Prediction of liver allograft fibrosis after transplantation for hepatitis C virus: Persistent elevation of serum transaminase levels versus necroinflammatory activity

Abstract

Recurrence of hepatitis C virus (HCV) after orthotopic liver transplantation (OLT) remains a significant source of morbidity and mortality. Factors that reliably predict allograft injury from HCV have not been identified. Demographics, clinical data, and histopathological characteristics of recipients with and without persistently elevated serum transaminase levels (PEST) were compared. Twenty-four patients with HCVinduced end-stage liver disease who underwent OLT between October 1995 and December 1998 were entered into a longitudinal, prospective evaluation for identification of parameters associated with graft injury. Liver biopsies were performed preoperatively and between posttransplantation days 1 to 28, 29 to 60, 61 to 180, 181 to 360, and then every 6 to 12 months thereafter. Biopsy specimens were reviewed in a blinded fashion and scored for rejection, necroinflammatory activity, extent of fibrosis, and infiltrating cell type, location, and magnitude. Transplant recipients with PEST (alanine transaminase level G1.5 times normal for 3 consecutive months) and cholestatic hepatitis showed an increased viral load compared with their own preoperative values (16-fold and 256-fold, respectively). Compared with control transplant recipients, PEST was associated with macrovesicular steatosis within 28 days after OLT (P F .05) and showed an increased rate of fibrosis (P F .003) despite similar degrees of rejection and necroinflammatory activity. There was no difference in demographics or immunosuppression. Macrovesicular steatosis may be the earliest predictor of graft fibrosis. Despite similar degrees of necroinflammatory activity, transplant recipients with PEST had an increased rate of fibrosis that could be predicted on average within 6 months posttransplantation.

Controversies in the management of hepatitis C virus infection after liver transplantation

“…There is near universal agreement that fibrosis progression to cirrhosis in patients with recurrent HCV after liver transplantation is on average far more rapid than in the nontransplantation setting. [4][5][6][7][8] In general, patients develop progressive fibrosis, cirrhosis, and liver failure after initial exposure to HCV over a period of 20 to 30 years or longer. 21,22 The 5-year survival of an HCVpositive patient with stable cirrhosis remains greater than 80%.…”

“…This can be detected in up to two-thirds of patients and occurs between 1 to 3 months after transplantation. 8,35 In some cases this is associated with a mild elevation in serum bilirubin. Although several studies have attempted to link the timing of this initial increase in serum liver transaminases to the risk of developing progressive fibrosis, there seems to be no consensus regarding this relationship.…”

“…[4][5][6][7][8] In addition, a limited group of patients (about 1% to 5% of recipients) develop rapidly progressive cholestatic hepatitis and liver failure within just 1 to 2 years. [8][9][10][11] Numerous studies have attempted to identify those factors that affect disease progression in these patients. Unfortunately, nearly all studies in this area have been retrospective in nature, conducted in patient populations of limited size, at single centers, utilized an array of immune suppressive medications in an uncontrolled manner, and have failed to consistently utilize protocol liver biopsy to investigate histologic progression.…”

“…[1][2][3] Progressive graft injury leading to cirrhosis occurs in about 25% to 33% of patients within just 5 years. [4][5][6][7][8] In addition, a limited group of patients (about 1% to 5% of recipients) develop rapidly progressive cholestatic hepatitis and liver failure within just 1 to 2 years. [8][9][10][11] Numerous studies have attempted to identify those factors that affect disease progression in these patients.…”

Predicting progressive hepatic fibrosis stage on subsequent liver biopsy in chronic hepatitis C virus infection1

“…In 148 consecutive patients increasing body mass index and steatosis correlated closely with the stage of fibrosis although in this particular series fibrosis correlated better with age than with steatosis [33]. In a transplant population, steatosis predicted accelerated HCV-related disease [34].…”