Finally, the invasive nature of the biopsy makes it unsuitable for serial hepatic sampling. Both of these tests have been developed and extensively validated in patients with hepatitis C [ 11 , 12 ], but their utility in hepatitis B has not been adequately evaluated.
In this study, we prospectively assessed the performance characteristics of FibroSURE as a noninvasive test for measuring liver inflammation and fibrosis in patients with chronic hepatitis B infection. All HBV-infected patients who underwent a liver biopsy at our institution between and were prospectively approached and offered participation in this study. We enrolled 45 HBV-infected patients, 12 Patients with HCV co-infection and other co-existing liver diseases were excluded.
The study was approved by the Weill Cornell Medical College institutional review board and was performed in accordance with the Declaration of Helsinki. All liver biopsies were evaluated according to the Scheuer classification [ 13 ] by the same hepatopathologist RKY. Aminotransferase levels were logarithmically transformed for the analysis. For continuous variables, comparisons between groups were performed using Wilcoxon rank-sum or Kruskal-Wallis tests.
Diagnostic abilities of FibroSURE were expressed through the estimated area under the receiver operating characteristic AUROC curve and by calculation of the respective sensitivity, specificity, positive and negative predictive values estimated for appropriate cut-off values. The AUROC was estimated by the trapezoidal rule and represents the probability that a randomly selected pair of subjects will be classified correctly.
In order to estimate the linear combination of the available variables, which detects fibrosis stage and inflammation grade, we used logistic regression. The significance level in all tests two-sided was set to 0. One patient was taking Lamivudine, two were on Tenofovir, four patients were on Truvada, and three patients, one of whom was HBV mono-infected, were on Entecavir. In addition, Only 8. FibroSURE test was performed an average of 11 days preceding or after the liver biopsy.
The number of people in each category is listed in parenthesis adjacent to the fibrosis stage. Based on logistic regression, the following linear score:.
When we evaluated the performance characteristics of the model, we found that a cut-off score of 0. Values of the area under ROC curves for the individual variables are indicated in parenthesis at the bottom of the image A. Sensitivity and specificity of the model score for a range of cut-off values B. Using a cut-off value of 0. Unlike HCV, in HBV, treatment endpoints include biochemical responses, as indicated by normalization of ALT, and histological responses, as indicated by reduced necroinflammation and reversion of fibrosis [ 2 ].
In the last decade, several non-invasive indices have been developed as liver biopsy alternatives. Given the therapeutic importance of necroinflammatory activity and fibrosis in HBV infection, a noninvasive index such as FibroSURE might have an important role in the management of the infection.
This is in accordance with prior observations that successful treatment with a biochemical response was associated with a decline in serum fibrosis marker indices or TE measurements in patients with chronic HCV[ 9 - 12 , 28 , 29 ]. A limitation of this study is that post-treatment biopsies were not required as part of these two clinical registration trials, which would have allowed for correlation between the observed declines in noninvasive test scores and changes in fibrosis or necro-inflammation.
TE measurements may vary significantly with immune-mediated inflammatory responses in patients with chronic hepatitis B virus[ 30 ]. In contrast to other studies in patients with chronic HCV[ 6 ], however, this study also demonstrated a significant association between TE and histological necro-inflammatory activity at baseline.
This association may have implications for establishing TE thresholds for different fibrosis stages in chronic HCV and may also explain the decline in liver stiffness measurements in patients with an established SVR in the present cohort. The observed accuracy and specificity for prediction of stages F in Asians, however, was higher in the small TE cohort.
The combination of FS and TE in Asian patients resulted in a high accuracy for prediction of F, with no false-positive results. Thus, biopsies for staging F could have been avoided in almost all Asian patients in this small cohort of 33 patients. There was excellent agreement between FS and TE in Asian patients, and this may partly relate to a slightly higher prevalence of advanced-stage disease and lower body mass index in the Asian cohort.
Furthermore, increased waist circumference appears to be a common reason for failure of TE in European cohorts[ 19 ]. Although there are potential issues in obtaining adequate TE measurements in Asian patients due to a narrow intercostal space, this was not a limiting factor in the present study[ 13 ].
One of the strengths of this study is that sample collections were standardized per protocol for the two phase III clinical trials, laboratory assessments were performed centrally, and all biopsies were evaluated by a single experienced liver histopathologist. Standardization significantly reduced the heterogeneity observed in prior studies comparing results across different geographic populations[ 23 ]. Biopsy sampling and observer error, however, are inherent limitations to the development and validation of all fibrosis biomarkers[ 31 ].
The experience of the pathologist may be more important than biopsy characteristics[ 32 ]. Furthermore, prior studies have indicated that the accuracy of liver biopsy and noninvasive tests is dependent on sample size[ 9 , 33 - 35 ]. Prior studies have suggested that noninvasive performance indices for stages F and F4 are improved using sequential algorithms of FS and TE[ 6 ], or aspartate aminotransferase-to-platelet ratio index and FS[ 36 ]. As expected, misclassification rates and discordance between FS and TE with biopsy were significantly reduced for prediction of F4.
With a broader range of available therapeutic options for patients with chronic HCV in the future, noninvasive measures that can accurately exclude advanced-stage disease will likely assume a more significant clinical role in the treatment decision process.
The observed heterogeneity among studies including the present one for optimized TE cutoffs indicates that a range of liver stiffness measurements for each fibrosis threshold in patients with chronic HCV may be more appropriate[ 39 ]. Standardization of AUROC curves or other methods to reduce effects of spectrum bias in disease prevalence allows for comparison of FS across studies, including selected cohorts within studies, but not for TE due to variable optimal thresholds[ 21 ].
No significant differences between observed and standardized AUROC values were found in the present study for either noninvasive measure.
In summary, this study demonstrates that a combination of serum and imaging noninvasive tests can be used for prediction of at least moderate-stage disease in a global cohort of patients with chronic HCV, including the potential of higher accuracy for the combination of FS and TE in Asian patients.
Furthermore, some baseline differences in index values for both FS and TE were dependent on virological response and merit further evaluation in the context of IFN-based therapy.
The authors also wish to thank all research staff and technicians who participated in this study. Goethe University Hospital, Frankfurt, Germany. Liver biopsy is an invasive procedure associated with significant costs and risk of complications. The combination of these two modalities appears to have a good predictive value for excluding cirrhosis. Fibrosis is a predictor of virological response to chronic hepatitis C virus HCV therapy, and noninvasive tests may also be useful in this regard.
Test values may vary with antiviral therapy for chronic HCV, perhaps due to changes in hepatic inflammation or with body habitus. Few studies have evaluated the utility of both these noninvasive modalities in patients with chronic HCV during interferon-based therapy, and there are limited data for these tests in Asian patients, particularly in comparison with non-Asian cohorts. Both FS and TE are validated measures for the noninvasive assessment of fibrosis.
One important research issue is the determination of their utility in following changes in fibrosis or inflammation, e. In this study, both FS and TE demonstrated good potential utility in the detection of moderate-severe-stage disease, but the performance characteristics of these noninvasive tests particularly TE may be somewhat better for exclusion of cirrhosis.
Agreement between these tests and their accuracy for predicting disease stage may be higher in Asian than in non-Asian patients with chronic HCV. Patients that achieved a sustained virological response with interferon therapy appeared to have lower noninvasive test values at baseline. Lower index scores at baseline may signify a better chance of responding to antiviral therapy. FS comprises a combination of simple biochemical blood tests that predict fibrosis.
TE is an ultrasound-based imaging method to measure liver stiffness, which also predicts fibrosis. This article is unique and interesting.
You will be subject to the destination website's privacy policy when you follow the link. CDC is not responsible for Section compliance accessibility on other federal or private website. Cancel Continue. Sample can be reported as nonreactive for HCV antibody. Provide person tested with appropriate counseling and link person tested to care and treatment. No further action required in most cases. Halo top ice cream is a reduced-calorie ice cream made with natural and organic ingredients, but is it really good for you?
This article takes a…. Health Conditions Discover Plan Connect. Medically reviewed by Daniel Murrell, M. Fibrosis score Testing Results Risk factors Diagnosis and treatment Talk to your doctor Understanding hepatitis C Hepatitis C is a serious and potentially life-threatening condition that affects your liver.
Why you need a fibrosis score. Testing for fibrosis. Understanding your fibrosis score. What are the risk factors for hepatitis C? Diagnosis and treatment of hepatitis C. Speaking with your doctor. Hepatitis C Remission. Liver Function Tests. Read this next. Liver Fibrosis. Medically reviewed by Alana Biggers, M. Medically reviewed by Graham Rogers, M.
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