Predictive Factors for Portal Fibrosis in Pediatric Liver Transplant Recipients

Peeters, Pmjg; Sieders, Egbert; Heuvel, M van der; Bijleveld, Cma; Jong, de Steven; TenVergert, Elisabeth M.; Slooff, Mjh; Gouw, Annette

doi:10.1097/00007890-200012150-00008

Cited by 46 publications

(65 citation statements)

References 35 publications

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“…The prevalence of fibrosis at 1 year in the current study (23%) is similar to that reported by Peeters et al, 19 who observed portal fibrosis in 31% of transplanted children within 1 year post-transplantation, mainly related to graft ischemia and biliary complications. In the current study, children with biliary obstruction also exhibited a high rate of fibrosis.…”

Section: Discussionsupporting

confidence: 91%

Progressive histological damage in liver allografts following pediatric liver transplantation

Evans¹,

Kelly²,

McKiernan³

et al. 2006

Hepatology

283

388

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The long-term histological outcome after pediatric liver transplantation (OLT) is not yet fully understood. De novo autoimmune hepatitis, consisting of histological chronic hepatitis associated with autoantibody formation and allograft dysfunction, is increasingly recognized as an important complication of liver transplantation, particularly in the pediatric population. In this study, 158 asymptomatic children with 5-year graft survival underwent protocol liver biopsies (113, 135, and 64 at 1, 5, and 10 years after OLT, respectively). Histological changes were correlated with clinical, biochemical, and serological findings. All patients received cyclosporine A as primary immunosuppression with withdrawal of corticosteroids at 3 months post OLT. Normal or near-normal histology was reported in 77 of 113 (68%), 61 of 135 (45%), and 20 of 64 (31%) at 1, 5, and 10 years, respectively. The commonest histological abnormality was chronic hepatitis (CH), the incidence of which increased with time [25/113 (22%), 58/135 (43%), and 41/64 (64%) at 1, 5, and 10 years, respectively) (P < .0001)]. The incidence of fibrosis associated with CH increased with time [13/25 (52%), 47/58 (81%), and 37/41 (91%) at 1, 5, and 10 years, respectively) (P < .0001)]. The severity of fibrosis associated with CH also increased with time, such that by 10 years 15% had progressed to cirrhosis. Aspartate aminotransferase (AST) levels were slightly elevated in children with CH (median levels 52 IU/L, 63 IU/L, and 48 IU/L at 1, 5, and 10 years, respectively), but this did not reach statistical significance compared with those with normal histology. On multivariate analysis, the only factor predictive of chronic hepatitis was autoantibody positivity (present in 13% and 10% of children with normal biopsies at 5 and 10 years, respectively, and 72% and 80% of those with CH at 5 and 10 years, respectively) (P < .0001). Four children with CH and autoantibodies, who also had raised immunoglobulin G (IgG) levels and AST greater than 1.5؋ normal fulfilled the diagnostic criteria for de novo autoimmune hepatitis (AIH). Another two were found to be hepatitis C positive. No definite cause for CH could be identified in the other cases. In conclusion, chronic hepatitis is a common finding in children after liver transplantation and is associated with a high risk of developing progressive fibrosis, leading to cirrhosis. Standard liver biochemical tests cannot be relied on either in the diagnosis or in the monitoring of progress of chronic allograft hepatitis. In contrast, the presence of autoantibodies is strongly associated with the presence of CH. The cause of chronic hepatitis in transplanted allografts is uncertain but may be immune mediated, representing a hepatitic form of chronic rejection.

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Section: Discussionsupporting

confidence: 91%

Progressive histological damage in liver allografts following pediatric liver transplantation

Evans¹,

Kelly²,

McKiernan³

et al. 2006

Hepatology

283

388

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“…27 In addition, the occurrence of biliary complications is an independent risk factor for portal fibrosis 1 year after transplantation. 38 These findings emphasize the importance of preventing biliary complications by securing vascularization of the bile ducts and checking the transection surface of technical-variant grafts for bile leakage.…”

Section: Discussionmentioning

confidence: 86%

Graft Loss After Pediatric Liver Transplantation

Sieders¹,

Peeters²,

TenVergert³

et al. 2002

Annals of Surgery

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ObjectiveTo describe the epidemiology and causes of graft loss after pediatric liver transplantation and to identify risk factors. Summary Background DataGraft failure after transplantation remains an important problem. It results in patient death or retransplantation, resulting in lower survival rates. MethodsA series of 157 transplantations in 120 children was analyzed. Graft loss was categorized as early (within 1 month) and late (after 1 month). Risk factors were identified by analyzing recipient, donor, and transplantation variables. ResultsKaplan-Meier 1-month and 1-, 3-, and 5-year patient survival rates were 85%, 82%, 77%, and 71%, respectively. Graft survival rates were 71%, 64%, 59%, and 53%, respectively. Seventy-one of 157 grafts (45%) were lost: 18 (25%) by death of patients with functioning grafts and 53 (75%) by graft-related complications. Forty-five grafts (63%) were lost early after transplantation. Main causes of early loss were vascular complications, primary nonfunction, and patient death. Main cause of late graft loss was fibrosis/cirrhosis, mainly as a result of biliary complications or unknown causes. Child-Pugh score, anhepatic phase, and urgent transplantation were risk factors for early loss. Donor age, donor/recipient weight ratio, blood loss, and technical-variant liver grafts were risk factors for late loss.

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“…Interstitial ET-1 was associated with a lower cellular rejection score, suggesting a dissociation between rejection and fibrosis, as has been shown in pediatric liver transplants. 14 The concept of fibrosis after transplantation has been thoroughly examined by Armstrong and his colleagues, 15 who evaluated serial endomyocardial biopsies on 50 cardiac transplant patients followed over 5 years. The investigators showed that myocardial fibrosis develops early and remains modestly elevated 2 months after transplant, indicating that peri-transplant factors might be responsible for this fibrotic process.…”

Section: Discussionmentioning

confidence: 99%

Patterns of Myocardial Endothelin-1 Expression and Outcome After Cardiac Transplantation

et al. 2002

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Background-Endothelin-1 (ET-1), a potent vasoconstrictor, is released in response to several inflammatory cytokines after heart transplantation. The present study correlated patterns of myocardial ET-1 expression in heart biopsies with acute rejection, post-transplantation ischemic injury, and subsequent development of coronary vasculopathy. Methods and Results-Patterns of myocardial ET-1 expression were evaluated in 47 heart transplant recipients at 3 months after transplant. Transplant vasculopathy was documented by coronary angiography at 2 years after transplant. Expression of ET-1 was tabulated for both blood vessels and the interstitium. Vascular ET-1 expression was positive in 7/17 (41%) of patients with greater than grade 2 (International Society Heart Lung Transplant) rejection compared with 3/30 (10%) of patients with grade 0 and grade 1A rejection (Pϭ0.02). Compared with patients with negative interstitial ET-1 expression (nϭ22), patients with positive interstitial ET-1 expression (nϭ25) had higher incidence of post-transplantation ischemic injury (52% versus 9%, Pϭ0.002), lower mean episodes of acute rejection (Ն grade 2) during the first 3 months of transplant (1.09Ϯ0.66 versus 1.86Ϯ1.6, Pϭ0.048), and more common vasculopathy at 2 years (50% versus 15%, Pϭ0.02), and they tended to have worse survival (83.2% versus 100%, Pϭ0.058). Conclusions-Vascular ET-1 expression is likely to be associated with acute rejection. Interstitial ET-1 expression, however, is more likely to be associated with post-transplantation ischemic injury and subsequent development of coronary vasculopathy.

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Predictive Factors for Portal Fibrosis in Pediatric Liver Transplant Recipients

Cited by 46 publications

References 35 publications

Progressive histological damage in liver allografts following pediatric liver transplantation

Progressive histological damage in liver allografts following pediatric liver transplantation

Graft Loss After Pediatric Liver Transplantation

Patterns of Myocardial Endothelin-1 Expression and Outcome After Cardiac Transplantation

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