Clinicopathological Analysis of Liver Allograft Biopsies With Late Centrilobular Necrosis

Nakazawa, Yūichi; Walker, Neal I.; Kerlin, Paul; Steadman, Charles; Lynch, Stephen V.; Strong, Russell W.; Clouston, Andrew D.

doi:10.1097/00007890-200004270-00014

“…All these findings support the concept that in the setting of CLN, lobular inflammation is a manifestation of AR. 1,10,[12][13][14] Our recent study also supports that notion by showing that lobular inflammation (when all the other etiologies have been excluded) is independently associated with AR in biopsies with CLN. 10 Cholestasis also has been recognized in association with CLN.…”

Section: Commentssupporting

confidence: 78%

“…10 Cholestasis also has been recognized in association with CLN. 2,10,14 Previous studies showed that the severity of cholestasis did not correlate with any other histopathologic findings, including those of AR. 12 However, a recent study showed that the presence of cholestasis in biopsies with CLN was the strongest independent predictor of the simultaneous presence of AR.…”

Section: Commentsmentioning

confidence: 98%

“…10 In a recent study, CLN occurring later after OLT, the findings defined as CLN were stratified in four groups: those associated with acute and chronic rejection, with hepatitis, predominantly of autoimmune etiology, and miscellaneous group, with a variety of underlying causes, the vascular being most frequent. 14 The timing of the histopathologic findings remain one of the most critical considerations in establishing the diagnosis or entertaining the differential diagnosis.…”

Section: Commentsmentioning

confidence: 99%

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Can early liver biopsies predict long-term outcome of the graft?

Petrovic

¹

2003

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Background: Chronic rejection (CR) in liver allografts show a rapid onset and progressive course, leading to graft failure within the first year after transplantation. Most cases are preceded by episodes of acute cellular rejection (AR), but histological features predictive for the transition toward CR are not well documented. Methods: We assessed the predictive value of centrilobular necrosis, central vein endothelialitis (CVE), central vein fibrosis, and lobular inflammation in the development of CR. One-week and one-month biopsy specimens of 12 patients with CR were compared with those of a control group consisting of 17 patients, who experienced AR without developing CR. The progress of the histological changes was further evaluated in follow-up biopsy specimens of the CR group taken at 2 months and beyond 3 months after transplantation. Results: Centrilobular necrosis, CVE, central vein fibrosis, and lobular inflammation were common features in both groups at 1 week. At 1 month, the incidence declined in the control group. The CR group showed an increased incidence and persistence of these features in the follow-up specimens. The incidence and median grade of severity of CVE was significantly higher in the CR group (p‫,40.0؍‬ and P<0.001). The severity of portal and lobular inflammation was also more pronounced in the CR group (P؉0.01 and 0.069). Conversely, in the control group the incidence of the lobular features decreased and the severity of CVE declined significantly (P‫.)30.0؍‬ Conclusion: The shift from a predominantly portal-based process toward lobular graft damage represents the early transition of AR to CR, for which a modification of immunosuppression might be necessary to prevent graft loss.

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“…59,60 As in native livers, central perivenulitis in allografts has several causes (Fig. 2), including various forms of rejection (pure perivenular rejection and early chronic rejection), early autoimmune hepatitis, 72,74,97 compromised afferent or efferent blood flow, 73,87,98 and adverse drug reactions. Perivenular rejection can be missed clinically and In cases with no or minor portal inflammation, the differential diagnosis includes acute rejection, chronic rejection, and prediagnostic autoimmune hepatitis.…”

Section: Differential Diagnosismentioning

confidence: 99%

Liver biopsy interpretation for causes of late liver allograft dysfunction

Demetris

¹

2006

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Evaluation of needle biopsies and extensive clinicopathological correlation play an important role in the determination of liver allograft dysfunction occurring more than 1 year after transplantation. Interpretation of these biopsies can be quite difficult because of the high incidence of recurrent diseases that show histopathological, clinical, and serological features that overlap with each other and with rejection. Also, more than one insult can contribute to allograft injury. In an attempt to enable centers to compare and pool results, improve therapy, and better understand pathophysiological disease mechanisms, the Banff Working Group on Liver Allograft Pathology herein proposes a set of consensus criteria for the most common and problematic causes of late liver allograft dysfunction, including late-onset acute and chronic rejection, recurrent and new-onset viral and autoimmune hepatitis, biliary strictures, and recurrent primary biliary cirrhosis and primary sclerosing cholangitis. A discussion of differential diagnosis is also presented. (HEPATOLOGY 2006;44:489-501.)

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“…[11][12][13][14]16 However, central venulitis more frequently is associated with acute allograft rejection. It remains uncertain whether the majority of cases of central venulitis represent some form, including the refractory form of acute allograft rejection.…”

Section: Commentsmentioning

confidence: 99%

Can early liver biopsies predict long-term outcome of the graft?

Petrovic¹

2003

Liver Transplantation

0

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Background: Chronic rejection (CR) in liver allografts show a rapid onset and progressive course, leading to graft failure within the first year after transplantation. Most cases are preceded by episodes of acute cellular rejection (AR), but histological features predictive for the transition toward CR are not well documented. Methods: We assessed the predictive value of centrilobular necrosis, central vein endothelialitis (CVE), central vein fibrosis, and lobular inflammation in the development of CR. One-week and one-month biopsy specimens of 12 patients with CR were compared with those of a control group consisting of 17 patients, who experienced AR without developing CR. The progress of the histological changes was further evaluated in follow-up biopsy specimens of the CR group taken at 2 months and beyond 3 months after transplantation. Results: Centrilobular necrosis, CVE, central vein fibrosis, and lobular inflammation were common features in both groups at 1 week. At 1 month, the incidence declined in the control group. The CR group showed an increased incidence and persistence of these features in the follow-up specimens. The incidence and median grade of severity of CVE was significantly higher in the CR group (p‫,40.0؍‬ and P<0.001). The severity of portal and lobular inflammation was also more pronounced in the CR group (P؉0.01 and 0.069). Conversely, in the control group the incidence of the lobular features decreased and the severity of CVE declined significantly (P‫.)30.0؍‬ Conclusion: The shift from a predominantly portal-based process toward lobular graft damage represents the early transition of AR to CR, for which a modification of immunosuppression might be necessary to prevent graft loss.

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Clinicopathological Analysis of Liver Allograft Biopsies With Late Centrilobular Necrosis

Abstract: With regard to most liver allograft biopsies showing late CLN, it is possible to make a specific diagnosis despite overlapping histologic features; this allows specific therapy to be instituted. Ultimately this is likely to contribute to improved graft survival.

Cited by 39 publications

References 22 publications

Can early liver biopsies predict long-term outcome of the graft?

Can early liver biopsies predict long-term outcome of the graft?

Liver biopsy interpretation for causes of late liver allograft dysfunction

Can early liver biopsies predict long-term outcome of the graft?

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