Liver transplantationChronic Liver Allograft Dysfunction
Section snippets
Rejection
Acute cellular rejection is diagnosed in up to 60% of liver recipients and occurs most commonly within the first 30 days after liver transplantation.2 The diagnosis is made on the basis of histology or cytology, and most episodes respond to high-dose corticosteroids. In contrast, late cellular rejection (>30 days posttransplant) occur in 15%–20% of recipients; this responds less well and a significant proportion progress to chronic, ductopenic rejection. Late acute rejection may be related to
Disease Recurrence
Many metabolic and immunologic diseases recur and may affect graft survival.8 Figure 1 (graft loss >90 days post liver transplantation to disease recurrence) shows the proportion of the all graft lost more than 90 days postoperative, to disease recurrence.9 Differentiating acute rejection (which usually occurs in the context of hepatitis C virus [HCV] infection) from recurrent hepatitis C alone may be difficult, but has important therapeutic implications10; similarly, with primary sclerosing
Chronic Hepatitis
Chronic hepatitis (CH) is defined as evidence of portal and lobular mononuclear infiltrate and variable interface hepatitis in the absence of rejection and other identifiable causes of graft dysfunction. CH is the most common histologic finding in late posttransplant biopsy samples and occurs in up to 40% of biopsy samples taken after 12 months.12, 13
We examined the frequency and natural history of CH and undertook a retrospective clinicopathologic study of unexplained CH occurring in liver
Graft Fibrosis
Sutedja et al16 examined the posttransplant histology of patients transplanted for cryptogenic cirrhosis to indentify initial underlying aetiology, with special attention on the findings of steatosis and steatohepatitis. Of 39 patients grafted for cryptogenic cirrhosis who survived for longer than 1 year, steatosis and steatohepatitis were present in 37.6% (control 16.7%); 18.8% had moderate steatosis at 1 year and half progressed to cirrhosis at 4 years. These findings suggests that the more
Graft Cirrhosis in the Absence of Primary Disease Recurrence
Liver allograft cirrhosis is a relatively uncommon complication of liver transplantation. Most cases can be attributed to disease recurrence, particularly recurrent HCV. Seyyam et al17 showed allograft cirrhosis with no evidence of disease recurrence in 19 (1.5%) of 1287 adult patients who survived more than 12 months after liver transplant over a 20-year period. In 9 (de novo AIH 4, biliary cirrhosis 4 and a de novo HBV infection), a potentially treatable or preventable cause could be
De Novo Autoimmune Hepatitis
A number of reports have been published in which a syndrome resembling AIH (de novo AIH) has developed post liver transplantation. The initial report of de novo AIH from Kerkar et al18 was of 7 children (4% of their series), grafted for indications other than AIH, who developed a characteristic form of graft damage at a median of 2 years postliver transplant, characterized by elevated transaminases, circulating autoantibodies (antinuclear, anti–smooth muscle, and anti–liver-kidney microsomal),
Other Causes of Graft Dysfunction
Azathioprine may result in graft damage and include nodular regenerative hyperplasia and hepatitis.23, 24 The presence of sinusoidal congestion and centrizonal necrosis on a liver allograft recipient on azathioprine should lead to a review and possible alteration of immunosuppression. The calcineurin inhibitors are associated with cholestasis; changes are usually mild and nonspecific.25
Monitoring Graft Function
Although all transplant clinicians use liver blood tests to assess graft function, liver tests may give incomplete and occasionally unreliable information. We lack consensus on the monitoring of graft function, particularly with regard to protocol liver biopsies. In our analysis of 667 annual protocol biopsies in 335 patients, despite normal liver biochemistry, 49.8% (331) had abnormal histology and only 4.9% had normal histology suggesting poor correlation between liver tests and liver
Conclusion
Rejection, disease recurrence, and CH are not infrequently found in liver allografts. The significance of CH is not clear and liver biochemistry does not reliably identify it. CH may progress and the presence of autoantibodies may help to identify those with progressive disease. The role of changing immunosuppression is unclear in such cases.
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Cited by (31)
Histological lesions in the graft in patients with long-term survival after transplantation. are protocol biopsies necessary?
2013, Gastroenterologia y HepatologiaEvaluating and interpreting bile duct changes in liver allograft biopsies
2012, Diagnostic HistopathologyCitation Excerpt :Bile duct ischaemia and injury can ultimately lead to biliary stricture. Recurrence of primary disease in the allograft liver is the culprit for a great proportion of liver dysfunction after 6 months post-transplant but the recurrence rate and burden of disease vary with the primary aetiology of the liver disease.21 Recurrent biliary diseases, mainly primary biliary cirrhosis (PBC) and sclerosing cholangitis (PSC) are among the causes of bile duct changes post liver transplant.
Nanoparticle delivery of mycophenolic acid upregulates PD-L1 on dendritic cells to prolong murine allograft survival
2011, American Journal of TransplantationHepatic overexpression of heme oxygenase-1 improves liver allograft survival by expanding t regulatory cells
2011, Journal of Surgical ResearchCitation Excerpt :The data indicate that HO-1-expressing donor livers tolerize the immune system of recipients to accept liver allografts. Immune rejection and IRI represent two major causes of liver dysfunction or failure following transplantation [26]. The dual effects of HO-1 in protecting grafts from IRI and modulating the immune response have made it an attractive candidate for application in liver transplantation.
Liver transplantation for glycogen storage disease type Ia
2009, Journal of HepatologyCitation Excerpt :Our approach to GSD Ia patients where there is concern for malignant adenoma transformation includes initial resection of suspicious lesions followed by listing for LT after further adenoma growth, which inevitably occurs in all patients [22]. Five-year patient survival after liver transplantation for all indications is 75% with disease recurrence a major cause of graft loss and long-term patient mortality [39]. Unlike more common indications for LT, recurrence of liver disease in GSD Ia is not observed as all possible adenomatous tissue is removed and the underlying hepatic enzyme deficiency is reversed.
Localization of apoptosis proteins and lymphocyte subsets in chronic rejection of human liver allograft
2010, Interventional Medicine and Applied Science