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PubMed1988

Comparison of rapid in situ, regular in situ, and ex vivo flushing on hepatic function.

The efficacy of three flushing techniques on subsequent liver function was assessed using the in vivo isolated liver perfusion model (ILPM). Livers from brain-dead mongrel dogs were flushed with cold Euro-Collins as follows: Group I, rapid in situ flushing (10 min); Group II, regular in situ flushing (45 min); Group III, ex vivo flushing (10 min). All livers were then heterotopically transplanted into recipients, using the ILPM, by anastomosis of the portal vein, vena cava, and hepatic artery to the recipient's portal vein, iliac vein, and iliac artery. Reperfusion followed for 30 min. Laboratory samples collected at 0, 5, 15, and 30 min showed that hepatic function was not altered by ex vivo flushing and was only slightly altered by rapid in situ flushing. Regular in situ flushing proved to be damaging to livers. Histological analysis confirmed these findings. Therefore, either rapid in situ or ex vivo flushing can be safely used by the transplant specialist.

Adenosine Triphosphate↗
PubMed1994

[Comparative study of organ storage solutions for rat liver preservation: effects of HX and Collins I solution on sinusoidal lining cells and hepatic functions].

The liver sinusoidal lining cell injury and biochemical function changes were studied with isolated perfusion after rat livers had been preserved in HX solution or in Collins II solution. Seventy inbred Wistar rats were randomly divided into control group (n = 10), group H (preserved with HX solution, n = 30), and group C (preserved with Collins II solution, n = 30). The effects of the storage solutions were assessed by measuring the sinusoidal lining cell mortality (SLCM), Krebs-Henseleit perfusate ketone body ratio (PKBR), the hepatic sugar release (SL), and the number of livers secreting bile during isolated perfusion. The results suggest that the HX solution be much superior to Collins II solution in preventing sinusoidal lining cell injury and maintaining normal hepatic functions.

Animals↗
PubMed1992

A correlation between arterial ketone body ratio and concentration of beta-hydroxybutyrate as an indicator of hepatic functional reserve.

We have investigated the correlation between the arterial blood ketone body ratio (AKBR) and beta-hydroxybutyric acid (HBAC) in the course of a 75 g glucose tolerance test. The correlation was revealed to be represented by an equation of Y = A + BX [X = log(HBAC), Y = log(AKBR)] with high significance. This expression existed in both normal individuals and patients with liver, biliary tract or pancreas disease. The postoperative course was unsatisfactory because of liver dysfunction in cases whose value B was more than -0.6 in bisegmentectomy and more than -0.45 in uni- or subsegmentectomy. The coefficient B in the equation was suggested to contribute to the evaluation of hepatic functional reserve.

3-Hydroxybutyric Acid↗
PubMed2006

Recovery of hepatic function determined by cytochrome P450-dependent drug metabolism lags after compensatory hepatic volume changes after portal vein ligation in rats.

BACKGROUND: Clinically, portal vein embolization has been proven to be useful as a preoperative treatment for major hepatic surgeries with impaired liver function. However, its effects on the metabolism and elimination of various drugs after portal vein embolization or ligation remain to be elucidated. MATERIALS AND METHODS: A portal vein branch that perfuses the central and left lobes of the liver of male Wistar rat was ligated, and changes in the weights of ligated and nonligated lobules as well as hepatic levels and activities of cytochrome P450 (CYP) isoforms, such as CYP3A2 and CYP2C11, were determined. To evaluate in vivo the effect of PVL on hepatic drug metabolism, the narcotic activity (sleep time) of midazolam, a specific substrate for CYP3A2, was measured. RESULTS: Although plasma levels of alanine aminotransferase and hepatic weight returned to basal levels at day 7 after the portal vein ligation, hepatic activities of CYP3A2 and CYP2C11 still remained low (53% and 54% of control levels, respectively), and returned to their initial levels after about day 14. The metabolism of midazolam was prolonged by approximately three times at day 7 after ligation and returned to basal levels at day 14. CONCLUSIONS: Because hepatic CYP-dependent drug metabolism by CYP isoforms recovered more slowly than the apparent recovery of hepatic volume and plasma alanine aminotransferase levels, the therapeutics of drugs metabolized by the CYP isoforms should be used carefully in patients who receive major hepatectomy with portal vein branch embolization.

Alanine Transaminase↗
PubMed2000

[Hepatic function after surgical repair of constrictive pericarditis].

We report the results of long-term follow up in 9 patients who underwent pericardiectomy for constrictive pericarditis. In order to test whether if congestive liver dysfunction due to the disease could be reversible or not after the surgical repair, the patients were evaluated by indocyanine green (ICG) clearance test. All the patients improved in NYHA classification after long-term periods following surgical repairs. The percentage of ICG retention at 15 minutes (ICG-R15) improved in most of the patients. However, two patients who had a long history from the onset before surgery became worse in ICG-R15. From the above reports, reversibility of hepatic function might be dependent on the duration of liver congestion before surgical repairs.

Adult↗
PubMed1997

Hepatic function in a family with a nonsense mutation (R154X) in the hepatocyte nuclear factor-4alpha/MODY1 gene.

Maturity-onset diabetes of the young (MODY) is a genetically heterogeneous monogenic disorder characterized by autosomal dominant inheritance, onset usually before 25 yr of age, and abnormal pancreatic beta-cell function. Mutations in the hepatocyte nuclear factor(HNF)-4alpha/MODY1, glucokinase/MODY2, and HNF-1alpha/MODY3 genes can cause this form of diabetes. In contrast to the glucokinase and HNF-1alpha genes, mutations in the HNF-4alpha gene are a relatively uncommon cause of MODY, and our understanding of the MODY1 form of diabetes is based on studies of only a single family, the R-W pedigree. Here we report the identification of a second family with MODY1 and the first in which there has been a detailed characterization of hepatic function. The affected members of this family, Dresden-11, have inherited a nonsense mutation, R154X, in the HNF-4alpha gene, and are predicted to have reduced levels of this transcription factor in the tissues in which it is expressed, including pancreatic islets, liver, kidney, and intestine. Subjects with the R154X mutation exhibited a diminished insulin secretory response to oral glucose. HNF-4alpha plays a central role in tissue-specific regulation of gene expression in the liver, including the control of synthesis of proteins involved in cholesterol and lipoprotein metabolism and the coagulation cascade. Subjects with the R154X mutation, however, showed no abnormalities in lipid metabolism or coagulation except for a paradoxical 3.3-fold increase in serum lipoprotein(a) levels, nor was there any evidence of renal dysfunction in these subjects. The results suggest that MODY1 is primarily a disorder of beta-cell function.

Adult↗
PubMed1978

Role of portal venous blood supply from the pancreas in maintaining hepatic functional reserve. Appraisal of Warren's shunt operation.

Mitochondrial phosphorylative activity was measured in the livers of various shunted or pancreatectomized dogs. In simple portal vein branch-ligated dogs, the mitochondrial phosphorylative activity in the nonligated lobe, which was supplied with excess portal blood, increased to approximately 150% of control values. In splenocaval-shunted or totally pancreatectomized dogs, the mitochondrial phosphorylative activity did not increase even in the nonligated lobe. However, the mitochondrial phosphorylative activity in the nonligated lobe increased to 120% of control in 80%-pancreatectomized and 150% in 50%-pancreatectomized dogs. In distal splenorenal-shunted (Warren-shunted) dogs, the mitochondrial phosphorylative activity increased to 150% of control values. Thus, the Warren's shunt operation is considered to be the more reasonable procedure for treatment of liver cirrhosis with esophageal varices, from the point of view of hepatic functional reserve based on the energetic metabolism of the liver.

Animals↗
PubMed1987

Hepatorenal syndrome. Studies of the effect of vascular volume and intraperitoneal pressure on renal and hepatic function.

Eleven patients with well-documented hepatorenal syndrome were studied by measurement of blood volume, glomerular filtration rate, renal plasma flow, plasma aldosterone concentration, renin substrate concentration, and plasma renin activity. They were then given 750 ml of stored plasma, 750 ml of fresh frozen plasma, and then an infusion of angiotensin II, in random order on successive days. Infusion of fresh frozen plasma improved function more than did stored plasma and in addition returned a very low filtration fraction toward normal. Angiotensin II infusion increased filtration fraction, but decreased glomerular filtration rate, renal plasma flow, and urine flow sharply. Patients were then given a daily infusion of 1,000 ml of fresh frozen plasma for seven to 18 days to expand the blood volume to supranormal levels as assayed by serial measurement of blood volume. Plasma aldosterone levels decreased to a normal range, glomerular filtration rate and renal plasma flow both increased, and urinary excretion of sodium and potassium both returned toward normal. The effect of intraperitoneal pressure was then studied by measuring glomerular filtration rate, renal plasma flow, pressure in the vena cava, hepatic vein free flow, and hepatic vein wedged pressure before, during, and after paracentesis to reduce the intraperitoneal pressure from 30 to 40 cm H2O to 12 to 17 cm H2O. Venous pressures moved parallel to ascitic fluid pressures, and glomerular filtration rate, renal plasma flow, and urine flow all improved sharply; then, as ascitic fluid continued to form, reducing vascular volume, urine flow, glomerular filtration rate, and renal plasma flow all decreased slowly. Six patients then underwent placement of a LeVeen shunt. Improvement in glomerular filtration rate and renal plasma flow and clinical condition was dramatic. During postoperative observation of up to two years, progressive improvement in hepatic function has occurred.

Angiotensin II↗
PubMed1999

Selective inhibition of inducible nitric oxide synthase maintains haemodynamic stability without untoward consequences for hepatic function or morphology.

OBJECTIVE: To examine the effects of the inducible nitric oxide synthase inhibitor aminoethyl-isothiourea (AE-ITU) on haemodynamic measurements, and correlate these with hepatic morphology and function in a porcine model of endotoxaemia. DESIGN: Experimental study. ANIMALS: 15 juvenile pigs. INTERVENTIONS: Flow probes were placed around the hepatic artery and portal vein. Catheters were introduced into the portal and hepatic veins, pulmonary artery, and aorta. Infusion of AE-ITU was started one hour before that of endotoxin (study group n = 6); thereafter both substances were infused simultaneously until the end of the study (6 hours). The controls (n = 9) had endotoxin alone. MAIN OUTCOME MEASURES: Hepatic morphology assessed by light and electron microscopy; and hepatic integrity and function by transaminase activities and oxygen consumption. Systemic, pulmonary, and hepatic blood flow and pressure. RESULTS: AE-ITU maintained systemic blood pressure (p < 0.05 compared with controls) without causing pulmonary hypertension. Neither hepatic morphology nor function were adversely influenced. CONCLUSION: In endotoxaemia AE-ITU has a favourable haemodynamic profile which is achieved without impairment of hepatic function or morphology.

Animals↗
PubMedDate not supplied

Transarterial chemoembolization (TACE) for unresectable hepatocellular carcinoma in cirrhotics: functional hepatic reserve and survival.

BACKGROUND/AIMS: Transarterial chemoembolization is widely used for palliative treatment of hepatocellular carcinoma, but patient's characteristics associated with maximal benefit are still undefined. METHODOLOGY: In 81 cirrhotic patients with unresectable hepatocellular carcinoma, who underwent transarterial chemoembolization, variables correlated with survival were studied. In 46/81, the antipyrine metabolism test has been performed before and 72 hours after first transarterial chemoembolization. RESULTS: Mean overall survival of whole population was 22 months. One-, two-, and three-year survival rates were respectively 85%, 38.6%, and 18.1%. Better survival was observed in those patients who received more than one treatment (p = 0.016), while no relationship was found with treatment response, drug used, or number of lobes involved. Univariate analysis of the subgroup with antipyrine pharmacokinetic data revealed a significant relation between survival and baseline albumin (p = 0.039), total cholesterol (p = 0.036), AST (p = 0.017), log of total bilirubin (p = 0.017), and Child-Pugh class (p = 0.029), but not with parameters of antipyrine metabolism. Antipyrine metabolism was not significantly modified by transarterial chemoembolization in the subgroup tested before and after the first treatment. Using Cox regression analysis and selecting AST and log of total bilirubin, a prognostic index was defined: prognostic index 0.006 (AST-83.044) + 0.638 [log of total bilirubin-0.1175]. One-, two-, and three-year survival rates were respectively 92%, 59.2%, and 29.6% for the patient group with prognostic index < 0, and 76%, 14.3%, and 4.8% for the group with prognostic index > 0 (p < 0.01). CONCLUSIONS: Transarterial chemoembolization is a safe procedure and appears beneficial for those patients with a good functional hepatic reserve. The antipyrine metabolism test does not provide any additional prognostic information.

Adult↗
PubMed2000

Preoperative portal vein embolization improves prognosis after right hepatectomy for hepatocellular carcinoma in patients with impaired hepatic function.

BACKGROUND: Percutaneous transhepatic portal vein embolization (PTPE) increases the safety of subsequent major hepatectomy. The aim of this study was to determine the effect of PTPE on long-term prognosis after hepatectomy in patients with hepatocellular carcinoma (HCC). METHODS: Seventy-one patients with HCC underwent right hepatectomy between 1984 and 1998. Preoperative PTPE was performed in 33 patients (group 1) and was not used in 38 patients (group 2). Outcome after operation was compared between the groups. The patients were further divided according to the median tumour diameter (cut-off 6 cm) and indocyanine green retention rate at 15 min (ICGR15) (cut-off 13 per cent). RESULTS: The cumulative survival rate was significantly higher in group 1 than in group 2 in patients with an ICGR15 of at least 13 per cent. Tumour-free survival rates were similar in both groups. Of patients with tumour recurrence after right hepatectomy, those in group 1 were more frequently subjected to further treatment. CONCLUSION: Preoperative PTPE improves the prognosis after right hepatectomy for HCC in patients with impaired hepatic function, although it does not prevent tumour recurrence.

Adult↗
PubMed1988

Determinants of hepatic function in liver cirrhosis in the rat. Multivariate analysis.

We investigated the determinants of hepatic clearance functions in a rat model of liver cirrhosis induced by phenobarbital/CCl4. Aminopyrine N-demethylation (ABT), galactose elimination (GBT), and serum bile acids (SBA) were determined in vivo. The livers were then characterized hemodynamically: intrahepatic shunting (IHS) was determined by microspheres and sinusoidal capillarization by measuring the extravascular albumin space (EVA) by a multiple indicator dilution technique. The intrinsic clearance was determined by assaying the activity of the rate-limiting enzymes in vitro. Hepatocellular volume (HCV) was measured by morphometry. ABT and SBA, but not GBT, differentiated cirrhotic from normal liver. IHS ranged from normal to 10%; all cirrhotic livers showed evidence of sinusoidal capillarization (reduced EVA). The cirrhotic livers showed a bimodal distribution of HCV, HCV being decreased in 50% of the cirrhotic livers. Multivariate analysis showed EVA and portal flow to be the main determinants of microsomal (ABT) and cytosolic (GBT) clearance function; SBA, by contrast, were determined solely by IHS. We conclude that sinusoidal capillarization is the main determinant of hepatic clearance, while serum bile acids reflect intrahepatic shunting. These findings emphasize the importance of alterations of hepatic nutritional flow to explain reduced clearance function in cirrhosis of the liver.

Animals↗
PubMed1986

Effects of in vivo treatment with a new fluorinated macrolide (P-0501A) and other erythromycins on drug clearance and hepatic functions in perfused rat liver.

The hepatic clearance and the effects of a new fluorinated macrolide (P-0501A) on the functions of the isolated, perfused rat liver were compared with two known erythromycins--the base and the estolate--after 7 days of treatment (1.36 mmol/kg po daily). The in vitro metabolism of the antibiotics was induced to different extent but only the base and P-0501A were cleared from the perfusate and the liver faster than in untreated animals. In untreated rats the therapeutically active form of P-0501A was excreted in the bile more than the base and the estolate; after pretreatment, biliary excretion of all erythromycins was nearly double. The content of inactive, complexed cytochrome P-450 was increased only by the base and estolate, with various effects on microsomal activities (some induced, e.g. aminopyrine demethylation, other reduced, e.g. pentobarbital clearance). The clearance and biliary excretion of sulphobromophthalein was not affected by treatment with P-0501A or the base, but was significantly reduced by estolate.

Animals↗
PubMedDate not supplied

Evaluation of hepatic functions and biliary dynamics in patients with liver cirrhosis by quantitative scintigraphy.

BACKGROUND/AIMS: Aim of the study is to determine the changes in hepatocyte and gallbladder motor functions, and biliary dynamics in patients with liver cirrhosis. METHODOLOGY: The study group consisted of 17 patients with liver cirrhosis (12 males, 5 females) who were diagnosed by clinical, laboratory and histopathologic findings. Control group consisted of 20 healthy persons (14 males, 6 females). Quantitative hepatobiliary scintigraphy was performed by using Tc99m-Mebrofenin i.v. and dynamic images were obtained and evaluated quantitatively by computer. Maximum excretion time of radiodiagnostic agent by liver (Tmax) and half excretion time of radio-diagnostic agent from liver (T 1/2), gallbladder filling time, gallbladder ejection fraction and the transit time of bile to duodenum were determined. RESULTS: Mean values of Tmax was 25.76 vs. 12.40 min, T 1/2 was 37.55 vs. 23.15 min, gallbladder filling time was 53.35 vs. 30.57 min, and transit time of bile to duodenum was 39.88 vs. 25.00 min in the patients and control group, respectively. These values increased significantly in the patient group (p < 0.05) compared to controls. Mean gallbladder ejection fraction was 37.55% in the patient group and 41.84% in the control group without any statistical significance (p > 0.05). The incidence of gallbladder stone was 29.41% in the cirrhosis group and 5% in the control group (p < 0.05). CONCLUSIONS: The quantitative hepatobiliary scintigraphy is a simple and reliable method in evaluation of hepatic functions and biliary dynamics in cirrhotic patients. Although the incidence of gallbladder stone is significantly increased in cirrhotic patients, it seems that a stone in the gallbladder does not affect the gallbladder motor functions.

Adult↗
PubMed2007

Evaluation of hepatic function with (99m)Tc-galactosylated serum albumin scintigraphy in patients with malaria: comparison with (99m)Tc-colloid scintigraphy and liver ultrasonography.

OBJECTIVE: Malarial parasites injected by the mosquito rapidly target hepatocytes, and hepatomegaly is commonly observed during the progress of the disease in malaria patients. To evaluate the degree of hepatic damage and functional status of hepatocytes in malaria patients, we performed liver scintigraphy using (99m)Tc-galactosylated serum albumin (GSA) prospectively and the findings were compared with those of (99m)Tc-colloid scintigraphy, ultrasonography and clinical results in the same subject. METHODS: Eight malaria patients (all male, mean age 22 years) confirmed to be infected with Plasmodium vivax underwent (99m)Tc-GSA liver scintigraphy, followed by liver ultrasonography and (99m)Tc-colloid scintigraphy using phytate within 3 days. For hepatocyte scintigraphy, anterior images of cardiac blood-pool and liver were continuously acquired for 30 min after injection of 185 MBq (99m)Tc-GSA (3 mg). In addition to visual interpretation of the images, quantitative measurement of hepatic function was performed with several functional parameters, such as hepatic uptake index (LHL15), blood clearance index (HH15) and modified receptor index (LHL/HH) calculated from the radioactivity of the liver and heart. (99m)Tc-colloid images were assessed and graded visually. Severity of hepatic dysfunction or reticuloendothelial system activation was classified as normal, mild, moderate and severe on GSA or colloid images. RESULTS: Hepatomegaly was observed in five and splenomegaly in seven of the eight patients. Serum levels of transaminase and alkaline phosphatase were mildly elevated in two. Visual assessment of GSA scintigraphy revealed normal findings in all subjects, except for mild increases in size. The mean values of LHL15, HH15 and LHL/HH were 0.928+/-0.014, 0.537+/-0.031 and 1.732+/-0.106, respectively. They were graded as normal in five, and near-normal to mild dysfunction in three subjects. In contrast, (99m)Tc-colloid scintigraphy revealed abnormal findings in all of the subjects, and graded as moderate in three or severe reticuloendothelial system activation in five subjects. Liver ultrasonographic findings were normal for all subjects except mild hepatomegaly. CONCLUSIONS: Malaria-induced injury of the hepatocyte is likely to be minimal whereas hepatomegaly is commonly seen during disease process. This suggests that hepatic damage in malarial infection is mainly due to involvement of the reticuloendothelial system. (99m)Tc-GSA scintigraphy can be used in differentiating hepatocellular damage from reticuloendothelial system involvement in patients with infectious disease showing hepatomegaly.

Adult↗
PubMed2000

Biliary copper excretion capacity in intact animals: correlation between ATP7B function, hepatic mass, and biliary copper excretion.

Copper toxicosis can occur in the absence of biliary copper excretion. To demonstrate whether biliary copper excretion capacity is correlated with hepatic mass and ATP7B function, we undertook studies in intact animals. Copper-histidine was injected intrasplenically after baseline bile collection, followed by measurement of copper excretion in Long-Evans Cinnamon (LEC) rats lacking atp7b function and in normal, syngeneic Long-Evans Agouti (LEA) rats. The basal biliary copper excretion was very low in LEC rats compared with LEA rats, 8+/-4 and 37+/-18 ng copper/min, respectively; p<0.05. After addition of copper, copper excretion increased significantly (by two- to five-fold) in LEA rats during the 30 minute study period, whereas LEC rats showed only a slight and transient increase in copper excretion. After one-third and two-thirds partial hepatectomy immediately before copper loading, copper excretion decreased progressively. The studies indicate that biliary copper excretion depends on hepatocyte mass and ATP7B gene function. Analysis of copper excretion with our non-radioactive method will facilitate testing of novel therapies and pathophysiological mechanisms in copper toxicity.

Adenosine Triphosphatases↗
PubMedDate not supplied

[Hepatic function and significance of the increase in serum concentrations of IgA in alcoholic cirrhosis].

Elevated serum gammaglobulin concentrations are frequently observed in patients with liver cirrhosis. Predominant elevation of the IgA is generally considered as suggestive of an alcoholic aetiology. The aim of this study was to define the factors that determine the serum concentration of IgA in alcoholic cirrhosis. Twenty-seven patients with alcoholic cirrhosis were studied. Serum concentrations of IgG, IgA and IgM were measured by immunonephelometry. Hepatocellular function was assessed by the Child-Turcotte score, the prothrombin time and the intrinsic clearance of indocyanine green. The importance of intra-hepatic shunts was estimated according to the intact hepatocyte theory, and the degree of hepatic necrosis by serum levels of transaminases. It was noted that: 1) the IgA concentration correlated significantly with the Child-Turcotte score and with the decrease of the prothrombin time, intrinsic clearance and the functional fraction of hepatic blood flow; 2) there was no such correlation between the serum concentration of IgA and the total hepatic blood flow or transaminase levels; 3) there was no correlation between serum concentration of IgG or IgM and the factors studied. These results suggest that in alcoholic cirrhosis, increase in serum IgA, reflects the degree of impairment of hepatic function and intrahepatic shunting.

Humans↗