EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Objectives: The aim of this study was to evaluate the usefulness of the hepatic parenchymal retention index in the early diagnosis of parenchymal complications in liver transplant recipients as determined by hepatobiliary scintigraphy.

Materials and Methods: This retrospective study reviewed 100 liver transplant recipients who had undergone orthotopic liver transplant. In all cases, hepatobiliary scintigraphy images recorded 7 to 10 days posttransplant were quantitatively reinterpreted according to hepatic parenchymal retention index. The hepatocyte extraction fraction value was also calculated. Scintigraphic findings as well as clinical, laboratory, and biopsy results were assessed.

Results: Quantitative analysis showed normal hepatocyte extraction fraction value in all subjects. However, significant differences in hepatic parenchymal retention index were observed. Thus, subjects were divided into 3 groups: group 1 (n=75), normal; group 2 (n=15), severely elevated; group 3 (n=10), mildly-to-moderately elevated hepatic parenchymal retention index. Evaluation of histopathological, clinical, and laboratory findings showed normal grafts in all group 1 recipients, acute rejection in all group 2 recipients, and hepatocyte damage/intrahepatic cholestasis in all group 3 recipients.

Conclusions: Based on these findings, we determined that hepatocyte extraction fraction value was not useful, whereas hepatic parenchymal retention index was beneficial for early and accurate diagnosis of parenchymal complications in liver transplant recipients.

Key words : Hepatobiliary scintigraphy, Liver transplant, Tc-99m IDA, Diagnosis

Liver transplant is the only survival approach for patients with life-threatening end-stage or acute hepatic failure that cannot be treated by other methods.1 It was first performed on a cadaver by Starzl in 1963; the technique subsequent gained worldwide popularity.^2-5 In Turkey, the first liver transplant from a cadaver was performed by Haberal and associates in 1988; then, they carried out the first pediatric living-related segmental liver transplant and adult-to-adult living-related liver transplant in 1990.^"

At the time, 1-year survival rates at onset of liver transplant were approximately 20%. Since recent advancements in surgical techniques, organ preservation, immunosuppressive treatments, eligibility criteria, and transplant timing, 1-year survival rates have increased to 90%, and 10-year survival rates to 70%.7 Despite this, various parenchymal, biliary, and vascular complications remain important causes of graft dysfunction. During the early posttransplant period, major parenchymal complications are rejection and ischemic injury/intrahepatic cholestasis; however, both complications resulted in similar clinical and laboratory findings, making differential diagnosis difficult. Also, radiological imaging techniques were inadequate at differentiating these complications. The criterion standard for evaluating them is histopathological examination of liver tissue by biopsy; however, this method is invasive and associated with complications such as pain, bleeding, biliary peritonitis, bacteremia/sepsis, pneumothorax, and hemothorax. Therefore, new, noninvasive methods are required for differential diagnosis of parenchymal complications that require different therapeutic approaches.^8-10

Hepatobiliary scintigraphy with Tc-99m imino-diacetic acid derivatives is a noninvasive, objective, and quantitative technique for evaluating hepato-biliary tree function and integrity. It is used to evaluate liver transplant recipients, and accurately detects biliary complications. However, its
role in parenchymal complications remains controversial.^1,8-11 As such, the present study aimed to determine the usefulness of quantitative hepatobiliary scintigraphy, specifically hepatic parenchymal retention index (HPRI), for differential diagnosis of parenchymal complications in liver transplant recipients in the early period. The efficacy of hepatocyte extraction fraction value (HEFV) also was assessed.

Materials and Methods

This retrospective study consisted of 100 recipients that underwent orthotopic liver transplant: 64 men, 36 women; mean age, 29 ± 14 years. All hepatobiliary scintigraphy images recorded 7 to 10 days after a liver transplant were quantitatively re-evaluated. Clinical findings, laboratory results, and histopathological evaluations of biopsy specimens were also reviewed.

Hepatobiliary scintigraphy was performed following intravenous injection of 1.85 MBq kg-¹ Tc-99m mebrofenin (CIS Bio International, Gif-sur-Yvette Cedex, France). Images were acquired using a large field-of-view dual-head gamma camera (E-Cam, Siemens, Erlangen, Germany) with a low-energy all-purpose collimator. To measure parenchymal function, data were recorded every 30 seconds for 40 minutes. Images were evaluated quantitatively according to HEFV and HPRI. To determine HEFV, similarly-sized regions over the left ventricle of the heart and graft liver were drawn. Time activity curves were obtained, and HEVFs calculated by deconvolution analysis.¹² To calculate HPRI, specialized software was used to determine graft radioactivity counts in the marked regions during minute 5 (maximum uptake) and at the end of minute 40. Hepatic parenchymal retention index was then determined by computing the residual quantity of minute 5 radioactivity that persisted until the end of the activity (minute 40).

Statistical analyses
Statistical analyses were performed with SPSS software (SPSS: An IBM Company, version 19.0, IBM Corporation, Armonk, NY, USA). Descriptive statistics were calculated and shown as mean ± SD. Comparison of variables was performed using paired t test. Statistical significance was set at P < .05.

Quantitative analysis showed normal HEFVs ( mean 96% ± 2%) in all recipients (normal value > 90%) (Figure 1, 2).

Recipients were divided into 3 groups according to HPRI values: group 1 (n=75), HPRI < 30%, (18% ± 4%); group 2 (n=15), > 60%, (82% ± 8%); group 3 (n=10), 30% to 60%, (43% ± 9%). Hepatic parenchymal retention index values were statistically compared, and significant differences were found in the 3 groups (P < .001). Clinical and laboratory findings showed that all recipients in group 1 had normal findings, but groups 2 and 3 showed findings compatible with graft dysfunction. Histopathological analysis showed that recipients in group 2 had acute rejection, and recipients in group 3 had hepatocyte damage/intrahepatic cholestasis.

Hepatobiliary scintigraphy is widely used to evaluate graft function and to identify complications during early and late posttransplant periods in recipients. It is a valuable diagnostic method in cases with suspected biliary complications, including segmental or total biliary obstruction and bile leakage.¹ Earlier studies reported that the sensitivity and specificity of hepatobiliary scintigraphy in identifying biliary complications were 100 and 77%, respectively, but the role of scintigraphy in identifying parenchymal complications remained controversial.⁹ Kuni and associates¹³ suggest that knowledge of the histopathological correlates of scintigraphic abnormalities could prove useful in differentiating rejection from other parenchymal pathologies in transplant recipients; however, other researchers found that scintigraphic differentiation between rejection and other parenchymal complications is difficult.^1,8,9,14,15

The present study evaluated the role of quantitative hepatobiliary scintigraphy in the diagnosis of parenchymal complications in postliver transplant recipients. Hepatocyte extraction fraction value and HPRI were used for quantitative analysis. Hepatocyte extraction fraction value was normal in all recipients, whereas HPRI values were < 30% in 75 (group 1), > 60% in 15 (group 2), and 30% to 60% in 10 patients (group 3). When these findings were compared with clinical, laboratory, and histopathological results, HEFV was deemed ineffective for diagnosing complications during early onset. Thus, it was within normal limits in both normal grafts and in grafts with complications detected by other diagnostics. However, HPRI was found to be effective for the differential diagnosis of parenchymal complications in the early period, since the HPRI values were significantly different between parenchymal complications detected grafts and normal grafts (P < .001). Also, cases with acute rejection and hepatocyte damage/intrahepatic cholestasis had distinct differences in HPRI (P < .001). For acute rejection, values were significantly higher, whereas for hepatocyte damage/intrahepatic choles-tasis, values increased only mildly to moderately.

Based on these findings, we conclude that HPRI by quantitative hepatobiliary scintigraphy is preferable for early detection and differentiation of parenchymal complications in liver transplant recipients.

Volume: 12 Issue: 1 March 2014 - Supplement - 1

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