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

✍ Scribed by Ziad Hassoun; Vijay Shah; Christine M. Lohse; V. Shane Pankratz; Lydia M. Petrovic

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 197 KB
• Volume: 10
• Category: Article
• ISSN: 1527-6465
• DOI: 10.1002/lt.20122

✦ Synopsis

Several studies have linked centrilobular necrosis (CN) to acute cellular rejection (ACR) following liver transplantation. However, it may be difficult to establish the diagnosis of ACR when the classic portal features are absent. The aim of the present study was to identify specific features that would help to recognize ACR in biopsies with CN. One hundred and forty liver biopsies with CN were identified from 97 patients who underwent liver transplantation. The following histopathologic features were assessed: CN, steatosis, lobular inflammation, cholestasis, endothelialitis, and fibrosis. CN was graded semiquantitatively. A number of clinical and biochemical parameters were also recorded. Biopsies with CN were assessed for the presence or absence of ACR and divided into two groups accordingly. The associations of the biochemical, pathologic, and clinical features with ACR were assessed using a multivariate logistic regression model. The outcomes of patients with and without rejection were compared using the Cox proportional hazards regression model. Seventy-four biopsies (52.9%) showed evidence of ACR, and 52 patients (53.6%) had evidence of ACR at the first biopsy with CN. The multivariate analysis showed the presence of cholestasis, lobular inflammation, the ALT level, and time since liver transplantation to be independent predictors of the presence of ACR in biopsies with CN. Patients with ACR on their first biopsy with CN were significantly more likely to experience graft loss compared with patients without ACR. In conclusion, the presence of cholestasis and lobular inflammation on biopsies with CN appeared helpful in predicting its association with ACR. (Liver Transpl 2004;10:480-487.)

C entrilobular necrosis (CN) has been reported in up to 30% of hepatic allografts following orthotopic liver transplantation (OLT). 1 Various insults have been incriminated in its etiopathogenesis, including ischemia-reperfusion injury, 2 vascular inflow or outflow obstruction, viral and autoimmune hepatitis, and drug toxicity. 3 In particular, CN has been attributed to tacrolimus toxicity in some cases, although definitive evidence to support this concept is lacking. 3,4 In contrast, a large body of evidence supports a frequent association of CN with acute cellular rejection (ACR). 1,5 -10 Traditionally, CN has been associated with ACR only if the classic portal findings of the latter are present. 11,12 However, it is has been suggested that ACR can manifest as isolated perivenular and subendothelial inflammation of the terminal hepatic venules without conspicuous portal-tract inflammation or bile-duct damage, and that this form of ACR is often associated with CN. 13 CN has been associated with an increased incidence of chronic rejection (CR) 1,5,7 -10 and with lower patient and graft survival rates, 1,5,7 -9 although this is controversial. Specifically, antirejection treatment of ACR with centrilobular localization appears to reverse the process in the majority of cases, and may thus prevent the evolution toward CR and graft loss. 10,14,15 Thus, it appears that CN is frequently associated with ACR and could be so even in the absence of the portal features of ACR. In the latter situation, the distinction between ACR and other causes of CN can be difficult. This distinction is important because the therapeutic approach and the prognosis are radically different depending on the etiology. Therefore, the main objective of the present study was to investigate the association of CN with ACR, and more specifically to identify specific clinical, biochemical, or histopathologic features that would help to recognize ACR in biopsies with CN. A secondary objective was to determine whether the association of CN with ACR impacted on patient and graft survival.