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PubMed2005

The endothelin/nitric oxide balance determines small-for-size liver injury after reduced-size rat liver transplantation.

Small-for-size (SFS) liver graft injury is probably related to microcirculatory disorders due to an imbalance of vasoconstricting, e.g. endothelin (ET)-1, and vasorelaxing mediators, e.g. nitric oxide (NO). We studied the role of ET-1/NO balance and the effect of an endothelin A receptor (ETAR) antagonist on SFS injury after liver resection and reduced-size liver transplantation (RSLT). One hundred twenty-six Lewis rats were divided into five groups: (I) 70% liver resection, (II) 70% liver resection treated with the ETAR antagonist LU 135252 (1 mg/kg b.w. i.v.), (III) RSLT (30% residual liver volume), (IV) RSLT treated with the ETAR antagonist, (V) sham operation. Liver microcirculation was measured by intravital microscopy. ET-1, ETAR, endothelial NO-synthase (eNOS), activation of Kupffer cells (KCs) and parenchymal injury were studied by immunohistology. Survival and liver function were followed up to 14 days. RSLT led to increased ET-1, ETAR and decreased eNOS protein expression, accompanied by activation of KC, reduced perfusion rate, vasoconstriction and elevated sinusoidal blood flow, as well as hepatocellular damage, impaired liver function and impaired survival. ETAR blockade (groups II + IV) improved the ET-1/NO balance, attenuated microcirculatory disorders and improved hepatocellular apoptosis and liver function. Microcirculatory disorders related to an ET-1/NO imbalance may contribute to SFS liver injury. Maintenance of ET-1/NO balance by blocking ETAR reduces SFS injury by protecting liver microcirculation, thus reducing hepatocellular damage.

Animals↗
PubMed1992

[Liver biopsy in suspected alcoholic liver damage].

Alcohol can induce a wide spectrum of histological changes in the liver. Three morphologic patterns of alcoholic liver injury are now generally accepted, i.e. fatty change, alcoholic hepatitis and alcoholic cirrhosis, but a broad array of lesions has been added to this list in recent years. These damage patterns differ considerably in their significance as to indication and diagnostic power of liver biopsies. Liver biopsy is recommended in patients with clinically suspected alcoholic liver disease for diagnostic and prognostic reasons. Moreover, clinicians want to exclude nonalcoholic liver diseases that might otherwise be missed. Alcoholic hepatitis, which is associated with increased morbidity and mortality, has the highest degree of diagnostic specificity in biopsies, because its features are well-defined and are mimicked by a rather small group of other causes. When associated with perivenular and pericellular fibrosis, it may provide prognostic parameters. In contrast, fatty liver, which may be induced by alcohol as well as other etiologies, usually does not need liver biopsy, with some exceptions. It may lead to cholestasis severe enough to mimic obstructive jaundice, or may result in abnormal imaging studies suggesting metastases. Verification of histological findings may be important when these circumstances arise. Cirrhosis is easily verified in biopsies of appropriate quality; however, advanced cirrhosis is a morphologically nonspecific alteration, because cirrhotic tissue patterns converge irrespective of their cause. Liver biopsy may help to identify nonalcoholic liver disease in patients suspected of harboring alcoholic liver disease. In fact, up to 20% of biopsies may show other, potentially treatable disorders, thus extending the indication for liver biopsy in situations of complex clinical and laboratory patterns.

Biopsy, Needle↗
PubMed2005

Liver regeneration after split liver transplantation.

BACKGROUND: The number of split liver transplantations (SLT) has increased in the last 5 years. Regeneration after the loss of hepatic tissue is a fundamental response to liver injury. Because partial-liver grafts may not be an optimal size for recipients,the purpose of this study was to investigate the regeneration of graft liver after SLT. METHODS: Four recipients have undergone SLT at our hospital since 2002. The graft liver volume (GLV) in the postoperative day (POD) was measured by computed tomography (CT) and the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TB), prealbumin (PA) and albumin (ALB) were monitored. The GLV at different postoperative times was compared to the recipient's standard liver volume (SLV) and the liver volume regeneration ratio (LVRR) was calculated. In order to compare SLV in recipient 2, we measured the total liver volume including the graft and the residual native liver as the GLV. RESULTS: The GLV/SLV at POD120 and POD360 of recipient 1 was measured 114% (1159.32 cm(3)/1016.95 cm(3)), 97% (986.44 cm(3)/1016.95 cm(3)) with the LVRR being -11.0%, -24.3%, respectively. For recipient 2, it was measured 96% (927.32 cm(3)/965.96 cm(3)) and 100% (968.98 cm(3)/965.96 cm(3)), with the LVRR being 24.4%, 30.0%, respectively. The initial graft volume of segment II, III was 265.36 cm(3) and increased to 335.24 cm(3) and 360.56 cm(3) at POD120 and POD360, respectively, with the LVRR being 26.3% and 35.9%, respectively. The GLV/SLV at POD60 of recipient 3 was 86% (893.04 cm(3)/1038.42 cm(3)) and the LVRR was 12.0%. For recipient 4, it was 90% (567.48 cm(3)/630.54 cm(3)) whereas the LVRR was 20.0%. The serum levels of ALT, AST and TB in all recipients declined gradually and returned to normal while the serum levels of PA and ALB increased to normal. The serum levels of ALT and AST peaked within 3 days after SLT. The neurological symptoms of Wilson's disease in recipient 2 were improved markedly. The levels of serum copper and copper-protein decreased to 30 mg/L, 120 mg/L at POD120 and the Kayser-Fleischer rings began to obliterate. CONCLUSIONS: The size of the transplanted liver after SLT tends to converge to the standard liver volume with time and it is adequate clinically for SLT to meet the need of the body's metabolic demands. The functional recovery of the graft liver occurs earlier than the morphological restoration.

Adult↗
PubMed2001

A comparison of aroclor 1254-induced and uninduced rat liver microsomes to human liver microsomes in phenytoin O-deethylation, coumarin 7-hydroxylation, tolbutamide 4-hydroxylation, S-mephenytoin 4'-hydroxylation, chloroxazone 6-hydroxylation and testosterone 6beta-hydroxylation.

Aroclor 1254-induced rat liver homogenate supernatant (liver S-9) is routinely used as an exogenous metabolic activation system for the evaluation of mutagenicity of xenobiotics. The purpose of this study is to evaluate whether results obtained with Aroclor 1254-induced liver microsomes would be relevant to human. Aroclor 1254-induced and uninduced rat liver microsomes were compared to human liver microsomes in the metabolism of substrates which are known to be selectively metabolized by the major human cytochrome P450 (CYP) isoforms. The activities studied and the major CYP isoforms involved were as follows: phenacetin O-deethylation (CYP1A2); coumarin 7-hydroxylation, (CYP2A6); tolbutamide 4-hydroxylation (CYP2C9), S-mephenytoin 4'-hydroxylation (CYP2C19); dextromethorphan O-demethylation (CYP2D6); chloroxazone 6-hydroxylation (CYP2E1); and testosterone 6beta-hydroxylation (CYP3A4). We found that both induced and uninduced rat liver microsomes were active in all the pathways studied with the exception of coumarin 7-hydroxylation. Coumarin 7-hydroxylation was observed with human liver microsomes but not the rat liver microsomes. Aroclor-1254 was found to induce all activities measured, with the exception of coumarin 7-hydroxylation. Dextromethorphan O-deethylation activity was higher in the rat liver microsomes than the human liver microsomes. Testosterone 6beta-hydroxylation activity was found to be similar between the human liver microsomes and the induced rat liver microsomes. Our results suggest that experimental data obtained with Aroclor 1254-induced rat liver microsomes may not always be relevant to human.

Animals↗
PubMed2002

Morphometric analysis of liver macrophages in patients with colorectal liver metastasis.

Kupffer cells, residential liver macrophages, have binding sites for carcinoembryonic antigen (CEA), but their role in metastatic liver tumor progression has not been well addressed clinically. Liver macrophages were analyzed morphometrically and their relationship with CEA and tumor microvessel density (MVD) was examined in 71 patients who underwent macroscopic curative hepatectomy for metastatic liver tumors from colorectal cancer. In paraffin-embedded sections, MVD was evaluated by CD34-positive cell counts, liver macrophages visualized using anti PG-M1 (CD68) antibody were analyzed, and membrane-bound CEA was assessed by immunoreactivity of tumor cells for CEA. The area of liver macrophages in peritumoral regions (43.0 +/- 11.6 microm2) was significantly larger than that in non-tumor regions (25.2 +/- 24.2 microm2) (P < 0.0001). The liver macrophage density in peritumoral regions was 154 +/- 49 per field, and was significantly higher than in non-tumor regions (74 +/- 24 per field) (P < 0.001). The density and the area of liver macrophages had no correlation with serum CEA levels and the degree of tumor CEA expression. A weak positive correlation was observed between MVD and liver macrophage density (P = 0.0104, Spearman rank correlation coefficient = 0.31). Cox multivariate regression analysis showed that MVD greater than 50 (P = 0.0233, hazard ratio = 2.463), and the area of liver macrophages larger than 40.9 microm2 (P = 0.0485, hazard ratio = 2.127), were significant independent prognostic factors. The present morphometric analysis suggests that the liver macrophages are accumulated and activated in peritumoral regions in patients with colorectal liver metastasis and this accumulation and activation of liver macrophages, with which soluble or membrane-bound CEA might not be associated, are related with patients' poor prognosis.

Adult↗
PubMed2004

Breast adenocarcinoma liver metastases, in contrast to colorectal cancer liver metastases, display a non-angiogenic growth pattern that preserves the stroma and lacks hypoxia.

Although angiogenesis is a prerequisite for the growth of most human solid tumours, alternative mechanisms of vascularisation can be adopted. We have previously described a non-angiogenic growth pattern in liver metastases of colorectal adenocarcinomas (CRC) in which tumour cells replace hepatocytes at the tumour-liver interface, preserving the liver architecture and co-opting the sinusoidal blood vessels. The aim of this study was to determine whether this replacement pattern occurs during liver metastasis of breast adenocarcinomas (BC) and whether the lack of an angiogenic switch in such metastases is due to the absence of hypoxia and subsequent vascular fibrinogen leakage. The growth pattern of 45 BC liver metastases and 28 CRC liver metastases (73 consecutive patients) was assessed on haematoxylin- and eosin-stained tissue sections. The majority of the BC liver metastases had a replacement growth pattern (96%), in contrast to only 32% of the CRC metastases (P<0.0001). The median carbonic anhydrase 9 (CA9) expression (M75 antibody), as a marker of hypoxia, (intensity x % of stained tumour cells) was 0 in the BC metastases and 53 in the CRC metastases (P<0.0001). There was CA9 expression at the tumour-liver interface in only 16% of the BC liver metastases vs 54% of the CRC metastases (P=0.002). There was fibrin (T2G1 antibody) at the tumour-liver interface in only 21% of the BC metastases vs 56% of the CRC metastases (P=0.04). The median macrophage count (Chalkley morphometry; KP-1 anti-CD68 antibody) at the interface was 4.3 and 7.5, respectively (P<0.0001). Carbonic anhydrase 9 score and macrophage count were positively correlated (r=0.42; P=0.002) in all metastases. Glandular differentiation was less in the BC liver metastases: 80% had less than 10% gland formation vs only 7% of the CRC metastases (P<0.0001). The liver is a densely vascularised organ and can host metastases that exploit this environment by replacing the hepatocytes and co-opting the vasculature. Our findings confirm that a non-angiogenic pattern of liver metastasis indeed occurs in BC, that this pattern of replacement growth is even more prevalent than in CRC, and that the process induces neither hypoxia nor vascular leakage.

Adenocarcinoma↗
PubMed1977

Relation between liver amino acid-catabolizing enzymes and free amino acids of liver and plasma in adult cockerels fed diets containing graded levels of protein.

Activities of liver amino acid-catabolizing enzymes and liver and plasma free amino acid concentrations in adult cockerels fed diets containing 3% to 21% casein were determined 2 hours after a meal. Liver tryptophan pyrrolase activity and liver tryptophan increased with an increase in dietary casein level, but plasma tryptophan decreased with the increase dietary casein level. As the dietary casein level increased, liver lysine-ketoglutarate reductase activity decreased, but liver and plasma lysine increased proportionally, and the rate of increase was larger in the plasma than in the liver. Liver phenylalanine hydroxylase activity increased with the increase in dietary casein level from 3% to 12%, and thereafter remained unchanged. Reflecting the change of this enzyme, phenylalanine increased in the liver and decreased in the plasma with the increase in dietary casein level from 3% to 12%, and thereafter the rate of increase in liver phenylalanine became small and plasms phenylalanine increased. Liver tyrosine was not influenced by the dietary casein level, whereas plasma tyrosine increased sharply from 3% to 12%, and thereafter the rate of increase decreased. Thus, the difference between liver and plasma free amino acid responses might be due to the changes in the activities of liver amino acid-catabolizing enzymes.

Amino Acids↗
PubMed2005

Preharvest feed withdrawal affects liver lipid and liver color in broiler chickens.

An Iowa grain processor attempted to alter the typical 12-h preharvest fasting period by giving broilers cornstarch derivative pellets and water for 6 h followed by 6 h of no feed or water. After slaughter, plant food inspectors determined that livers from the treatment group were lighter in color than normal, and consequently a significant number of chicken carcasses were condemned for human consumption. The study reported herein was conducted to determine the effects of fasting or 3 feeding programs applied before processing on liver color, liver lipids, and liver glycogen of broilers. Dietary treatment groups consisted of 1) full-fed control broilers, 2) fasted broilers, 3) maltodextrin-fed broilers, and 4) and chickens given maltodextrin and methionine. Full-fed chickens had lighter liver coloration than chickens without access to feed for 6 or 12 h immediately prior to slaughter (P < 0.05). Lightness values for livers from full-fed control chickens (L* = 54.41) were 38% higher than those for livers from fasted broilers (L* = 39.30). Lighter liver colors in full-fed broilers were associated with higher hepatic lipid concentrations (6.38%) and more total liver lipid (4.96 g/liver) than was found in broilers without feed for 12 h. In contrast, darker livers from fasted broilers had lower levels of lipid (4.42%) and less total lipid (2.68 g/liver) than the full-fed broilers. Feeding maltodextrin pellets resulted in liver colors that were lighter (P < 0.05) than those found in fasted chickens but darker (P < 0.05) than livers from full-fed broilers. If carbohydrate supplements are fed prior to slaughter, producers should notify processing plant officials so that inspectors do not interpret light livers as an abnormal physiological state.

Animals↗
PubMed2002

Laparoscopic liver resection for malignant liver tumors: preliminary results of a multicenter European study.

OBJECTIVE: To assess the feasibility, safety, and outcome of laparoscopic liver resection for malignant liver tumors. SUMMARY BACKGROUND DATA: The precise role of laparoscopy in resection of liver malignancies (hepatocellular carcinoma [HCC] and liver metastases) remains controversial despite an increasing number of publications reporting laparoscopic resection of benign liver tumors. METHODS: A retrospective study was performed in 11 surgical centers in Europe regarding their experience with laparoscopic resection of liver malignancies. Detailed questionnaires were sent to each surgeon focusing on patient characteristics, clinical data, type and characteristics of the tumor, technical details of the operation, and early and late clinical outcome. All patients had radiologic investigations at follow-up to exclude disease recurrence. RESULTS: From February 1994 to December 2000, 37 patients with malignant liver tumors were included in this study. Ten patients had HCC, including 9 with cirrhotic liver, and 27 patients had liver metastases. The mean tumor size was 3.3 cm, and 89% of the tumors were located in the left lobe or in the anterior segments of the right liver. Liver procedures included 12 wedge resections, 9 segmentectomies, 14 bisegmentectomies (including 13 left lateral segmentectomies), and 2 major hepatectomies. The transfusion rate, the use of pedicular clamping, the conversion rate (13.5% in the whole series), and the complication rate were significantly greater in patients with HCC. There were no deaths. Postoperative complications occurred in eight patients (22%). The surgical margin was less than 1 cm in 30% of the patients. During a mean follow-up of 14 months, the 2-year disease-free survival was 44% for patients with HCC and 53% for patients having hepatic metastases from colorectal cancer. No port-site metastases were observed during follow-up. CONCLUSIONS: In patients with small malignant tumors, located in the left lateral segments or in the anterior segments of the right liver, laparoscopic resection is feasible and safe. The complication rate is low, except in patients with HCC on cirrhotic liver. By using laparoscopic ultrasound, a 1-cm free surgical margin should be routinely obtained. The late outcome needs to be evaluated in expert centers.

Adult↗
PubMed2003

Analysis of the expression of aquaporin-1 and aquaporin-9 in pig liver tissue: comparison with rat liver tissue.

Aquaporins (AQPs) are cellular proteins involved with the movement of water across cell membranes and are fundamentally important to the fluid transport in the bile ducts and ductules of the liver. An immunohistochemical analysis of AQP-1 and AQP-9 was undertaken to describe their expression in fetal and adult pig liver, while immunoreagents specific to some other AQPs were screened for their efficacy on pig liver tissues. Anti-AQP-1 antibody reacted with the bile duct of the portal space and the bile ductules at the periphery of the liver lobules. Histological identification of bile ductules was confirmed by positive reactivity with anti-cytokeratin-7 and antilaminin immunostaining. Anti-AQP-1 signals were also pronounced in the endothelium of the portal space blood vessels and peripheral distributing venules. Antibody to AQP-9 reacted strongly with small ductules peripheral to the liver lobules, but only weakly with the bile ducts of the portal space. Anti-AQP-adipose antibody bound to the smooth muscle cells of the arteries in the portal space and sporadically with certain binucleated cells in the liver lobule. Antibodies to AQP-3, AQP-4, AQP-7, and AQP-8 were nonreactive with any of the tissues of the adult pig liver. For comparative purposes, immunohistochemical analysis of rat liver tissue was done with the anti-AQP-1 and AQP-9 antibodies. Anti-AQP-1 reacted weakly with the rat liver's bile ducts, but robustly with the endothelium of the liver's veins and arteries. It also reacted strongly with the central vein of the rat liver lobules, and, because the staining was continuous with hepatic sinusoids, it appeared that the reactivity was specific to the endothelial cells. Anti-AQP-9 antibodies reacted with rat hepatocytes and was not associated with the canaliculi, as judged by concurrent phalloidin staining of actin. The results indicate that specific AQPs are expressed in the tissues of the pig liver and that AQP-9 expression is distinct from its expression in the rat liver.

Animals↗
PubMed1994

Reduction of insulin-like growth factor-I (IGF-I) in protein-restricted rats is associated with differential regulation of IGF-binding protein messenger ribonucleic acids in liver and kidney, and peptides in liver and serum.

To investigate the influence of the insulin-like growth factor binding-proteins (IGFBPs) on the nutritional regulation of IGF-I's actions, we compared the gene expression of IGF-I and the six IGFBPs in liver and kidney of protein-restricted (P5) and normally fed (P15) young rats. Using poly(A)+ Northern blot analysis, we observed a decrease in IGF-I messenger RNA (mRNA) at steady state in liver (-50%) and kidney (-60%). The increases in IGFBP-1 mRNA were parallel in these two tissues (liver, 5.7-fold; kidney, 4-fold). In contrast, the expression of the other IGFBP genes exhibited organ-specific regulation during protein restriction; although IGFBP-2 mRNA increased in liver in the P5 group (3-fold), it decreased slightly in kidney (-15%). IGFBP-3 mRNA declined by 30% in liver and was unchanged in kidney. IGFBP-4 mRNA increased by 50-88% in liver and was not modified in kidney. IGFBP-5 mRNA was not detected in liver and was identical in kidney of P15 and P5 rats. IGFBP-6 mRNA was not changed in either liver or kidney during protein restriction. To determine whether the changes in IGFBP mRNAs induced by protein restriction were associated with changes in the respective peptides, IGFBPs in supernatants of liver homogenates and in serum of the same rats were measured by ligand blot analyses. IGFBP-1 and IGFBP-2 Western immunoblot analyses were also performed in serum. By ligand blot, a 45,000 mol wt (M(r)) band (IGFBP-3) decreased in liver and serum of P5 rats, paralleling the changes in liver IGFBP-3 mRNA. A 30,000 M(r) band, consistent with IGFBP-1 and/or IGFBP-2, increased in liver. By immunoblot in serum, IGFBP-1 was only detectable in P5 rats, whereas IGFBP-2 decreased in the P5 group. By ligand blot, a 24,000 M(r) band (IGFBP-4) declined slightly in serum (not detected in liver). Our study shows that protein restriction regulates the expression of four of six IGFBPs in rats, and this regulation is organ specific. The nutritional regulation of IGFBP peptides in biological fluids, in particular serum, seems to involve additional mechanisms.

Animal Nutritional Physiological Phenomena↗
PubMedDate not supplied

Liver glutathione level influences myocardial reperfusion injury following liver ischemia-reperfusion.

BACKGROUND: N-acetyl-L-cysteine (NAC) both replenishes reduced glutathione (GSH) and mitigates reperfusion injury. We hypothesized that liver content of GSH could affect remote myocardial reperfusion injury following liver ischemia-reperfusion. MATERIAL AND METHODS: Following stabilization (30 min), isolated rat livers (6/group) were perfused with Krebs-Henseleit solution (two control groups) or made globally ischemic (two ischemia groups) for 120 min. Paired livers + paced hearts (Langendorff preparation) were then reperfused for 15 min after which the hearts were recirculated alone for 50 min. NAC was added to Krebs (2 mM) that perfused livers during stabilization and reperfusion phases in one control and one ischemia group. RESULTS: GSH levels in the two control liver groups were identical (30.1 +/- 5.7 [SD] nmol/mg protein), and similar to that of the ischemia + NAC livers (28.6 +/- 2.8) but 2-fold that of the ischemia + 0 livers (15.8 +/- 2.4 nmol/mg protein, p<0.05). While hearts paired with control livers maintained unchanged their myocardial velocity of contraction, the contraction in the ischemia + NAC-paired hearts reduced, but was better than in the ischemia + 0-paired hearts (71 +/- 8% vs. 41 +/- 6% off baseline, p<0.05). Coronary flow also decreased dissimilarly in the two ischemia-associated groups of heart: 72 +/- 9% (ischemia + NAC) vs. 46 +/- 7% (ischemia + 0, p<0.05). Xanthine oxidase in the ischemia + 0 livers was 7.5-folds higher than in the ischemia-treated livers. CONCLUSIONS: NAC treatment of ischemia-reperfused livers, associated with GSH replenishment, prevents remote myocardial reperfusion injury. The role of NAC and GSH in reducing liver-associated oxidative burst propagation is discussed.

Acetylcysteine↗
PubMed1995

[Lipoprotein (a) in liver diseases. Correlation between low levels and liver function].

OBJECTIVES: To analyze the role of the liver function on the serum levels of lipoprotein(a) (Lp(a)), a lipoprotein considered to be a risk factor for atherosclerosis. METHODS: To measure the Lp(a) levels in patients with liver disease (n = 68) due to various causes and in patients with no liver disease and of similar age and sex-ratio (n = 62) and to analyze the relationship between Lp(a) levels on one hand and liver function and lipid and apoprotein levels on the other hand. RESULTS: Patients with liver disease had significantly lower levels of Lp(a). Lp(a) levels were significantly lower in patients with more severe liver disease (Child Turcotte classification) and significantly correlated with liver function tests, in particular those related to the microsomal function and the synthetic capacity of the liver (albumin, coagulation tests, apoprotein A-II). In patients with liver disease, mean Lp(a) levels were not significantly different between those with and those without chronic alcohol intake. CONCLUSIONS: Patients with liver disease have low levels of Lp(a) that are related to reduced synthetic capacity of this organ and are not linked to a specific cause of liver disease, in particular excess alcohol intake.

Adult↗
PubMed1994

Liver injury following normothermic ischemia in steatotic rat liver.

The influence of normothermic ischemia on steatotic liver was compared with that on healthy liver in rats. Steatotic liver was induced with 4 wk of a choline-deficient diet. We used a procedure of subcutaneous spleen transposition to develop portosystemic collaterals to avoid splanchnic stasis during total hepatic vascular occlusion. One-week survival rates after 30, 45, and 60 min of normothermic ischemia were 75%, 20% and 0% in the steatotic liver group and 100%, 90% and 70% in the control group, respectively. Significantly poor restoration of energy metabolism was observed in the steatotic liver group. After 1 hr of reflow following 45 and 60 min of ischemia, ATP was restored to 74% and 50%, respectively, of the preischemic level in healthy liver but to only 44% and 27% respectively, in steatotic liver. Microscopically, focal hemorrhage, disruption of the sinusoidal microvasculature and occasional spotty necrosis of hepatocytes were demonstrated after 1 hr of reflow following ischemia in steatotic liver, but no significant changes were evident in healthy liver. This microcirculatory alteration seems to be responsible for the loss of organ viability in steatotic liver. We suggest that steatotic liver is more vulnerable than healthy liver to normothermic ischemia in the rat.

Adenine Nucleotides↗
PubMed2005

Progressive microvascular injury in liver and colorectal liver metastases following laser induced focal hyperthermia therapy.

BACKGROUND AND OBJECTIVES: Focal hyperthermia by laser or radiofrequency is currently the preferred method for local ablation of liver tumors. The underlying mechanism of action of focal hyperthermia, in particular the relationship between the microvascular and tissue effect is uncertain and was investigated in a murine model. STUDY DESIGN/MATERIALS AND METHODS: Focal hyperthermia produced by a Neodymium-Yttrium-Aluminium-Garnet laser (wavelength 1,064 nm) was applied to the normal liver and colorectal cancer liver metastases in inbred male CBA strain mice at 2 W for 50 seconds (100 J). Tissue injury was assessed at 0, 24, 48, 72, 120, and 168 hours following therapy by measurements of necrosis in tissue sections stained for nicotinamide adenine dinucleotide (NADH) diaphorase activity. Characteristics of microvascular injury were assessed at the various time points by scanning electron microscopy (SEM) of vascular resin casts, Laser Doppler flowmetry, and confocal in vivo microscopy. RESULTS: Focal hyperthermia produced progressive tissue and vascular injury. There was an initial reduction in blood flow and increased vascular permeability in the microcirculation of both tumor and liver tissue immediately following heat application as assessed by laser Doppler flowmetry and confocal in vivo microscopy, respectively. SEM of vascular casts showed heterogeneous regions of microvascular injury immediately following heat application. The extent of initial vascular disruption or occlusion on SEM of vascular resin casts (mean+/-SE) was significantly less than the tissue necrosis in liver (1.9+/-0.1 mm vs. 3.0 mm+/-0.2 mm P<0.001), but was equivalent to the tissue injury in tumor tissue (3.5 mm+/-0.2 mm vs. 3.6 mm+/-0.1 mm P = 0.907). This was followed by a progressive increase in both microvascular and tissue injury in liver and tumor that peaked by 72 hours following treatment. The peak microvascular injury and tissue damage in liver (6.6 mm+/-0.2 and 6.3 mm+/-0.2 mm, respectively) was significantly greater than the extent of microvascular and tissue damage in tumors (4.8 mm+/-0.2 mm and 4.5 mm+/-0.2 mm, respectively) (P<0.001). The progression of microvascular injury in liver and tumor at times preceded the tissue injury. CONCLUSION: Focal hyperthermia produces both progressive microvascular and tissue damage in liver and colorectal liver metastases. An increase in tissue injury following focal hyperthermia may be a direct result of progressive microvascular damage. Tumor vessels appear more susceptible to direct focal hyperthermia destruction than liver sinusoids. The liver sinusoids are however more susceptible to progressive damage or occlusion following the initial laser thermal stimulus.

Animals↗
PubMed2004

Estimation of liver size for liver transplantation: the impact of age and gender.

In general, the liver is considered to be larger in males than in females. In the present study, data on liver weight from 728 legal autopsies were analyzed with respect to gender, age, body height (BH), body weight (BW), body mass index (BMI), and body surface area (BSA). Descriptive statistics revealed that liver weight increases with age, reaching maximum values between 41 and 50 years in men and between 51 and 60 years in women. Thereafter, liver weight decreases again. Because this loss in liver weight starts earlier in men while liver weight continues to rise in women, the difference in liver weight between men and women is lost above the age of 50. Thus, this age defines a threshold value below which gender is expected to be a critical factor in the calculation of liver weight. When demographic data mentioned above were subjected to multiple stepwise linear regression analysis, liver weight (LW) was best predicted in younger people (16-50 years) by body weight, age, and gender: LW (g) = 452 + 16.34 x BW + 11.85 x age - 166 x gender (r(2) = 0.381; "gender": 1 = female, 0 = male). In contrast, in elderly people (51-70 years) LW was best predicted by BW and age only. Gender was not a significant factor. LW (g) = 1390 + 15.94 x BW - 12.86 x age (r(2) = 0.35). When these formulas were applied to demographic data from 97 organ donors and compared to published formulas (which, however, do not consider the age-dependent effects of gender), the new formulas best predicted male to female liver weight ratios in younger and elderly donors. In conclusion, the new formulas might better predict liver weight in organ donors and transplant recipients to avoid liver size mismatch.

Adolescent↗
PubMed2001

A useful ELISA system for human liver-type arginase, and its utility in diagnosis of liver diseases.

OBJECTIVES: To develop a new ELISA system for liver-type arginase using monoclonal antibodies against the enzyme, and to verify the utility of the arginase in diagnosis of hepatic disorders. DESIGN AND METHODS: We have developed an enzyme-linked immunosorbent assay (ELISA), using two kinds of monoclonal antibodies (Mo6G3 and Mo9C5) for human liver-type arginase as the first and second antibodies respectively. We have also developed a new method to eliminate the influence of erythrocyte-derived arginase contamination in hemolytic samples. This ELISA was applied to specimens received from patients with acute and chronic hepatic disease and also patients who had undergone partial hepatectomy. RESULTS: This assay is sensitive and reproducible for the measurement of liver-type arginase in the sera of patients with liver dysfunction, and enabled us to detect enzyme concentrations as low as 27 pmol/L without any processing of the samples. The assay showed within-run coefficients of variation (CV) ranging from 1.9 to 4.1% and between-day CV from 3.6 to 5.1% for arginase concentrations varying from 57.1 to 1200 pmol/L. The recovery was 113% (mean) with a range of 96 to 129%. These antibodies reacted strongly with both recombinant and native liver-type arginases, while, to some extent, with erythrocyte-derived arginase. Correction for erythrocyte-derived arginase contamination in hemolytic samples was, however, easily made by assaying peroxidase-like activity of hemoglobin. From the view of a limited localization of arginase in the liver, the marked increase of the enzyme in serum reflects initiation of liver injury, while the rapid decrease reflects termination of the damage. Such quick normalization in circulating liver-type arginase indicated another merit of the enzyme in diagnosis of liver diseases. CONCLUSIONS: The changes in circulating liver-type arginase level could be helpful not only in the diagnosis of liver diseases but also subsequent treatment of the patients with liver damage.

Acute Disease↗
PubMed2000

The liver in collagen diseases: pathologic study of 160 cases with particular reference to hepatic arteritis, primary biliary cirrhosis, autoimmune hepatitis and nodular regenerative hyperplasia of the liver.

AIMS/BACKGROUND: Among patients with collagen diseases, liver enzyme abnormalities are a relatively common phenomenon. To establish the liver pathology in collagen diseases, detailed pathologic studies were performed on the hepatic diseases in many patients, including various kinds of collagen diseases. METHODS: The livers from 160 patients (120 autopsy and 40 liver biopsy patients) were examined pathologically: 73 with systemic lupus erythematosus (SLE), 32 with rheumatoid arthritis (RA), 18 with polymyositis and dermatomyositis (PM and DM), 15 with systemic sclerosis (SSc), 11 with mixed connective tissue disease (MCTD) and 11 with polyarteritis nodosa (PAN). RESULTS: Liver diseases were divided into three groups: hepatic arteritis, liver diseases associated with collagen diseases (primary biliary cirrhosis, PBC; autoimmune hepatitis, AIH; nodular regenerative hyperplasia of the liver, NRH) and other liver diseases. Hepatic arteritis presenting the features of the PAN type of necrotizing arteritis was found in 27 autopsy patients. The incidence of arteritis in autopsy patients was 100% in PAN and 8.3-25% in other collagen diseases. Primary biliary cirrhosis was observed in 9 patients, 7 of whom (3 with SSc, 2 with RA, 1 with PM and DM, and 1 with MCTD) had antimitochondrial antibodies (AMA)-positive PBC, and 2 SLE patients had AMA-negative PBC. Three patients (2 with SLE and 1 with MCTD) were diagnosed clinicopathologically as having AIH. However, 3 patients (1 with SLE, 1 with MCTD and 1 with PM and DM) with clinical, biochemical and serologic data indicating probable AIH were excluded from the group with AIH association because of the liver histology (no characteristic features of AIH) and clinical course. These results indicated that data without histologic assessments of the liver are not adequate for diagnosing AIH in collagen diseases. Nodular regenerative hyperplasia of the liver was observed in 7 patients (5 with SLE, 1 with SSc and 1 with PAN). CONCLUSION: The present study offers data that are useful for the diagnosis and treatment of patients with collagen diseases and liver abnormalities.

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