepatic veins. The aim of this study was to correlate pretransplant course and vascular imaging with pathologic findings in livers explanted for BCS. Seventeen consecutive white patients who underwent transplantation for severe classic BCS were retrospectively analyzed. Pretransplant course was 1 year or less in 8 patients and more than 1 year in 9 patients. Thrombophilia was found in 16 patients (94%). Imaging showed decreased portal perfusion in 16 patients (94%) and increased arterial perfusion in 9 patients. Histology showed obstructive portal venopathy and nodular regenerative hyperplasia (NRH) aspects in all cases, large regenerative nodules resembling focal nodular hyperplasia (FNH) in 9 cases, and cirrhosis in 2 cases. Patients with increased arterial inflow had large regenerative nodules and a protracted pretransplant course. Patients with acute thrombi in portal veins had parenchymal infarcts (2 cases) and a short pretransplant course. In conclusion, patients with severe BCS have a constant impaired perfusion inflow unrelated to progression of cirrhosis but related to the outcome. An early decrease in portal perfusion is observed in the short term and is responsible for NRH or infarcts if complicated with large thrombi. An increase in arterial perfusion compensates impaired portal flow in chronic BCS. Arterial hyperemia contributes to the development of large regenerative nodules that are FNH-like. This pathologic situation offers an interesting vascular model to further understand the parenchymal response to changes in hepatic blood flow.

Background: Late graft dysfunction after orthotopic liver transplantation is commonly due to chronic rejection, recurrence of primary disease, sepsis, lympho-proliferative disease, or vascular or biliary complications. Herein we describe a subset of pediatric liver transplant patients in whom late graft dysfunction was associated with autoimmune markers, bile ductular proliferation, and portal infiltrates, which progress to fibrosis. This subset of patients has not been previously described., Methods: Six of the 115 children followed for greater than 5 years after transplantation developed this unusual form of graft dysfunction. All children were on a low-dose single immunosuppressive therapy (mean trough cyclosporine concentration 89 microg/L) and had been tapered off steroids for a median duration of 1.5 year. Liver biopsies were performed in all children to evaluate the graft dysfunction, and the histologic findings were interpreted by an experienced hepato-pathologist. All patients were tested for antibodies to hepatitis C virus, hepatitis B surface antigen, and IgM antibodies to hepatitis A. Smooth muscle antibody, antinuclear antibody, and antibody to liver/kidney microsome type 1 were sought by indirect immunofluorescence. International Autoimmune Hepatitis Group scores were calculated. All patients underwent ultrasonography with doppler studies at the onset of graft dysfunction. Three patients with marked bile duct proliferation on histology had cholangiograms., Results: Histology in all patients showed mononuclear cell infiltrates in the portal area with interface hepatitis, portal fibrosis, and ductular proliferation without duct damage or loss. All six patients had positive antinuclear antibody or smooth muscle antibody titers. Viral studies for hepatitis A, B, and C were negative in all patients. On the International Autoimmune Hepatitis Group scoring system, five patients had probable autoimmune hepatitis (score of 10-15) and one had definite autoimmune hepatitis (score > 15) at the onset of graft dysfunction. All were treated with azathioprine and prednisone similar to treatment for autoimmune hepatitis. However, despite aggressive treatment, four patients developed bridging portal fibrosis resulting in graft loss in two patients., Conclusion: This clinical constellation is associated with worse outcome then that previously described for pediatric patients with posttransplantation de novo autoimmune hepatitis. Further studies are needed to find an optimal treatment regimen for these patients.

Background: Recent histopathological studies showed an unexpected high incidence of pathological changes in asymptomatic survivors after pediatric liver transplantation. The aim of this study was to analyze the occurrence of histological abnormalities, to assess the clinical significance, and to identify predictive factors for these pathological changes., Methods: The first annual protocol graft biopsies of 84 consecutive liver transplants were analyzed and correlated with concomitant liver function tests. Identification of predictive factors for the histological abnormalities in the biopsies was performed by a multivariate logistic regression analysis., Results: The incidence of portal fibrosis (PF) was 31%. Liver function tests showed except for the albumin level, an increase in the PF group compared with the group without PF. Mean values of alkaline phosphatase and direct bilirubin were 264 U/liter and 3 micromol/liter, respectively, in the normal group, and 435 U/liter and 23 micromol/liter, respectively, in the PF group (P=0.043 and 0.037). Eight of 19 univariantly tested variables were entered into a logistic regression model: cold ischemia time, preservation solution, type of allograft, cytomegalovirus recipient status, type of biliary reconstruction, biliary complications, graft complications, and rejection. A significant positive correlation with PF was found for cold ischemia time, biliary complications, and cytomegalovirus status. Acute rejection showed a negative correlation., Conclusions: The incidence of PF within 1 year post liver transplantation was 31%. This finding was accompanied by cholestatic liver function test abnormalities. Factors predisposing to PF were a prolonged cold ischemia time, biliary complications, and a positive cytomegalovirus recipient status. Acute rejection seemed to prevent for PF.

Objective: To study the effect of Ginaton on liver microcirculation disturbance following liver xenotransplantation in rats., Methods: Ginaton was injected intravenously to recipients at a dosage of 14 mg/kg before graftng liver of guinea pigs. The portal blood flow (PBF) was measured by Doppler ultrasound at 0, 30 and 60 minutes after transplantation, and the pathologic changes of liver and heart were observed., Results: The reperfusion status of control group was poor and leukocyte infiltration appeared in the center of lobute following transplantation and myocardial cells were impaired. Significant reduction in PBF was found in rats following transplantation. Ginaton pretreatment distinctly ameliorated PBF. The speed of PBF was closely correlated with the pathologic changes following transplantation., Conclusion: In the process of liver transplantation, ischemia reperfusion damage may lead to xenoheptic microcirculaton disturbance. Ginaton could improve the xenoheptic microcirculation and reduce ischemic reperfusion damage.

An accurate and functional system for grading acute liver allograft rejection is important for patient management, research, and communication. The Banff schema is a consensus document designed to provide an internationally accepted standard for this purpose. The aim of this study is to determine if application of the Banff schema would significantly alter the grading of acute liver allograft rejection compared with the Birmingham system. One hundred twenty-four post-liver transplantation biopsies performed by the Western Australian Liver Transplantation Service between 1992 and 1997 were retrospectively analyzed by a pathologist and a hepatologist. Each was supplied with a brief clinical history before applying the Banff and Birmingham criteria. Results were compared with each other and to the diagnosis made at the time of the biopsy, which was based on the European grading system. Rejection was diagnosed by the reviewers in 61 of 124 biopsy specimens according to the criteria of Snover. The Banff schema and Birmingham system agreed on the grade of rejection in 22 of the 61 biopsy specimens. The Banff schema elevated the grade of rejection in 39 specimens by an increment of one. In no instance did the Banff schema reduce the grade. Comparison between the Banff schema and diagnosis made at the time of biopsy showed agreement in 39 specimens, whereas the Banff schema elevated the grade in 15 specimens and reduced the grade in 23 specimens. In comparison to the Birmingham system, the Banff schema elevated the grade of liver allograft rejection in the majority of biopsy specimens, and this has the potential to alter clinical management with the adoption of the Banff schema or if the systems are used interchangeably.

Rationale and Objectives: The accuracy of gadolinium-enhanced magnetic resonance venography (GdMRV) in identifying visceral venous abnormalities was assessed in patients before they underwent transjugular intrahepatic portosystemic shunt (TIPS) or orthotopic liver transplantation (OLT)., Methods: Twenty-seven patients with portal hypertension underwent GdMRV and transcatheter venography prior to OLT or TIPS. The gadolinium dose was 0.5 mL/kg (0.25 mmol/kg), administered by rapid hand injection. Coronal 3D spoiled gradient-echo GdMRV was performed in a single breath-hold. Four blinded reviewers retrospectively evaluated coronal maximum intensity projection (MIP) images, while two reviewers evaluated the MIPs and multiplanar reconstructions. Abnormalities that could affect transjugular intrahepatic portosystemic shunt or transplantation were noted and compared with the results of corresponding catheter venograms read by a separate blinded reviewer., Results: Abnormalities were identified by GdMRV with a sensitivity and specificity of 83% and 97% for the right hepatic vein, 86% and 100% for the main portal vein (MPV), 42% and 99% for the right portal vein, 54% and 94% for the left portal vein, 61% and 96% for the superior mesenteric vein, and 74% and 91% for the splenic vein. Varices and shunts were correctly identified with a sensitivity of 96%. Multiplanar reconstruction increased MPV sensitivity to 100%., Conclusion: Vascular abnormalities that affect TIPS and OLT can be identified by GdMRV. Multiplanar reconstruction increased the accuracy to 100% for the MPV.

Background: Recurrence of primary biliary cirrhosis (PBC) within liver allografts remains a controversial issue. The aims of this study were to evaluate this risk and to determine the presence, if any, of a predictive histological feature., Methods: We reviewed the most recent and the 1-year protocol liver biopsies of 69 patients who received transplants for PBC and of 53 control patients. Histological features consistent with PBC recurrence included nonsuppurative destructive cholangitis, mixed portal infiltrate, fibrosis, and ductopenia. A complete evaluation was undertaken in each patient with these histological features., Results: These histological features were present in six patients who received transplants for PBC (8.7% vs. 0% in the control group) and occurred between 1 and 8 years after transplant. In five of the six patients, anti-mitochondrial antibody-2 (anti-M2) antibodies remained at high titers. Cholestasis was present in four patients, and clinical symptoms in two patients. All six patients were negative for hepatitis C antibodies and hepatitis C RNA in their serum. None had bile duct obstruction. The presence of plasma cells in the portal infiltrate at 1 year after transplant was predictive of this risk of recurrence., Conclusion: The risk of PBC recurrence is real (8.7%). The presence of plasma cells in the portal infiltrate seems to be an early marker of recurrence of PBC in patients transplanted for this indication.

A study was conducted to assess the inter and intrarater agreement for the histopathologic features and diagnosis of chronic rejection (CR) and several other important causes of late liver allograft dysfunction. On two occasions, five pathologists, experienced with liver transplantation, reviewed a set of 49 slides representing a range of diagnoses, without knowledge of the clinical history or liver injury test results. The readings were correlated with the original histopathologic diagnosis, liver injury tests, and clinicopathologic follow-up. Assessment of biopsy adequacy (kappa = 0.69) and portal tract counts (kappa = 0.79) showed good to excellent intrarater agreement, whereas interrater agreement for these variables was moderate to good, respectively (kappa = 0.44 and 0.65). Likewise, the intrarater agreement for the diagnosis of CR (kappa = 0.68), hepatitis (kappa = 0.77), and obstructive cholangiopathy (kappa = 0.55) showed good to excellent agreement, whereas the interrater agreement for these same diagnoses ranged from fair to good (kappa = 0.58, 0.46, and 0.25, respectively). In 18 specimens, there was a near unanimous diagnosis of CR across both readings. These biopsies were obtained at a median of 7.1 months (range, 42 days to 4.9 years) after transplantation, and the average number of portal tracts was 8.4 (range, 4-15). Interestingly, only 13 of these 18 specimens showed bile duct loss in >50% of the portal triads; the remaining cases showed atrophy/pyknosis of the biliary epithelium in a majority of small bile ducts. Clinicopathologic correlation showed that these 18 biopsies were obtained from 16 grafts from 15 patients, 14 of whom ultimately required retransplantation or died of or with CR, whereas two of the grafts/patients recovered. A high rate of sensitivity (92%) and a somewhat lower, but acceptable, rate of specificity (71% to 80%) was found for the diagnosis of CR. Chronic rejection and other causes of late liver allograft dysfunction can be diagnosed reliably by a group of pathologists experienced with liver transplantation, and the diagnosis of CR correlates with clinical course and liver function abnormalities. Expanded criteria for the diagnosis of CR are presented, and potential problem areas for practicing pathologists are discussed.

The authors describe the case of a 9-year-old girl who underwent liver transplantation because she suffered from severe hypoxemia caused by patent ductus venosus (PDV). Generally, severe hypoxemia (PaO2 < 50 mm Hg in room air or < 300 mm Hg in pure oxygen) is not an indication for liver transplantation because the hypoxemia may not be improved, and may lead to a fatal outcome. PDV, which is associated with mild liver dysfunction, is not an indication for liver transplantation by itself. But in our patient, most of the mesenteric venous flow directly entered the systemic circulation through the PDV just like the portosystemic shunt, and this caused the pulmonary arteriovenous shunt and hypoxemia. Thus, the authors operated on the patient in an attempt to restore her pulmonary function. Nitric oxide (10 to 20 ppm) was added to the inhaled gas to dilate the functional pulmonary capillaries and to deliver sufficient oxygen after the transplantation. Although the patient suffered various complications after the operation, the final results were excellent.

Sequential two-dimensional phase-contrast MR angiography can be used to accurately evaluate the anatomy, patency, and flow direction of the portal venous system and the presence, extent, and distribution of portosystemic collaterals. Its large field of view, insensitivity to the patient's body habitus, and graphic display format make this MR technique extremely useful for preoperative evaluation of patients with chronic liver disease and portal hypertension. This pictorial essay illustrates the spectrum of abnormalities seen on phase-contrast MR angiography of the portal venous system in patients with endstage liver diseases and portal hypertension.

Aims: To see how useful the application of a bile duct specific cytokeratin antibody (AE1) was in identifying and counting bile ducts in liver allograft biopsy specimens., Methods: Eighteen liver biopsy specimens showing acute rejection and 17 biopsy specimens plus six hepatectomy specimens showing chronic rejection were studied. Serial sections were cut and stained with haematoxylin and eosin and AE1 antibody. Two pathologists (RFH and KP) examined the sections with respect to a range of histological features., Results: Similar numbers of bile ducts were identified on haematoxylin and eosin sections as on corresponding sections stained by AE1 in cases of acute rejection and end stage chronic rejection. Greater numbers of bile ducts were identified by AE1 during the early stages of chronic rejection, especially when dense portal inflammatory infiltrates were present. These were often incomplete structures or individual cells within portal tracts, and bile ducts subsequently disappeared in all cases. Ductular proliferation was clearly shown by AE1 in acute rejection and the extent seemed to correlate with the severity of rejection present. By contrast, no ductular proliferation was observed in chronic rejection., Conclusions: Haematoxylin and eosin stained sections are adequate for counting bile ducts in most biopsy specimens from patients with suspected chronic rejection. Immunostaining for biliary cytokeratins using AE1 is of limited use in occasional cases where bile ducts are obscured by inflammatory cells.

In liver allograft rejection, interlobular bile ducts are thought to be the main target of rejection. In contrast, in other organ allografts the capillary bed of the graft appears to be the primary target. To determine whether portal tract microvasculature is destroyed in liver allografts during rejection, we have identified portal tract microvasculature in 11 normal livers and 38 liver allograft biopsy specimens using monoclonal antibodies to capillary endothelium in immunohistochemical staining. E1.5, CD31 and EL-4 antibodies identified portal microvascular endothelium in normal liver that had the morphology of capillaries. In allograft biopsies the number of microvascular structures per portal tract was reduced markedly in acute cellular rejection to 1.1 +/- 0.6 (n = 25) and to 0.65 +/- 0.9 (n = 15) in chronic ductopenic rejection compared with nonrejecting allografts (2.8 +/- 0.6) (n = 4) or normal liver (3.8 +/- 0.7) (n = 11). To determine whether loss of microvascular structures preceded bile duct destruction in rejection, sections were double-stained to identify both microvasculature and bile ducts. The number of microvascular structures per bile duct was significantly lower in acute cellular rejection (0.5 +/- 0.4) (n = 18) or chronic rejection (0.3 +/- 0.4) (n = 8) compared with normal liver (2.3 +/- 0.6) (n = 7) (P < 0.0001), demonstrating that components of the portal vasculature are destroyed prior to bile ducts. There was a correlation between the severity of rejection and the loss of microvascular structures per bile duct (P < 0.001). In conclusion, in common with other allografted organs, the microvasculature of liver allografts appears to be an early target of rejection.

Thirty patients (mean age, 45 years) were evaluated with magnetic resonance (MR) angiography before liver transplantation to assess the accuracy of MR angiography. A series of breath-hold, two-dimensional images were acquired and subsequently processed to form three-dimensional projection angiograms. Graphic information on blood flow in the portal vein was acquired by using presaturation bolus tracking. Correlative duplex ultrasound (US) was performed in 28 patients, and surgical or autopsy correlation was available in all cases. MR angiography demonstrated patency of the portal vein in 26 (96%) of 27 patients, made possible the diagnosis of portal venous occlusion in three of three patients, depicted reversed portal flow in one patient, and provided clear delineation of the extent of varices and specific portosystemic collateral vessels. When duplex US was successful, there was full agreement with MR angiographic results in assessing portal vein patency and flow direction. All of the MR findings were corroborated at surgical exploration or autopsy. The authors conclude that MR angiography is very accurate in the portal system and is valuable in preoperative assessment for liver transplantation.

Changes in the qualitative character of the portal tract infiltrate of hepatic allografts can influence the diagnosis of acute rejection. Since qualitative data rely on subjective findings, the aim of this study was to perform a quantitative analysis of portal tract infiltrates to improve the accuracy of the diagnosis of acute rejection. A total of 431 serial hepatic biopsies in 58 consecutive adult patients were obtained. The average number of eosinophils, neutrophils, and lymphocytes in each portal tract were counted. The area of each portal tract was determined using an optical micrometer. Rejection was confirmed by an independent investigator using both clinical and histologic criteria. Using a backward stepwise logistic regression analysis, we found that eosinophils were the only variable predictive of rejection. Using this model, the probability of having rejection on a single biopsy can be determined with greater than 90% accuracy.

Monoclonal antibodies were used to identify helper T cells (TH) and suppressor/cytotoxic T cells (TS/C) in liver allograft biopsy specimens obtained 7,21,90,180, and 365 days postoperatively and then annually or during episodes of graft dysfunction and after treatment of rejection episodes. Biopsy specimens were obtained from 70 hepatic allografts from patients treated with cyclosporine and corticosteroids. Rejection was diagnosed by the presence of appropriate laboratory and light microscopic findings and at least 16 weeks of follow-up to exclude other causes of graft dysfunction. Three immunohistologic patterns were noted: no or only a trace of T lymphocytes, predominantly TH infiltrate with or without a small amount of TS/C cells (portal TH), and a mixture of TH with an equal or greater number of TS/C infiltrate (portal mix). Of 68 biopsy specimens obtained during quiescent periods, only 3 had a portal tract T-lymphocyte infiltrate. Of 30 protocol biopsy specimens, 24 contained such an infiltrate a mean of 12.4 days before biochemical and routine histologic indications of rejection in the allograft. At the time of the rejection episode, 33 biopsy specimens were immunohistologically labeled; portal tract T-lymphocyte infiltrate was predominantly TH in 8 and a mixture of TH and TS/C in 25. All rejection episodes with a predominantly TH pattern responded to methylprednisolone. Of the 25 rejection episodes with a portal mix pattern, only 3 responded to methylprednisolone. Eighty-seven biopsy specimens were obtained more than 10 days after treatment of rejection.(ABSTRACT TRUNCATED AT 250 WORDS)