- Email: [email protected]
The Acoustic Radiation Force Impulse Elastography Evaluation of Liver Fibrosis in Posttransplantation Dysfunction of Living Donor Liver Transplantation
The Acoustic Radiation Force Impulse Elastography Evaluation of Liver Fibrosis in Posttransplantation Dysfunction of Living Donor Liver Transplantation C.C. Liao, T.Y. Chen, L.C. Tsang, S.Y. Ou, C.Y. Yu, H.W. Hsu, Y.F. Cheng, K.W. Chiu, H.L. Eng, C.L. Chen, and T.L. Huang ABSTRACT Background. The acoustic radiation force impulse elastography (ARFI) is a new technology of elastography integrated into B-mode ultrasonography. It has been a reliable method to evaluate liver fibrosis of chronic liver disease in recent years, but less applied in the posttransplantation liver. The aim of the study was to evaluate liver fibrosis by the ARFI with correlation of pathological stages in living donor liver transplantation (LDLT). Materials and Methods. From August 2010 to August 2012, there were 57 LDLT patients with liver biopsy (LB) due to posttransplantation dysfunction; all patients also received posttransplantation ARFI liver stiffness measurement (LSM) after transplantation for liver fibrosis staging. The ARFI elastography was performed using a Siemens Acuson S2000 ultrasound system with 4V1 transducers (Acusion, Siemens Medical Systems Co. Ltd. Erlangen, Germany). The ARFI LSM value was presented by shear wave velocity (SWV, m/s). The fibrosis staging as F0 to F4 was in accordance with the Metavir scoring system. Results. A total of 57 patients had both posttransplantation LB and effective ARFI fibrosis staging for correlation. The ARFI LSM value increased with severity of liver fibrosis and had significant linear correlation with the results of histological fibrosis staging. The ARFI LSM sensitivities (Se), specificities (Sp), and cutoff values based on receiveroperator characteristic curve were F0: 0.75 m/s (Se: 93.8%, Sp: 4%), F1: 1.06 m/s (Se: 95.5%, Sp: 25.7%), F2: 1.81 m/s (Se: 50%, Sp: 83.6%) and F3: 2.33 m/s (Se: 100%, Sp: 92.9%). Predictive value of ARFI LSM reported a significant difference between early fibrosis stage (F0eF1) and advanced fibrosis stage (F S 2) (P < .05). Conclusion. In this study, ARFI demonstrated a strong linear correlation and severity of liver fibrosis with LB pathologic staging. ARFI can be an alternative and compensatory method for frequent LB in the posttransplantation liver.
L
IVER TRANSPLANTATION allograft dysfunction is the major posttransplantation problem of living donor liver transplantation (LDLT) [1,2]. Early allograft dysfunction may present by elevated liver function test results; the common etiologies of allograft include acute or chronic hepatitis, acute rejection, and malignancy [2]. Eventually, the prognosis of the posttransplantation dysfunction may lead to liver graft parenchyma stiffness change and fibrosis. Liver biopsy (LB) remains the gold standard method for evaluating liver parenchyma change, and can well demonstrate fibrosis, portal infiltrate, and lobular necrosis [3]. However, biopsy is an invasive procedure that may cause major complications, such as bleeding. Additionally, a small 0041-1345/14/$esee front matter http://dx.doi.org/10.1016/j.transproceed.2013.12.012 876
From the Liver Transplantation Program and Departments of Diagnostic Radiology (C.C.L., T.Y.C., L.C.T., S.Y.O., C.Y.Y., H.W.H., Y.F.C., T.L.H.), Internal Medicine (K.W.C.), Pathology (H.L.E.), and General Surgery (C.L.C.), Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. This study was supported in part by grants NSC100-2314B-182A-071 and NSC101-2314-B-182A-074-MY2 from the National Science Council and CMRPG 891261 from Chang Gung Memorial Hospital, Taiwan. Address reprint requests to Dr. Tung-Liang Huang, Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, Taiwan. E-mail: [email protected] ª 2014 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 46, 876e879 (2014)
ACOUSTIC RADIATION FORCE IMPULSE ELASTOGRAPHY EVALUATION
biopsied sample size may lead to misdiagnosis of fibrosis stage [4]. Frequent biopsy in posttransplantation liver graft is not an ideal option; therefore, a noninvasive, repeatable, and reliable method is important. Recently, transient elastography (TE) has been found to be a noninvasive and quantitative way to measure liver stiffness change in chronic hepatitis or cirrhosis [5]; it has provided reliable correlation with fibrosis staging results. However, TE has many limitations, such as high body mass index and ascites; it may overestimate liver stiffness in acute hepatitis; additionally, it cannot measure the specific site of liver parenchyma [6,7]. Acoustic radiation force impulse (ARFI) imaging is a new elastography method for the evaluation of tissue stiffness. It is integrated into conventional B-mode ultrasound examination. ARFI can generate acoustic radiation force as a pressure wave that spreads through tissue, and can be measured as shear wave velocity (SWV) that presents the degree of tissue stiffness [8]. Using ARFI and TE for liver fibrosis evaluation has been adopted in patients with chronic hepatitis or cirrhotic liver, and they both reported a promising and reliable correlation with liver fibrosis change [7]. The ARFI examination seems to have more advantage in varied types of liver graft. Therefore, we designed this study of posttransplantation liver parenchyma fibrotic change measured by ARFI liver stiffness measurement (LSM) and correlated with biopsy pathological staging. PATIENTS From August 2010 to August 2012, a total of 57 patients with LDLT (43 men, 14 women, mean age 57 7.62 years) received LB due to posttransplantation dysfunction. The liver function test, blood platelet count, prothrombin time, and viral titer were collected. The fibrosis staging was based on the Metavir scoring system. Indications for biopsy in these 57 patients were abnormal graft dysfunctions in posttransplantation follow-up, which were suspected rejection-related or recurrent hepatitis; the definition of posttransplantation dysfunction was AST and ALT >100 IU/dL or persistent hyperbilirubinemia. The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki and was approved by our institutional review boards. Written informed consent was obtained from all participants for the use of their data for research purposes.
ARFI LSM Both B-mode standard ultrasonography scanning and LSM by ARFI were performed using the Siemens Acuson S2000 ultrasound system with 4V1 transducers (Acusion, Siemens Medical Systems Co. Ltd. Erlangen, Germany). Technically, ARFI LSM had focused on a specific segment of liver (the right lobe graft was accessed in S5-6, the left lobe graft in S3-4), avoiding motion artifacts and hepatic vessels as much as possible. The measurement was performed at a portion of the liver that was about 4 to 6 cm in depth from the skin surface. The values of LSM were presented by shear wave velocity (SWV ¼ m/s) and calculated as the median ARFI value from 10 measurements. The procedures were performed by senior radiologists who were blinded to the clinical, serological, and histological data.
877
LB and Pathological Fibrosis Staging LB was performed percutaneously with ultrasonography assistance by senior physicians, using 17- to 18-gauge modified Menghini needles (Biomol, Boca Raton, Florida). All specimens were sealed, fixed, and examined by pathologists in our facility. The scoring system of fibrosis stage was based on the Metavir scoring system, in which fibrosis was classified on a F0 to F4 scale as follows: F0 ¼ no fibrosis, F1 ¼ portal fibrosis without septa, F2 ¼ portal fibrosis and few septa, F3 ¼ numerous septa without cirrhosis, F4 ¼ cirrhosis [9].
Statistical Analysis The diagnostic performance of ARFI and the stage of liver fibrosis sensitivity and specificity were developed as area under the receiveroperator characteristic (ROC) curves. The areas under the curves and 95% confidence intervals (CI) used the Mann-Whitney statistic calculation. The optimal cutoff value was chosen to maximize the sum of the sensitivity and specificity on the Youden index. Differences were considered significant at P < .05. Correlation between ARFI LSM liver fibrosis staging and LB pathological fibrosis stage was analyzed using both the Kendall tau-b and the Spearman rho methods.
RESULTS
A total of 57 LDLT patients (43 men, 14 women, mean age 57 7.62 years) were enrolled in our study and had effective ARFI LSM and valid LB due to posttransplantation dysfunction; 44 patients received right lobe liver graft, (n ¼ 44 of 57, 77%) and 13 patients received left lobe liver graft (n ¼ 13 of 57, 23%). Two major indications for LB in posttransplantation dysfunction were recurrent viral hepatitis (n ¼ 44 of 57, 77.2%), and acute or chronic rejection (n ¼ 28 of 57, 49.1%). The LB stages were 32 patients at F0 (56%), 22 patients at F1 (38.5%), 2 patients at F2 (3.5%), and 1 patient at F3. The calculated cutoff values of ARFI LSM were analyzed based on the ROC curve (Fig 1A). There were F0: 0.75 m/s (sensitivity [Se]: 93.8%, specificity [Sp]: 4%), F1: 1.06 m/s (Se: 95.5%, Sp: 25.7%), F2: 1.81 m/s (Se: 50%, Sp: 83.6%), and F3: 2.33 m/s (Se: 100%, Sp: 92.9%), but the F4 cutoff value was not available (Table 1). The values of ARFI LSM of liver fibrosis staging demonstrated linear correlation with the LB pathological fibrosis stage in either the Kendall tau-b or the Spearman rho method (Fig 1B). A significant difference between F0 (SWV cutoff value ¼ 0.75 m/s) and F1 (SWV cutoff value ¼ 1.06 m/s) was found in the early liver fibrosis stage (P < .0001). The advanced liver fibrosis stage (F S 2) also had high specificity, with an SWV cutoff value of 1.8 m/s, which was statistically different in fibrosis stages between F0 and F S 2 (P < .05). DISCUSSION
TE and ARFI have been used as noninvasive methods in the evaluation of liver fibrosis, and they both provide diagnosis of significant fibrosis and cirrhosis accurately [7,10,11]. However, TE has many limitations in measurement; the
878
LIAO, CHEN, TSANG ET AL
Fig 1. (A) Receiver-operator characteristic (ROC) curves for the calculated sensitivity and specificity of each acoustic radiation force impulse (ARFI) liver stiffness measurement (LSM) cutoff value. (B) Correlation between ARFI LSM liver fibrosis staging and liver biopsy pathological fibrosis stage. **Correlation is significant at the .01 level (2-tailed).
performance of TE may be limited in patients with a high body mass index (>28 kg/m2), narrow intercostal space, or ascites [6,7]. On the other hand, the advantage of choosing ARFI for posttransplantation liver evaluation was its LSM ability in LDLT during routine follow-up ultrasonography study. It also allowed us to measure the specific site and
depth of allograft on either right or left graft type. Furthermore, it can avoid nearby interfering structures, such as hepatic vessels and ascites. Regarding the accuracy of ARFI LSM in cirrhotic liver disease, previous studies have reported that ARFI has an excellent predictive value for liver fibrosis. The ARFI
ACOUSTIC RADIATION FORCE IMPULSE ELASTOGRAPHY EVALUATION
879
Table 1. The Predictive Value of Liver Fibrosis Evaluated by Acoustic Radiation Force Impulse and Histological Biopsy for Liver Fibrosis Stage According to the Metavir Score System in a Total of 57 Effective Cases 95% Confidence Interval Metavir
F0 F1 F2 F3 F4
Case (N)
Area
Standard Error
P Value
Lower Bound
Upper Bound
Cutoff Values
Sensitivity (%)
Specificity (%)
32 22 2 1 0
0.203 0.721 0.895 0.929 NA
0.059 0.068 0.056 0.034 NA
<.001 .005 .05 .145 NA
0.088 0.589 0.779 0.861 NA
0.317 0.854 1.000 0.996 NA
0.750* 1.058* 1.809* 2.331* NA
93.8 95.5 50 100 NA
4 25.7 83.6 92.9 NA
Abbreviations: NA, not available. *Receiver-operator characteristic curve.
SWV values increased in parallel with fibrosis staging, but were not accurate enough to differentiate between F1 and F2 in Metavir scoring. In the study published by Sporea et al. [11], ARFI was well correlated with liver fibrosis caused by viral hepatitis; however, ARFI was not accurate enough to differentiate between F 1 vs F 2 due to the small proportion of F0 and F1 patients. Crespo et al. [12] reported that ARFI LSM had been adopted for evaluation of liver fibrosis change, which included transplant and nontransplant patients with liver disease of varied etiologies. It has shown high accuracy only in advanced fibrosis patients (F S 2). In our study, for posttransplantation graft dysfunction of varied underlying causes, there was a larger proportion (n ¼ 54 of 57, 94.5%) of early fibrosis stage patients (F & 1); sensitivity was up to 95.9% using an SWV cutoff value of 1.058 m/s. There was a significant difference in F0 compared with F1. The results were satisfying for early fibrosis detection. In cases of advanced fibrosis stage, ARFI LSM had a high specificity (92.9%) using a cutoff value of 1.8 m/s and allowed us to identify patients with chronic liver parenchyma change. This was similar to other studies. Posttransplantation liver graft dysfunction is a critical issue in LDLT patients. The dysfunction of graft from varied causes developed diffuse liver parenchyma change as liver fibrosis. Early detection of underlying causes of graft dysfunction is important for intensive treatment and prevention of graft loss [2]. Usually, advanced fibrosis patients are more prominent, with abnormal liver function or diagnosed with recurrent viral hepatitis or acute or chronic rejection. Most of these patients need retransplantation. In conclusion, the real-time ultrasound-based ARFI imaging is easy and convenient to perform in the evaluation of posttransplantation dysfunction in LDLT patients. The results of this study showed reliable and significant correlation
with liver fibrosis change. This can be an alternative to frequent biopsy in the posttransplantation liver. REFERENCES [1] Ikegami T, Shirabe K, Yoshizumi T, Aishima S, Taketomi YA, Soejima Y, et al. Primary graft dysfunction after living donor liver transplantation is characterized by delayed functional hyperbilirubinemia. Am J Transplant 2012;12:1886. [2] Salvalaggio PR, Felga GE, Afonso RC, Ferraz-Neto BH, et al. Early allograft dysfunction and liver transplant outcomes: a single center retrospective study. Transplant Proc 2012;44:2449. [3] Bravo AA, Sheth SG, Chopra S. Liver biopsy. N Engl J Med 2001;344:495. [4] Colloredo G, Guido M, Sonzogni A, et al. Impact of liver biopsy size on histological evaluation of chronic viral hepatitis: the smaller the sample, the milder the disease. J Hepatol 2003;39:239. [5] Sporea I, Sirli R, Popescu A, et al. Acoustic radiation force impulse (ARFI)da new modality for the evaluation of liver fibrosis. Med Ultrason 2010;12:26. [6] Kim BK, Fung J, Yuen MF, et al. Clinical application of liver stiffness measurement using transient elastography in chronic liver disease from longitudinal perspectives. World J Gastroenterol 2013;19:1890. [7] Nierhoff J, Chavez Ortiz AA, Herrmann E, et al. The efficiency of acoustic radiation force impulse imaging for the staging of liver fibrosis: a meta-analysis. Eur Radiol 2013 Nov;23(11):3040e53. [8] Fierbinteanu-Braticevici C, Andronescu D, Usvat R, et al. Acoustic radiation force imaging sonoelastography for noninvasive staging of liver fibrosis. World J Gastroenterol 2009;15:5525. [9] Poynard T, Bedossa P, Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet 1997;349:825. [10] Friedrich-Rust M, Ong MF, Martens S, et al. Performance of transient elastography for the staging of liver fibrosis: a metaanalysis. Gastroenterology 2008;134:960. [11] Sporea I, Sirli R, Bota S, et al. Is ARFI elastography reliable for predicting fibrosis severity in chronic HCV hepatitis? World J Radiol 2011;3:188. [12] Crespo G, Fernández-Varo G, Mariño Z, et al. ARFI, FibroScan, ELF, and their combinations in the assessment of liver fibrosis: a prospective study. J Hepatol 2012;57:281.
L
IVER TRANSPLANTATION allograft dysfunction is the major posttransplantation problem of living donor liver transplantation (LDLT) [1,2]. Early allograft dysfunction may present by elevated liver function test results; the common etiologies of allograft include acute or chronic hepatitis, acute rejection, and malignancy [2]. Eventually, the prognosis of the posttransplantation dysfunction may lead to liver graft parenchyma stiffness change and fibrosis. Liver biopsy (LB) remains the gold standard method for evaluating liver parenchyma change, and can well demonstrate fibrosis, portal infiltrate, and lobular necrosis [3]. However, biopsy is an invasive procedure that may cause major complications, such as bleeding. Additionally, a small 0041-1345/14/$esee front matter http://dx.doi.org/10.1016/j.transproceed.2013.12.012 876
From the Liver Transplantation Program and Departments of Diagnostic Radiology (C.C.L., T.Y.C., L.C.T., S.Y.O., C.Y.Y., H.W.H., Y.F.C., T.L.H.), Internal Medicine (K.W.C.), Pathology (H.L.E.), and General Surgery (C.L.C.), Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. This study was supported in part by grants NSC100-2314B-182A-071 and NSC101-2314-B-182A-074-MY2 from the National Science Council and CMRPG 891261 from Chang Gung Memorial Hospital, Taiwan. Address reprint requests to Dr. Tung-Liang Huang, Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niao-Sung, Kaohsiung, Taiwan. E-mail: [email protected] ª 2014 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710 Transplantation Proceedings, 46, 876e879 (2014)
ACOUSTIC RADIATION FORCE IMPULSE ELASTOGRAPHY EVALUATION
biopsied sample size may lead to misdiagnosis of fibrosis stage [4]. Frequent biopsy in posttransplantation liver graft is not an ideal option; therefore, a noninvasive, repeatable, and reliable method is important. Recently, transient elastography (TE) has been found to be a noninvasive and quantitative way to measure liver stiffness change in chronic hepatitis or cirrhosis [5]; it has provided reliable correlation with fibrosis staging results. However, TE has many limitations, such as high body mass index and ascites; it may overestimate liver stiffness in acute hepatitis; additionally, it cannot measure the specific site of liver parenchyma [6,7]. Acoustic radiation force impulse (ARFI) imaging is a new elastography method for the evaluation of tissue stiffness. It is integrated into conventional B-mode ultrasound examination. ARFI can generate acoustic radiation force as a pressure wave that spreads through tissue, and can be measured as shear wave velocity (SWV) that presents the degree of tissue stiffness [8]. Using ARFI and TE for liver fibrosis evaluation has been adopted in patients with chronic hepatitis or cirrhotic liver, and they both reported a promising and reliable correlation with liver fibrosis change [7]. The ARFI examination seems to have more advantage in varied types of liver graft. Therefore, we designed this study of posttransplantation liver parenchyma fibrotic change measured by ARFI liver stiffness measurement (LSM) and correlated with biopsy pathological staging. PATIENTS From August 2010 to August 2012, a total of 57 patients with LDLT (43 men, 14 women, mean age 57 7.62 years) received LB due to posttransplantation dysfunction. The liver function test, blood platelet count, prothrombin time, and viral titer were collected. The fibrosis staging was based on the Metavir scoring system. Indications for biopsy in these 57 patients were abnormal graft dysfunctions in posttransplantation follow-up, which were suspected rejection-related or recurrent hepatitis; the definition of posttransplantation dysfunction was AST and ALT >100 IU/dL or persistent hyperbilirubinemia. The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki and was approved by our institutional review boards. Written informed consent was obtained from all participants for the use of their data for research purposes.
ARFI LSM Both B-mode standard ultrasonography scanning and LSM by ARFI were performed using the Siemens Acuson S2000 ultrasound system with 4V1 transducers (Acusion, Siemens Medical Systems Co. Ltd. Erlangen, Germany). Technically, ARFI LSM had focused on a specific segment of liver (the right lobe graft was accessed in S5-6, the left lobe graft in S3-4), avoiding motion artifacts and hepatic vessels as much as possible. The measurement was performed at a portion of the liver that was about 4 to 6 cm in depth from the skin surface. The values of LSM were presented by shear wave velocity (SWV ¼ m/s) and calculated as the median ARFI value from 10 measurements. The procedures were performed by senior radiologists who were blinded to the clinical, serological, and histological data.
877
LB and Pathological Fibrosis Staging LB was performed percutaneously with ultrasonography assistance by senior physicians, using 17- to 18-gauge modified Menghini needles (Biomol, Boca Raton, Florida). All specimens were sealed, fixed, and examined by pathologists in our facility. The scoring system of fibrosis stage was based on the Metavir scoring system, in which fibrosis was classified on a F0 to F4 scale as follows: F0 ¼ no fibrosis, F1 ¼ portal fibrosis without septa, F2 ¼ portal fibrosis and few septa, F3 ¼ numerous septa without cirrhosis, F4 ¼ cirrhosis [9].
Statistical Analysis The diagnostic performance of ARFI and the stage of liver fibrosis sensitivity and specificity were developed as area under the receiveroperator characteristic (ROC) curves. The areas under the curves and 95% confidence intervals (CI) used the Mann-Whitney statistic calculation. The optimal cutoff value was chosen to maximize the sum of the sensitivity and specificity on the Youden index. Differences were considered significant at P < .05. Correlation between ARFI LSM liver fibrosis staging and LB pathological fibrosis stage was analyzed using both the Kendall tau-b and the Spearman rho methods.
RESULTS
A total of 57 LDLT patients (43 men, 14 women, mean age 57 7.62 years) were enrolled in our study and had effective ARFI LSM and valid LB due to posttransplantation dysfunction; 44 patients received right lobe liver graft, (n ¼ 44 of 57, 77%) and 13 patients received left lobe liver graft (n ¼ 13 of 57, 23%). Two major indications for LB in posttransplantation dysfunction were recurrent viral hepatitis (n ¼ 44 of 57, 77.2%), and acute or chronic rejection (n ¼ 28 of 57, 49.1%). The LB stages were 32 patients at F0 (56%), 22 patients at F1 (38.5%), 2 patients at F2 (3.5%), and 1 patient at F3. The calculated cutoff values of ARFI LSM were analyzed based on the ROC curve (Fig 1A). There were F0: 0.75 m/s (sensitivity [Se]: 93.8%, specificity [Sp]: 4%), F1: 1.06 m/s (Se: 95.5%, Sp: 25.7%), F2: 1.81 m/s (Se: 50%, Sp: 83.6%), and F3: 2.33 m/s (Se: 100%, Sp: 92.9%), but the F4 cutoff value was not available (Table 1). The values of ARFI LSM of liver fibrosis staging demonstrated linear correlation with the LB pathological fibrosis stage in either the Kendall tau-b or the Spearman rho method (Fig 1B). A significant difference between F0 (SWV cutoff value ¼ 0.75 m/s) and F1 (SWV cutoff value ¼ 1.06 m/s) was found in the early liver fibrosis stage (P < .0001). The advanced liver fibrosis stage (F S 2) also had high specificity, with an SWV cutoff value of 1.8 m/s, which was statistically different in fibrosis stages between F0 and F S 2 (P < .05). DISCUSSION
TE and ARFI have been used as noninvasive methods in the evaluation of liver fibrosis, and they both provide diagnosis of significant fibrosis and cirrhosis accurately [7,10,11]. However, TE has many limitations in measurement; the
878
LIAO, CHEN, TSANG ET AL
Fig 1. (A) Receiver-operator characteristic (ROC) curves for the calculated sensitivity and specificity of each acoustic radiation force impulse (ARFI) liver stiffness measurement (LSM) cutoff value. (B) Correlation between ARFI LSM liver fibrosis staging and liver biopsy pathological fibrosis stage. **Correlation is significant at the .01 level (2-tailed).
performance of TE may be limited in patients with a high body mass index (>28 kg/m2), narrow intercostal space, or ascites [6,7]. On the other hand, the advantage of choosing ARFI for posttransplantation liver evaluation was its LSM ability in LDLT during routine follow-up ultrasonography study. It also allowed us to measure the specific site and
depth of allograft on either right or left graft type. Furthermore, it can avoid nearby interfering structures, such as hepatic vessels and ascites. Regarding the accuracy of ARFI LSM in cirrhotic liver disease, previous studies have reported that ARFI has an excellent predictive value for liver fibrosis. The ARFI
ACOUSTIC RADIATION FORCE IMPULSE ELASTOGRAPHY EVALUATION
879
Table 1. The Predictive Value of Liver Fibrosis Evaluated by Acoustic Radiation Force Impulse and Histological Biopsy for Liver Fibrosis Stage According to the Metavir Score System in a Total of 57 Effective Cases 95% Confidence Interval Metavir
F0 F1 F2 F3 F4
Case (N)
Area
Standard Error
P Value
Lower Bound
Upper Bound
Cutoff Values
Sensitivity (%)
Specificity (%)
32 22 2 1 0
0.203 0.721 0.895 0.929 NA
0.059 0.068 0.056 0.034 NA
<.001 .005 .05 .145 NA
0.088 0.589 0.779 0.861 NA
0.317 0.854 1.000 0.996 NA
0.750* 1.058* 1.809* 2.331* NA
93.8 95.5 50 100 NA
4 25.7 83.6 92.9 NA
Abbreviations: NA, not available. *Receiver-operator characteristic curve.
SWV values increased in parallel with fibrosis staging, but were not accurate enough to differentiate between F1 and F2 in Metavir scoring. In the study published by Sporea et al. [11], ARFI was well correlated with liver fibrosis caused by viral hepatitis; however, ARFI was not accurate enough to differentiate between F 1 vs F 2 due to the small proportion of F0 and F1 patients. Crespo et al. [12] reported that ARFI LSM had been adopted for evaluation of liver fibrosis change, which included transplant and nontransplant patients with liver disease of varied etiologies. It has shown high accuracy only in advanced fibrosis patients (F S 2). In our study, for posttransplantation graft dysfunction of varied underlying causes, there was a larger proportion (n ¼ 54 of 57, 94.5%) of early fibrosis stage patients (F & 1); sensitivity was up to 95.9% using an SWV cutoff value of 1.058 m/s. There was a significant difference in F0 compared with F1. The results were satisfying for early fibrosis detection. In cases of advanced fibrosis stage, ARFI LSM had a high specificity (92.9%) using a cutoff value of 1.8 m/s and allowed us to identify patients with chronic liver parenchyma change. This was similar to other studies. Posttransplantation liver graft dysfunction is a critical issue in LDLT patients. The dysfunction of graft from varied causes developed diffuse liver parenchyma change as liver fibrosis. Early detection of underlying causes of graft dysfunction is important for intensive treatment and prevention of graft loss [2]. Usually, advanced fibrosis patients are more prominent, with abnormal liver function or diagnosed with recurrent viral hepatitis or acute or chronic rejection. Most of these patients need retransplantation. In conclusion, the real-time ultrasound-based ARFI imaging is easy and convenient to perform in the evaluation of posttransplantation dysfunction in LDLT patients. The results of this study showed reliable and significant correlation
with liver fibrosis change. This can be an alternative to frequent biopsy in the posttransplantation liver. REFERENCES [1] Ikegami T, Shirabe K, Yoshizumi T, Aishima S, Taketomi YA, Soejima Y, et al. Primary graft dysfunction after living donor liver transplantation is characterized by delayed functional hyperbilirubinemia. Am J Transplant 2012;12:1886. [2] Salvalaggio PR, Felga GE, Afonso RC, Ferraz-Neto BH, et al. Early allograft dysfunction and liver transplant outcomes: a single center retrospective study. Transplant Proc 2012;44:2449. [3] Bravo AA, Sheth SG, Chopra S. Liver biopsy. N Engl J Med 2001;344:495. [4] Colloredo G, Guido M, Sonzogni A, et al. Impact of liver biopsy size on histological evaluation of chronic viral hepatitis: the smaller the sample, the milder the disease. J Hepatol 2003;39:239. [5] Sporea I, Sirli R, Popescu A, et al. Acoustic radiation force impulse (ARFI)da new modality for the evaluation of liver fibrosis. Med Ultrason 2010;12:26. [6] Kim BK, Fung J, Yuen MF, et al. Clinical application of liver stiffness measurement using transient elastography in chronic liver disease from longitudinal perspectives. World J Gastroenterol 2013;19:1890. [7] Nierhoff J, Chavez Ortiz AA, Herrmann E, et al. The efficiency of acoustic radiation force impulse imaging for the staging of liver fibrosis: a meta-analysis. Eur Radiol 2013 Nov;23(11):3040e53. [8] Fierbinteanu-Braticevici C, Andronescu D, Usvat R, et al. Acoustic radiation force imaging sonoelastography for noninvasive staging of liver fibrosis. World J Gastroenterol 2009;15:5525. [9] Poynard T, Bedossa P, Opolon P. Natural history of liver fibrosis progression in patients with chronic hepatitis C. The OBSVIRC, METAVIR, CLINIVIR, and DOSVIRC groups. Lancet 1997;349:825. [10] Friedrich-Rust M, Ong MF, Martens S, et al. Performance of transient elastography for the staging of liver fibrosis: a metaanalysis. Gastroenterology 2008;134:960. [11] Sporea I, Sirli R, Bota S, et al. Is ARFI elastography reliable for predicting fibrosis severity in chronic HCV hepatitis? World J Radiol 2011;3:188. [12] Crespo G, Fernández-Varo G, Mariño Z, et al. ARFI, FibroScan, ELF, and their combinations in the assessment of liver fibrosis: a prospective study. J Hepatol 2012;57:281.