99mTc-mebrofenin Hepatobiliary Scintigraphy Research Articles

Physiological and Biochemical Basis of Clinical Liver Function Tests

To review the literature on the most clinically relevant and novel liver function tests used for the assessment of hepatic function before liver surgery. Postoperative liver failure is the major cause of mortality and morbidity after partial liver resection and develops as a result of insufficient remnant liver function. Therefore, accurate preoperative assessment of the future remnant liver function is mandatory in the selection of candidates for safe partial liver resection. A MEDLINE search was performed using the key words "liver function tests," "functional studies in the liver," "compromised liver," "physiological basis," and "mechanistic background," with and without Boolean operators. Passive liver function tests, including biochemical parameters and clinical grading systems, are not accurate enough in predicting outcome after liver surgery. Dynamic quantitative liver function tests, such as the indocyanine green test and galactose elimination capacity, are more accurate as they measure the elimination process of a substance that is cleared and/or metabolized almost exclusively by the liver. However, these tests only measure global liver function. Nuclear imaging techniques ((99m)Tc-galactosyl serum albumin scintigraphy and (99m)Tc-mebrofenin hepatobiliary scintigraphy) can measure both total and future remnant liver function and potentially identify patients at risk for postresectional liver failure. Because of the complexity of liver function, one single test does not represent overall liver function. In addition to computed tomography volumetry, quantitative liver function tests should be used to determine whether a safe resection can be performed. Presently, (99m)Tc-mebrofenin hepatobiliary scintigraphy seems to be the most valuable quantitative liver function test, as it can measure multiple aspects of liver function in, specifically, the future remnant liver.

Utility of Tc99m-Mebrofenin hepato-biliary scintigraphy (HIDA scan) for the diagnosis of biliary atresia

To determine the utility of Tc99m-Mebrofenin hepato-biliary scintigraphy (HIDA scan) for diagnosis of biliary atresia in patients with neonatal cholestasis. Our study involves the retrospective analysis of 46 patients with neonatal cholestasis who underwent HIDA scans at the Pediatric Hepatobiliary Clinic, BJ Wadia Hospital for Children from May 2005 to July 2007. Biliary atresia (BA) was diagnosed on the basis of intra-operative cholangiogram. Non-BA patients were included in the neonatal hepatitis (NH) group. All patients received phenobarbitone and ursodeoxycholic acid for 5 days, prior to the HIDA scan. The HIDA scan was evaluated on the basis of uptake of the radioactive tracer by the liver at 5 minutes after intravenous injection; retention of radioactive tracer within the liver at 24 hours after injection and visualization of excretion of tracer into the intestine upto 24 hours after administration. The results of the HIDA scans were analyzed and correlated with the final diagnosis, gender and age of the patients. Chi-square test was employed for statistical analysis. The age of presentation of our patients ranged from 5 days to 6 months. The male: female ratio was 37:9. Of the total 46 patients, 28 had BA and 18 had NH. All 28 (100%) patients diagnosed with BA showed persistent radiotracer in the liver at 24 hours whereas 17 (94.4%) of the 18 NH patients showed hepatic radiotracer retention (p = 0.207), the difference being statistically insignificant. Twenty two (78.6%) patients of BA showed no excretion of the radiotracer at 24 hours whereas only 7 (38.9%) of the NH group did not excrete the radiotracer (p = 0.007), which was statistically significant. Neither the sex nor the age of the child contributed to any difference on the hepatic retention (p = 0.618 and 0.235, respectively) or on the intestinal excretion (p = 0.307 and 0.9, respectively) of the radiotracer. HIDA scan is a useful tool for screening of biliary atresia in patients with neonatal cholestasis. Non excretion of the radioactive radiotracer into the intestines even after 24 hours of radiotracer administration can suggest biliary atresia in majority of patients.

Utility of 99mTc-mebrofenin hepato-biliary scintigraphy (HIDA scan) for the diagnosis of biliary atresia

Utility of 99mTc-mebrofenin hepato-biliary scintigraphy (HIDA scan) for the diagnosis of biliary atresia

Transporters involved in the hepatic uptake of 99mTc-mebrofenin and indocyanine green

(99m)Tc-mebrofenin hepatobiliary scintigraphy (HBS) and the indocyanine green (ICG) clearance test are used for the assessment of hepatic function before and after liver surgery. The hepatic uptake of (99m)Tc-mebrofenin and ICG is considered similar to the uptake of organic anions such as bilirubin and bile acids. Little is known about hepatic uptake mechanisms of both compounds and recent evidence suggests that the hepatic transporters for ICG and (99m)Tc-mebrofenin are distinct. The aim of this study was to identify the specific human hepatic transporters of (99m)Tc-mebrofenin and ICG. The uptake of (99m)Tc-mebrofenin was investigated in cRNA-injected Xenopus laevis oocytes expressing human OATP1B1, OATP1B3, OATP2B1, or NTCP. Chinese hamster ovary (CHO) cells stably expressing OATP1B1, OATP1B3, OATP2B1, or NTCP were used as a mammalian expression system. ICG transport into CHO cells was additionally imaged with confocal microscopy. We demonstrated that OATP1B1 and OATP1B3 are involved in the transport of (99m)Tc-mebrofenin. OATP1B1 showed an approximately 1.5-fold higher affinity for (99m)Tc-mebrofenin compared to OATP1B3. ICG is transported by OATP1B3 and NTCP. The transporter specificity of (99m)Tc-mebrofenin and ICG partially overlaps as both compounds are transported by OATP1B3. (99m)Tc-mebrofenin is also taken up by OATP1B1, whereas ICG is additionally transported by NTCP.

Quantitative Assessment of Liver Function after Ischemia-Reperfusion Injury and Partial Hepatectomy in Rats

Liver function after hepatic ischemia-reperfusion (I/R) injury and partial liver resection (PHx) is influenced by the extent of PHx, hepatocellular damage, and liver regeneration. This study investigates the effect of minor PHx with increasing degrees of I/R-induced damage on postoperative liver function parameters and compares the indocyanine green (ICG) clearance test with (99m)Tc-mebrofenin hepatobiliary scintigraphy (HBS) for quantitative measurement of hepatic function in a standardized rat model. Rats were subjected to 70% partial liver I/R combined with resection of the nonischemic lobes. Various degrees of hepatic damage were induced by 0, 15, 30, 45, and 60 min ischemia. Prothrombin time and bilirubin were used as indirect parameters of liver function. (99m)Tc-mebrofenin HBS and ICG clearance were used as dynamic quantitative liver function tests. After 24 h reperfusion hepatocellular damage increased with prolonged ischemia times. Hepatocellular damage and liver regeneration were closely interrelated. Moderate I/R-induced damage enhanced regeneration, while extensive damage debilitates the regenerative capacity. PHx alone resulted in no significant decrease in liver uptake function measured by HBS or ICG. Increasing severity of hepatic I/R injury had a differential effect on ICG clearance and (99m)Tc-mebrofenin uptake and excretion. The specific impact of 30% PHx combined with progressive ischemia times is different for each liver function test. Albeit (99m)Tc-mebrofenin HBS and the ICG clearance test provide complementary quantitative information to biochemical parameters, they only quantify one or two components of liver function. ICG and (99m)Tc-mebrofenin uptake profiles differed significantly, suggesting that the specific hepatic transporters may be distinct.

A Clinical Perspective on the Criteria for Liver Resection and the Use of Liver Function Tests

To the Editor, In a recently published survey of 100 liver centers, Breitenstein et al. [1] reported that on a global scale, (1) the average minimal remnant liver volume for resection is 25% (range = 15-40%) for normal liver parenchyma and 50% (range = 25–90%) for cirrhotic livers, (2) portal vein occlusion is employed in 89% of the centers for purposes of augmenting liver volume before surgery, and that (3) 38% of the centers employed liver function tests as part of their clinical routine, of which 76% used the ICG clearance test. The interesting survey provoked a few issues that we feel obliged to address. The authors contend that “below a certain volume, a remnant liver cannot sustain metabolic, synthetic, and detoxifying functions” [1]—a statement that is unequivocal and uncontested. However, it should be born in mind that liver volume is not a directly proportional measure of liver function. We have demonstrated a few fundamental aspects of the volume-function relationship that support this notion: (i) Whereas liver function correlates with volume in uncompromised livers [2], there is significantly less correlation between liver volume and function in patients with coexisting parenchymal liver disease [3, 4]. (ii) This discrepancy also applies to the regenerating liver [3]. (iii) The liver often exhibits functional heterogeneity [3]. These findings have been corroborated to some extent by others [5]. Consequently, a marginal remnant liver volume (e.g., 25% for cirrhotic livers [1]) may translate to functional deficiencies following resection and hence predisposes the organ to the “small-for-size” or, rather, the “small-for-function” syndrome. Likewise, allowing the organ to regenerate to a predetermined volume before resection bears comparable implications and strongly pleads for the use of dynamic liver function tests rather than CT volumetry as the gold standard, particularly for borderline surgical decisions. We emphasize specifically the use of quantitative dynamic liver function tests [i.e., ICG clearance, 99mTc-mebrofenin hepatobiliary scintigraphy (HBS) [2–4], galactose elimination capacity (GEC) [5], and 99mTc-labeled galactosyl human serum albumin scintigraphy (GSAS)] inasmuch as conventional liver function tests such as prothrombin time, serum bilirubin, and the Child-Pugh score are relatively insensitive and are thus lagging indicators for determining whether a liver resection can be safely performed. It is well known that there are notable discrepancies between the above-mentioned dynamic liver function tests in the assessment of liver function. In our patient population, ICG and 99mTc-mebrofenin uptake exhibited similar pharmacokinetics in regenerating rat livers (that also corresponded well to the extent of hepatic damage), whereas the GSAS and GEC tests displayed an underestimation and an overestimation, respectively, of liver function in comparison to ICG and 99mTc-mebrofenin uptake (unpublished). This is because liver function encompasses a broad spectrum of processes, ranging from uptake, synthesis, biotransformation, and systemic and canalicular secretion, whereby each test measures a different component of that spectrum. In summary, criteria on the basis of which extended liver resections are performed should preferably be dictated by functional parameters rather than volume alone, especially when livers are resected to a minimally accepted remnant volume. Furthermore, we advocate the use of dynamic liver function tests such as ICG or 99mTc-mebrofenin uptake for testing liver function due to their sensitivity and prognostic strength. We acknowledge that each of these tests reflects a limited aspect of liver function only. However, currently no better, clinically viable alternatives are available.

Assessment of Future Remnant Liver Function Using Hepatobiliary Scintigraphy in Patients Undergoing Major Liver Resection

Background99mTc-mebrofenin hepatobiliary scintigraphy (HBS) was used as a quantitative method to evaluate liver function. The aim of this study was to compare future remnant liver function assessed by 99mTc-mebrofenin hepatobiliary scintigraphy with future remnant liver volume in the prediction of liver failure after major liver resection. MethodsComputed tomography (CT) volumetry and 99mTc-mebrofenin hepatobiliary scintigraphy were performed prior to major resection in 55 high-risk patients, including 30 patients with parenchymal liver disease. Liver volume was expressed as percentage of total liver volume or as standardized future remnant liver volume. Receiver operating characteristic (ROC) curve analysis was performed to identify a cutoff value for future remnant liver function in predicting postoperative liver failure. ResultsPostoperative liver failure occurred in nine patients. A liver function cutoff value of 2.69%/min/m2 was calculated by ROC curve analysis. 99mTc-mebrofenin hepatobiliary scintigraphy demonstrated better sensitivity, specificity, and positive and negative predictive value compared to future remnant liver volume. Using 99mTc-mebrofenin hepatobiliary scintigraphy, one cutoff value suffices in both compromised and noncompromised patients. ConclusionPreoperative 99mTc-mebrofenin hepatobiliary scintigraphy is a valuable technique to estimate the risk of postoperative liver failure. Especially in patients with uncertain quality of the liver parenchyma, 99mTc-mebrofenin HBS proved of more value than CT volumetry.

Bronchobiliary Fistula Detected With Hepatobiliary Scintigraphy

Bile leakage into the thoracic cavity is a rare complication of invasive cancer. A 12-year-old boy was diagnosed with undifferentiated sarcoma of the right lobe of the liver invading the diaphragm. An extended right hepatectomy and total resection of the mass was performed, leaving a patchy tumoral invasion at the anterior diaphragmatic surface. Surgery was followed with a combined chemotherapy regimen. In the sixth postoperative month, he was readmitted with bilious expectoration. Tc-99m mebrofenin hepatobiliary scintigraphy revealed radiotracer accumulation in the right hemithorax. Bile leakage into the right thoracic cavity was diagnosed based on the hepatobiliary scintigraphic findings. For this patient; hepatobiliary scintigraphy, which is routinely used to visualize the liver and biliary tree, provided a noninvasive mean for the precise diagnosis of a bronchobiliary fistula. The fistula was then confirmed and corrected with surgery. The patient recovered uneventfully.

Traumatic Biliopleural Communication Detected by Hepatobiliary Scintigraphy

A 24-year-old man presented with a recent history of a stab injury followed by dyspnea and a right-sided pleural fluid collection. Tc-99m mebrofenin hepatobiliary scintigraphy demonstrated passage of bile from the liver across the diaphragm, into the right pleural cavity, confirming a biliopleural communication.

Comparison of early postoperative function of liver and renal allografts with radionuclide imaging

Objectives Radionuclide imaging is a valuable tool during the early posttransplantation period for evaluating the functional status of renal and liver allografts. The aim of this study was to compare the early postoperative function of renal and liver allografts with serial radionuclide imaging. Methods Twenty-two renal and 22 liver allograft recipients were evaluated with serial radionuclide imaging. All grafts were from living related donors. For renal scintigraphy, recipients were injected with Tc-99m DTPA, and imaging was performed on postoperative days 3 and 7. Liver allograft recipients were evaluated with Tc-99m mebrofenin hepatobiliary scintigraphy within the first postoperative week and as required thereafter. The following parameters were computed for each scintigraphy: uptake, time to excretion of the radiopharmaceutical (T ex), and retention of radioactivity at the end of the study. Results Among 22 renal transplant recipients, 19 (86%) had normal uptake and T ex values on day 7 posttransplantation. Nine (41%) renal grafts exhibited retention. Among 22 liver transplant recipients, 7 (32%) had normal findings on the first hepatobiliary scan. All except eight liver grafts (64%) had a delay in T ex, and 15 (68%) had parenchymal retention on the first scan, with improvement of function observed on serial scintigraphies obtained during follow-up. Decreases in uptake were seen less frequently and correlated with a prolonged postoperative hospital stay. Conclusion Renal transplant recipients are more likely than liver allograft recipients to have a normal scintigraphy in the early posttransplantation period. Retention of radioactivity at the end of the study was the most frequently observed abnormality for both renal and liver allografts. Most liver transplant recipients exhibited a delay in excretion, and parenchymal retention, of radioactivity on the first evaluation, with subsequent improvement on follow-up serial scintigraphy studies.

COMPARISON OF EARLY POSTOPERATIVE FUNCTION OF LIVER AND RENAL ALLOGRAFTS WITH RADIONUCLIDE IMAGING

P539 Aims: Radionuclide imaging is a valuable tool during the early posttransplantation period for the evaluation of the functional status of the renal and liver allografts. In addition to providing information related to posttransplantation complications, it has been reported to ensure prognostic information as well. The aim of this study was to compare the early postoperative functional course of renal and liver allografts with serial radionuclide imaging. Methods: Fifteen renal and 15 liver allograft recipients have been evaluated with serial radionuclide imaging. All grafts were from a living-related donor. For renal scintigraphy, every recipient was injected with Tc-99m DTPA and imaging has been performed on postoperative days 3 and 7. Liver allograft recipients were evaluated with Tc-99m mebrofenin hepatobiliary scintigraphy within the first postoperative week and as required thereafter. Region of interests have been drawn over the graft and the background (for hepatobiliary scintigraphy, the left ventricle and for renal scintigraphy, perirenal region was chosen). After generation of background-corrected time-activity curves, the following parameters were computed for each scintigraphy : Uptake (the ratio of maximum counts on the graft to that of background counts), time to excretion of radiopharmaceutical from the graft parenchyma and parenchymal retention at the end of the study. Results: Among 15 renal transplant recipients, 12 had normal uptake and Tex values on day 7 posttransplantation (80%). Eight renal grafts exhibited parenchymal retention (53%). Among 15 liver transplant recipients, 7 had normal uptake on first hepatobiliary scan (47%). All except 4 liver grafts had delayed excretion (73%) and 12 had parenchymal retention (80%) on the first scan with improvement of function observed on serial scintigraphies obtained during follow-up. Conclusions: The results indicate that renal transplant recipients are more likely to have a normal scintigraphy early post-transplantation compared to liver allograft recipients. This may be explained by the intensity of immune reaction in different organ grafts. Parenchymal retention was the most frequently observed functional abnormality for both renal and liver allografts. Most liver transplant recipients exhibit a delay in excretion and parenchymal retention on the first evaluation, with improvement on serial scintigraphy studies.