Morphometry of terminal hepatic veins

Summary In the present study, hepatic venous distribution per unit of liver surface area on normal wedge biopsies from man (n=11) and baboon (n=8) were analysed and compared. Terminal hepatic veins (THV - man:n=100; baboon:n=200) morphometric size variables were obtained with a Leitz ASM 68K morphometric equipment. THV, defined as hepatic veins up to 150 m in internal diameter (ID), in the centrolobular position and with sinusoidal openings, represented 84% and 74% of hepatic veins of man and baboon, respectively. Four or more THV were generally found on 8 mm² of liver surface. Transversely sectioned THV selected by the ratio IDminimum/IDmaximum >0.67, was found to be only 25% of the total THV. In baboon, THV merge with other terminal veins and the interlobular veins present sinusoidal inlets. The baboon THV wall surface (WS) and wall thickness (WT) values were higher than in man. Positive correlations between the number of mesenchymal cells (Mc) in the vein wall and wall surface of terminal hepatic veins (man: r= 0.79; baboon: r=0.83) and between wall surface and internal surface (IS) (man: r=0.80; baboon: r=0.72) were found. Two ratios were selected as the most reliable parameters: (1) for the THV wall rim, wall surface/internal surface (WS/IS - man: 0.43±0.16; baboon: 0.63±0.23), regarding transversely sectioned THV; and (2) for the evaluation of wall cell density (WS/Mc-man: 550±231; baboon: 558±183 m²/cell) as they did not depend on THV caliber.Dr. Porto was supported by a fellowship from MEC-CAPES, Brazil. A grant for morphometric equipment was obtained from the Fondation pour la Recherche Médicale and from the Societé d'Hépatologie Expérimentale, 77 rue Pasteur, Lyon, France     

Hepatic arterial variations and liver-related diseases of 100 consecutive donors

We prospectively studied anatomical variations and diseases of the liver in 100 consecutive donor operations during a period of 1 year. The normal arterial anatomy with a single hepatic artery (HA) from the celiac trunk was seen in 76% of all cases. Seven of twelve different major variations of the HA may be considered as rare, one of which cannot be found in the earlier literature. During harvesting, 6% of the livers were discarded, 3% on the basis of infection and 1% because of a polycystic disease. Two cases were rejected as the liver was found to be severely hypoperfused or hypoxic in an otherwise stable donor. Severe steatosis was macroscopically and histologically diagnosed in 3% of the cases, and in three donors a benign tumour was found in the liver or in the gall bladder. Two primarily nonfunctioning livers in the present series of 94 recipient operations were retrieved from this group of severely steatotic livers. As the donor liver was totally normal in only 2 out of 3 of the cases, the present study underlines the importance of searching for extremely variable anomalies of the HA and for liver-related diseases during organ harvesting.     

Progressive tubulointerstitial nephritis and chronic cholestatic liver disease

We report the clinical and morphological features of a distinctive hepatorenal disorder in four patients and review the five similar patients in the literature. The main clinical characteristics were early onset of cholestatic liver disease and progressive tubulointerstitial nephritis leading to renal death in early childhood. Liver histology showed disturbed architecture with nodular and acinar formations and portal fibrosis and bile duct proliferation. Histological abnormalities in the kidney were severe interstitial fibrosis and tubular atrophy and dilatation, while the typical features of nephronophthisis were lacking. These clinical and morphological characteristics distinguish our patients from the majority described, as having nephronophthisis and congenital hepatic fibrosis or any other known syndrome with concomitant hepatorenel involvement. We suggest that the association of cholestatic liver disease and progressive tubulointerstitial nephritis represents a new syndrome.     

Hepatic Steatosis and Morbid Obesity

One hundred and twenty-seven consecutive morbidly obese patients who presented for bariatric surgery underwent open wedge liver biopsy at the completion of their gastric restrictive procedure. All hepatic specimens were graded histologically for degrees of steatosis. Three-quarters of the patients had histological evidence of hepatic steatosis and in one-fifth this was severe and diffuse. No patient had histological evidence of fatty hepatitis, portal fibrosis, or cirrhosis. There was no significant correlation between the degree of obesity (measured as percentage over ideal weight), age, sex, or preoperative liver function tests and the degree of fatty change observed. Insufficient data were available to implicate alcohol and poor protein nutrition in the aetiology of the observed fatty liver change. Other factors such as diabetes mellitus or drugs were not aetiological factors in this series of patients.     

Clinical features of hepatic artery thrombosis after pediatric liver transplantation

Thrombosis of the hepatic artery (HAT) is a severe complication of liver transplantation, and most cases need regrafting. The aim of this study was to review our experience with this complication. From January 1986 through January 1992, 76 liver transplants were performed in 59 pediatric patients at the Children's Hospital La Paz, Madrid. The diagnosis of HAT was made in 12 cases (15.7%). The common patterns of clinical presentation were: fulminant liver necrosis (5), bile leak due to necrosis of the bile duct (4), and relapsing bacteremia (3). Clinical symptoms of fulminant liver necrosis started within the first 2 weeks after transplantation, with rapid deterioration and steep rises in SGOT and SGPT levels. All these patients were retransplanted on an urgent basis, but only 1 is alive 4 years later. Four patients developed bile leaks 13 to 60 days after transplantation; SGOT, SGPT, and total bilirubin were only slightly increased. Three children were retransplanted electively and are alive with a mean follow-up of 3 years. One exceptional patient had a Roux-en-Y jejunostomy and is doing well 30 months later with his original graft. The 3 remaining children had episodes of septicemia with hepatic abscess, liver infarction, and pleural effusion. Liver function tests were normal, with bilirubin levels below 2 mg/dl. All patients were retransplanted, but only 1 is alive and well 13 months later. In the present series, we found that early HAT produces fulminant clinical deterioration requiring an urgent regraft. Late HAT presenting with either infection or bile leak allows time for treatment by elective retransplantation. The best survival was obtained in the latter group. Correspondence to: J. Vázquez     

High Bilirubin Levels Interfere with Serum Tartrate-Resistant Acid Phosphatase Determination: Relevance as a Marker of Bone Resorption in Jaundiced Patients

Serum tartrate-resistant acid phosphatase (TRAcP) activity is considered to be a biochemical marker of bone resorption. Recently, a lack of specificity of collagen-related markers for assessing bone turnover has been observed in patients with chronic liver disease. Thus, it could be of great interest to determine serum TRAcP activity in such patients. However, nonspecificity of the analytical reaction could occur when hemolyzed, lipemic, or icteric specimens are analyzed. Therefore, we have studied the interference caused by bilirubin in the measurement of serum TRAcP activity using the Hillmann method. The interference was assessed in two pools of serum containing different bilirubin concentrations but with similar total AcP levels. Mixing proportional parts of the two pools, 10 samples were also obtained. Serum activities of total AcP and TRAcP, and the concentration of bilirubin were measured in the 10 samples. Both the actual and the expected values obtained by theoretical calculations were compared. Serum bilirubin values of 2.4 mg/dl showed a negative interference of 15% in the determination of serum TRAcP activity, whereas values of bilirubin higher than 10 mg/dl interfered totally with the measurement of serum TRAcP. Bilirubin did not interfere with the total AcP determination. This study clearly shows the interference of bilirubin in the determination of serum TRAcP. This finding should be considered when bone metabolism disorders are evaluated in jaundiced patients. Received: 6 April 1998 / Accepted: 1 October 1998     

Dopamine,dopexamine and dobutamine in liver transplant recipients: a comparison of their effects on hemodynamics,oxygen transport and hepatic venous oxygen saturation

The purpose of this study was to determine the effects of vasoactive treatment with dopamine (DO), dopexamine (DX), and dobutamine (DOB) on hemodynamics, oxygen transport and hepatic venous oxygen saturation (SvhO₂) after orthotopic liver transplantation (OLT). A pulmonary artery catheter was inserted into the right hepatic vein of 17 OLT patients. Timed infusion of DO, DX, and DOB was performed at the following rates: DO at 4 and 8 g/kg per minute, and DOB at 5 and 10 g/kg per minute. Hemodynamics, oxygen transport variables, and SvhO₂ were assessed. Each catecholamine induced a significant increase in cardiac index, oxygen delivery, and SvhO₂. Mean arterial pressure was increased during DO and DOB, but significantly reduced during DX. Each inotrope increased oxygen delivery in parallel with SvhO₂, suggesting a corresponding increase in hepatic oxygen supply. Therefore, it appears that each vasoactive drug may be utilized in OLT patients to provide oxgen delivery without impairment of splanchnic oxygenation.     

Steady-state kinetics of imipramine in patients

Steady-state plasma level kinetics were studied in 76 patients given imipramine (IP) 150 to 225 mg/day for 2–5 weeks. IP was given in three divided doses at 8.00 a.m., 1.00 p.m. and 5.00 p.m. Plasma concentrations of IP and its active metabolite desipramine (DMI) were determined by quantitative in situ thin-layer chromatography. The plasma levels of IP and DMI showed pronounced flucutations throughout the day with a ratio of about 2 between highest and lowest level. Patients with steady-state levels of IP and/or DMI below 50 g/l reached this within 1 week of treatment. Patients with higher steady-state levels reached steady-state concentrations within 2–3 weeks. There were some intraindividual fluctuations in plasma levels from week to week after steady state had been reached (coefficient of variation: 10–20%). Interindividually, the steady-state levels corrected to a dose of 3.5 mg/kg per day varied considerably: IP: 6–356 g/l, DMI: 24–659 g/l and IP+DMI: 58–809 g/l. The steady-state plasma levels showed a skew distribution that became normal by logarithmic transformation. The IP/DMI ratio ranged from 0.07 to 5.5 with a median value of 0.47. Compared to data from amitriptyline treated patients the IP/DMI ratios had significantly lower median value and larger variation than the corresponding plasma level ratios of amitriptyline/nortriptyline. Several statistically significant differences in steady-state levels between age groups were found. For IP: Women aged 30–39 had lower levels than women aged 20–29, 40–49, and 50–59, and men aged 50–59 and 60–65; men aged 30–39 had lower levels than men aged 60–65. For DMI: Women aged 30–39 had lower levels than women aged 50–59.     

Efficacy of bleomycin treatment for symptomatic hemangiomas in children

Five children aged 5–19 years had pain in massive, inoperable hemangiomas. They were treated with intralesional injections of 2 mg bleomycin as a 0.4 mg/ml solution in the painful area. The injections were repeated after 4-6 weeks for a total of 6–10 times. All children were relieved of pain, and the swelling was reduced in all cases. There were no complications or side effects. Bleomycin therapy of painful, massive hemangiomas can be recommended in older children.     

Homotypic Adhesion through Carcinoembryonic Antigen Plays a Role in Hepatic Metastasis Development

We established a cell line with high metastatic potential to the liver (LS-LM4) after four successive repetitions of splenic injection of liver-metastatic cells in SCID mice. This cell line strongly expressed CEA and showed increased homotypic adhesion as compared with the parent cell line (LS174T). To examine the role of CEA in the increased homotypic adhesion, LS-LM4 cells were treated with anti-CEA antibody and subjected to an in vitro adhesion and aggregation assay. Further, to study the role of CEA in the hepatic metastasis of cells with high metastatic potential, LS-LM4 cells were treated with anti-CEA antibody, and the inhibition of hepatic metastasis after splenic injection in vivo was examined. There was a 62% decrease in the homotypic adhesion of anti-CEA antibody-treated (100 μg/ml) LS-LM4 cells under a Ca²⁺-free condition as compared with the control ( P <0.01). Anti-CEA antibody (100 μg/ml) inhibited cell aggregation under a Ca²⁺-free condition ( P <0.05). Treatment with anti-E-cadherin antibody (60 μ/ml) plus anti-CEA antibody (100 μg/ml) inhibited cell aggregation more potently than anti-E-cadherin antibody treatment alone in the presence of Ca²⁺. In vivo , there was a 75% decrease in the number of hepatic metastatic nodules in the G125 anti-CEA antibody-treated group as compared with the control group ( P <0.01). Similarly, there was a 40% decrease in the diameter of metastatic nodules and there was a 90% decrease in total tumor volume of hepatic metastasis in the G125 anti-CEA antibody-treated group as compared with the control ( P <0.01). These results suggest that increased metastatic potential to the liver is at least partly due to increased homotypic binding mediated by CEA.