Centrilobular necrosis after orthotopic liver transplantation: Association with acute cellular rejection and impact on outcome

Hassoun, Ziad; Shah, Vijay; Lohse, Christine M.; Pankratz, V. Shane; Petrovic, Lydia M.

doi:10.1002/lt.20122

Cited by 26 publications

(26 citation statements)

References 25 publications

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“…The other conditions presenting with graft inflammation at this stage are all likely to have an allo/autoimmune basis and should, therefore, benefit from an increase in immunosuppression. Late rejection with features of CP often presents with raised transaminase levels, contrasting with the cholestatic liver biochemistry that is more typically seen in early portal-based AR [33,34,41]. It tends to be less responsive to immunosuppression and is associated with an increased frequency of adverse outcomes -these include further episodes of acute rejection [36,42], progression to chronic rejection [32,33,39,[42][43][44][45], and the development of de novo autoimmune hepatitis [39,43].…”

Section: Key Pointsmentioning

confidence: 95%

“…Studies dating back to the late 1980s have suggested that late AR may have different histological features to early acute rejection [3,25,26] -these include a predominantly mononuclear portal inflammatory cell infiltrate (contrasting with the mixed population of cells more typically seen in early AR), less severe inflammation of bile ducts and portal venules, more prominent interface hepatitis (in some cases associated with periportal fibrosis), and more prominent lobular hepatitis [27,28]. Lobular inflammatory changes tend to be most prominent in centrilobular regions and are often associated with foci of centrilobular or bridging necrosis [29][30][31][32][33][34][35][36][37] -these changes are collectively referred to as ''central perivenulitis'' (CP) [30,37] and can occur in the absence of significant portal inflammation (''isolated central perivenulitis'') [29,30,[37][38][39] (Fig. 1).…”

Section: Acute Rejection (Ar)mentioning

confidence: 98%

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What is the long-term outcome of the liver allograft?

Hübscher

2011

Journal of Hepatology

122

127

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With improved long-term survival following liver transplantation (LT), issues relating to the assessment of the liver allograft in long-term survivors are becoming increasingly relevant. Histological abnormalities are commonly present in late post-transplant biopsies, including protocol biopsies from patients who appear to be well with good graft function. Recurrent disease is the commonest recognised cause of abnormal graft histology, but may be modified by the effects of immunosuppression or interactions with other graft complications, resulting in complex or atypical changes. Other abnormalities seen in late post-transplant biopsies include rejection (which often has different appearances to those seen in the post-transplant period), de novo disease, "idiopathic" post-transplant hepatitis (IPTH) and nodular regenerative hyperplasia. In many cases graft dysfunction has more than one cause and liver biopsy may help to identify the predominant cause of graft damage. Problems exist with the terminology used to describe less well understood patterns of graft injury, but there is emerging evidence to suggest that late rejection, de novo autoimmune hepatitis and IPTH may all be part of an overlapping spectrum of immune-mediated injury occurring in the late post-transplant liver allograft. Careful clinico-pathological correlation is very important and the wording of the biopsy report should take into account therapeutic implications, particularly whether changes in immunosuppression may be indicated. This article will provide an overview of the main histological changes occurring in long-term survivors post-LT, focusing on areas where the assessment of late post-transplant biopsies is most relevant clinically.

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Section: Key Pointsmentioning

confidence: 95%

Section: Acute Rejection (Ar)mentioning

confidence: 98%

What is the long-term outcome of the liver allograft?

Hübscher

2011

Journal of Hepatology

122

127

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“…CPV can be mild, moderate or severe, and occurs with or without perivenular hepatocellular necrosis 42. Allograft CPV can be isolated or associated with hepatitic lobular inflammation, and/or portal-based features of ACR, including duct injury 45 46 47. When it occurs in association with portal features of ACR, the diagnosis is usually easy to make, and the treatment approach often follows established anti-rejection protocols.…”

Section: Rejectionmentioning

confidence: 99%

Liver allograft pathology: approach to interpretation of needle biopsies with clinicopathological correlation

2009

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The spectrum of diseases encountered in post-transplant liver pathology biopsies is broad. In this review, these have been divided as belonging to one of three categories: (1) new-onset/de novo post-transplant abnormalities (early and late), (2) rejection, and (3) recurrence of original disease. The clinical and pathological features of the entities making up each category, with the relevant differential diagnosis and overlaps between and within these groups, are discussed and illustrated. Recurrent or de novo neoplasms make up a fourth category not included in this review. Early new-onset conditions are mostly related to surgical complications, donor factors and ischaemia to the graft. These include reperfusion/preservation injury, lipopeliosis, small-for-size-syndrome, biliary sludge syndrome and hepatic artery thrombosis. The various forms of rejection (cellular, chronic, antibody-mediated, and late atypical rejection) are detailed. Most chronic liver diseases can and do recur in the graft. They may display features that overlap with de novo conditions (eg, primary sclerosing cholangitis versus chronic rejection). As with most cases of allograft biopsy interpretation, accurate diagnosis rests with careful correlation of histological features with clinical, imaging and laboratory findings, and often comparison with previous sequential and follow-up biopsies. Late-onset new diseases include biliary strictures, idiopathic chronic hepatitis and de novo autoimmune hepatitis, among others. This review provides a practical approach to the interpretation of these challenging biopsies. Selected difficult scenarios or conundrums are identified and discussed in the relevant sections.

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“…CLN has been reported in up to 30% of hepatic allografts following DDLT,17 and various insults have been implicated in its etiopathogenesis, including ischemia‐reperfusion injury,18 vascular inflow or outflow obstruction, viral and autoimmune hepatitis, and drug toxicity 19. Recently, CLN was found to be associated with an increased incidence of chronic rejection, and with lower patient and graft survival rates 14. A clear understanding of the specific etiology and the impact of CLN on graft outcome remains elusive, but CLN could be attributed, at least in part, to graft dysfunction and hypoattenuation in CT scans after LDLT.…”

Section: Discussionmentioning

confidence: 99%

“…CLN was graded semiquantitatively on a scale of 0 to 3: 0, absent; 1, scattered hepatocyte necrosis limited to the immediate perivenular area; 2, small foci of necrosis; and 3, confluent foci of necrosis with more extensive involvement of the lobule. When hemorrhagic necrosis was present, hemorrhage extent was also taken into account during CLN grading 14…”

Section: Methodsmentioning

confidence: 99%

Hypoattenuation in unenhanced CT reflects histological graft dysfunction and predicts 1-year mortality after living donor liver transplantation

et al. 2006

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Early postoperative graft function assessments are essential after living donor liver transplantation (LDLT) to predict patient and graft outcome. Computed tomography (CT) is usually used to evaluate various complications and parenchymal abnormalities after LDLT. Here, we attempted to determine the prognostic values of CT attenuation changes of grafts for predicting 1-year patient survival. Liver attenuation indices (LAIs), derived from differences between hepatic and splenic attenuations, were calculated on unenhanced CT images obtained 10 days after LDLT in 62 adult LDLT recipients between September 2002 and August 2004. Patients were assigned to 1 of 2 groups according to LAI value on the 10th postoperative day, as follows: group L (LAI Յ 5, n ϭ 14) or group H (LAI Ͼ 5, n ϭ 48). Parenchymal dysfunction scores, summed parameters for histological dysfunction including both portal tract and centrilobular features, were also assessed on the 10th postoperative day using liver biopsy specimens. Histological parenchymal dysfunction, especially in the centrilobular area, in terms of cholestasis, centrilobular necroinflammation, central vein fibrosis, steatosis, mononuclear infiltrates, and hepatocyte ballooning, was more prominent in group L than in group H, while that in the portal area was similar between the 2 study groups. Significant negative linear correlations were observed between LAI and parenchymal dysfunction scores (r ϭ 0.486, P Ͻ 0.001). Group L patients showed lower 1-year survival (69.7%) than group H patients (95.8%; P ϭ 0.0002). Moreover, group H patients died with a functioning graft (n ϭ 3), whereas group L patients died of graft failure (n ϭ 6). After multivariate analysis, LAI alone remained independently associated with 1-year mortality (P ϭ 0.014; odds ratio ϭ 0.845; 95% confidence interval, 0.739-0.967). The sensitivity and specificity of LAI were 84.6% and 75%, respectively, and LAI outperformed MELD score as a predictor of 1-year mortality after LDLT by receiver operating characteristic curve analysis. In conclusion, LAI, as determined by unenhanced CT 10 days after LDLT, well predicts 1-year patient survival after LDLT. Liver Transpl 12:1403-1411 AASLD. Received February 2, 2006 accepted February 15, 2006. See Editorial on Page 1320A critical shortage of cadaveric organs has resulted in a high mortality rate among patients awaiting liver transplantation (LT). It is hoped that an increasing number of living donor liver transplant (LDLT) procedures will significantly reduce the number of deaths among those on waiting lists. During the last 10 years, adult-to-adult LDLT has been developed on an international scale. A graft size of about 50% of the standard liver volume or 1.0% of the graft-to-recipient weight ratio (GRWR) is necessary to secure a favorable outcome after LDLT. Therefore, the widespread application of LDLT is limited

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Centrilobular necrosis after orthotopic liver transplantation: Association with acute cellular rejection and impact on outcome

Cited by 26 publications

References 25 publications

What is the long-term outcome of the liver allograft?

What is the long-term outcome of the liver allograft?

Liver allograft pathology: approach to interpretation of needle biopsies with clinicopathological correlation

Hypoattenuation in unenhanced CT reflects histological graft dysfunction and predicts 1-year mortality after living donor liver transplantation

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