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Aging delays the post-necrotic restoration of liver function.

Age-associated changes in liver injury and post-necrotic regeneration were studied in rats aged 6 and 30 months in a period of 96 h following a dose of thioacetamide (6.6 mmol/kg body weight). Hepatocellular necrosis was detected in both groups by serum aspartate aminotransferase, but the severity of injury was significantly lower (one fourth, p < 0.001) in the oldest. Differences were observed in hepatocyte FAD monooxygenase activity between 6 and 30 months old rats at 24 h (278 versus 170%, p < 0.001, respectively) and also in GSH/GSSG ratio, in protein thiol groups and in malondialdehyde. Glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase activities rose markedly in both groups, this increase being slightly lower in the oldest. Superoxide dismutase and catalase did not show significant changes between both groups. At the end of the 96 h experimental period the restoration towards normal of GSG/GSSG, protein thiols malondialdehyde and the activities of Cu-Zn superoxide dismutase and catalase were significantly lower in hepatocytes from 30 months old rats. We summarize that the main age-related changes in the sequenced process of liver injury and regeneration occurred to a lesser extent in severity of injury and delayed response in the post-necrotic restoration of liver function, probably due to a lower increase in antioxidant enzyme system.

Aging↗

The pattern and significance of abnormal liver function tests in community-acquired pneumonia.

BACKGROUND: The pattern of liver function tests (LFTs) in community-acquired pneumonia has not been investigated in detail. Although abnormal tests are thought to be more frequent in patients with atypical pneumonia, the prognostic value of LFTs have not been clearly established. METHODS: We assessed 96 consecutive patients admitted to one hospital with a chest infection over a period of 6 weeks. The infection was classified as bronchitis or lobar pneumonia on clinical and radiological criteria. The site and severity of the infection were assessed and correlated with LFTs and standard British Thoracic Society prognostic criteria. Mortality and length of stay in survivors were used as major outcome measures. RESULTS: There were 17 deaths (18%) overall and patients with abnormal LFTs were significantly more likely to die than those with normal tests (25% vs. 5%; p=0.026). Length of stay was significantly longer in survivors with abnormal liver function than in those with normal tests (9.7 vs. 5.8 days; p=0.006). A low albumin was the most useful predictor of poor outcome and carried a relative risk of dying of 1.8, comparable to the predictive value of tachypnoea. ALT was increased threefold in those succumbing to their disease, but alkaline phosphatase levels were not predictive of outcome and an increase in gamma GT appeared to be protective. CONCLUSIONS: Abnormal LFTs are common in community-acquired pneumonia and are of prognostic value. Patients with a low albumin or raised ALT are significantly more likely to die from their disease or to stay in hospital for a prolonged period. However, other LFTs are of less value in predicting prognosis.

Journal Article↗

[Effect of prostaglandin E1 infusion during and after total hip arthroplasty under hypotensive anesthesia on postoperative liver function and hemorrhage].

We evaluated the effects of prostaglandin E1 (PGE1) on the liver function and hemorrhage after total hip arthroplasty (THA). Twenty patients with normal liver function were randomly divided into two groups. The patients were anesthetized with spinal anesthesia using 0.5% bupivacaine 4 ml and epidural anesthesia. The laryngeal mask was inserted after administrations of 1.5-2 mg.kg-1 of propofol and 0.8 mg.kg-1 of succinylcholine. PGE1 was infused in the PGE1 group at a rate of 0.01 microgram.kg-1.min-1 (PGE1 group) during and after the operation (30-40 hrs). GOT and GPT values were evaluated before, and at the end of operation, and on 1, 4 and 7 postoperative days in each group. The amount of hemorrhage was measured at the end of operation and on 1, 2, 3 and 4 postoperative days in each group. GOT values on 1 and 4 postoperative days in PGE1 group were significantly lower than those in the control group. GPT values on 1, 4 and 7 postoperative days in PGE1 group were also significantly lower than those in the control group. The amount of bleeding during the operation and postoperative hemorrhage did not differ significantly between the two groups. These results suggest that PGE1 may prevent postoperative liver damage, but it may not affect the amount of postoperative bleeding.

Adult↗

[The pathogenesis of liver functional disorders after cholecystectomy in cholelithiasis].

AIM: To study hepatic function after cholecystectomy and the role of absorptive-excretory function of the liver and hormonal factors in development of postcholecystectomy syndrome. MATERIALS AND METHODS: 106 patients long after cholecystectomy for cholelithiasis were examined for absorptive-excretory function of the liver and blood hormones (hydrocortisone, insulin, gastrin, thyroxine, triiodothyronine, thyrotropine). I-131-bengal-rose hepatography, dynamic hepatobiliscintigraphy with brommeside-Tc-99m, radioimmunoassay were employed. RESULTS: Impairment, often subclinical, of hepatic absorption and excretion after cholecystectomy was found in 94% of the patients. External function of the liver after cholecystectomy was disturbed depending on the condition of its absorptive-excretory function. Hepatic dysfunctions and changes in blood hormones correlated. CONCLUSION: Absorptive-excretory function and hormonal factors are essential in pathogenesis of postcholecystectomy syndrome.

Cholelithiasis↗

Enhanced cell aggregation and liver functions using polymers modified with a cell-specific ligand in primary hepatocyte cultures.

Hepatocytes cultured as multicellular aggregates called spheroids exhibit enhanced liver functions and maintain them over a long period compared with monolayer culture. We previously reported the induction of hepatocyte spheroids using the synthetic polymer Eudragit (a copolymer of methacrylic acid and methylmethacrylate) as an artificial matrix in a cell suspension system (Yamada et al., J. Biochem., 123, 1017-1023, 1998). In this method, hepatocyte aggregation was promoted by the effects of electrostatic and hydrophobic interactions between cells and the polymer. To enhance the cell aggregation ability and cell-specificity of the polymer, in the present study, we prepared hepatocyte-targeting polymers containing lactone, a ligand of the asialoglycoprotein receptor. Addition of the lactone-modified polymers to the medium promoted cell aggregation and spheroid formation more effectively than unmodified Eudragit. The spheroids induced by the polymers exhibited enhanced liver functions, i.e., albumin secretion, ammonia removal, and urea synthesis, from early in the culture. We also investigated the induction of hetero-spheroids composed of various liver constitutive cells by this method. The hetero-spheroids induced by the polymers showed improved liver functions.

Journal Article↗

Changes in liver function parameters after occlusion of gastrorenal shunts with balloon-occluded retrograde transvenous obliteration.

OBJECTIVE AND METHODS: To evaluate the effects of portal blood flow on liver function, this pilot study investigated the correlation between changes in portal blood flow as measured by image-directed Doppler ultrasonography and liver function tests in nine patients with cirrhosis who were treated with balloon-occluded retrograde transvenous obliteration. All patients had large gastric varices and prominent gastrorenal shunts. RESULTS: Treatment caused a significant increase (p < 0.01) in portal blood flow; we documented reversion from hepatofugal to hepatopetal portal flow in one patient and increases in hepatopetal flow from 5.4 +/- 1.1 to 7.85 +/- 1.4 cm/s (mean +/- SD) in eight patients. All patients showed decreases in gastric variceal size. However, portal pressure rose significantly in all patients after treatment from 25.4 +/- 7.6 to 30.7 +/- 5.8 mmH2O (n = 7, mean +/- SD), and two of nine patients had worsening of esophageal varices. All nine patients showed improvement in the 15-min retention rate of indocyanine green from 31.8 +/- 16.1 to 21.8 +/- 12.4% (mean +/- SD, p < 0.01), whereas seven patients showed increased serum albumin levels after treatment. CONCLUSIONS: These results suggest balloon-occluded retrograde transvenous obliteration increases hepatic portal blood flow, which may be accompanied by improvements in liver function.

Adult↗

[Selectivity of glomerular proteinuria and liver function in gestosis].

Proteinuria in preeclamptic women was qualitatively differentiated and in cases of pure glomerular proteinuria three groups according to the low-, medium- or high selectivity of glomerular proteinuria were formed. In these patients the incidence of liver dysfunction and severe proteinuria together with an increase in mean arterial blood pressure was investigated. The aim of this study was to find out if there is any connection between glomerular proteinuria of different selectivity and disturbed liver function. In patients with EPH-gestosis a pure glomerular proteinuria in SDS-PAA-disc electrophoresis of the urine was found. Together with the increase in glomerular selectivity an increase in quantitative urinary protein loss was found. In patients with high selective glomerular proteinuria the extent of proteinuria was about three times higher than in patients with low selectivity. In all patients a moderate elevation of the liver enzymes was found. In all patients disturbed liver function returned to normal within a few days after delivery. We conclude from these data that glomerular functional lesions pregnancy in patients with preexisting glomerulopathies or pregnancy induced renal dysfunction are accompanied in a high rate by moderate disorders of liver function.

Alanine Transaminase↗

Use of hepatocytes in primary culture for biochemical studies on liver functions.

Rat parenchymal hepatocytes isolated with collagenase were cultured as monolayers in Williams medium E supplemented with calf serum. Freshly isolated cells showed very low activities of various liver functions, and they had to be cultured for 6-24 h to allow recovery of these functions. Insulin and dexamethasone greatly increased cell viability in primary. After culture for 24 h, these cells showed various liver functions as seen in vivo and responded well to various added hormones and amino acids. The concentrations of amino acids in the medium regulated synthesis of serum proteins and insulin stimulated lipogenesis, which in turn regulated synthesis of lipoproteins. Insulin also stimulated glycogen synthesis and the stimulation was parallel with the number of insulin receptors. Glucagon stimulated glycogenolysis and its stimulation involved the function of the cytoskeleton. Glucagon and dexamethasone induced various enzymes of amino acid catabolism, such as tryptophan oxygenase, tyrosine aminotransferase and serine dehydratase. These inductions were inhibited by insulin or catecholamine. The effect of catecholamine was due to its alpha-adrenergic action. The beta-action of isoproterenol was low in freshly isolated cells, but increased during culture of the cells. Acquirement of hormonal responses during neonatal development can be studied in this culture system. Mature hepatocytes in culture are usually quiescent, but when insulin and epidermal growth factor were added, DNA synthesis by the cells increased markedly and they showed density-dependent growth. In this culture system, serum could be omitted for 2 days when the dishes were coated with fibronectin without appreciable change of functions, but serum was needed for longer culture of the cells. A factor that increased cell survival was found in serum and in pituitary gland. These results show that hepatocytes in primary culture are a simple and useful system for studies of liver functions in vitro and related works were also reviewed.

Adrenergic beta-Agonists↗

Effects of taurine and ursodeoxycholic acid on liver function tests in patients with cystic fibrosis.

In 9 CF patients with clinical and biochemical evidence of liver disease, taurine (30 mg/kg/day) was administered one month before and during the successive treatment with ursodeoxycholic acid (10-15 mg/kg/day). Standard liver function tests were determined before and after each period of treatment. Taurine administration produced only inconsistent changes of liver function tests from baseline, whereas after the addition of ursodeoxycholic acid a substantial improvement in all abnormal indices was observed. The effects of longer period of treatment are currently investigated, with purpose of establishing their clinical impact and their relationship with changes in bile acid metabolism.

Bile Acids and Salts↗

Liver function, plasma dexamethasone, and DST results in detoxified alcoholics.

Alcohol abuse, alcohol withdrawal, and deterioration of hepatic function have been associated with abnormal dexamethasone suppression test (DST) results. Chronic alcohol abuse may also directly alter the pharmacokinetic disposition of dexamethasone. Plasma dexamethasone concentrations following a DST were determined in 53 detoxified alcoholics. Those with abnormal liver function had higher 4 p.m. plasma dexamethasone concentrations and lower DST cortisol concentrations. Those with normal liver function had lower plasma dexamethasone and higher DST cortisol concentrations consistent with induction of hepatic metabolic enzymes from chronic use of alcohol. The data indicate that liver function is one of the variables influencing dexamethasone disposition and DST cortisol suppression.

Adult↗

Liver function test abnormalities in users of aqueous kava extracts.

INTRODUCTION: Hepatic toxicity from manufactured herbal remedies that contain kava lactones has been reported in Europe, North America, and Australia. There is no evidence for serious liver damage in kava-using populations in Pacific Island societies or in Indigenous Australians who have used aqueous kava extracts. This article presents evidence that liver function changes in users of aqueous kava extracts appear to be reversible. Data from one Arnhem Land community [Northern Territory (NT), Australia] with 340 indigenous people older than 15 years of age in 2000 are used. METHODS: This study was a cross-sectional study with 98 participants, 36 of whom had never used kava. Among 62 kava users, 23 had discontinued kava at least 1 year before the study. Continuing users had not used kava for 1 to 2 months (n = 10) or 1 to 2 weeks previously (n = 15). Some (n = 14) had used kava within the previous 24 hr. Liver function tests were compared across these groups, taking into account differences due to age, sex, alcohol, and other substance use. RESULTS: The average quantity of kava powder consumed was 118 g/week, and median duration of use was 12 years (range, 1-18 years). Kava usage levels were less than one-half of those found in previous studies. More recent kava use was independently associated with higher levels of liver enzymes gamma-glutamyl transferase (GGT) (p < 0.001) and alkaline phosphatase (ALP) (p < 0.001), but not with alanine aminotransferase or bilirubin, which were not elevated. In those who were not heavy alcohol users, only those who used kava within the previous 24 hr showed GGT levels higher than nonusers (p < 0.001), whereas higher ALP levels occurred only in those who last used kava 1 to 2 weeks (p = 0.015) and 24 hr previously (p = 0.005). DISCUSSION: Liver function changes in users of aqueous kava extracts at these moderate levels of consumption appear to be reversible and begin to return to baseline after 1 to 2 weeks abstinence from kava. No evidence for irreversible liver damage has been found.

Adult↗

Liver function and hepatitis markers in carriers of hepatitis B virus in New Zealand.

AIMS: The Hepatitis Foundation has identified many chronic carriers of hepatitis B virus (HBV) in community surveys of schools and family contacts. This study reports the characteristics of carriers and the relationship between hepatitis markers and liver function. METHODS: Demographic data from confirmed chronic carriers of HBV in the North Island were correlated with liver function and hepatitis markers. Longitudinal data were obtained by following a cohort for two years with regular blood tests. RESULTS: Of 2778 confirmed carriers of HBV most were children or young adults and 56% were male. Sixty percent were Maori and 26% Pacific Island people. Loss of HBsAg occurred at less than 1% per year compared to 9% for HBeAg. Mean ages for 50% loss of HBeAg were 14 years for children of HBV negative mothers and 19 years for those of HBV carrier mothers. Fewer adult males than females were HBeAg positive. Alanine aminotransferase levels above 50 IU/L were found in 16% of HBeAg positive and 6% HBeAg negative cases. Other factors significantly associated with raised alanine aminotransferase were male gender (OR 1.8) and age more than 15 years (OR 2.0). Thirty five percent of HBeAg positive carriers with raised alanine aminotransferase levels spontaneously seroconverted to HBeAg negative in two years. However, raised alanine aminotransferase in HBeAg negative carriers was persistent in most cases and 38% had HBV-DNA detectable in serum. CONCLUSIONS: HBV carriage is less benign in adults than children, even after loss of HBeAg. It is recommended that all HBV carriers have regular checks of liver function. Those with persistent abnormality should be strongly advised to restrict alcohol and be assessed for possible antiviral treatment.

Adolescent↗

Sequential changes in relative liver function assessed by 99mTc-HIDA scintigraphy after auxiliary heterotopic liver transplantation in dogs.

Auxiliary heterotopic liver transplantation (HLT) was used to achieve functional repair in a dog model with an inborn error of metabolism. For the interpretation of the results, information on separate liver function is essential when a normal host liver is also present. We developed a radionuclear method to quantitate the relative contribution of each liver to the total uptake of intravenously (IV) injected 99mTc-HIDA. The HLT was performed between 20 mismatched pairs of dogs from two different strains. Four surgical procedures were used. After autopsy the outcome of the premortem HIDA-scan was compared with the wet weight of the graft and the host liver. A good linear correlation was noted between the relative contribution of the uptake and weight of the graft to the total HIDA uptake and total liver weight. Therefore, the relative contribution of an auxiliary heterotopic liver graft to the total liver function can be quantitated with a 99mTc-HIDA scan. With this technique, changes in relative function after an HLT under various flow conditions can be sequentially followed.

Animals↗

[The effect of chronic internal irradiation from incorporated radionuclides on liver function].

On chronic supply to the body of a mixture of nuclear division products lanthanum-140, barium-140, tellurium-132, neodymium-147, neptunium-239, zirconium-95, niobium-95, iodine-131, cerium-141, -144, cesium-134, -137, and ruthenium-103 are detectable in liver tissue within the first months. In the 2 to 4 years following the disaster, liver tissue primarily accumulates cerium-144, radium-226, thorium-228, -232, ruthenium-106, antimony-125, and europium-154. Within the first periods the liver radionuclide content was 19 to 31% higher than that in the blood, and in the following years it was 24 to 38% higher. The radionuclides indicated were actively excreted with the bile into the gastrointestinal lumen. Within the first months after the chronic internal radiation the functional liver disorders were detectable in 30 to 40% of the patients. Later on diverse acute and chronic diseases of the liver, gallbladder and pancreas were detectable in 20 to 30% of the patients. The radionuclide content in the body was found to be in parallel with functional liver disorders. Acceleration of radionuclide excretion from the body results in liver function improvement.

Bile↗

Effects of long-term tea polyphenols consumption on hepatic microsomal drug-metabolizing enzymes and liver function in Wistar rats.

AIM: To investigate the effects of long-term tea polyphenols (TPs) consumption on hepatic microsomal drug-metabolizing enzymes and liver function in rats. METHODS: TPs were administered intragastrically to rats at the doses of 833 mg.kg(-1).d(-1) (n=20) and 83.3 mg.kg(-1).d(-1) (n=20) respectively for six months. Controlled group (n=20) was given same volume of saline solution. Then the contents of cytochrome P450, b5, enzyme activities of aminopyrine N-demethylase (ADM), glutathione S-transferase (GST) and the biochemical liver function of serum were determined. RESULTS: The contents of cytochrome P450 and b5 in the livers of male rats in high dose groups (respectively 2.66 +/- 0.55, 10.43 +/- 2.78 nmol.mg MS pro(-1)) were significantly increased compared with the control group (1.08 +/- 1.04, 5.51 +/- 2.98 nmol.mg MS pro(-1); P<0.01, respectively). The enzymatic activities of ADM in the livers of female rats in high dose groups (0.91 +/- 0.08 mmol.mg MS pro(-1)min(-1)) were increased compared with the control group (0.82 +/- 0.08 mmol.mg MS pro(-1).min(-1); P<0.05). The GST activity was unchanged in all treated groups, and the function of liver was not obviously changed. CONCLUSION: The antidotal capability of rats' livers can be significantly improved after long-term consumption of TPs. There are differences in changes of drug-metabolizing enzymes between the sexes induced by TPs and normal condition.

Aminopyrine N-Demethylase↗

Hepatic resection of hepatocellular carcinoma in cirrhotic livers: is it unjustified in impaired liver function?

BACKGROUND: Resection for hepatocellular carcinoma in patients with cirrhosis and impaired liver function is usually unjustified because of higher surgical risks and poorer long-term prognosis. METHODS: A retrospective comparison of the background and resectional results of patients with cirrhosis and hepatocellular carcinoma was carried out between those with preoperative indocyanine green 15-minute retention rate of 20% or greater (group A, impaired function group, n = 36) and those with indocyanine green 15-minute retention rate of 10% or less (group B, normal function group, n = 34). RESULTS: The group A patients had significantly lower serum albumin level and higher serum bilirubin level, longer prothrombin time, higher incidence of associated esophageal varices, and poorer Child's classifications for cirrhosis. Although the tumor diameter in both groups was similar (A, 6.9 versus B, 7.1 cm; p = 0.94), the resected liver amount in group B was greater (227.4 versus 473.2 gm; p = 0.038) because of a greater extent of liver resection (p < 0.001) and a wider surgical margin (0.34 versus 1.85 cm; p < 0.0001). The amount of operative blood loss and blood transfusion, operative morbidity, and operative mortality were not different between the two groups. The pathologic characteristics and staging were also comparable. The 5-year disease-free and actuarial survival rates of groups A and B were 30.9% and 29.6% (p = 0.16) and 45.2% and 33.4% (p = 0.11), respectively. CONCLUSIONS: If the amount of resected nontumorous liver parenchyma could be reduced, resection of hepatocellular carcinoma in selected patients with cirrhosis and impaired liver function is still justified in spite of a narrow surgical margin.

Adult↗

[The effects of induced hypotension with sevoflurane and PGE1 on liver functions during neurosurgery].

The effects of induced hypotension with sevoflurane and PGE1 (Group S) on liver functions during neurosurgery that can avoid direct invasion of the liver were retrospectively studied in 35 cases, in comparison with 8 cases of isoflurane and PGE1 induced hypotension (Group I). GOT, GPT and gamma-GTP increased slightly in both groups 1 day and 1 week after operation, but they returned to preoperative levels 1 month later. ChE decreased in both groups, and the decrease was greater in group S. Three cases in Group S (8.6%) and one case in Group I (12.5%) showed GOT or GPT over 100 and there was no significant difference in the two groups. Hypotensive anaesthesia induced with sevoflurane and PGE1 in neurosurgery, as that induced with isoflurane and PGE1, has little effect on postoperative liver functions.

Aged↗

Effect of in utero exposure of Toddy (coconut palm wine) on liver function and lipid metabolism in rat fetuses.

The objective of this study was to determine the effects of a country liquor Toddy (Coconut palm wine) and an equivalent quantity of ethanol on liver function and lipid metabolism in utero. Female albino rats with an average weight of 125 +/- 5 g were exposed to Toddy from coconut palm (24.5 ml/kg body weight/day) and ethanol (0.52 ml/kg body weight/day) for 15 days before conception and during pregnancy. On day 13 and day 19 of gestation, altered liver function and hyperlipidemia were seen in the fetuses of both the treated groups. Altered liver function was evidenced by the increased activity of alcohol dehydrogenase, aldehyde dehydrogenase, glutamic oxaloacetic transaminase (aspartate amino transferase (GOT)), glutamic pyruvic transaminase (alanine amino transferase (GPT)). Hyperlipidemia was caused by increased biosynthesis since the incorporation of 14C acetate into lipids and activities of HMG CoA reductase and lipogenic enzymes were elevated. Toddy treated fetuses were more severely affected than those exposed to an equivalent quantity of ethanol. Toddy seemed to potentiate the toxicity induced by alcohol suggesting the role of non alcoholic components. Hepatic functions of the day 13 fetuses were effected to a lesser degree than those in the day 19 hepatic liver.

Alanine Transaminase↗