Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “LIVER”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 235 records · Page 13Linked to original sources

Effect of hens fed dietary flaxseed with and without a fatty liver supplement on hepatic, plasma and production characteristics relevant to fatty liver haemorrhagic syndrome in laying hens.

1. Two long-term experiments were conducted with Single Comb White Leghorn (SCWL) hens (line UCD-003) predisposed to fatty liver haemorrhagic syndrome (FLHS). The first investigated the effect of adding a fatty liver supplement to the diet of laying hens prior to the onset of lay, and continuing either until peak production or throughout 39 weeks into lay. The second experiment, lasting 9 months into lay, investigated the effect of adding a fatty liver supplement, with or without 100 g/kg dietary ground flaxseed, to the diet. Body weight, feed intake, plasma triglycerides (in experiment 2) and egg production were measured throughout the experiment. Liver weight, liver fat content, liver malondialdehyde (MDA) content and liver haemorrhage score and fatty acid content of liver fat (in experiment 2) were measured at the end of each experiment. 2. In experiment 1, hens given diets containing the fatty liver supplement had higher egg production and eggshell strength, but there was no difference in liver parameters including MDA content or haemorrhage score compared with controls. 3. At the end of experiment 2, hens on 100 g/kg flaxseed diets had lower body weight, liver weight, liver dry matter and fat content, and plasma triglyceride concentrations than hens given the control diets. 4. Liver haemorrhage score was positively correlated with liver weight, but not with liver fat content, plasma triglyceride concentration or liver MDA content. This suggests that reducing the liver lipid content or feeding fatty liver supplements may not be as effective in controlling FLHS as controlling the size of the liver.

Animal Feed↗

Artificial liver support devices for fulminant liver failure.

Artificial liver-support devices attempt to bridge patients with fulminant hepatic failure until either a suitable liver allograft is obtained for transplantation or the patient's own liver regenerates sufficiently to resume normal function. It is thought that toxins contribute to the clinical picture of fulminant hepatic failure. The earliest reports of successful toxin removal were blood- and plasma-exchange transfusions. Given these successful case reports, mechanical liver-support devices were designed to filter toxins. These mechanical devices used hemodialysis, charcoal hemoperfusion, hemoperfusion through cation-exchange resins, hemodiabsorption, and combinations of all of these techniques as in the MARS liver-support device. Despite promising case reports and small series, no controlled studies of mechanical devices have ever showed a long-term survival benefit. Thus, the removal of presumed toxins seems to be insufficient to support patients with fulminant hepatic failure, and the biologic function of the liver must also be replaced. Attempts at replacing the biologic function have included extracorporeal liver perfusion, cross-circulation, and hepatocyte transplantation. Current technologies have combined mechanical and biologic support systems in hybrid liver-support devices. The mechanical component of these hybrid devices serves both to remove toxins and to create a barrier between the patient's serum and the biologic component of the liver-support device. The biologic component of these hybrid liver support devices may consist of liver slices, granulated liver, or hepatocytes from low-grade tumor cells or porcine hepatocytes. These biologic components are housed within bioreactors. Currently the most clinically studied bioreactors are those that use capillary hollow-fiber systems. Both the bioartificial liver by Demetrious and the extracorporeal liver-assist device by Sussman and Kelly are in clinical trials. Although the trials seemed to have yielded good survival data when the devices are used as a bridge to transplantation, the type and degree of liver support provided by these devices remains uncertain. Thus, despite decades of great progress in the field of artificial liver support, no one technique alone yet provides sufficient liver support. A hybrid system seems to be the best option at present. Still to be determined is the best tissue to use, how much liver tissue should be used, and the optimal design of the bioreactor.

Cell Transplantation↗

Changes in laminin content in livers of patients with alcoholic liver disease.

An increase in serum laminin levels has been reported in patients with liver disease; however, the mechanisms for this increase have not yet been clarified. In the present study, the laminin content of liver biopsy specimens obtained from patients with alcoholic liver disease and non-alcoholic liver disease was determined with a one-step sandwich enzyme-immunoassay system, using monoclonal antibodies for human placental laminin. Hepatic laminin content was significantly higher in patients with liver disease than in normal controls. In alcoholic liver disease, the content in patients with mild fibrosis was lower than in patients with advanced types of alcoholic liver disease. In non-alcoholic liver disease, the hepatic laminin content tended to increase in parallel with the progression of fibrosis. The laminin content in alcoholic liver disease was significantly higher than in the corresponding type of non-alcoholic liver disease. The ratio of laminin to total collagen content was highest in alcoholic liver disease showing mild fibrosis and decreased in parallel with the progression of fibrosis. In contrast, the ratio was low in all types of nonalcoholic liver disease. The ratio in patients with alcoholic liver disease was significantly higher than these with the corresponding non-alcoholic liver disease. Hepatic laminin content increased in parallel with the increase in hepatic type IV collagen in alcoholic liver disease, and the correlation was statistically significant. However, similar correlation was not found in non-alcoholic liver disease. These results indicate that the response to laminin synthesis to alcoholic liver disease is strong in mild fibrosis and reached a plateau at a relatively early stage of fibrosis. The stimulation for laminin synthesis in non-alcoholic liver disease is different from that in alcoholic liver disease.

Adult↗

Tissue inhibitor of metalloproteinase-1 in the liver of patients with chronic liver disease.

BACKGROUND/AIMS: Tissue inhibitor of metalloproteinase (TIMP)-1 is an important regulator of matrix metalloproteinase activity. To clarify the changes in TIMP-1 in diseased livers, we measured TIMP-1 concentrations in liver tissue samples from patients with chronic liver disease. The relationship between serum and liver levels of TIMP-1 was also examined in some patients. METHODS: The subjects were 68 patients who underwent liver biopsy. The liver TIMP-1 concentration was measured using an enzyme immunoassay after the extraction of TIMP-1 with 2 M guanidine. RESULTS: As compared with the controls (n=10), the liver TIMP-1 level was increased 2.2-fold in the 24 chronic active hepatitis 2A patients, 2.9-fold in the 10 chronic active hepatitis 2B patients and 4.1-fold in the six liver cirrhosis patients, but no significant increase was observed among the 18 chronic persistent hepatitis patients. The liver TIMP-1 levels were closely correlated with the histological degrees of periportal necrosis, portal inflammation, and liver fibrosis. When the localization of TIMP-1 was examined immunohistochemically, TIMP-1 was stained mainly in hepatocytes, and the intensity was stronger in the livers of chronic active hepatitis and liver cirrhosis patients than in those of the chronic persistent hepatitis patients. The serum TIMP-1 and liver TIMP-1 levels were significantly correlated, indicating that serum TIMP-1 could reflect the change of liver TIMP-1 in patients with chronic liver disease. CONCLUSION: Liver TIMP-1 concentration increases with progression of the liver disease, when the degradation of extracellular matrix proteins is decreased, resulting in the development of liver fibrosis.

Adult↗

Liver bridging techniques in the treatment of acute liver failure.

The introduction of orthotopic liver transplantation in the management of acute liver failure has dramatically increased the survival rates of patients at the cost of removing the patient's native liver and life-long dependence on immunosuppression. However, it is well known that in many patients with acute liver failure the diseased liver has the potential to recover. Death in these patients is often due to increased intra-cranial pressure or infection. Liver bridging techniques are assigned to temporarily provide liver function and enable the native liver to recover in patients with acute liver failure. They represent an attractive alternative to conventional liver transplantation in the management of acute liver failure, since after recovery of the native liver the patient is freed from immuno-suppression with all associated side-effects and risks. Auxiliary liver transplantation, artificial liver support devices and hepatocyte transplantation represent different ways of bridging liver function in acute liver failure. The aim of this review is to present the ideas and principles of these three different liver bridging techniques. We will discuss the relative importance and the future potential of theses bridging techniques in the treatment of acute liver failure by comparing the experimental and clinical results.

Hepatocytes↗

Changes in liver regenerative factors in a case of living-related liver transplantation.

Liver regeneration in a patient with fulminant hepatic failure (FHF) who underwent living-related partial liver transplantation (LRLT) was investigated regarding hepatic growth factors. The patient was a 16-yr-old Japanese male who developed severe subacute FHF. LRLT was performed using an extended left lobe of the ABO matched patient's mother. In the recipient, the pre-transplant levels of both plasma hepatocyte growth factor (HGF) and transforming growth factor (TGF)-beta were extremely high and rapidly decreased following the liver replacement. The liver volume evaluated using a CAT scan increased 195% after 2 wk in graft liver and 110% after 2 wk in the hepatectomized donor. The explanted liver (FHF liver), the liver from donor (normal liver), and the graft liver [the 3rd post-transplant day (POD 3)] were all investigated immunohistochemically. FHF liver: No liver regeneration was observed [proliferative cell nuclear antigen (PCNA) labeling index (L.I.): 0%]. In the liver, both HGF in the hepatocytes and c-met on the membrane of the hepatocytes were positive. TGF-beta was positive in the hepatocytes and no apoptosis was detected by the TUNEL method. Donor liver (POD 0): Few PCNA stained hepatocytes were detected. No HGF was detected but c-met was clearly detected on the cell membrane of the hepatocytes. Neither TGF-beta nor apoptosis was detected. Graft liver (POD 3): The PCNA L.I. was conspicuous at 40%. HGF was positive in non-parenchymal cells and c-met was positive in the cytoplasm of the hepatocytes. TGF-beta was negative while apoptosis was positive in the zone 3 hepatocytes. In conclusion, these findings suggested that the liver of the patient with FHF did not respond to liver regenerative stimulus, in part, through involvement of inhibitor TGF-beta. On POD 3, the transplanted graft was in a vigorous regenerative status in comparison to that in the hepatectomized donor. The HGF/c-met system is thought to be involved in the mechanism of regeneration. Intrahepatic apoptosis was detected in the graft on the 3rd post-transplant day probably due to transient ischemia in the liver, which was not related to the Fas/Fas-ligand system.

Adolescent↗

Cobalamin (vitamin B12) and holotranscobalamin changes in plasma and liver tissue in alcoholics with liver disease.

OBJECTIVE: We wanted to know if alterations in plasma cobalamin (B12) concentration and B12 carriers, e.g., holotranscobalamins (holo TC), occur in blood and liver tissue from patients with severe alcoholic liver disease. Our purpose was to test the hypothesis that liver disease may disrupt B12 distribution. METHOD: Total B12, as well as B12 bound to transcobalamin I, II, III (holo TC), were measured to determine their concentration in plasma and in liver tissue; Poteriochromonas malhamensis--a protozoan reagent served to measure only metabolically active (true) B12. Total B12 as distributed in holo TC in plasma and liver tissue of healthy subjects (controls) were compared to patients with severe alcoholic liver disease. RESULTS: Severe liver disease initiates highly elevated B12 levels in plasma and a lowered liver tissue total B12 concentration. The percent of B12 distributed to holo TC II is significantly depleted during liver disease. In contrast, holo TC I and III are elevated in plasma during liver disease and contain more B12 than controls. Total B12 and B12 distributed to TC are lower in diseased liver tissue. CONCLUSION: Severe alcoholic liver disease involves leakage of total B12 from liver tissue into the plasma. Holo TC I and III concentration increases in plasma; this preserves the high plasma B12 from being excreted. However, plasma holo TC II B12 distribution is decreased, indicating that there is a depression of exogenous B12 entering the plasma and tissues. In severe liver disease, liver tissue B12 binding and storage by TC is disrupted and causes B12 to leak out of the liver into the circulation. Eventually liver disease could produce enough severe tissue B12 deficits to cause metabolic dysfunction despite elevated plasma total B12. Elevation of plasma B12, accompanied by a lowering of holo TC II distribution, seemed to be a useful index of liver disease severity suggesting preventive treatment.

Humans↗

Liver glutathione concentrations in dogs and cats with naturally occurring liver disease.

OBJECTIVE: To determine total glutathione (GSH) and glutathione disulfide (GSSG) concentrations in liver tissues from dogs and cats with spontaneous liver disease. SAMPLE POPULATION: Liver biopsy specimens from 63 dogs and 20 cats with liver disease and 12 healthy dogs and 15 healthy cats. PROCEDURE: GSH was measured by use of an enzymatic method; GSSG was measured after 2-vinylpyridine extraction of reduced GSH. Concentrations were expressed by use of wet liver weight and concentration of tissue protein and DNA. RESULTS: Disorders included necroinflammatory liver diseases (24 dogs, 10 cats), extrahepatic bile duct obstruction (8 dogs, 3 cats), vacuolar hepatopathy (16 dogs), hepatic lipidosis (4 cats), portosystemic vascular anomalies (15 dogs), and hepatic lymphosarcoma (3 cats). Significantly higher liver GSH and protein concentrations and a lower tissue DNA concentration and ratio of reduced GSH-to-GSSG were found in healthy cats, compared with healthy dogs. Of 63 dogs and 20 cats with liver disease, 22 and 14 had low liver concentrations of GSH (micromol) per gram of tissue; 10 and 10 had low liver concentrations of GSH (nmol) per milligram of tissue protein; and 26 and 18 had low liver concentrations of GSH (nmol) per microgram of tissue DNA, respectively. Low liver tissue concentrations of GSH were found in cats with necroinflammatory liver disease and hepatic lipidosis. Low liver concentrations of GSH per microgram of tissue DNA were found in dogs with necroinflammatory liver disease and cats with necroinflammatory liver disease, extrahepatic bile duct occlusion, and hepatic lipidosis. CONCLUSIONS AND CLINICAL RELEVANCE: Low GSH values are common in necroinflammatory liver disorders, extrahepatic bile duct occlusion, and feline hepatic lipidosis. Cats may have higher risk than dogs for low liver GSH concentrations.

Animals↗

Laparoscopic liver resection of benign liver tumors.

OBJECTIVE: The objective of this study was to assess the feasibility, safety, and outcome of laparoscopic liver resection for benign liver tumors in a multicenter setting. BACKGROUND: Despite restrictive, tailored indications for resection in benign liver tumors, an increasing number of articles have been published concerning laparoscopic liver resection of these tumors. METHODS: A retrospective study was performed in 18 surgical centres in Europe regarding their experience with laparoscopic resection of benign liver tumors. Detailed standardized questionnaires were used that focused on patient's characteristics, clinical data, type and characteristics of the tumor, technical details of the operation, and early and late clinical outcome. RESULTS: From March 1992 to September 2000, 87 patients suffering from benign liver tumor were included in this study: 48 patients with focal nodular hyperplasia (55%), 17 patients with liver cell adenoma (21%), 13 patients with hemangioma (15%), 3 patients with hamartoma (3%), 3 patients with hydatid liver cysts (3%), 2 patients with adult polycystic liver disease (APLD) (2%), and 1 patient with liver cystadenoma (1%). The mean size of the tumor was 6 cm, and 95% of the tumors were located in the left liver lobe or in the anterior segments of the right liver. Liver procedures included 38 wedge resections, 25 segmentectomies, 21 bisegmentectomies (including 20 left lateral segmentectomies), and 3 major hepatectomies. There were 9 conversions to an open approach (10%) due to bleeding in 45% of the patients. Five patients (6%) received autologous blood transfusion. There was no postoperative mortality, and the postoperative complication rate was low (5%). The mean postoperative hospital stay was 5 days (range, 2-13 days). At a mean follow-up of 13 months (median, 10 months; range, 2-58 months), all patients are alive without disease recurrence, except for the 2 patients with APLD. CONCLUSIONS: Laparoscopic resection of benign liver tumors is feasible and safe for selected patients with small tumors located in the left lateral segments or in the anterior segments of the right liver. Despite the use of a laparoscopic approach, selective indications for resection of benign liver tumors should remain unchanged. When performed by expert liver and laparoscopic surgeons in selected patients and tumors, laparoscopic resection of benign liver tumor is a promising technique.

Adolescent↗

Clinical features of liver disturbance in rheumatoid diseases: clinicopathological study with special reference to the cause of liver disturbance.

BACKGROUND: Liver disturbance in rheumatoid diseases results not only from liver disease associated with the rheumatoid diseases themselves but also from various other causes. This study aimed to elucidate the clinical features of liver disturbance in rheumatoid diseases, focusing on the cause of this disturbance. METHODS: A clinicopathological study was performed in 306 patients (106 with systemic lupus erythematosus, 71 with Sjögren's syndrome, 59 with rheumatoid arthritis, 27 with scleroderma, 30 with polymyositis, and 13 with polyarteritis nodosa). RESULTS: Liver disturbance occurred in 43% of these patients and resulted from various causes. Its degree and duration varied from one cause to another. Liver disease associated with rheumatoid diseases was the leading cause of the liver disturbance in these patients and was characterized by mild and transient liver disturbance (maximum alanine aminotransferase [ALT] level during the study period, 68 +/- 8 IU/ml; maximum alkaline phosphatase [ALP] level, 410 +/- 31 IU/ml; duration of liver disturbance, 6 +/- 2 months). Most patients with this type of liver disease showed minimal change in liver histology, although two-thirds of those evaluated by the international scoring system for autoimmune hepatitis (AIH) were classified as "probable" or "definite". Eight of 14 patients with histologically proven chronic hepatitis or cirrhosis were infected with hepatotropic virus (7 with hepatitis C virus [HCV] and 1 with hepatitis B virus [HBV]). Five of 9 patients in whom the hepatic lesion progressed had hepatotropic virus infection (4 with HCV and 1 with HBV), and the other 4 patients suffered from autoimmune liver diseases. CONCLUSIONS: Liver disease associated with rheumatoid diseases was the leading cause of liver disturbance in these patients and was characterized by mild and transient liver disturbance, whereas progressive liver diseases were often associated with hepatotropic virus, mainly HCV, or autoimmune liver diseases. Liver histology is indispensable for differentiating AIH from liver disease associated with rheumatoid diseases.

Alanine Transaminase↗

Effects of a high-fiber diet on hepatocyte apoptosis and liver regeneration after partial hepatectomy in rats with fatty liver.

BACKGROUND: The morbidity and mortality that accompany fatty liver may occur as a result of increased apoptosis of hepatocytes and decreased liver regeneration. We determined the effects of a high-fiber diet on hepatocyte apoptosis and liver regeneration after partial hepatectomy in rats with fatty liver. METHODS: Fatty liver was induced in male Wistar rats weighing around 200 g through feeding of a high-fat diet for 4 weeks. The rats were then randomly assigned to 3 groups that received a high-fat diet, a normal diet, or a high-fiber diet for another 4 weeks. Partial hepatectomy (around 70%) was performed, and rats were killed 6, 24, 48, or 72 hours after hepatectomy. We then measured (1) the ratio of remnant liver weight to body weight and assessed the histology of the remnant liver as indicators of fatty liver, (2) caspase-3 activity and in situ cell death detection of DNA fragmentation as indicators of apoptosis, and (3) 5-bromo-2-deoxyuridine (BrdU) activity and (4) ornithine decarboxylase (ODC) contents in remnant livers as markers of regeneration. RESULTS: We found that (1) a high-fat diet for 4 weeks can markedly induce fatty liver, (2) apoptosis of hepatocytes is greater in fatty liver than in normal liver (98 +/- 19 vs 36 +/- 7) at 6 hours after partial hepatectomy (p < .05), (3) the capacity of liver regeneration decreases significantly (BrdU index: 30 +/- 5 vs 12 +/- 3, and ODC contents: 604 +/- 48 vs 390 +/- 42 mg/dL) in fatty liver 24 hours after partial hepatectomy (p < .05), (4) a normal diet can partially reverse the effects of fatty liver; (5) a high-fiber diet can significantly reverse the effects of fatty liver (p < .05). CONCLUSIONS: A high-fiber diet can reverse the negative effects of fatty liver on apoptosis and regenerative capacity after partial hepatectomy.

Animals↗

Phagocytic function and metabolite production in thioacetamide-induced liver cirrhosis: a comparative study in perfused livers and cultured Kupffer cells.

BACKGROUND/AIMS: The aim of the study presented here was to evaluate the basal and stimulated phagocytic activities and the metabolite production of isolated perfused livers, and also the phagocytic capacity of cultured Kupffer cells from rats with macronodular cirrhosis. METHODS: Rats were made cirrhotic by oral administration of thioacetamide. The phagocytic activity was assessed by the rate of removal of colloidal carbon. The Kupffer cells were prepared by a pronase/collagenase digestion method followed by elutriation. RESULTS: The phagocytic activity and production of glucose, lactate and pyruvate were reduced in cirrhotic livers when calculated per g liver. Due to hyperplastic-regenerative processes the mass of the cirrhotic livers was markedly augmented so that the colloidal carbon uptake calculated per cirrhotic liver was not significantly different from the controls. Colloidal carbon-induced glucose release increased more markedly in the controls than in cirrhotic livers. Isoproterenol considerably stimulated phagocytosis and glucose production in controls, whereas the response was clearly reduced in cirrhotic livers when calculated either per g liver or per total liver weight. The cyclic AMP analogue elicited a marked glycogenolytic response in the controls, whereas there was only a slight increase in glucose production in cirrhotic livers. Phagocytosis of cirrhotic livers was only moderately stimulated by opsonized zymosan when compared with the controls. Freshly isolated Kupffer cells exhibited a reduced phagocytic activity. Stimulation by zymosan was observed only in cell suspensions of the controls. In contrast, Kupffer cells from cirrhotic livers did not differ from controls with respect to basal or zymosan-stimulated phagocytic activity after 48-h cultivation. CONCLUSION: The stimulated phagocytic function was disturbed in perfused macronodular-cirrhotic livers as compared to controls. In contrast, 48-h cultured Kupffer cells from cirrhotic livers exhibited the same basal and stimulated phagocytic capacity as controls. The glucose release from perfused livers, initiated by stimulation of Kupffer cells or hepatocytes, was significantly reduced in cirrhotic livers. Therefore, we postulate an impaired intra- and/or intercellular signalling in macronodular-cirrhotic livers.

Animals↗

Elevated liver enzymes following open Roux-en-Y gastric bypass for morbid obesity - does timing of liver retraction affect the rise in the levels of transaminases?

BACKGROUND: Liver retraction in open Roux-en-Y gastric bypass (RYGBP) for morbid obesity may cause an elevation in liver transaminase levels postoperatively. This study attempts to ascertain whether timing of placement of the liver retractor would have any effect on the degree of derangement of the liver function tests. METHODS: 12 patients undergoing open RYGBP were prospectively randomized into 2 groups. One group had the liver retractor applied early on in the operation, and had the gastric pouch constructed first, followed by construction of the jejunojejunostomy and Roux-en-Y gastrojejunostomy. The second group had the jejunojejunostomy performed first, followed by placement of the liver retractor to allow construction of the gastric pouch and Roux-en-Y gastro-jejunostomy. Liver function tests were monitored postoperatively in both groups, and these were then statistically analyzed with respect to the duration of liver retraction. RESULTS: Delayed liver retraction resulted in statistically significantly smaller increases in aspartate transaminase (AST) and alanine transaminase (ALT) compared with early liver retraction. AST levels returned to normal values within 1 week in both groups of patients. ALT levels returned to normal values within 1 week in the delayed liver retraction group, whereas levels took >1 week to return to normal in the early liver retraction group. CONCLUSIONS: Liver retraction causes abnormal transaminase levels following open RYGBP. Delayed liver retraction results in less rise in the AST and ALT levels compared with early liver retraction. Surgeons should construct the Roux-en-Y limb and jejunoje junostomy first, before proceeding with construction of the gastric pouch and gastrojejunostomy, thereby decreasing the duration of liver retraction and consequent relative liver ischemia.

Gastric Bypass↗

[Outcome of liver transplantation in patients with alcoholic liver disease].

BACKGROUND: Liver transplantation is accepted as effective therapeutic option for end-stage liver disease, including alcoholic liver disease AIM: To evaluate the outcome of liver transplantation for alcoholic liver disease in the Liver Transplantation Program at "Hospital de Clínicas" of the Federal University of Paraná, Curitiba, PR, Brazil. PATIENTS AND METHODS: It was performed a retrospective study of the patients who underwent liver transplantation for alcoholic end-stage liver disease between September 1991 and January 2001. The minimum abstinence period required was 6 months before liver transplantation. Identification of alcohol consumption after liver transplantation was determinated by information provided by patient or family and biochemical or histological anormalities. RESULTS: Twenty patients underwent liver transplantation for alcoholic liver disease in the study period, 95% (19/20) were men and the median age was 50 years (29-61 years). Seventy-five percent of the patients (15/20) had severe liver disfunction (Child C class) in the pre-transplant period. In six of them (30%) there was association with viral hepatitis and in one, with hepatocarcinoma. Median abstinence period before liver transplantation was 24 months, varying from 9 to 120 months. One-year and 3-year survival rate were 75% and 50%, respectively. The main complications were: acute cellular rejection (40%), chronic rejection (5%), hepatic artery thrombosis (15%), biliary complications (15%), bacterial or fungal infections (45%), cytomegalovirus infection (20%). Three patients returned to alcohol use after liver transplantation CONCLUSION: The survival of patients who received liver transplant for alcoholic cirrhosis are satisfactory. In the present study there was a small index of alcohol use after liver transplantation.

Adult↗

Reducing equivalents for mixed function oxidation in periportal and pericentral regions of the liver lobule in perfused livers from normal and phenobarbital-treated rats.

The supply of NADPH for cytochrome P-450-dependent mixed function oxidation from the pentose cycle and mitochondria in periportal and pericentral regions of the liver lobule was evaluated in perfused rat liver. Rates of 7-ethoxycoumarin O-deethylation in livers from fed, normal rats monitored with micro-light guides placed on periportal and pericentral regions were 1.2 mumol/g/hr in both regions of the liver lobule. In livers from fed, phenobarbital-treated rats, rates were 3.6 and 7.0 mumol/g/hr in periportal and pericentral regions, respectively. Following treatment of rats with 6-aminonicotinamide, an inhibitor of the pentose cycle, rates of 7-hydroxycoumarin production were approximately 0.9 mumol/g/hr in both regions of the lobule in livers from normal rats and 2.1 and 3.4 mumol/g/hr in periportal and pericentral regions, respectively, in livers from phenobarbital-treated rats. Based on the difference in rates of 7-hydroxycoumarin production in the presence and absence of 6-aminonicotinamide, we conclude that the pentose cycle supplies NADPH for 7-ethoxycoumarin metabolism at rates around 0.3 mumol/g/hr in both regions of the liver lobule in livers from normal rats and 1.5 and 3.6 mumol/g/hr in periportal and pericentral regions, respectively, in livers from phenobarbital-treated rats. Potassium cyanide, an inhibitor of mitochondrial oxidation, reduced rates of 7-ethoxycoumarin O-deethylation to approximately 0.6 mumol/g/hr in both regions of the liver lobule in livers from fed, normal rats and to around 0.2 mumol/g/hr after fasting or treatment with 6-aminonicotinamide. In livers from fasted, phenobarbital-treated rats, 7-hydroxycoumarin was produced at rates of 0.3 and 0.7 mumol/g/hr in periportal and pericentral regions, respectively, in the presence of KCN. Decreases in rates of 7-hydroxycoumarin production during KCN infusion indicate that the mitochondria supply about 0.7 mumol of NADPH/g/hr for 7-ethoxycoumarin metabolism in both regions in livers from normal rats and 1.3 and 2.7 mumol/g/hr in periportal and pericentral regions in livers from phenobarbital-treated rats. The sum of KCN and 6-aminonicotinamide-sensitive rates of 7-ethoxycoumarin metabolism closely approximated rates measured in the absence of the inhibitors. These data indicate that mitochondria supply 50 to 70% of the reducing equivalents for mixed function oxidation of 7-ethoxycoumarin in both regions of the liver lobule in livers from fed rats.

7-Alkoxycoumarin O-Dealkylase↗

Changes of liver-resident NK cells during liver regeneration in rats.

To determine the role of NK cells in regulation of tissue growth, the phenotype and function of liver-resident NK cells were studied after 70% partial hepatectomy in rats. The process of liver regeneration was generally completed by day 14. In contrast, the number of liver-resident NK cells (NKR-P1bright) was restored as early as day 3 after partial hepatectomy. However, spontaneous functions of liver-resident NK cells, including killing of YAC-1 and P815 targets, Ab-dependent cellular cytotoxicity, and redirected killing via NKR-P1, were continuously suppressed throughout the entire period of liver regeneration (from 3 h to 14 days). Augmentation of NK cytotoxicity against P815 targets and induction of NK cell adherence to plastic following 24 h of IL-2 stimulation showed a similar pattern of suppression. However, IL-2-induced augmentation of YAC-1 killing, proliferation and generation of adherent NK cells, and LAK activity in 5- to 7-day cultures were found to be suppressed only during the first 24 h and increased between days 2 and 7 after hepatectomy. Sorted NK cells (> or = NKR-P1bright) from liver-resident mononuclear leukocytes 24 h after partial hepatectomy showed the same pattern of suppression as unsorted mononuclear leukocytes. In contrast to liver-resident NK cells, no significant changes were detected in peripheral blood or spleen NK cells of rats following partial hepatectomy. Of particular interest, in normal liver, hepatocytes were resistant to NK lysis, while resident NK cells were cytotoxic for various NK-sensitive targets. In contrast, during the early period of liver regeneration, when hepatocytes were sensitive to lysis by liver-resident NK cells of normal rats, NK cells obtained from regenerating liver tissues were unable to mediate cytotoxicity. At the final phase of liver regeneration (days 7-14 after hepatectomy), both resistance of hepatocytes to killing by NK cells and cytotoxicity of liver-resident lymphocytes against hepatocytes from regenerating liver were simultaneously restored. In vivo depletion of NK cells by injection of rats with anti-NKR-P1 mAb resulted in a significant augmentation of liver regeneration subsequent to partial hepatectomy. Our data suggest that liver-resident NK cells may be involved in regulation of the extent of liver regeneration.

Animals↗

MR imaging enhancement with superparamagnetic iron oxide in chronic liver disease: influence of liver dysfunction and parenchymal pathology.

PURPOSE: To analyze the influence of liver dysfunction and parenchymal pathology on the accumulation of superparamagnetic iron oxide (SPIO). METHODS: We evaluated MR images of 13 patients having small hepatic neoplasms before and after administration of SPIO (10 micronol/kg). Biopsy and laboratory data confirmed the presence of severe cirrhosis in two patients, mild cirrhosis in four, chronic hepatitis in five, and normal livers in two. Degrees of liver dysfunction or liver parenchymal pathology were correlated with reductions in signal intensity of the liver and spleen after administration of SPIO. Signal intensity reduction was evaluated using a 1.5 Tesla MR unit. RESULTS: Response to SPIO of the liver and spleen did not correlate with liver parenchymal pathology, although reductions in signal intensity of the liver were somewhat small in severely cirrhotic livers. There were slight correlations between signal intensity alterations of the liver and laboratory data such as the indocyanine green retention rate (correlation coefficient 0. 47), albumin (0.36), total bilirubin (0.36), and serum glutamic oxaloacetic transaminase (GOT) (0.46). Signal intensity reduction of spleen did not correlate with liver function tests except for serum GOT. In patients with cirrhosis, heterogeneous structures were detected in the nontumorous portions of the liver. However, these did not prevent the diagnosis of small hepatomas. CONCLUSION: The uptake of SPIO showed some correlation with liver function but not with chronic liver parenchymal pathology. SPIO provided sufficient contrast between tumor and surrounding liver parenchyma among patients with chronic liver disease.

Adult↗

Findings on liver biopsy to investigate abnormal liver function tests in the absence of diagnostic serology.

BACKGROUND/AIMS: The significance of abnormal liver function tests in the absence of diagnostic serology is unclear. The aim of this study was to report liver biopsy findings in a large group of patients with unexplained abnormal liver biochemistry. METHODS: Histological findings were examined in 354 patients who underwent liver biopsy to investigate abnormal liver function tests. RESULTS: Six percent of patients had a normal liver biopsy while 26% were found to have some degree of fibrosis and 6% were cirrhotic. Thirty four and 32% of biopsies suggested non-alcoholic steatohepatits or fatty liver respectively. Other diagnoses included cryptogenic hepatitis, drug toxicity, primary and secondary biliary cirrhosis, autoimmune hepatits, alcohol-related liver disease, primary sclerosing cholangitis, haemochromatosis, amyloid and glycogen storage disease. Patient management was directly altered in 18% of patients due to liver biopsy findings and three families were entered into screening programmes for inheritable liver disease. CONCLUSIONS: The finding of abnormal liver function tests in the absence of diagnostic serology may indicate significant liver disease. Liver biopsy yields a range of liver diseases of diverse nature and extent. Liver diseases may be uncovered for which specific treatment is indicated.

Biopsy, Needle↗