Evaluation of Hepatobiliary Excretion and Enterobiliary Reflux in Rats with Biliary Obstruction Submitted to Bilioduodenal or Biliojejunal Anastomosis

Bilioduodenal and biliojejunal anastomoses are effective for the treatment of biliary obstruction. The objective of this study was to compare the effects of these anastomoses on hepatobiliary excretion and enterobiliary reflux. Enterobiliary reflux and biliary excretion were evaluated respectively after oral administration of technetium (^99mTc) in combination with sodium phytate and intravenous infusion of ^99mTc with diisopropyl-iminodiacetic acid. Enterobiliary reflux occurred to an equal degree in the bilioduodenal and biliojejunal groups. Maximum hepatic activity time (T_max) and radiotracer clearance half-time (T^1/2) were similar in both groups. However, when compared with that found for the sham-operated group, T_max, and T^1/2 were higher in the biliojejunal group (P = 0.02 and P = 0.01, respectively). Histopathological analysis showed marked reduction in ductal proliferation in both groups. These data undermine the theoretical advantages attributed to biliojejunal anastomosis and further the understanding of the pathophysiology of cholangitis that occurs even with patent anastomosis.     

Assessment of liver function in primary biliary cirrhosis using Gd-EOB-DTPA-enhanced liver MRI

Objectives

Gd-EOB-DTPA (gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid) is a gadolinium-based hepatocyte-specific contrast agent for magnetic resonance imaging (MRI). The aim of this study was to determine whether the hepatic uptake and excretion of Gd-EOB-DTPA differ between patients with primary biliary cirrhosis (PBC) and healthy controls, and whether differences could be quantified.

Methods

Gd-EOB-DTPA-enhanced liver MRI was performed in 20 healthy volunteers and 12 patients with PBC. The uptake of Gd-EOB-DTPA was assessed using traditional semi-quantitative parameters (C_max, T_max and T_1/2), as well as model-free parameters derived after deconvolutional analysis (hepatic extraction fraction [HEF], input-relative blood flow [irBF] and mean transit time [MTT]). In each individual, all parameters were calculated for each liver segment and the median of the segmental values was used to define a global liver median (GLM).

Results

Although the PBC patients had relatively mild disease according to their Model for End-stage Liver Disease (MELD), Child–Pugh and Mayo risk scores, they had significantly lower HEF and shorter MTT values compared with the healthy controls. These differences significantly increased with increasing MELD and Child–Pugh scores.

Conclusions

Dynamic hepatocyte-specific contrast-enhanced MRI (DHCE-MRI) has a potential role as an imaging-based liver function test. The high spatial resolution of MRI enables hepatic function to be assessed on segmental and sub-segmental levels.     

Improved scintigraphic assessment of severe cholestasis with the hepatic extraction fraction

In previous studies, we found that biliary scintigraphy with technetium-99m-labeled iminodiacetic acid ([^99mTc]IDA) provided excellent discrimination between intrahepatic and extrahepatic cholestasis, except in patients with profound cholestasis who had poor visualization of the biliary tree. In this study, we have used deconvolution analysis to determine the hepatic extraction fraction (HEF) of a hypothetical single circulatory pass of[^99mTc]IDA. Our hypothesis was that extraction of radionuclide from the blood would be normal in patients with extrahepatic obstruction alone, but would be impaired in patients with intrahepatic disease (IHD). The purpose of this study was to compare the HEF in patients with profound cholestasis (bilirubin3.0 mg/dl) due to either IHD or common bile duct obstruction (CBDO). Normal subjects (N=13) had an HEF of 100%. Patients with CBDO (N=13) had slightly reduced HEF values (92.8±3.2%) despite profound hyperbilirubinemia (6.1±1.0 mg/dl). Patients with IHD (N=23) had a markedly reduced HEF (43.1±4.1%) which was significantly lower than patients with CBDO and normal subjects (P<0.001). We conclude that the determination of the HEF during biliary scintigraphy is helpful in distinguishing between intrahepatic and extrahepatic disease in patients with hyperbilirubinemia (bilirubin3.0 mg/dl).     

Hepatobiliary scintigraphy for detecting biliary strictures after living donor liver transplantation

AIM:To investigate the diagnostic accuracy of hepatobiliary scintigraphy(HBS) in detecting biliary strictures in living donor liver transplantation(LDLT) patients.METHODS:We retrospectively reviewed 104 adult LDLT recipients of the right hepatic lobe with duct-toduct anastomosis,who underwent HBS and cholangiography.The HBS results were categorized as normal,parenchymal dysfunction,biliary obstruction,or bile leakage without re-interpretation.The presence of biliary strictures was determined by percutaneous...     

Donor ductal anomaly is not a contraindication to right liver lobe donation

BackgroundData of living-donor liver transplantation (LDLT) suggested that donor ductal anomaly may contribute to postoperative biliary complications in recipients and in donors. This retrospective study aimed to determine if the occurrence of postoperative biliary stricture in donors or recipients in right-lobe LDLT (RLDLT) is related to donor biliary anatomy type.MethodsWe analyzed our RLDLT recipients’ clinical data and those of their graft donors. The recipients were divided into 2 groups: with and without postoperative biliary stricture. The 2 groups were compared. The primary endpoints were donor biliary anatomy type and postoperative biliary complication incidence; the secondary endpoints were 1-, 3- and 5-year graft and patient survival rates.ResultsTotally 127 patients were included in the study; 25 (19.7%) of them developed biliary anastomotic stricture. In these 25 patients, 16 had type A biliary anatomy, 3 had type B, 2 had type C, 3 had type D, and 1 had type E. In the 127 donors, 96 (75.6%) had type A biliary anatomy, 13 (10.2%) had type B, 6 (4.7%) had type C, 10 (7.9%) had type D, and 2 (1.6%) had type E. Biliary stricture was seen in 2 donors, who had type A biliary anatomy. None of the recipients or donors developed bile leakage. No association between the occurrence of postoperative biliary stricture and donor biliary anatomy type was found (P = 0.527).ConclusionsThe incidence of biliary stricture in donors or recipients after RLDLT was not related to donor biliary anatomy type. As postoperative complications were similar in whatever type of donor bile duct anatomy, donor ductal anomaly should not be considered a contraindication to donation of right liver lobe.     

Usefulness of measuring hepatic functional volume using technetium-99m galactosyl serum albumin scintigraphy in hilar bile duct carcinoma

This case involved a 75-year-old woman with obstructive jaundice who was diagnosed with hilar bile duct carcinoma. After endoscopic retrograde biliary drainage, the total bilirubin level was normalized. The indocyanine green test retention rate at 15 min (ICGR15) was 26%. The liver uptake ratio (LHL15) by technetium-99m galactosyl human serum albumin (^99mTc-GSA) liver scintigraphy was 0.87. Left hepatectomy was scheduled by CT volumetry. However, biliary drainage was insufficient, and the functional liver volume showed functional deterioration of the left liver. After percutaneous transhepatic biliary drainage, future remnant liver volume by ^99mTc-GSA liver scintigraphy changed to 52% from 42%, and ICGR15 and LHL15 were improved to 16% and 0.914, respectively. Scheduled left hepatectomy was performed following the results of functional liver volume. The measurement of functional volume by ^99mTc-GSA liver scintigraphy provides useful information with respect to segmental liver function for deciding operative indications.     

Hepatobiliary scintigraphy and kinetic growth rate predict liver failure after ALPPS: a multi-institutional study

BackgroundPost hepatectomy liver failure (PHLF) after ALPPS has been related to the discrepancy between liver volume and function. Pre-operative hepatobiliary scintigraphy (HBS) can predict post-operative liver function and guide when it is safe to proceed with major hepatectomy. Aim of this study was to evaluate the role of HBS in predicting PHLF after ALPPS, defining a safe cut-off.MethodsA multicenter retrospective study was approved by the ALPPS Registry. All patients selected for ALPPS between 2012 and 2018, were evaluated. Every patient underwent HBS during ALPPS evaluation. PHLF was reported according to ISGLS definition, considering grade B or C as clinically significant.Results98 patients were included. Thirteen patients experienced PHLF grade B or C (14%) following ALPPS-2. The HBS and the daily gain in volume (KGR_FLR) of the future liver remnant (FLR) were significantly lower in PHLF B and C (p = .004 and .041 respectively). ROC curves indicated safe cut-offs of 4.1%/day (AUC = 0.68) for KGR_FLR, and of 2.7 %/min/m² (AUC = 0.75) for HBS_FLR. Multivariate analysis confirmed these cut-offs as variables predicting PHLF after ALPPS-2.ConclusionPatients presenting a KGR_FLR ≤4.1%/day and a HBS_FLR ≤2.7%/min/m² are at high risk of PHLF and their second stage should be re-discussed.     

Scintigraphic evaluation of synovial inflammation in rheumatoid arthritis with 99mtechnetium-labelled human polyclonal immunoglobulin G

The aim of this study was to investigate whether ^99mtechnetium-labelled polyclonal human immunoglobulin G (^99mTc-IgG) scintigraphy reflects synovial inflammation in patients with rheumatoid arthritis (RA). We evaluated 29 patients with RA for this reason and found a highly significant correlation between total scintigraphic scores and total tenderness scores (r=0.781, P < 0.001). A significant correlation was also found between ^99mTc-IgG scintigraphic scores and tenderness in all joints other than the shoulders. The ^99mTc-IgG scintigraphy had a sensitivity of 69% and specificity of 88% in cases with tenderness and 72% and 81%, respectively, in cases with swelling. Total scintigraphic scores were correlated with serum levels of C-reactive protein (r=0.401, P < 0.05) but not with erythrocyte sedimentation rate (r=0.149, P > 0.05). The correlation between disease activity scores and total scintigraphic scores was also found to be significant (r=0.812, P < 0.001). We suggest that ^99mTc-IgG scintigraphy is a reliable and objective method in detecting synovial activity and can be appropriate for observing disease prognosis in clinical trials with RA. Received: 16 June 2000 / Accepted: 27 August 2000     

Measurement of liver function using hepatobiliary scintigraphy improves risk assessment in patients undergoing major liver resection

Background^99mTc-mebrofenin-hepatobiliary-scintigraphy (HBS) enables measurement of future remnant liver (FRL)-function and was implemented in our preoperative routine after calculation of the cut-off value for prediction of postoperative liver failure (LF). This study evaluates our results since the implementation of HBS. Additionally, CT-volumetric methods of FRL-assessment, standardized liver volumetry and FRL/body-weight ratio (FRL-BWR), were evaluated.Methods163 patients who underwent major liver resection were included. Insufficient FRL-volume and/or FRL-function <2.7%/min/m² were indications for portal vein embolization (PVE). Non-PVE patients were compared with a historical cohort (n = 55). Primary endpoints were postoperative LF and LF related mortality. Secondary endpoint was preoperative identification of patients at risk for LF using the CT-volumetric methods.Results29/163 patients underwent PVE; 8/29 patients because of insufficient FRL-function despite sufficient FRL-volume. According to FRL-BWR and standardized liver volumetry, 16/29 and 11/29 patients, respectively, would not have undergone PVE. LF and LF related mortality were significantly reduced compared to the historical cohort. HBS appeared superior in the identification of patients with increased surgical risk compared to the CT-volumetric methods.DiscussionImplementation of HBS in the preoperative work-up led to a function oriented use of PVE and was associated with a significant decrease in postoperative LF and LF related mortality.     

Molecular scintigraphic imaging using <Superscript>99m</Superscript>Tc–transferrin is useful for early detection of synovial inflammation of collagen-induced arthritis mouse

Transferrin receptor (TfR) is highly expressed on rapidly dividing inflammatory cells, but not in nonproliferating cells. We investigated whether scintigraphic imaging using ^99mTechnetium-radiolabeled transferrin (^99mTc–Tf) is useful for early detection of synovial inflammation of collagen-induced arthritis (CIA) mouse. ^99mTc–Tf conjugate was synthesized to target the TfR in inflamed synovium. ^99mTc–Tf scintigraphic images were obtained in nonarthritic normal mouse and advanced phase of CIA mouse. ^99mTc–Tf and ^99mTc–methylenediphosphonate (^99mTc–MDP) bone scintigraphic images were obtained in same early phase of CIA mouse. Western blot analysis, hematoxylin & eosin (H&E), and immunohistochemical staining were performed to determine development of arthritis and expression of TfR. Image analyses revealed that the uptake of ^99mTc–Tf in inflamed joints of advanced phase of CIA mouse was markedly higher than those by normal nonarthritic mouse. ^99mTc–Tf scintigraphy also showed higher uptake in knee joint prior to significant joint swelling in early phase of CIA mouse but ^99mTc–MDP bone scintigraphy does not. These scintigraphic findings are well correlated with the results of Western blot, H&E and immunohistochemical analysis. In conclusion, TfR can be used as a specific target for molecular imaging in CIA mouse, and ^99mTc–Tf scintigraphy detects synovial inflammation prior to significant clinical findings in CIA mouse. Sang-Il Lee and Eun-Mi Kim contributed equally to this work.     

Hepatocyte and Kupffer cell function after liver transplantation in the rat –in vivo evaluation with dynamic scintigraphy

Abstract: In vivo physiological measurements of hepatocyte and Kupffer cell function after liver transplantation are desirable. Orthotopic liver transplantation was performed in 54 rats. Hepatocyte and Kupffer cell function were measured with dynamic liver scintigraphy. Hepatic clearance of ^99mTc-Nanocoll (%/min), an albumin colloid phagocytosed by the Kupffer cells, was used to evaluate Kupffer cell function. Hepatic clearance of ^99mTc-IODIDA (%/min), an imino-diacetic-acid taken up and secreted by the hepatocytes, was used to evaluate the hepatocyte function. Hepatic clearance in control rats was 27±2 %/min for Nanocoll and 30±3 %/min for IODIDA. After syngenic liver transplantation, without rejection, there was a rise in Nanocoll clearance (34±2 %/min p<0.01) after 3 weeks, but no change in IODIDA clearance (32±3 %/min N.S.). After syngenic liver transplantation with preservation time prolonged to 16 h, there were no changes in IODIDA or Nanocoll clearance 1 day after transplantation. Both IODIDA (11±2 %/min) and Nanocoll clearance (22±2 %/min) were decreased (p<0.001) during rejection after allogenic transplantation. An in vivo method of measuring the hepatocyte and Kupffer cell function in the transplanted liver is described. Kupffer cell function was increased after syngenic liver transplantation. Kupffer cell and hepatocyte function were decreased during rejection. Dynamic liver scintigraphy seems a suitable procedure for examining liver injury after liver transplantation in the experimental setting.     

Model-derived assessment of urea appearance in response to alanine infusion: A quantitative measure of liver function in cirrhosis

A three compartment mathematical model was used to analyse the urea response to an alanine infusion in six control subjects, and in 15 patients with liver cirrhosis and variable degree of hepatocellular failure. Model-derived coefficients were used to calculate two parameters (Y_max and T_max), able to describe the theoretical response of the conversion of amino acid derived nitrogen into urea, in response to a unit impulse in alanine concentration. They correspond to the maximum rate of conversion of nitrogen from an intermediary pool into urea and to the time delay between the impulse and Y_max, respectively. In cirrhosis, the apparent volume of distribution of infused alanine was smaller than in controls, while the conversion of alanine nitrogen into an intermediary pool of nitrogen and finally into urea nitrogen were both reduced. Also Y_max was reduced by 50% in cirrhosis, whereas T_max was increased by 50%, and both significantly correlated with galactose elimination capacity (GEC; R²= 0.706 and R²= 0.505, respectively) and with antipyrine clearance (Ap Cl; R²= 0.823 and R²= 0.576, respectively). Model-derived assessment of urea appearance in response to alanine infusion is able to quantify the functional liver cell mass, and may prove useful for the study of nitrogen metabolism in cirrhosis, mainly in relation to encephalopathy.     

Usefulness of measuring hepatic functional volume using Technetium-99m galactosyl serum albumin scintigraphy in bile duct carcinoma: report of two cases

We report the usefulness of measuring functional liver volume in two patients undergoing hepatectomy. Case 1 involved a 47-year-old man with hepatitis B virus infection. The indocyanine green test retention rate at 15 min (ICGR15) was 14%. Liver uptake ratio (LHL15) by technetium-99 m galactosyl human serum albumin (^99mTc-GSA) liver scintigraphy was 0.91. The patient displayed hilar bile duct carcinoma necessitating right hepatectomy. After preoperative portal vein embolization (PVE), future remnant liver volume became 54% and functional volume by ^99mTc-GSA became 79%. Although the permitted resected liver volume was lower than the liver volume, scheduled hepatectomy was performed following the results of functional liver volume. Case 2 involved a 75-year-old man with diabetes. ICGR15 was 27.4% and LHL15 was 0.87. The patient displayed bile duct carcinoma located in the upper bile duct with biliary obstruction in the right lateral sector. The right hepatectomy was scheduled. After PVE, future remnant volume became 68% and functional volume became 88%. Although ICGR15 was worse as 31%, planned hepatectomy was performed due to the results of functional volume. In the liver with biliary obstruction or portal embolization, functional liver volume is decreased more than morphological volume. Measurement of functional volume provides useful information for deciding operative indication.     

Pravastatin transport across the hepatocyte canalicular membrane requires both ATP and a transmembrane pH gradient

Hepatic excretion of non-bile acid organic anions is reported to be ATP-dependent and a defect of this transport has been reported in congenitally jaundiced rats, animal models of human Dubin-Johnson syndrome. To investigate the effect of the transmembrane pH gradient on hepatocyte canalicular membrane transport of ATP-dependent organic anions, uptake of pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase-inhibiting organic anion, by hepatocyte canalicular membrane vesicles was observed in the presence or absence of transmembrane pH gradients. Uptake was assessed by a rapid filtration technique. ATP-dependent pravastatin uptake was stimulated in the presence of a transmembrane pH gradient (in > out) in Sprague-Dawley (SD) rats. Uptake was dependent on both pravastatin and ATP concentrations and showed saturation kinetics. After intravenous injection of [¹⁴C]-pravastatin (0.3 μmol), 81% of the dose was excreted in the bile within 35 min in SD rats, whereas only 20% was excreted in the bile in Eisai hyperbilirubinuria rats. ATP and the pH gradient also co-stimulated the uptake of pravastatin in Eisai hyperbilirubinuria rats, although the K_m was much higher and V_max was much lower than corresponding values in SD rats. This coincided well with the marked reduction in in vivo biliary excretion of pravastatin in jaundiced rats.     

Thyroid Hormone Deiodination Pathways in Brain and Liver of Rainbow Trout,Oncorhynchus mykiss

Outer-ring (5′) deiodination (ORD) and inner-ring (5) deiodination (IRD) ofl-thyroxine (T₄) and 3,5,3′-triiodo-l-thyronine (T₃) were studied in whole-brain microsomes of rainbow trout and compared with liver deiodination. Brain T₄ORD activity (apparentK_m= 1.2–2.5 nM;V_max= 0.10–0.14 pmol/hr/mg microsomal protein) was less than T₄IRD activity (apparentK_m= 4.9;V_max= 0.32) and T₃IRD activity (apparentK_m= 5.2–5.4;V_max= 1.1–2.0); T₃ORD activity was negligible. All three brain deiodinase pathways shared the following properties: pH optima between 7.0 and 7.3, activity enhanced by dithiothreitol (10 mM), weak inhibition by 6-n-propyl-2-thiouracil and iodoacetate, but stronger inhibition by aurothioglucose. Based on competitive inhibition, the substrate preference for brain T₄ORD was T₄= tetraiodothyroacetic acid (TETRAC) > 3,3′,5′-triiodo-l-thyronine (rT₃) > 3,5,3′-triiodothyroacetic acid (TRIAC) >> T₃> 3,5-diiodo-l-thyronine (3,5-T₂). A comparable substrate preference profile was obtained for liver T₄ORD (K_m1 nM). Both T₄IRD and T₃IRD in brain had similar substrate preference profiles (rT₃> 3,5-T₂> T₄> T₃) which differed from that of T₄ORD. Negligible T₄IRD and T3IRD activities existed in liver. We conclude that for rainbow trout (i) T₄ORD systems in brain and liver are similar, and consistent with a common enzyme that does not match exactly either mammalian type I or II deiodinases, (ii) brain T₄IRD and T₃IRD enzymes share several common properties, and correspond functionally to the mammalian type III deiodinase, and (iii) under normal physiological conditions the predominant deiodinase pathways in brain (T₄IRD and T₃IRD) are poised toward T₄and T₃degradation, while that in liver (T₄ORD) is poised toward T₃generation.     

Perioperative hepatic functional risk assessed with technetium-99m diethylenetriamine pentaacetic acid-galactosyl human serum albumin liver scintigraphy in patients undergoing pancreaticoduodenectomy complicated by obstructive jaundice

Summary Conclusion: Liver scintigraphy with technetium-99m diethylenetriamine pentaacetic acid-galactosyl human serum albumin (Tc-GSA) can be used to predict outcome of biliary drainage and hepatic function after pancreaticoduodenectomy in patients with pancreatic, biliary, and ampullary carcinomas complicated by obstructive jaundice. Background: Preoperative obstructive jaundice has been reported as a crucial risk factor for serious postoperative complications in patients undergoing pancreaticoduodenectomy. The aim of the present study was to investigate whether Tc-GSA liver scintigraphy can assess hepatic functional risk in patients with pancreatic, biliary, and ampullary carcinomas complicated by obstructive jaundice. Methods: Liver scintigraphy was performed before biliary drainage in 18 patients with obstructive jaundice. The maximum removal rate of Tc-GSA (GSA-R_max; standard normal value ≥0.60) was calculated. These patients underwent pancreaticoduodenectomy with wide lymphadenectomy. The efficacy of preoperative biliary drainage was assessed with the decrease in serum bilirubin concentration in the first week after biliary drainage. Postoperative liver function was assessed with the increase in serum bilirubin concentration, which was the difference between the immediate preoperative and maximal postoperative bilirubin concentrations. Results: Serum bilirubin decreased more in the first week after biliary drainage in patients with GSA-R_max≥0.60 (7.64±1.09 mg/Dl/wk) than in patients with GSA-R_max<0.60 (3.56±1.25 mg/DL/wk, p=0.042). Postoperative bilirubin increased less in patients with GSA-R_max≥0.60 (0.81±0.30 mg/dL) than in patients with GSA-R_max<0.60 (4.00±0.69 mg/DL, p=0.0012). Multivariate analysis showed that GSA-R_max significantly predicted the postoperative bilirubin increase (p=0.020).     

Role of the 13C-methacetin breath test in the assessment of acute liver injury in a rat model

AIM: To evaluate the role of the ¹³C-methacetin breath test (¹³C-MBT) in the assessment of acute liver injury in a rat model.METHODS: Acute liver injury in rats was induced by a single intraperitoneal injection of D-galactosamine (D-GalN). Forty-eight male Sprague-Dawley rats were randomly assigned to a control group (n = 8) and five model groups (each n = 8), and acute liver injury was assessed at different time points (6, 12, 24, 48 and 72 h) after D-GalN injection. The ¹³C-MBT, biochemical tests, 15-min retention rate of indocyanine green (ICG_R15), and liver biopsy were performed and compared between the control and model groups. Correlations between parameters of the ¹³C-MBT (T_max, MV_max, CUM₁₂₀ and DOB_max), biochemical tests, ICG_R15 and liver necrosis score were also analyzed using Spearman’s correlation analysis.RESULTS: T_max, MV_max, CUM₁₂₀ and DOB_max, as well as most of the traditional methods, correlated with the liver necrosis score (r = 0.493, P < 0.05; r = -0.731, P < 0.01; r = -0.618, P < 0.01; r = -0.592, P < 0.01, respectively). MV_max, CUM₁₂₀ and DOB_max rapidly decreased and were lower than those in the controls as early as 6 h after D-GalN injection (3.84 ± 0.84 vs 5.06 ± 0.78, P < 0.01; 3.35 ± 0.72 vs 4.21 ± 1.44, P < 0.05; 52.3 ± 20.58 vs 75.1 ± 9.57, P < 0.05, respectively) and reached the lowest point 24 h after D-GalN injection. MV_max, CUM₁₂₀ and DOB_max returned to normal levels 72 h after D-GalN injection and preceded most of the traditional methods, including liver biopsy.CONCLUSION: The ¹³C-MBT is a sensitive tool for the timely detection of acute liver injury and early prediction of recovery in a rat model. Further clinical studies are warranted to validate its role in patients with acute liver injury.     

Ethanol Increases Hepatocyte Water Volume

Mouse hepatocytes respond to osmotic stress with adaptive changes in transmembrane potential, V_m, such that hypotonic stress hyperpolarizes cells and hypertonic stress depolarizes them. These changes in V_m provide electromotive force for redistribution of ions such as CI^?, and this comprises part of the mechanism of hepatocyte volume regulation. We conducted the present study to determine whether ethanol administered in vitro to mouse liver slices increases hepatocyte water volume, and whether this swelling triggers adaptive changes in the V_m. Cells in mouse liver slices were loaded with tetramethylammonium ion (TMA). Changes in hepatocyte water volume were computed from measurements with Ion sensitive micro-electrodes of changes in intracellular activity of TMA (a¹_TMA) that resulted from water fluxes. Ethanol (70 mM) increased hepatocyte water volume Immediately, and this peaked at 17% by 7 to 8 min, by which time a plateau was reached. Liver slices also were obtained from mice treated 12 hr prior with 4-methylpyrazole (4 mM). The effect of ethanol on their hepatocyte water volume was identical to that from untreated mice, except that the onset and peak were delayed 2 min. Hepatocyte V_m showed no differences between control or ethanol-treated cells during the course of volume changes. In contrast, hyposmotic stress, created by dropping external osmolality 50 mosm, increased V_m from –30 mV to –46 mV. Ethanol did not inhibit this osmotic stress-induced hyperpolarization, except partially at high concentrations of 257 mM or greater. We infer that ethanol-induced swelling of hepatocytes differs from that resulting from hyposmotic stress. Cellular events associated with increased activity of intracellular water most likely trigger the hyperpolarization of V_m that accompanies the latter. We conclude, therefore, that ethanol-induced swelling occurs without change in cell water activity. This may result from the retention of macromolecules by ethanol in cells that constitutively secrete protein.     

Biliary hamartomas with delayed 99mTc-diisopropyl iminodiacetic acid clearance

We report a 61-year-old asymptomatic man who had a hepatic lesion whose nature was undetermined, based on biochemistry, serology, ultrasonography, computed tomography, and magnetic resonance imaging studies. Biliary hamartomas were diagnosed by echo-guided needle biopsy. Functional studies of bile excretion, using ^99mTc-diisopropyl iminodiacetic acid (^99mTc-DISIDA) scintigraphy liver single-photon emission computed tomography (SPECT) showed the delayed transit of tracers from hepatocytes to the biliary hamartomas and the delayed emptying of tracers to the neighboring bile ducts. Therefore, biliary hamartomas should be included in the differential diagnosis of single or multiple hepatic lesions whose nature is undetermined, and a liver biopsy would be warranted for further treatment plans. We believe this is the first functional study of bile excretion in biliary hamartomas using radionucleotide studies; such studies may have prognostic implications.     

Measurement of parenchymal function and bile duct flow in primary sclerosing cholangitis using dynamic 99mTc-HIDA SPECT

BACKGROUND AND AIM: Primary sclerosing cholangitis is a chronic cholestatic disease characterized by obliterative fibrosis of intrahepatic and/or extrahepatic bile ducts. The unpredictable clinical course of the disease can be relentless, leading to premature death in a large percentage of patients. Prognostic index formulas, the revised Mayo model being the most frequently used, have been developed to predict clinical course and prognosis. The aim of this study was to investigate the potential value of dynamic (99m)Tc-HIDA SPECT in patients with primary sclerosing cholangitis by correlating scintigraphic results with cholangiographic and biochemical findings and prognostic scoring systems used in clinical practice. METHODS: In 18 patients with primary sclerosing cholangitis, segmental parenchymal and bile duct functions were measured using dynamic (99m)Tc-HIDA SPECT. Quantitative scintigraphic results were compared to cholangiographic findings, as graded by a biliary classification system, the Child-Pugh score and revised Mayo prognostic score, as well as the individual biochemical parameters included in the scoring systems. RESULTS: In individual segments, scintigraphic quantitative parameters indicative of bile flow showed a statistically significant correlation with the state of the bile-flow path for the respective segments as assessed by the biliary classification system. The revised Mayo score correlated with the scintigraphic quantitative parameters indicative of parenchymal function and bile flow as calculated for the whole liver. CONCLUSIONS: Dynamic (99m)Tc-HIDA SPECT, capable of assessing different aspects of liver function for the total liver, as well as for individual segments, has potential value in the management of patients with primary sclerosing cholangitis.