Development of nonalcoholic fatty liver disease after orthotopic liver transplantation for cryptogenic cirrhosis

Abstract

Many subjects with cryptogenic cirrhosis have underlying nonalcoholic steatohepatitis (NASH). The natural history of NASH-related cryptogenic cirrhosis after orthotopic liver transplantation (OLT) is not well defined. A primarily retrospective study of patients with the clinical histological phenotype of NASH-related cirrhosis undergoing OLT was performed. Data were compared with 2 sets of age-and weight-matched controls with (1) primary biliary cirrhosis or primary sclerosing cholangitis or (2) alcoholic liver disease. After OLT, all patients were managed by a standard immunosuppressive protocol. Liver biopsies were performed at 6 and 12 months after OLT and at 1-to 2-year intervals thereafter, as well as when liver enzyme levels were elevated enough to warrant diagnostic biopsy. Twenty-seven subjects with cryptogenic cirrhosis and a clinical histological phenotype of NASH and 3 patients with a long-standing diagnosis of NASH before OLT were included. The 30-day perioperative mortality was 1 in 30 patients. During a median follow-up of 3.5 ؎ 2.7 years, 2 additional patients died of sepsis. There was a timedependent increase in the risk for allograft steatosis that approached 100% by 5 years compared with only an approximately 25% incidence of steatosis in the control groups (P < .009, log-rank test). On multivariate analysis, only the cumulative steroid dose correlated with time to development of allograft steatosis. Three patients developed histological progression from hepatic steatosis to steatohepatitis. Of these, 1 patient developed progressive fibrosis. Four patients experienced at least 1 episode of acute cellular rejection; however, no patient developed chronic rejection or graft failure. In conclusion, nonalcoholic fatty liver disease occurs frequently after OLT in patients with the phenotype of NASH-related cirrhosis.

Successful Treatment of Rapid Onset, Symptomatic de novo Non-alcoholic Steatohepatitis Following Liver Transplantation: A Case Report

“…6 The time course of de novo NAFLD and NASH is less well defined. Seo et al documented de novo NAFLD and NASH during liver biopsy at 16 months or more post-LT. Contos et al found steatosis grades 3 and 4 only in allograft biopsies performed more than six months after LT. 2 To our knowledge, no trial or case report has documented such rapid development of severe, de novo NAFLD or NASH as seen in here.…”

“…For example, the incidence of NAFLD in those transplanted for cryptogenic cirrhosis has been seen in up to 100% of patients after five years. 2 Up to 40% of patients transplanted for non-NAFLD related disease have been found to develop post-LT steatosis with 13% developing steatohepatitis at a mean follow up of 44 +/À 4 months. 3 There is a significant association with higher post-transplant BMI, with an odds ratio reported as high as 19 if the increase in BMI is greater than 10.…”

“…3,4 Risk factors for recurrent or de novo NAFLD from crosssectional, post-transplant studies include post-transplant weight gain, diabetes mellitus/insulin resistance, decreased HDL-cholesterol, elevated total cholesterol, and hypertension-with the use of corticosteroids and calcineurin inhibitors contributing to the development of these conditions in the post-transplant setting. 2,5 When steatosis recurs, it usually does so in an insidious fashion. Approximately 25% of patients develop steatosis within one year, and nearly 50% develop it by four years post-transplant.…”

“…Approximately 25% of patients develop steatosis within one year, and nearly 50% develop it by four years post-transplant. 2,3 In patients whose underlying disease is alcohol, 12.5% will develop grade 2 or higher steatosis at 4 months, and 15% by 12 months. 6 The time course of de novo NAFLD and NASH is less well defined.…”

Long-term Medical Management of the Liver Transplant Recipient: What the Primary Care Physician Needs to Know

“…With the increasing burden of metabolic syndrome posttransplant, there is a risk of recurrent or de novo NASH in transplanted livers. 76,77 Late biliary and vascular complications, including hepatic artery thrombosis and stenosis, cause progressive ischemic biliary destruction and manifest as jaundice, intrahepatic biliary strictures, recurrent cholangitis, and intrahepatic abscesses. Because the allograft is not innervated, patients do not always develop right upper quadrant abdominal pain, nor do bile ducts necessarily dilate; thus, biliary imaging is needed if clinical suspicion is present.…”