Histologic abnormalities are common in protocol liver allograft biopsies from patients with normal liver function tests.
ABSTRACT The utility of protocol liver allograft biopsies remains controversial, particularly in patients with normal liver function tests (LFTs). However, histologic evaluation of these biopsies provides an opportunity to examine the types and severity of liver diseases that can occur in livers with normal clinical and biochemical function. We studied 165 protocol allograft biopsies taken from 100 liver transplant patients at the time of normal LFTs and normal clinical function at 3 to 8 months (n=36), 1 year (n=52), 2 to 3 years (n=54), and 4 to 5 years (n=23). Biopsies were classified as normal, minimal changes (eg, nonaggressive portal or lobular mononuclear inflammation, steatosis <10%), fatty liver disease, recurrent primary liver disease, and transplant-related disease (portal-based rejection or central venulitis, an inflammatory pattern that encompasses perivenular hepatocyte dropout, mononuclear inflammation, pigment-laden macrophages, and variable zone 3 fibrosis). Among these 100 patients, a total of 394 protocol biopsies were performed, and 165 (42%) were taken at the time of normal LFTs and normal clinical function. One hundred twenty-one (73%) were normal or showed minimal/nonspecific changes. Forty-four (27%) showed histologic abnormalities that included fatty liver disease (n=19, nonalcoholic in 18 cases; 13 with mild steatosis, 6 with moderate steatosis, 7 with grade 1/3 steatohepatitic activity, and 2 with stage 1/4 steatohepatitic fibrosis), recurrent primary biliary cirrhosis (n=9; all stage 1/4), recurrent hepatitis C infection (n=6; grade 0/4 in 1, grade 1/4 in 5, stage 0/4 in 4, stage 1/4 in 1, and stage 2/4 in 1), recurrent sarcoidosis (n=1), Ito cell hyperplasia (n=4; marked in 2 and mild in 2), central venulitis (n=10; 5 with mild zone 3 fibrosis or central vein obliteration and 1 with central-portal bridging fibrosis), and mild acute portal rejection (n=2). We judged the histologic changes to be of clinical significance in 19 (11.5%) cases. These results indicate that even at the time of normal clinical and laboratory function, a significant fraction of protocol allograft biopsies harbor histologic (27%) and clinically significant (11.5%) abnormalities. These most commonly include fatty liver disease, low-grade/low-stage recurrent hepatitis C and primary biliary cirrhosis, and central venulitis (including some cases with subsequent fibrosis progression). The data support performance of protocol biopsies to assess allograft status, and provide insight into the types and severity of liver diseases that can smolder in transplanted (and by extension, probably also in native) livers with apparent normal function.
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ABSTRACT: Advances in pharmacologic immunosuppression are responsible for the excellent outcomes experienced by recipients of liver transplants. However, long-term follow-up of these patients reveals an increasing burden of morbidity and mortality that is attributable to these drugs. The authors summarize the agents used in contemporary liver transplantation immunosuppression protocols and discuss the emerging trend within the community to minimize or eliminate these agents from use. The authors present recently published data that may provide the foundation for immunosuppression minimization or tolerance induction in the future and review studies that have focused on the utility of biomarkers in guiding immunosuppression management.
Article: The SPLIT Research Agenda 2013[Show abstract] [Hide abstract]
ABSTRACT: This review focuses on active clinical research in pediatric liver transplantation with special emphasis on areas that could benefit from studies utilizing the SPLIT infrastructure and data repository. Ideas were solicited by members of the SPLIT Research Committee and sections were drafted by members of the committee with expertise in those given areas. This review is intended to highlight priorities for clinical research that could successfully be conducted through the SPLIT collaborative and would have significant impact in pediatric liver transplantation.Pediatric Transplantation 08/2013; 17(5). DOI:10.1111/petr.12090 · 1.63 Impact Factor
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ABSTRACT: Primary biliary cirrhosis (PBC) is an immune-mediated chronic progressive inflammatory liver disease, predominantly affecting middle-aged women, characterized by the presence of antimitochondrial antibodies (AMAs), which can lead to liver failure. Genetic contributions, environmental factors including chemical and infectious xenobiotics, autoimmunity and loss of tolerance have been aggressively investigated in the pathogenesis of PBC, however, the actual impact of these factors is still controversial. Survival of PBC patients has been largely improved with the widespread use of ursodeoxycholic acid (UDCA), however, one third of patients still do not respond to the treatment and proceed to liver cirrhosis, requiring liver transplantation as a last resort for cure. The outcome of liver transplantation is excellent with 5- and 10-year survival rates around 80% and 70%, respectively, while along with long survival, the recurrence of the disease has become an important outcome after liver transplantation. Prevalence rates of recurrent PBC rage widely between 1% and 35%, and seem to increase with longer follow-up. Center-specific issues, especially the use of protocol biopsy, affect the variety of incidence, yet, recurrence itself does not affect patient and graft survival at present, and retransplantation due to recurrent disease is extremely rare. With a longer follow-up, recurrent disease could have an impact on patient and graft survival.