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Scintigraphic evaluation of graft and native liver function after heterotopic liver transplantation
Scintigraphic Evaluation of Graft and Native Liver Function After Heterotopic Liver Transplantation E.A. Gencog˘lu, A. Aktas¸, R. Emiroglu, H. Karakayalı, E.A. Niron, and M. Haberal
H
ETEROTOPIC liver transplantation (HLT), in which the failing native liver is left in place and a portion of healthy donor liver is added, is a good treatment option for patients with end-stage liver disease. The advantages of HLT over orthotopic liver transplantation are that HLT is less technically difficult to perform, and does not involve the risks associated with hepatectomy.1 HLT requires that graft and native liver function be assessed separately in the posttransplantation period. Biochemical tests are of limited clinical value because they only test overall function, and do not distinguish between the native and transplant organs. Radiologic imaging provides information about liver morphology and respective liver volumes, but reveals nothing about the functional changes occurring. Although liver biopsy is the definitive method for separately evaluating graft and native liver function, it is an invasive procedure.2,3 The aim of this study was to assess the value of quantitative hepatobiliary scintigraphy for assessing native and graft liver function after HLT. We used this technique to monitor the changes in recipient livers during follow-up, and also assessed its accuracy by comparison with liver biopsy findings.
MATERIALS AND METHODS Patients We studied the livers of ten patients (seven males and three females) who underwent HLT for end-stage liver disease. The mean patient age at transplantation was 26.3 ⫾ 3.5 years (range 13 to 52 years). Each patient underwent hepatobiliary scintigraphy and liver biopsy during the follow-up period.
Biopsy
Graft liver specimens were obtained by percutaneous biopsy at the time each hepatobiliary scintigraphy was done, and the tissue samples were routinely processed for light microscopy. Slides from each biopsy were examined for features of acute rejection, hepatocyte damage, and/or cholestasis, as well for other pathology. We made statistical comparisons using the chi-square test, and P ⬍ .05 was considered statistically significant. RESULTS Biopsy Results
Early in follow-up, one patient’s graft biopsy showed histologic features of acute rejection, and three patients’ specimens exhibited hepatocellular damage. However, once the episode of acute rejection and hepatocellular damage resolved, biopsy results of these patients were normal. The other six patients’ biopsies were normal throughout the entire study period. Scintigraphy Results
Graft liver function. In the early posttransplantation period, six patients’ grafts had normal HEF (ⱖ90%), T ⁄ (approximately 30 minutes), and Tmax (approximately 15 minutes), and this group’s transplant function parameters remained normal throughout follow-up. The HEF, T ⁄ and Tmax values for the grafts of the other four patients, whose biopsies had showed either acute rejection or hepatocellular damage, were outside the normal range in the early phase of the study; however, these values gradually improved after the episode of acute rejection and hepatocellular damage resolved. We found a significant positive correlation between biopsy and scintigraphy results (P ⬍ .01). Native liver function. In the early posttransplantation period, the native livers of the six patients with normal graft 12
12
Hepatobiliary Scintigraphy In total, 56 hepatobiliary scans were done during follow-up. In all cases, the initial scan was done within 1 week of transplantation, and scanning was then repeated at regular intervals over the next 6 months. All scans were done after intravenous bolus injection of 185 MBq Tc-99m mebrofenin (Cis-Bio International). A largefield-of-view single-head gamma camera (Siemens, Diacam) with a low-energy all-purpose collimator was used for acquisition. To test parenchymal function, data were acquired every 30 seconds for 40 minutes, and the images were then evaluated quantitatively. The quantitative parameters used were hepatocyte extraction fraction (HEF), time to maximum activity (Tmax), and time to half-maximum activity (T ⁄ ). HEF was calculated by comparing the count rates measured in each of the livers to the count rate in the left ventricle at 8 minutes after injection. For this, equally sized regions of interest were drawn over the left ventricle and over the each of the livers. Tmax and T ⁄ were calculated using commercial software. 12
12
From the Bas¸kent University Faculty of Medicine, Departments of Nuclear Medicine, Surgery and Radiology, Ankara, Turkey. Address reprint requests to Dr E.A. Gencog˘lu, Bas¸kent University Faculty of Medicine, 1 Cad No 77, Bahc¸elievler, 06490, Ankara, Turkey. E-mail: [email protected]
0041-1345/01/$–see front matter PII S0041-1345(01)02219-9
© 2001 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
2858
Transplantation Proceedings, 33, 2858–2859 (2001)
SCINTIGRAPHIC EVALUATION
2859
Fig 1. Hepatobiliary scans in HLT patients 1 week (A) and 6 months (B) after transplantation. At the end of week 1, graft liver is functional but native liver function is insufficient. Six months later, native liver is almost completely absent.
function had lower HEF and higher Tmax and T ⁄ values than the graft livers. These values gradually deteriorated during follow-up, and, by the end of the 6 months, the native livers had ceased to function. In the four patients who showed impaired graft function initially, the functional parameters for the native livers were either better or similar to those of the grafts. However, in each case, the native liver HEF, T ⁄ , and Tmax values diminished as graft function approached normal. 12
12
DISCUSSION
Hepatobiliary scintigraphy with Tc-99m imidodiacetic acid (IDA) is an effective imaging method that gives quantitative information about the functional status of the liver parenchyma, and also allows the observer to visualize the excretion pathways.4 These features make hepatobiliary scintigraphy very valuable for evaluating graft liver function and diagnosing complications, and the technique has been used for 20 years.5 Hepatobiliary scintigraphy is particularly important in end-stage liver disease patients who undergo HLT. When HLT is successful, the liver graft functions normally and native liver function gradually drops off. As mentioned earlier, in order to monitor an HLT recipient’s postoperative progress it is necessary to separately assess graft and native liver function during follow-up. Biochemical and radiologic testing do not have this capability, and hepatobiliary scintigraphy is the only method that noninvasively distinguishes the functional performance of the two organs.2,3 Very few studies have focused on the scintigraphic evaluation of patients who have undergone HLT for end-stage liver disease. Willemse et al studied the sizes of graft and native livers in HLT patients using planimetry on two-
dimensional IDA scintigrams. They found that graft livers showed regenerative growth together with the native liver atrophy.5 Houssin et al reported comparable findings in a similar study.1 In contrast to these investigations, we used serial quantitative hepatobiliary scintigraphy to yield more specific data on graft and native liver function in HLT patients. Specifically, we calculated HEF, Tmax, and T ⁄ values to evaluate graft and native liver function. Our data show that quantitative hepatobiliary scintigraphy is a highly sensitive (100%) imaging method for diagnosing parenchymal complications after heterotopic liver transplantation. Also, we found that, in HLT patients with normal graft function, the function of the native liver gradually diminishes over time, to become completely nonfunctional by 6 months posttransplantation. We conclude that serial quantitative hepatobiliary scintigraphy is a valuable noninvasive method for distinguishing the functional performance of native and graft livers, and for monitoring the changes that occur over time in endstage liver disease patients who have undergone HLT. 12
REFERENCES 1. Houssin D, Franco D, Berthelot P: Lancet i:990, 1980 2. Buyck D, Bonnin F, Bernau J, et al: Eur J Nucl Med 24:138, 1992 3. Sakahara H, Kiuchi T, Nishizawa S, et al: J Nucl Med 40:1463, 1999 4. Jonge MWC, Pauwels EKJ, Hennis PJ, et al: Eur J Nucl Med 8:485, 1983 5. Brunot B, Petras S, Germain P, et al: J Nucl Med 36:1321, 1994 6. Willemse PJA, Ausema L, Terpstra OT, et al: Hepatology 15:54, 1992
H
ETEROTOPIC liver transplantation (HLT), in which the failing native liver is left in place and a portion of healthy donor liver is added, is a good treatment option for patients with end-stage liver disease. The advantages of HLT over orthotopic liver transplantation are that HLT is less technically difficult to perform, and does not involve the risks associated with hepatectomy.1 HLT requires that graft and native liver function be assessed separately in the posttransplantation period. Biochemical tests are of limited clinical value because they only test overall function, and do not distinguish between the native and transplant organs. Radiologic imaging provides information about liver morphology and respective liver volumes, but reveals nothing about the functional changes occurring. Although liver biopsy is the definitive method for separately evaluating graft and native liver function, it is an invasive procedure.2,3 The aim of this study was to assess the value of quantitative hepatobiliary scintigraphy for assessing native and graft liver function after HLT. We used this technique to monitor the changes in recipient livers during follow-up, and also assessed its accuracy by comparison with liver biopsy findings.
MATERIALS AND METHODS Patients We studied the livers of ten patients (seven males and three females) who underwent HLT for end-stage liver disease. The mean patient age at transplantation was 26.3 ⫾ 3.5 years (range 13 to 52 years). Each patient underwent hepatobiliary scintigraphy and liver biopsy during the follow-up period.
Biopsy
Graft liver specimens were obtained by percutaneous biopsy at the time each hepatobiliary scintigraphy was done, and the tissue samples were routinely processed for light microscopy. Slides from each biopsy were examined for features of acute rejection, hepatocyte damage, and/or cholestasis, as well for other pathology. We made statistical comparisons using the chi-square test, and P ⬍ .05 was considered statistically significant. RESULTS Biopsy Results
Early in follow-up, one patient’s graft biopsy showed histologic features of acute rejection, and three patients’ specimens exhibited hepatocellular damage. However, once the episode of acute rejection and hepatocellular damage resolved, biopsy results of these patients were normal. The other six patients’ biopsies were normal throughout the entire study period. Scintigraphy Results
Graft liver function. In the early posttransplantation period, six patients’ grafts had normal HEF (ⱖ90%), T ⁄ (approximately 30 minutes), and Tmax (approximately 15 minutes), and this group’s transplant function parameters remained normal throughout follow-up. The HEF, T ⁄ and Tmax values for the grafts of the other four patients, whose biopsies had showed either acute rejection or hepatocellular damage, were outside the normal range in the early phase of the study; however, these values gradually improved after the episode of acute rejection and hepatocellular damage resolved. We found a significant positive correlation between biopsy and scintigraphy results (P ⬍ .01). Native liver function. In the early posttransplantation period, the native livers of the six patients with normal graft 12
12
Hepatobiliary Scintigraphy In total, 56 hepatobiliary scans were done during follow-up. In all cases, the initial scan was done within 1 week of transplantation, and scanning was then repeated at regular intervals over the next 6 months. All scans were done after intravenous bolus injection of 185 MBq Tc-99m mebrofenin (Cis-Bio International). A largefield-of-view single-head gamma camera (Siemens, Diacam) with a low-energy all-purpose collimator was used for acquisition. To test parenchymal function, data were acquired every 30 seconds for 40 minutes, and the images were then evaluated quantitatively. The quantitative parameters used were hepatocyte extraction fraction (HEF), time to maximum activity (Tmax), and time to half-maximum activity (T ⁄ ). HEF was calculated by comparing the count rates measured in each of the livers to the count rate in the left ventricle at 8 minutes after injection. For this, equally sized regions of interest were drawn over the left ventricle and over the each of the livers. Tmax and T ⁄ were calculated using commercial software. 12
12
From the Bas¸kent University Faculty of Medicine, Departments of Nuclear Medicine, Surgery and Radiology, Ankara, Turkey. Address reprint requests to Dr E.A. Gencog˘lu, Bas¸kent University Faculty of Medicine, 1 Cad No 77, Bahc¸elievler, 06490, Ankara, Turkey. E-mail: [email protected]
0041-1345/01/$–see front matter PII S0041-1345(01)02219-9
© 2001 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
2858
Transplantation Proceedings, 33, 2858–2859 (2001)
SCINTIGRAPHIC EVALUATION
2859
Fig 1. Hepatobiliary scans in HLT patients 1 week (A) and 6 months (B) after transplantation. At the end of week 1, graft liver is functional but native liver function is insufficient. Six months later, native liver is almost completely absent.
function had lower HEF and higher Tmax and T ⁄ values than the graft livers. These values gradually deteriorated during follow-up, and, by the end of the 6 months, the native livers had ceased to function. In the four patients who showed impaired graft function initially, the functional parameters for the native livers were either better or similar to those of the grafts. However, in each case, the native liver HEF, T ⁄ , and Tmax values diminished as graft function approached normal. 12
12
DISCUSSION
Hepatobiliary scintigraphy with Tc-99m imidodiacetic acid (IDA) is an effective imaging method that gives quantitative information about the functional status of the liver parenchyma, and also allows the observer to visualize the excretion pathways.4 These features make hepatobiliary scintigraphy very valuable for evaluating graft liver function and diagnosing complications, and the technique has been used for 20 years.5 Hepatobiliary scintigraphy is particularly important in end-stage liver disease patients who undergo HLT. When HLT is successful, the liver graft functions normally and native liver function gradually drops off. As mentioned earlier, in order to monitor an HLT recipient’s postoperative progress it is necessary to separately assess graft and native liver function during follow-up. Biochemical and radiologic testing do not have this capability, and hepatobiliary scintigraphy is the only method that noninvasively distinguishes the functional performance of the two organs.2,3 Very few studies have focused on the scintigraphic evaluation of patients who have undergone HLT for end-stage liver disease. Willemse et al studied the sizes of graft and native livers in HLT patients using planimetry on two-
dimensional IDA scintigrams. They found that graft livers showed regenerative growth together with the native liver atrophy.5 Houssin et al reported comparable findings in a similar study.1 In contrast to these investigations, we used serial quantitative hepatobiliary scintigraphy to yield more specific data on graft and native liver function in HLT patients. Specifically, we calculated HEF, Tmax, and T ⁄ values to evaluate graft and native liver function. Our data show that quantitative hepatobiliary scintigraphy is a highly sensitive (100%) imaging method for diagnosing parenchymal complications after heterotopic liver transplantation. Also, we found that, in HLT patients with normal graft function, the function of the native liver gradually diminishes over time, to become completely nonfunctional by 6 months posttransplantation. We conclude that serial quantitative hepatobiliary scintigraphy is a valuable noninvasive method for distinguishing the functional performance of native and graft livers, and for monitoring the changes that occur over time in endstage liver disease patients who have undergone HLT. 12
REFERENCES 1. Houssin D, Franco D, Berthelot P: Lancet i:990, 1980 2. Buyck D, Bonnin F, Bernau J, et al: Eur J Nucl Med 24:138, 1992 3. Sakahara H, Kiuchi T, Nishizawa S, et al: J Nucl Med 40:1463, 1999 4. Jonge MWC, Pauwels EKJ, Hennis PJ, et al: Eur J Nucl Med 8:485, 1983 5. Brunot B, Petras S, Germain P, et al: J Nucl Med 36:1321, 1994 6. Willemse PJA, Ausema L, Terpstra OT, et al: Hepatology 15:54, 1992