The Banff Working Group on Liver Allograft Pathology reviewed and discussed literature evidence regarding antibody-mediated liver allograft rejection at the 11th (Paris, France, June 5-10, 2011), 12th (Comandatuba, Brazil, August 19-23, 2013), and 13th (Vancouver, British Columbia, Canada, October 5-10, 2015) meetings of the Banff Conference on Allograft Pathology. Discussion continued online. The primary goal was to introduce guidelines and consensus criteria for the diagnosis of liver allograft antibody-mediated rejection and provide a comprehensive update of all Banff Schema recommendations. Included are new recommendations for complement component 4d tissue staining and interpretation, staging liver allograft fibrosis, and findings related to immunosuppression minimization. In an effort to create a single reference document, previous unchanged criteria are also included.

The value of late protocol biopsies after liver transplantation remains to be evaluated to highlight the therapeutic policies. The study population was composed of patients who survived with the initial graft and with an available 10-year protocol biopsy (n ‫؍‬ 143). The long-term histologic outcome of the graft, particularly the rate of ductopenia in cases with chronic rejection (CR), and Metavir scoring of fibrosis in cases with viral chronic hepatitis (VCH), were assessed. Fibrosis progression (FP) rates were compared over 3 periods (0-5, 5-10, and 0-10 years). At 10 years, histologic abnormalities present in 80% of the patients were not identifiable from liver function tests (LFTs), which were strictly normal in 52% of the patients. Histologic CR occurred in 24% at 10 years, with a mean rate of ductopenia higher at 10 years than at 5 years (49% vs. 34%, P < .001). In cases of VCH, fibrosis worsened, with a median FP rate of 0.20 fibrosis units/year. During the first 5 years, FP was as follows; hepatitis B virus infection was greater than recurrent hepatitis C virus (HCV) infection, which was greater than acquired HCV infection (P ‫؍‬ .029). In patients with HCV, FP was higher during the second 5-year period than during the first one (P ‫؍‬ .042). In conclusion, given the high prevalence of histologic abnormalities and the lack of sensitivity and specificity of LFTs, late protocol biopsies clearly are justified to adjust treatments, not only in HCV-infected patients in whom FP was fast and not linear, but also in the whole population of recipients. (HEPATOLOGY 2003;37:1293-1301

BackgroundCaveolin-1 is the main component of caveolae membrane structures and has different roles during tumorigenesis in different cancer types with varying expression profiles, indicating that the role of caveolin-1 varies according to tumor type. In this study, we investigated the role and expression of caveolin-1 in hepatocellular carcinogenesis.MethodsWe analyzed the expression of Caveolin-1 in 96 hepatocellular carcinoma (HCC), 29 cirrhosis, 20 normal liver tissues and 9 HCC cell lines by immunostaining and western blotting, respectively. After caveolin-1 was stably transfected to HepG2 and Huh7 cells, the effects of Caveolin-1 on the cellular motility, matrix invasion and anchorage-independent growth were studied. Also, caveolae structure was disrupted in endogenously caveolin expressing cells, SNU 449 and SNU 475 by addition of methyl-β-cyclodextrin and analyzed cellular motility and invasion.ResultsIn HCC cell lines, Caveolin-1 expression is correlated to differentiation and basal motility status of these cells. The percentage of Caveolin-1 positivity was found extremely low in normal liver tissue (5%) while it was increased in cirrhosis (45%) and in HCC (66%) (p = 0.002 and p = 0.001 respectively). Cav-1 expression in poorly differentiated HCC samples has been found significantly higher than well differentiated ones (p = 0.001). The caveolin-1 expression was found significantly higher in tumor cells than its peritumoral cirrhotic tissues in HCC samples (p < 0.001). Additionally, the patients with positive staining for Caveolin-1 had significantly higher portal vein invasion than those with negative staining (p = 0.02). Caveolin-1 overexpression increased motility and invasion of HepG2 and Huh7 cells. And disruption of caveolae results in a dramatic decline in both motility and invasion abilities in SNU-449 and SNU-475 cells. Furthermore, caveolin-1 overexpression resulted in down-regulation of E-cadherin while up-regulation of Vimentin. Also, it increased secreted MMP-2 and expression levels of MMP-9 and MT1-MMP. There was no significant difference in colony formation in soft agar between stable clones and parental ones.ConclusionIn conclusion, stepwise increase in Cav-1 expression in neoplastic stage with respect to pre-neoplastic stage during hepatocellular carcinogenesis and its ability to stimulate HCC cell motility and invasiveness indicate that this protein plays a crucial role in tumor progression.

In this study, we analyze the demographic features, clinical and histopathological findings in patients who underwent liver transplantation for progressive familial intrahepatic cholestasis. We also analyze outcome and impact of liver transplantation on growth and bone mineral content. Most of the patients were presented with jaundice mainly beginning within the first six months. At the time of initial admission; eight patients had short stature (height SD score<2), and four patients had weight SD score<2. Liver transplantation were performed at the age of 43.2+/-27 months (range 9 to 96 months), 6.5+/-3.5 months later after the first admission. Infection, surgical complications and osmotic diarrhea associated with severe metabolic acidosis were noted in 41.4%, 16.6% and 33.3%, respectively. One patient developed posttransplant lymphoproliferative disorder. Overall; 1 year graft and patient survival was 69.2% and 75%, respectively. At the end of the 1st year only 2 patients had height SD score<2. Linear regression of height gain against increase in total body BMD measured at the time of transplantation and 1 year after liver transplantation gave a coefficient r=0.588 (p=0.074). No correlation was found between the height gain and age and PELD score at time of transplantation, and no difference was noted between the sexes and donor type. Liver transplantation is effective treatment modality with good outcome and little morbidity, and increases the growth acceleration in patients with PFIC associated with cirrhosis.

No abstract