Prediction of Liver Fibrosis in Kidney Transplant Patients With Chronic HCV
Prediction of Liver Fibrosis in Kidney Transplant Patients With Chronic HCV
HCV infection is highly prevalent among kidney transplant (KT) recipients. The natural history and management of these patients are controversial. We sought to assess the diagnostic value of noninvasive markers of liver fibrosis in KT HCV-infected patients. This cross-sectional study included 102 KT individuals with positive HCV-RNA. Bivariate and multivariate analyses were used to identify variables associated with significant fibrosis (METAVIR ≥ F2). Significant fibrosis was observed in 20 patients (20%). Time after transplantation, AST level, and platelet count were identified as independent predictors of significant fibrosis. Based on the regression model, a simplified index was devised. The AUROC for the TX-3 model was 0.867 ± 0.081 (0.909, when adjusted by DANA). Values ≤4.0 of TX-3 showed a NPV of 97% and scores >9.6 exhibited a PPV of 71%. If biopsy indication was restricted to scores in the intermediate range of TX-3, this could have been correctly avoided in 68% of cases. The APRI score provided a correct diagnosis in only 47 individuals (46%) and exhibited lower diagnostic indices for both cutoffs, as compared to the TX-3 index. Comparison of AUROCs showed a trend towards superior diagnostic accuracy for TX-3 over APRI, although the difference between AUROCs did not reach statistical significance (0.867 ± 0.053 vs 0.762 ± 0.066, respectively, P = 0.064). In conclusion, significant liver fibrosis can be reliably predicted in KT HCV-infected subjects by simple and widely available parameters. If additional studies confirm our results, this model might obviate the requirement for a liver biopsy in a significant proportion of those patients.
Hepatitis C virus (HCV) infection is still highly prevalent among subjects with end-stage renal disease and, consequently, in kidney transplant (KT) recipients. Although controversial, increased liver-related mortality and fibrosis progression has been observed among HCV-infected KT patients. Recent evidence also suggests that KT recipients with chronic HCV infection have an increased risk of graft failure, and higher prevalence of post-transplant diabetes mellitus. Moreover, given the risk of treatment-induced graft dysfunction and poor tolerance of interferon-based therapy, treatment is generally contraindicated in HCV-infected KT subjects. However, there has been mounting evidence that some patients may benefit from antiviral therapy and an accurate characterization of liver disease in those individuals is mandatory for optimal management and therapeutic decisions.
Liver biopsy is currently the gold standard procedure for staging liver disease. Although widely performed, liver biopsy is costly and it is an invasive technique with associated morbidity, including pain in the right upper quadrant or right shoulder, transient hypotension and other serious complications such as significant intraperitoneal haemorrhage, biliary ascites and pneumothorax. In addition, the immunosuppressive state and the frequent comorbidities of KT patients represent additional risks for invasive procedures. Furthermore, the heterogeneity of liver fibrosis in chronic hepatitis C, the potential inter- and intra-observer variability in the estimation of fibrosis, and the need for adequately sized specimens are major disadvantages of liver biopsy. Therefore, there is a need to develop accurate and reliable noninvasive tools to assess the stage of liver fibrosis, especially among HCV-infected KT subjects in whom the safety of liver biopsy has not yet been evaluated.
Recently, many studies have been performed to evaluate the use of biomarkers to predict significant fibrosis or cirrhosis in patients with chronic HCV infection outside the setting of renal transplantation. However, few data are available regarding this issue in the KT population. The aim of our study was to assess the diagnostic value of routine laboratory tests as noninvasive markers of liver fibrosis in treatment-naive KT HCV-infected patients.
Abstract and Introduction
Abstract
HCV infection is highly prevalent among kidney transplant (KT) recipients. The natural history and management of these patients are controversial. We sought to assess the diagnostic value of noninvasive markers of liver fibrosis in KT HCV-infected patients. This cross-sectional study included 102 KT individuals with positive HCV-RNA. Bivariate and multivariate analyses were used to identify variables associated with significant fibrosis (METAVIR ≥ F2). Significant fibrosis was observed in 20 patients (20%). Time after transplantation, AST level, and platelet count were identified as independent predictors of significant fibrosis. Based on the regression model, a simplified index was devised. The AUROC for the TX-3 model was 0.867 ± 0.081 (0.909, when adjusted by DANA). Values ≤4.0 of TX-3 showed a NPV of 97% and scores >9.6 exhibited a PPV of 71%. If biopsy indication was restricted to scores in the intermediate range of TX-3, this could have been correctly avoided in 68% of cases. The APRI score provided a correct diagnosis in only 47 individuals (46%) and exhibited lower diagnostic indices for both cutoffs, as compared to the TX-3 index. Comparison of AUROCs showed a trend towards superior diagnostic accuracy for TX-3 over APRI, although the difference between AUROCs did not reach statistical significance (0.867 ± 0.053 vs 0.762 ± 0.066, respectively, P = 0.064). In conclusion, significant liver fibrosis can be reliably predicted in KT HCV-infected subjects by simple and widely available parameters. If additional studies confirm our results, this model might obviate the requirement for a liver biopsy in a significant proportion of those patients.
Introduction
Hepatitis C virus (HCV) infection is still highly prevalent among subjects with end-stage renal disease and, consequently, in kidney transplant (KT) recipients. Although controversial, increased liver-related mortality and fibrosis progression has been observed among HCV-infected KT patients. Recent evidence also suggests that KT recipients with chronic HCV infection have an increased risk of graft failure, and higher prevalence of post-transplant diabetes mellitus. Moreover, given the risk of treatment-induced graft dysfunction and poor tolerance of interferon-based therapy, treatment is generally contraindicated in HCV-infected KT subjects. However, there has been mounting evidence that some patients may benefit from antiviral therapy and an accurate characterization of liver disease in those individuals is mandatory for optimal management and therapeutic decisions.
Liver biopsy is currently the gold standard procedure for staging liver disease. Although widely performed, liver biopsy is costly and it is an invasive technique with associated morbidity, including pain in the right upper quadrant or right shoulder, transient hypotension and other serious complications such as significant intraperitoneal haemorrhage, biliary ascites and pneumothorax. In addition, the immunosuppressive state and the frequent comorbidities of KT patients represent additional risks for invasive procedures. Furthermore, the heterogeneity of liver fibrosis in chronic hepatitis C, the potential inter- and intra-observer variability in the estimation of fibrosis, and the need for adequately sized specimens are major disadvantages of liver biopsy. Therefore, there is a need to develop accurate and reliable noninvasive tools to assess the stage of liver fibrosis, especially among HCV-infected KT subjects in whom the safety of liver biopsy has not yet been evaluated.
Recently, many studies have been performed to evaluate the use of biomarkers to predict significant fibrosis or cirrhosis in patients with chronic HCV infection outside the setting of renal transplantation. However, few data are available regarding this issue in the KT population. The aim of our study was to assess the diagnostic value of routine laboratory tests as noninvasive markers of liver fibrosis in treatment-naive KT HCV-infected patients.