Serum Fibrosis Markers Identify Patients With Mild and Progressive Hepatitis C Recurrence After Liver Transplantation (original) (raw)
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Transplant Infectious Disease, 2009
oz-Ferna¤ ndez, S. Resino. Serum levels of ¢brosis biomarkers measured early after liver transplantation are associated with severe hepatitis C virus recurrence. Transpl Infect Dis 2009: 11: 183^188. All rights reserved Abstract: This prospective study analyzed the relationship between several biological markers related to liver ¢brosis at 3 months and 1year post liver transplantation in 37 patients (19 with hepatitis C virus [HCV], 18 with alcoholic liver disease). Severe HCV recurrence (HCV-SR) was de¢ned as ¢brosis stage F1 (METAVIR score) at 1 year and/or a value of hepatic venous pressure gradient 6 mmHg. We found HCV-SR patients had higher values of monocyte chemotactic protein-1 (MCP-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and hyaluronic acid (HA) than non-severe HCVrecurrence patients (Po0.05). Moreover, receiver operating characteristic curve analysis showed that interferoninducible protein 10 (IP-10) (area under the curve [AUC]: 0.74; con¢dence interval [CI] 95%: 0.49^0.91; P 5 0.043), MCP-1 (AUC: 0.78; CI 95%: 0.540 .94; P 5 0.007 ), sVCAM-1 (AUC: 0.89; CI 95%: 0.67^0.98; P 5 0.005), and HA (AUC: 0.80; CI 95%: 0.55^0.94; P 5 0.035) have good predictive capacity for identifying severe HCV infection. The evaluation of these biomarkers may be useful in the early identi¢cation of patients in whom a more aggressive therapeutic approach could be necessary.
Liver Transplantation, 2008
Although recurrent hepatitis C virus (HCV) after liver transplantation (LT) is universal, a minority of patients will develop cirrhosis within 5 years of surgery, which places them at risk for allograft failure. This retrospective study investigated whether 2 serum fibrosis markers, serum hyaluronic acid (HA) and YKL-40, could be used to predict rapid fibrosis progression (RFP) post-LT. These markers were compared with conventional laboratory tests, histological assessment, and hepatic stellate cell activity (HSCA), a key step in fibrogenesis, as assessed by immunohistochemical staining for alpha-smooth muscle actin. Serum and protocol liver biopsy samples were obtained from 46 LT recipients at means of 5 Ϯ 2 (biopsy 1) and 39 Ϯ 6 (biopsy 2) months post-LT, respectively. RFP was defined as an increase in the fibrosis score Ն 2 from biopsy 1 to biopsy 2 (a mean interval of 33 Ϯ 6 months). The ability of parameters at biopsy 1 to predict RFP was compared with the areas under receiver operating characteristic curves (AUROCs). Of the 46 subjects, 15 developed RFP. Serum HA and YKL-40 performed significantly better than conventional parameters and HSCA in predicting RFP post-LT for HCV at biopsy 1, with AUROCs of 0.89 and 0.92, respectively. The accuracy of serum HA Ն 90 g/L and YKL-40 Ն 200 g/L in predicting RFP at biopsy 1 was 80% and 96%, respectively. In conclusion, we found that elevated levels of serum HA and YKL-40 within the first 6 months after LT accurately predicted RFP. Larger studies evaluating the role of serum HA and YKL-40 in post-LT management are warranted.
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.
Hepatology, 2006
Liver biopsy is essential in the follow-up of HCV-infected liver transplant recipients. The aim of this study was to prospectively compare percutaneous (PLB) versus transjugular liver biopsy (TLB) in the assessment of liver damage. We also explored the diagnostic value of hepatic venous pressure gradient (HVPG) to identify patients at risk of severe HCV disease recurrence after liver transplantation (LT). One hundred sixteen paired PLB and TLB (with HVPG measurement) were performed 3 or 12 months after LT in 80 patients. Concordance for necroinflammation and fibrosis was fair or good, particularly 1 year after LT (kappa > 0.6). At this point, a significant positive association was seen between the median HVPG and the fibrosis stage (2.5 mm Hg for F0; 5 mm Hg for F1, 6 mm Hg for F2, and 11.5 mm Hg for F3; Kruscal-Wallis < 0.001). Despite this strong association, portal hypertension (HVPG > 6 mm Hg) was detected in 1 (5%) of 22, 4 (16%) of 25, and 6 (60%) of 10 patients with fibrosis stages 0, 1, and 2, respectively. After a median follow-up of 38 months, clinical decompensation occurred in 15 (19%) of 80 patients. Although the presence of significant fibrosis (F2-F3) 1 year after transplantation was good to predict clinical decompensation (AUC: 0.80), an HVPG of 6 mm Hg or greater was extremely accurate at identifying patients at risk of disease progression (AUC: 0.96). In conclusion, HVPG determination is a valuable tool for follow-up in patients with HCV recurrence after LT. (HEPATOLOGY 2006;43:492-499.)
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.
Digestive and Liver Disease, 2019
patients with HRS. The aim of this study was to evaluate the impact of response to treatment on post-transplant outcomes. We analyzed 2 cohorts of cirrhotic patients listed for LT at our Centre: a) patients who developed HRS before LT treated with terlipressin and albumin and b) patients without HRS transplanted during the study period. Patients with HRS were classified as responders or non-responders. Patients with previous LT or indication for SLK transplantation were excluded. 82 patients were treated with terlipressin and albumin with a rate of response of 52%. Responders had better transplantfree survival (60% vs 33%, p = 0.006), longer LT list-waiting time (37 vs 17 days, p = 0.041) and lower MELD-score at LT (23 vs 29, p = 0.007). Among patients in first cohort, non-responders showed a worse renal function, higher need for RRT (0% vs 26%, p < 0.001) and higher rate of post-transplant infections (63% vs 87%, p = 0.037) than responders. Non-responder had a significantly higher incidence of CKD 1 year after LT than responders (60% vs 33%, p = 0.019). When second cohort was included in multivariate analysis, age (sHR = 1.04; p = 0.024), diabetes (sHR = 1.64; p = 0.048), AKI post-transplant (sHR = 1.81; p = 0.012), MELD at LT (sHR = 1.03; p = 0.028), and no response to treatment were found to be independent predictors for CKD at 1 year. Responders had a similar risk of CKD than control group. There was no difference in survival comparing responder, no responder and control group. Response to treatment improves renal function before LT, reduces need for RRT and is associated with a lower prevalence of CKD after LT.
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.
Clinical Transplantation, 2007
Serum globulin levels in predicting the extent of hepatic fibrosis in patients with recurrent post-transplant hepatitis C infection Liver failure caused by hepatitis C virus (HCV) infection is the leading indication for orthotopic liver transplantation worldwide. After transplantation, however, HCV infection recurs in virtually all patients and has a particularly aggressive course. Most patients acquire allograft hepatitis after at least five yr (1). Fibrosis progresses significantly faster than in immunocompetent patients, suggesting that the time to development of cirrhosis is shorter-approximately 9-12 yr (2). The estimated cumulative probability of developing HCV-related graft cirrhosis at five yr is 30% (1-4), and once cirrhosis is established, the one-yr actuarial risk for decompensation is 42% (3). Liver biopsy is the gold-standard procedure, for determining the severity of necro-inflammatory activity and fibrosis, features potentially useful for predicting treatment response (4-7) and prognosis in HCV (5). Repeated biopsies are performed in patients with recurrent HCV to estimate disease progression, to exclude other causes of elevated serum liver enzyme levels (8, 9) and to evaluate antiviral treatment response (10, 11). However, the procedure is limited by adverse effects (12),