Measurement Of Liver Fibrosis Research Articles

Correlation Between Fibroscan and ARFI with Metavir Liver Fibrosis Score

Non-invasive assessment of liver fibrosis with Fibroscan and acoustic radiation force impulse (AFRI) imaging are two most popular modalities to measure liver fibrosis. Fibroscan is a well-established modality which measure both liver fibrosis and steatosis. However, there is considerable failure rate, and without image quidding the data may be misleading in the present of focal lesion in R hepatic lobe. ARFI may select an optimal location for measurement but there are concerns on the inter-observer and inter-location variations. We try to decrease the variation by measuring ARFI at two different locations. In a consecutive series of patients who received liver histology study were prospectively enrolled. All participant received hemogram, liver biochemistry, viral markers, ARFI and Fibroscan within 4 weeks of histology study. A standardized protocol was used to both Fibroscan and ARFI on the same day by a single technologist. Then both data from Fibroscan and ARFI were correlated with liver histology. Additional series of non-biopsy cases with chronic hepatitis B, chronic hepatitis C and non-alcoholic liver disease were also included for validation analysis. A total of 83 patients with liver histology study were included. This series included 34 NonB and NonC, 8 autoimmune liver diseases, 29 chronic hepatitis B and 12 hepatitis C. We excluded patients with alcoholism, dual HBV and HCV infection and unknown etiology. The correlation between Fibroscan and ARFI two-location measurement is good (R2=0.589, P<0.001). The area under the curve for Metavir 4 fibrosis are 0.877 and 0.919 for Fibroscan and ARFI respectively. A relatively lower value in Fibroscan than in ARFI is noted in the present of severe steatosis (CAP≥293, P<0.001). Similar situation was found in non-biopsy patients received both studies. The phenomenon of lower slope in patients with high CAP value are presented in all HBV, HCV or NBNC non-biopsy groups. We conclude that the correlation between Fibroscan and ARFI two location measurement is good. ARFI tends to have a better linearity with histology fibrosis grades than Fibroscan in patients with severe steatosis.

Transient elastography in clinical detection of liver cirrhosis: A systematic review and meta-analysis.

Background/Aims:Transient elastography is a noninvasive method for measuring liver fibrosis. This meta-analysis assesses the diagnostic performance of transient elastography of detecting liver cirrhosis in patients with liver disease.Patients and Methods:We searched MEDLINE, Cochrane, EMBASE databases until Jan 31, 2015, using the following search terms: elastography and liver cirrhosis. Included studies assessed patients with a diagnosis of liver cirrhosis, with an index test of transient elastography, and with the reference standard being a histopathological exam by liver biopsy. Sensitivity analysis and assessment of risk of bias and publication bias were performed.Results:Fifty-seven studies were included in the meta-analysis with a total of 10,504 patients. The pooled estimate for the sensitivity of transient elastography for detecting liver fibrosis was 81% and the specificity was 88%. The imputed diagnostic odds ratio (DOR) was 26.08 and the area under the receiver-operating characteristic (AUROC) curve was 0.931.Conclusion:Our findings indicate that transient elastography shows good sensitivity, specificity and a high accuracy for detecting liver cirrhosis. Transient elastography can be used as an additional method for the clinical diagnosis of liver fibrosis and cirrhosis.

Evaluation of liver fibrosis: “Something old, something new…”

Hepatic fibrogenesis may gradually result to cirrhosis due to the accumulation of extracellular matrix components as a response to liver injury. Thus, therapeutic decisions in chronic liver disease, regardless of the cause, should first and foremost be guided by an accurate quantification of hepatic fibrosis. Detection and assessment of the extent of hepatic fibrosis represent a challenge in modern Hepatology. Although traditional histological staging systems remain the “best standard”, they are not able to quantify liver fibrosis as a dynamic process and may not accurately substage cirrhosis. This review aims to compare the currently used non-invasive methods of measuring liver fibrosis and provide an update in current tissue-based digital techniques developed for this purpose, that may prove of value in daily clinical practice.

Serial change of liver stiffness measured by acoustic radiation force impulse imaging in chronic liver disease: correlation with biochemical markers.

In patients with chronic diffuse liver diseases, liver fibrosis severity is an important element for prognosis and for selecting therapy. Acoustic radiation force impulse (ARFI) imaging techniques were recently developed to measure liver fibrosis, but their specificity is impaired by cholestasis, inflammation, or edema in acute hepatitis. Herein, our objectives were to evaluate serial changes in shear wave velocity (SWV) and to correlate these changes with biochemical activity. This study included 108 patients who underwent ARFI because of viral hepatitis [hepatitis B (HBV) or C (HCV)] with serial follow-up after 3-6months at our institution between August 2011 and May 2013. Based on baseline and follow-up ARFI, we divided patients with HBV and HCV into two groups: a decreasing SWV group and a non-decreasing SWV group. We evaluated serial SWV changes and correlated these changes with biochemical activity changes. The patients were divided into SWV groups as follows: decreasing SWV group (HBV, n=23; HCV, n=7) and non-decreasing SWV group (HBV, n=40; HCV, n=38). In both HBV and HVC patients, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were significantly decreased at follow-up in the decreasing SWV group. The liver stiffness value assessed by ARFI became lower over time in patients who had decreasing AST and ALT levels. According to this study, ARFI overestimates fibrosis grade in patients with high AST and ALT. Thus, assessment of liver fibrosis by ARFI elastography should include consideration of biochemical markers such as AST and ALT levels and additional follow-up using ARFI elastography.

Tissue Elasticity Quantification by Acoustic Radiation Force Impulse for the Assessment of Renal Allograft Function

Acoustic radiation force impulse (ARFI) quantification, a novel ultrasound-based elastography method, has been used to measure liver fibrosis. However, few studies have been performed on the use of ARFI quantification in kidney examinations. We evaluated renal allograft stiffness using ARFI quantification in patients with stable renal function (n = 52) and those with biopsy-proven allograft dysfunction (n = 50). ARFI quantification, given as shear wave velocity (SWV), was performed. The resistance index (RI) was calculated by pulsed-wave Doppler ultrasound, and clinical and laboratory data were collected. Morphologic changes in transplanted kidneys were diagnosed by an independent pathologist. Mean SWV was more significantly negatively correlated with estimated glomerular filtration rate (eGFR) (r = –0.657, p < 0.0001) than was RI (r = –0.429, p = 0.0004) in transplanted kidneys. Receiver operating characteristic curve analysis revealed that the sensitivity and specificity of quantitative ultrasound in the diagnosis of renal allograft dysfunction were 72.0% and 86.5% (cutoff value = 2.625), respectively. The latter values were better than those of RI, which were 62.0% and 69.2% (cutoff value = 0.625), respectively. The coefficient of variation for repeat SWV measurements of the middle part of transplanted kidney was 8.64%, and inter-observer agreement on SWV was good (Bland-Altman method, ICC = 0.890). In conclusion, tissue elasticity quantification by ARFI is more accurate than the RI in diagnosing renal allograft function.

JSUM ultrasound elastography practice guidelines: liver.

In diffuse liver disease, it is extremely important to make an accurate diagnosis of liver fibrosis prior to determining indications for therapy or predicting treatment outcome and malignant potential. Although liver biopsy has long been the gold standard in the diagnosis of liver fibrosis, it is still an invasive method. In addition, the sampling error is an intrinsic problem of liver biopsy. Non-invasive serological methods for the diagnosis of liver fibrosis can be affected by factors unrelated to the liver. Recently, after the introduction of FibroScan, it became possible to measure liver fibrosis directly and non-invasively by elastography, which has attracted attention as a non-invasive imaging diagnostic tool for liver fibrosis. In addition, real-time tissue elastography is currently being used to conduct clinical trials at many institutions. Moreover, virtual touch quantification enables the observation of liver stiffness at any location by simply observing B-mode images. Furthermore, the recently developed ShearWave elastography visualizes liver stiffness on a color map. Elastography is thought to be useful for all types of diffuse liver diseases. Because of its association with portal hypertension and liver carcinogenesis, elastography is expected to function as a novel prognostic tool for liver disease. Although various elastographic devices have been developed by multiple companies, each device has its own measurement principle, method, and outcome, creating confusion in clinical settings. Therefore, it is extremely important to understand the characteristics of each device in advance. The objective of this guideline, which describes the characteristics of each device based on the latest knowledge, is for all users to be able to make the correct diagnosis of hepatic fibrosis by ultrasound elastography.

Non-invasive assessment of liver fibrosis using ARFI with pathological correlation, a prospective study

Introduction.ARFI is a new technique that uses acoustic push pulse to generate tissue displacement resulting in shear wave propagation, can be used to measure elasticity of tissue. We aim to assess feasibility of ARFI as a non-invasive method to measure liver fibrosis compared to histological fibrosis scores and to compare our results with the published pooled-meta-analysis cut off values.Material and methods. Prospective study to compare median velocities of ARFI shear wave measurements (Virtual Touch Imaging™ ACUSON S2000, Siemens, Mountain View CA) with Batts and Ludwig liver fibrosis scoring system F0-F4.Results. 70 patients (mean = 49 years) were included. Etiologies were chronic hepatitis C (n = 43), chronic hepatitis B (n = 7) and others (n = 20). Median ARFI values (m/sec) for fibrosis stages and inflammatory stages measured were F0: 1.52, 1.42; F1: 1.50, 1.37; F3: 2.36, 2.41 and F4: 2.61. Areas under the curve for grade 3 = 0.875, stage 3 = 0.867; grade 2 = 0.4, stage 2 = 0.3.Using the cut-off ARFI value of 1.34 m/s for F ≥ 2 suggested in the meta-analysis, we found sensitivity of detecting true F > 2 is 68%, specificity 66%, PPV 74% and NPV 59%. For F ≥ 3 using the cut-off ARFI value of 1.55 m/s, we found sensitivity of 95%, specificity 86%, PPV 74% and NPV 98%. No stage 4 was compared due to insufficient cases.Conclusion. ARFI has strong correlation with higher fibrosis scores compared to lower. When compared to the pooled meta-analysis cut off values, the sensitivity and specificity for detecting true F ≥ 3 are higher than that of F ≥ 2.

Unhealthy Alcohol Use, HIV Infection and Risk of Liver Fibrosis in Drug Users with Hepatitis C

AimTo analyze alcohol use, clinical data and laboratory parameters that may affect FIB-4, an index for measuring liver fibrosis, in HCV-monoinfected and HCV/HIV-coinfected drug users.Patients and MethodsPatients admitted for substance abuse treatment between 1994 and 2006 were studied. Socio-demographic data, alcohol and drug use characteristics and clinical variables were obtained through hospital records. Blood samples for biochemistry, liver function tests, CD4 cell count, and serology of HIV and HCV infection were collected at admission. Multivariate linear regression was used to analyze the predictors of FIB-4 increase.ResultsA total of 472 (83% M, 17% F) patients were eligible. The median age at admission was 31 years (Interquartile range (IQR) 27–35 years), and the median duration of drug use was 10 years (IQR 5.5–15 years). Unhealthy drinking (>50 grams/day) was reported in 32% of the patients. The FIB-4 scores were significantly greater in the HCV/HIV-coinfected patients (1.14, IQR 0.76–1.87) than in the HCV-monoinfected patients (0.75, IQR 0.56–1.11) (p<0.001). In the multivariate analysis, unhealthy drinking (p = 0.034), lower total cholesterol (p = 0.042), serum albumin (p<0.001), higher GGT (p<0.001) and a longer duration of addiction (p = 0.005) were independently associated with higher FIB-4 scores in the HCV-monoinfected drug users. The effect of unhealthy drinking on FIB-4 scores disappeared in the HCV/HIV-coinfected patients, whereas lower serum albumin (p<0.001), a lower CD4 cell count (p = 0.006), higher total bilirubin (p<0.001) and a longer drug addiction duration (p<0.001) were significantly associated with higher FIB-4 values.ConclusionsUnhealthy alcohol use in the HCV-monoinfected patients and HIV-related immunodeficiency in the HCV/HIV-coinfected patients are important risk factors associated with liver fibrosis in the respective populations

Management and Treatment of Chronic Hepatitis C in HIV Patients

Progression to cirrhosis occurs faster whereas response to peginterferon/ribavirin therapy is lower in patients with chronic hepatitis C coinfected with human immunodeficiency virus (HIV), as compared with hepatitis C virus (HCV) monoinfected individuals. The use of antiretroviral therapy may ameliorate poor outcomes in HIV/HCV coinfected patients. However, in the best scenario peginterferon/ribavirin therapy provides cure to 30% of patients harboring HCV genotypes 1 or 4 and to 70% of HCV genotypes 2 or 3 carriers, a rate lower than that seen in HCV monoinfection. Moreover, a substantial proportion of HIV/HCV coinfected patients are not treated due to contraindications, or do not complete therapy due to serious adverse events, or just do not wish to receive such a poorly tolerated medication. For these reasons, the advent of direct acting antivirals (DAA) has been eagerly awaited for treating HIV/HCV coinfected patients. However, new challenges have arisen, including the potential for harmful drug interactions with antiretroviral agents, poor drug adherence due to polymedication, increased risk for selection of drug-resistant HCV mutants, and unaffordable coverage in an environment of economic constraints. The use of noninvasive tools to measure liver fibrosis (i.e., elastometry) and pharmacogenomics (testing for IL28B and perhaps ITPA polymorphisms), along with consideration of early viral kinetics to guide length and drugs needed could help to individualize and improve the cost effectiveness of therapeutic decisions using DAA in HIV-infected patients with chronic hepatitis C.

Staging Liver Fibrosis in Hepatitis C: A Challenge for This Decade

The limitations of and the invasive nature of liver biopsy has spurred extensive interest in the development of non-invasive tests to measure liver fibrosis in patients with chronic hepatitis C. Clinically applicable non-invasive tests, including radiological studies, elastography, and serum markers, all of which perform extremely well in excluding significant disease and diagnosing cirrhosis. FibroScan and acoustic radiation force impulse elastography are two elastography-based tests that show promise. In this new era of increased cure rates with newly Food and Drug Administration-approved drugs and the availability of multiple non-invasive tests of liver fibrosis, we anticipate a decreasing need for liver biopsies in the management of chronic hepatitis C.

Different Answers to the Crucial Problem of Replacing Needle Biopsy: Different Elastographic Methods for Measuring Liver Fibrosis in Patients with Chronic Liver Disease

Different Answers to the Crucial Problem of Replacing Needle Biopsy: Different Elastographic Methods for Measuring Liver Fibrosis in Patients with Chronic Liver Disease

The use of transient elastography in the management of chronic hepatitis B

There has been increasing interest in noninvasive methods of assessing liver fibrosis over the last decade. The use of transient elastography in measuring liver stiffness has become the forefront of a wide range of noninvasive tools. Most of the other methods are based on measurements of biomarkers associated with fibrosis. There are several reasons for its wide acceptance, including the ease of performing a scan, the short procedure time, the results being immediately available on completion of the examination, and its reproducibility. For chronic hepatitis B (CHB), the cut-off values for F3 and F4 fibrosis range between 7.5–12.0 and 11.0–13.4 kPa, respectively, although the cut-offs may be slightly lower in those with normal ALT. In addition to measuring liver fibrosis, recent studies have demonstrated several other roles for transient elastography, including selecting patients who will benefit from antiviral therapy, monitoring response to antiviral therapy, and predicting long-term outcomes. However, there are limitations associated with transient elastography, including the confounding effects of inflammatory activity, and to a lesser extent, steatosis, on liver stiffness. There is also reduced accuracy observed in lower fibrosis stages (F0–F2). Furthermore, the incidences of failed and unreliable scan have been reported to be ~ 3 and 16%, respectively. Although liver biopsy can be avoided in an estimated 50–60% using transient elastography, in situations where liver stiffness measurement is nondiagnostic or inconsistent with the clinical picture, a biopsy is still recommended. Further studies are needed to consolidate the role of transient elastography in the management of CHB, and for incorporation of this method into current treatment guidelines.

Risk factors for advanced liver fibrosis in HIV-infected individuals: role of antiretroviral drugs and insulin resistance

Liver damage may result from multiple factors in HIV-infected patients. The availability of reliable noninvasive tools to measure liver fibrosis has permitted the screening of large patient populations. Cross-sectional study of all consecutive HIV outpatients who underwent examination by transient elastometry (FibroScan) at one HIV reference clinic during 2007. Advanced liver fibrosis (ALF) was defined as hepatic stiffness >9.5 kilopascals, which corresponds to Metavir stages F3-F4 in the liver biopsy. A total of 681 consecutive HIV-infected patients (64% injecting drug users; mean age 43; 78% male; 98% on antiretroviral therapy) had at least one valid FibroScan evaluation. ALF was diagnosed in 215 (32%) of them. In the univariate analysis, ALF was significantly associated with older age, low CD4 counts, chronic hepatitis C, past alcohol abuse, elevated ALT, high triglycerides, low cholesterol, high homeostasis model assessment (HOMA) index and exposure to didanosine and/or stavudine. In a multivariate model (OR, 95% CI), chronic hepatitis C (2.83, 1.57-5.08), past alcohol abuse (2.26, 1.37-3.74), exposure to didanosine and/or stavudine (1.85, 1.14-3.01), high HOMA index (1.25, 1.04-1.51), older age (1.09, 1.05-1.14) and elevated ALT (1.04, 1.03-1.06) remained as independently associated with ALF. Therefore, in addition to chronic hepatitis C and alcohol abuse, insulin resistance and/or exposure to dideoxy-nucleosides may contribute to ALF in HIV-infected patients.

Transient Elastography (FibroScan®) for Noninvasive Assessment of Liver Amyloidosis.

Abstract 4894 BackgroundLiver involvement is frequent in AL amyloidosis patients, and is found in 70% of cases in autopsy series. Histologic diagnosis of amyloid deposition is mandatory, preferably by biopsies of non-hepatic tissue, liver biopsy being associated with an increased risk of bleeding. FibroScan, a non invasive method for measuring liver stiffness, is used to measure liver fibrosis in patients with viral hepatitis. We postulated that amyloid liver deposition in AL could enhance liver stiffness and that may help for the diagnosis of liver amyloidosis. Methods41 consecutive AL patients with systemic disease seen at the French Reference Center for AL amyloidosis were analyzed: 17 had liver AL, 23 cardiac AL, and 13 no liver or cardiac involvement according to the criteria defined by the Tours Consensus Opinion on Amyloidosis (2005). All had liver stiffness measured by FibroScan simultaneously with 76 controls: 16 healthy controls, 10 multiple myeloma and 50 consecutive patients chronically infected with hepatitis C virus (HCV). According to the manufacturer's criteria, liver stiffness was interpretable in 32 (78%) of AL patients and in 68 (89%) of the control group. The Mann Whitney test with Bonferroni correction for multiple comparisons was used to compare the interpretable liver stiffness values between the groups. ResultsThe liver stiffness was not statistically different between the healthy (median 4,6 range 2,8-6,5 KPa) and the myeloma controls (median 5,4 range 3,3-11,9 KPa) and both were considered as the negative control group. The negative control group had a liver stiffness significantly different from the HCV group (median 6,8 range 2,9-69,1 KPa, p<0.001), but not from the AL group without liver or cardiac involvement (median 6,1 range 4,2-17,5 KPa, p=0,25). The liver stiffness of AL patients with liver (with or without cardiac) involvement, was significantly higher (median 27,4 range 10,3-75 KPa) than the one of the negative control group (p<0.001), or the HCV group (p=0.001), and the AL group without liver or cardiac involvement (p=0.001). The relationship between AL liver involvement and the liver stiffness value was tested using ROC curve analysis with an optimal cut-off value of 9,8 KPa, a sensitivity of 100% (95%CI71,5 - 100,0), a specificity of 75.6% (95%CI64,6 - 84,7) and a ROC AUC of 0.92 (p=0.0001). In order to favour specificity for the diagnosis of AL liver involvement in non specific clinical situations, we chose the cut-off value of 17.5 KPa (specificity 94,87% (95%CI87,4 - 98,6), sensitivity 63,64% (95%CI30,8 - 89,1). ConclusionFibroScan is a useful non invasive tool which may suggest that a patient with undefined signs (enlarged liver, asymptomatic cholestasis, isolated monoclonal gammopathy) has liver amyloidosis and may help to define liver involvement in patients with proven amyloidosis, especially when liver stiffness reaches the cut-off value of 17,5 KPa. DisclosuresNo relevant conflicts of interest to declare.

Liver fibrosis on account of chronic hepatitis C is more severe in HIV‐positive than HIV‐negative patients despite antiretroviral therapy

The recent availability of non-invasive tools to measure liver fibrosis has allowed examination of its extent and determination of predictors in all patients with chronic hepatitis C virus (HCV) infection. On the other hand, most information on hepatic fibrosis in HCV/human immunodeficiency virus (HIV)-coinfected patients has been derived from liver biopsies taken before highly active antiretroviral therapy (HAART) was widely available. All consecutive HCV patients with elevated aminotransferases seen during the last 3 years were evaluated and liver fibrosis measured using transient elastography (FibroScan) and biochemical indexes. Patients were split according to their HIV serostatus. A total of 656 (69.6%) HCV-monoinfected and 287 (30.4%) HIV/HCV-coinfected patients were assessed. Mean CD4 count of coinfected patients was 493 cells/muL and 88% were under HAART (mean time, 4.2 +/- 2.4 years). Advanced liver fibrosis or cirrhosis was recognized in 39% of the coinfected and 18% of the monoinfected patients (P < 0.005). A good correlation was found between FibroScan) and biochemical indexes [AST to platelet ratio index (r = 0.405, P < 0.0001), FIB-4 (r = 0.393, P < 0.0001) and Forns (r = 0.407, P < 0.0001)], regardless of the HIV status. In the multivariate analysis, age >45 years, body mass index (BMI) >25 kg/m(2), and HIV infection were independently associated with advanced liver fibrosis or cirrhosis. HIV/HCV-coinfected patients have more advanced liver fibrosis than HCV-monoinfected patients despite the immunologic benefit of HAART.

Noninvasive Assessment of Liver Fibrosis and Portal Hypertension With Transient Elastography

Hepatic fibrogenesis, the "final" common result of injury to the liver, is believed to be a critical factor leading to hepatic dysfunction and may be important in the pathogenesis of portal hypertension. Thus, accurate assessment of the degree of fibrosis is important clinically. For many years, examination of hepatic histopathology has been considered to be the "gold standard" tool used to assess fibrosis. However, liver biopsy is invasive, and in many instances not favored by patients or physicians. Thus, alternative approaches to measure liver fibrosis would be extremely attractive. To the extent that transient elastography is able to measure "liver stiffness," which is proportional to the degree of liver fibrosis, this technique holds great promise.

577 Liver stiffness measurement (LSM) as a tool to measure liver fibrosis in treated patients with chronic hepatitis C (CHC)

577 Liver stiffness measurement (LSM) as a tool to measure liver fibrosis in treated patients with chronic hepatitis C (CHC)

708 Monitoring liver elasticity: A new tool to measure liver fibrosis during therapy

708 Monitoring liver elasticity: A new tool to measure liver fibrosis during therapy