Serum levels of fibrosis biomarkers measured early after liver transplantation are associated with severe hepatitis C virus recurrence (original) (raw)
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Journal of Hepatology, 2014
Background & Aims: Significant liver fibrosis (F P2) and portal hypertension (hepatic venous pressure gradient [HVPG] P6 mmHg) 1 year after liver transplantation (LT) are predictors of severe hepatitis C recurrence. Periportal sinusoidal fibrosis (SF) is an early expression of the fibrogenic process in response to liver injury. We aimed to evaluate whether SF in early liver biopsies represents an early and accurate marker for identifying patients with severe HCV recurrence after LT. Methods: A total of 101 HCV LT patients with early biopsy (<6 months), and HVPG measurement and/or liver biopsy one year after LT were included. Early biopsies were stained with Sirius Red and SF was graded semi-quantitatively. Results were compared between groups (significant SF vs. non-significant SF) and correlated with the development of severe HCV recurrence one year after LT. Results: Patients with early significant SF had older donor age and higher necroinflammatory activity (NIA). The presence of early significant SF enabled identification of 78.9% and 90.6% of patients with F P2 and HVPG P6 mmHg, respectively, one year after LT. Donor age and NIA were independent predictors of significant fibrosis (F P2) one year after LT, whereas donor age, ALT (3 months), NIA, and SF grade were independent predictors of portal hypertension (HVPG P6). Conclusions: Significant SF in early biopsies is a good predictor of severe hepatitis C recurrence. This histological finding, when combined with simple variables, may be useful to select the best candidates for early antiviral therapy after LT.
Prediction of fibrosis in HCV-infected liver transplant recipients with a simple noninvasive index
Liver Transplantation, 2005
Recurrent hepatitis C is a frequent event in liver transplantation (LT). Serial liver biopsies remain the best way of monitoring disease progression. Due to the limitations of a liver biopsy, there is an interest in developing noninvasive markers of liver fibrosis. While several models for predicting fibrosis have been constructed in patients who have not undergone transplantation, these are lacking in the transplant population. The aim of this study was to construct one simple model based on routine laboratory data to predict fibrosis in hepatitis C virus (HCV)-infected LT patients. A total of 510 yearly protocol liver biopsies performed in 188 LT patients (67% male; median age 54 years) were divided into 2 groups: training set (n ؍ 414) and validation set (n ؍ 96). Laboratory variables at time of biopsies were recorded. Multivariate analysis identified 4 variables as independent predictors of fibrosis: prothrombin time (PT), albumin/total protein ratio, aspartate aminotransferase (AST), and time since LT. The area under the receiver operating characteristic (ROC) curves (AUCs) were 0.80 and 0.84 for the training and the validation set, respectively. In the training set, using a cutoff of 0.2, the model had a sensitivity, specificity, positive predictive value, and negative predictive value of 74%, 69%, 42%, and 90%, respectively, to differentiate significant (bridging fibrosis and cirrhosis) from mild fibrosis (none or portal). In the validation cohort, these values increased to 87%, 71%, 49%, and 95%, respectively. In conclusion, in the LT setting, a simple fibrosis index is useful to select HCV-infected patients with a very low risk of significant fibrosis in whom protocol liver biopsies may be avoided. (Liver Transpl 2005;11:456-462.)
Role of simple biomarkers in predicting fibrosis progression in HCV infection
World Journal of Gastroenterology, 2010
Author contributions: Mummadi RR collected the data, interpreted it, helped in preparation of the manuscript, and performed in fulfillment of requirements for MSc in Clinical Science; Petersen JR helped design the project, interpret the data, perform the statistics, and prepare the manuscript; Xiao SY read the liver biopsies and helped in the preparation of the manuscript; Snyder N helped design the project, collect the data, interpret the data, and prepare the manuscript.
Journal of Viral Hepatitis, 2009
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 (META-VIR ‡ 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.
Explanted liver inflammatory grade predicts fibrosis progression in hepatitis C recurrence
Liver Transplantation, 2011
Factors present prior to liver transplantation (LT) that predict fibrosis progression in recurrent hepatitis C infection (HCV) after LT would be important to identify. This study sought to determine if histologic grade of HCV in the explant predicts fibrosis progression in recurrent HCV. The clinical and histologic data of all 159 patients undergoing their first LT for HCV at our center from 1998 to 2001 were retrospectively reviewed with follow-up through June 2008. Twenty-five cases were excluded for: non-HCV-related graft loss <90 days , recidivism (4), or unavailable explant or follow-up biopsies (2). A single pathologist scored (Ishak) explants in a blinded fashion. Patients were grouped by explant inflammatory grade 4 (group1) and >4 (group 2). Prospectively scored liver biopsies (protocol months 1 and 4, annually, and as indicated clinically) were reviewed for development of advanced fibrosis (bridging or cirrhosis). Cox proportional hazard regression was used to analyze the association of explant grade, donor, viral and LT factors with progression to advanced fibrosis. The groups were well-matched for patient, viral, donor, and transplant factors. Five-year advanced fibrosis-free survival in group 1 versus group 2 was 63% versus 28%, P < 0.001. Explant grade >4 was associated with increased HCV-related graft loss at 1 (6% versus 3%) and 5 (36% versus 14%) years post-LT (P ¼ 0.003). On univariate and multivariate Cox regression analysis, predictors of advanced fibrosis were explant grade >4 (hazard ratio [HR] ¼ 3.3, 95% confidence interval [CI] ¼ 1.9-5.6, P < 0.001) donor age >50 (HR ¼ 3.3, 95% CI ¼ 1.9-5.7, P < 0.001) and viral load at LT of >158,730 IU/mL (HR ¼ 1.8, 95% CI ¼ 1.05-3.1, P ¼ 0.03). Conclusion: Explant histologic grade can identify patients requiring more aggressive monitoring and intervention for HCV recurrence post-LT. Liver Transpl 17:685-694,
Hepatology, 2000
Approximately half of patients undergoing liver transplantation (LT) for hepatitis C virus (HCV) develop histologic evidence of recurrence within the first postoperative year. Early identification of recipients at risk for more severe recurrence of HCV may be useful in selecting patients for antiviral therapy. We determined whether recipients at greatest risk for more severe recurrence of HCV can be identified by pre-and/or early post-LT HCV-RNA levels in serum or tissue. Serum and tissue samples were prospectively collected pre-LT and at 7 days, 4 months, 1 year, and at 3 years posttransplantation from patients undergoing LT for HCV. Hepatitis activity index (HAI) and fibrosis stage (FS) were assessed in all liver biopsies. Forty-seven patients (32 men) were studied. Higher HCV-RNA levels at 4 months post-LT (>10 9 copies/mL, n ؍ 29) were associated with higher HAI at 1 year and at 3 years post-LT. The HAI seen on protocol biopsies at 4 months correlated significantly with fibrosis stage (FS) at 1 year (r ؍ .56, P < .001) and 3 years (r ؍ .53, P ؍ .002). Higher HCV-RNA levels at 7 days and 4 months post-LT were sensitive (66% and 84%, respectively) and specific (92% and 63%, respectively) in identifying recipients with an HAI greater than 3 at 3 years. Higher pre-and early post-LT HCV-RNA levels are associated with more severe recurrence of HCV. The correlation of early HAI with subsequent FS suggests that higher mean HAI will eventually translate into more advanced stages of fibrosis. Patients at risk for more severe post-LT recurrence of HCV can be identified by early posttransplant HCV-RNA levels. (HEPATOLOGY 2000;32: 1125-1130 Abbreviations: HCV, hepatitis C virus; LT, liver transplantation; EIA2, second generation enzyme-linked immunosorbent assay; RIBA, recombinant immunoblot assay; RT-PCR, reverse-transcriptase polymerase chain reaction; bDNA, branched DNA; HAI, hepatitis activity index; FS, fibrosis stage; ROC, receiver operating characteristic; AUC, area under the curve.
Hepatic Fibrosis in HCV, Non Invasive and Economical Biochemical Markers, A Review
Hepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ.By using Non-invasive biomarkers there is significant decrease in discomfort and risks and there can befrequent re-evaluation, objective interpretation and easy patient acceptance as compared to invasive markers in which there is higher cost along with intra and inter-observer variability.
Clinical Chemistry, 2006
Background: FibroTest, a noninvasive method of measuring biomarkers of liver fibrosis, is an alternative to liver biopsy for determining the severity of chronic hepatitis C virus (HCV) infection. We compared the 5-year prognostic value of the FibroTest with biopsy staging for predicting cirrhosis decompensation and survival in patients with chronic HCV infection. Methods: Fibrosis stage was assessed on the same day by FibroTest and biopsy in a prospective cohort of 537 patients. Disease classification at baseline was 157 patients with severe fibrosis (FibroTest >0.58), 137 with moderate fibrosis (FibroTest 0.32-0.58), and 243 with no or minimal fibrosis (FibroTest <0.32). Results: In 64 untreated patients with severe fibrosis, survival without HCV complications was 73% [95% confidence interval (CI), 59%-086%; 13 complications], and survival without HCV-related death was 85% (95% CI, 73%-96%; 7 HCV deaths). Survival rates were higher in patients with moderate fibrosis, [99% (95% CI, 97%-100%; 1 complication; P <0.001) and 100% (no HCV death; P <0.001) for patients with and without HCVrelated complications, respectively], and in patients with minimal fibrosis [100% (no complication; P <0.001 vs severe) and 100% (no HCV death; P <0.001 vs severe), respectively]. FibroTest was a better predictor than biopsy staging for HCV complications, with area under the ROC curves (AUROC) ؍ 0.96 (95% CI, 0.93%-0.97%) vs 0.91 (95% CI, 0.85%-0.94%; P ؍ 0.01), respectively; it was also a better predictor for HCV deaths: AUROC ؍ 0.96 (95% CI, 0.93%-0.98%) vs 0.87 (95% CI, 0.70%-0.94%; P ؍ 0.046), respectively. The prognostic value of FibroTest was still significant (P <0.001) in multivariate analyses after taking into account histology, treatment, alcohol consumption, and HIV coinfection. Conclusion: The FibroTest measurement of HCV biomarkers has a 5-year prognostic value similar to that of liver biopsy.