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PubMed2003

Liver-specific reactivation of the inactivated Hnf-1alpha gene: elimination of liver dysfunction to establish a mouse MODY3 model.

Mice deficient in hepatocyte nuclear factor 1 alpha (HNF-1alpha) develop dwarfism, liver dysfunction, and type 2 diabetes mellitus. Liver dysfunction in HNF-1alpha-null mice includes severe hepatic glycogen accumulation and dyslipidemia. The liver dysfunction may appear as soon as 2 weeks after birth. Since the HNF-1alpha-null mice become diabetic 2 weeks after birth, the early onset of the liver dysfunction is unlikely to be due to the diabetic status of the mice. More likely, it is due directly to the deficiency of HNF-1alpha in liver. Although the HNF-1alpha-null mice have an average life span of 1 year, the severe liver phenotype has thwarted attempts to study the pathogenesis of maturity-onset diabetes of the young type 3 (MODY3) and to examine therapeutic strategies for diabetes prevention and treatment in these mice. To circumvent this problem, we have generated a new Hnf-1alpha mutant mouse line, Hnf-1alpha(kin/kin), using gene targeting to inactivate the Hnf-1alpha gene and at the same time, to incorporate the Cre-loxP DNA recombination system into the locus for later revival of the Hnf-1alpha gene in tissues by tissue-specifically expressed Cre recombinase. The Hnf-1alpha(kin/kin) mice in which the expression of HNF-1alpha was inactivated in germ line cells were indistinguishable from the HNF-1alpha-null mice with regard to both the diabetes and liver phenotypes. Intriguingly, when the inactivated Hnf-1alpha gene was revived in liver (hepatic Hnf-1alpha revived) by the Cre recombinase driven by an albumin promoter, the Hnf-1alpha(kin/kin) mice, although severely diabetic, grew normally and did not develop any of the liver dysfunctions. In addition, we showed that the expression of numerous genes in pancreas, including a marker gene for pancreas injury, was affected by liver dysfunction but not by the deficiency of HNF-1alpha in pancreas. Thus, our hepatic-Hnf-1alpha-revived mice may serve as a useful mouse model to study the human MODY3 disorder.

Alleles↗

PubMed1991

Euro-Collins solution versus UW-solution for long-term liver preservation in the isolated rat-liver perfusion model.

To compare UW-solution (UW) and Euro-Collins (EC) for long-term liver preservation we investigated the morphology and metabolic capacity of rat liver after 18 and 42-hours cold-storage in either UW or EC. After harvesting the rat liver was transferred to a perfusion chamber where it was perfused for 10 min with UW or EC at 4 degrees C. Thereafter livers were stored at 4 degrees C in UW or EC for 18 hours (both groups n = 6) or for 42 hours (both groups n = 8). After 18-hr or 42-hr cold-storage a 2-hr warm perfusion (37 degrees C) was started with Krebs-Ringer solution with carbogen to which 125Iodine-triiodothyronine (T3) was added. Control livers (n = 8) were immediately perfused with Krebs-Ringer without cold-storage. The following parameters were assessed: ASAT-levels in the perfusate, T3-metabolites in the bile and the perfusate, the perfusion pressure, the volume of bile secreted and light-microscopical morphology at the end of the warm perfusion period. After cold storage in UW-solution the ASAT-levels in the perfusate were lower than after storage in EC as well as the perfusion pressures. These livers demonstrated a better T3-metabolism and secreted more bile than EC-stored livers. Histological examination showed more tissue damage in the EC-stored livers than in the UW stored livers. We conclude that cold-storage of rat liver in UW-solution resulted in a better morphology and metabolic capacity as compared with EC-solution.

Adenosine↗

PubMed2001

Cytochrome P450 3A expression in the human fetal liver: evidence that CYP3A5 is expressed in only a limited number of fetal livers.

CYP3A is the major cytochrome P450 subfamily constitutively expressed in the human liver. CYP3A4 is the predominant hepatic P450 form in adults and it is expressed at high but very variable levels among individuals. The fetal liver contains mainly CYP3A7, while the presence of the other CYP3A enzymes in fetal liver has remained controversial. In this study, the relative levels of CYP3A4, CYP3A5 and CYP3A7 expression were determined in a panel of 9-11 fetal livers with a similar gestation age (9-12 weeks) and compared to adult livers. CYP3A7 was found to be the major CYP3A form in all the fetal liver samples. The abundance of CYP3A7 varied more at the mRNA (77-fold variation) than at the protein level (4.8-fold variation). CYP3A5 mRNA was also detected in all of the fetal liver samples, but the average level was 700-fold lower than that of CYP3A7. CYP3A5 protein was detected by immunoblot analysis in only 1 fetal liver out of the 9 investigated, the level of expression being moderately high in this sample. CYP3A4 mRNA was detected in only a subset of the fetal liver samples and its level was the lowest of the CYP3A forms. This is the first study to demonstrate the polymorphic expression of CYP3A5 and the variability of CYP3A7 expression in fetal liver and suggests that significant interindividual differences in the metabolism of xenobiotics may already exist at the prenatal stage. These differences may contribute to individual pharmacological and/or toxicological responses in the fetus.

Aryl Hydrocarbon Hydroxylases↗

PubMed1980

Fluorophosphate-sensitive esterases in mammalian liver: the radioautographic localization and measurement of fluorophosphate-reactive sites in adult rat liver.

Fluorophosphate-reactive (FPR) sites in the adult male rat liver, tentatively identified as esterase active centers, were localized and measured using the combined techniques of quantitative electron microscope radioautography and morphometric analysis with the light and electron microscope. The FPR sites were measured in liver which had been prefixed by perfusion with 1.5% glutaraldehyde and reacted with 10(-4) M tritium-labeled diisopropyl fluorophosphate (3H-DFP). Under the experimental conditions 64-67% of the esterase activity in fresh liver was retained for reaction with the 3H-DFP, which is known to bind irreversibly to the active sites of certain esterases. In light and electron microscope radioautographs the developed silver grains were concentrated over the cytoplasm of hepatocytes. A low concentration occurred over erythrocytes. All other areas in the liver had a concentration of grains resembling the background concentration. Quantitative measurements of grain density in the electron microscope radioautographs revealed the highest density, after correcting for radiation spread, in cytoplasmic granules (mainly cytolysomes). The grain densities over the rough and smooth endoplasmic reticulum and associated structures were also equal to or above the average hepatocyte grain density. Due to the large fractional volume of endoplasmic reticulum per hepatocyte (58% of cell volume) and the fraction of the liver occupied by hepatocytes (79% of liver volume) the majority of FPR sites in the liver occurred in the rough and smooth endoplasmic reticulum and associated structures. The average numbers of FPR sites were calculated per micrometer3 of hepatocyte (5.0 x 10(5) sites/micrometer3) and per unit volume of each significantly labeled organelle. In addition, the number of FPR sites per hepatocyte (2.5 X 10(9) sites/cell), per cm3 liver (4.1 X 10(17) sites/cm3) and in the total liver of an average 100 g male rate (2.2 X 10(18) sites/total liver) were also calculated.

Animals↗

PubMed1981

Role of the hypothalamo-pituitary-liver axis in sex differences in susceptibility of the liver to toxic agents.

At birth testicular androgens irreversibly program brain centers involved in hypothalamopituitary control of hepatic sex-dependent steroid and drug metabolism. This imprinting process results in activation of a hypothalamic "feminostatin"-a secreting center that is turned on just before puberty. Feminostatin inhibits pituitary secretion of "feminizing factor," a pituitary hormone that feminizes the basal type of metabolism characterizing the liver of hypophysectomized and gonadectomized rats. Consequently, female rats that are devoid of feminostatin will secrete feminizing factor from the pituitary, leading to a feminine type of hepatic metabolism. Male rats have an active feminostatin-secreting center, and inhibition of pituitary feminizing factor release results in an autonomous type of liver metabolism. Female rats show a relative androgen unresponsiveness and seem incapable of releasing feminostatin after treatment with natural androgens, possibly because of more efficient metabolism (breakdown) of androgen in the female than in the male rat brain. Frontal deafferentation at the retrochiasmatic and suprachiasmatic level resulted in a complete "feminization" of hepatic steroid metabolism in male rats. Such an effect was also seen when lesions involving mainly the anterior periventricular hypothalamic area and the suprachiasmatic nucleus were performed in male rats. No effects were seen in analogous lesions in female rats in any of the cases studied. These findings suggest that a region including the anterior hypothalamic periventricular area, the suprachiasmatic nucleus and adjacent areas is involved in the control of hepatic steroid metabolism. It is postulated that the neuronal cell bodies that produce feminostatin have their origins in this area of the hypothalamus or may send axons through this area to the basal hypothalamus and thus directly or indirectly influence the anterior pituitary gland. Regulation by the central nervous system of a "lactogenic" (prolactin, Prl) receptor, present in the female rat liver, was also studied. This receptor is present in very low concentration or absent in the male rat. Anterior hypothalamic deafferentation at the retrochiasmatic level in male rats increased the hepatic Prl receptor concentration to the female level 3-4 days following the operation. A transection rostral to the suprachiasmatic nucleus had no effect on the concentration of Prl receptors in male animals. Our results demonstrate that the number of Prl receptors is regulated by the hypothalamo-pituitary system. The receptor-inducing pituitary factor might be related to the feminizing factor. Experiments were carried out to elucidate the nature of the Prl receptor-inducing pituitary factor. Human growth hormone (hGH) continuously administered was shown to induce Prl receptors in livers from male and female hypophysectomized-gonadectomized rats. The prolactin receptors were increased to a level found in control female rat livers. This inductive effect of hGH was also seen in adrenalectomized and thyroidectomized male rats. The induced Prl receptors in male rats had similar characteristics as hepatic Prl receptors in female rats. Also the endogenous rat hormones, rPrl and rGH, were administered in minipumps. In the concentration used (10 mug/mul), rPrl had no effect whereas rGH increased Prl receptor levels to approximately 37% of the female control level. These results indicate that GH or a peptide related to GH may be involved in the regulation of hepatic Prl receptors. The hypothalamo-pituitary-liver axis represents a new concept in endocrine regulation of drug toxicity. The male rat liver has been shown to be more susceptible than the female rat liver to the hepatocarcinogenic action of certain drugs, and it is conceivable that sex differences in the metabolic activation of the drugs in the liver may explain the greater sensitivity of male rats to chemically induced hepatocellular carcinoma. Similar sex differences in liver cancer incidence have been reported in the human.

Aging↗

PubMed1986

Conversion of T4 to T3 in perfused liver of rats with carbontetrachloride-induced liver injury.

To evaluate the effect of hepatocellular damage on thyroid hormone metabolism, the conversion of T4 to T3 in the perfused liver of rats with carbontetrachloride (CCl4)-induced liver injury was investigated. The liver was perfused non-recyclically with a synthetic medium containing 10 micrograms/dl T4 for 30 min, and the T3 production and the conversion of T4 to T3 were examined. The serum T3 level was significantly (P less than 0.05) lower in liver-injury rats (72 +/- 9 ng/dl) compared with controls (88 +/- 10 ng/dl). The uptake of T4 (4.15 +/- 0.85 micrograms/g/30 min), net T3 production (180 +/- 48 ng/g/30 min), and conversion rate of T4 to T3 (4.4 +/- 0.9%) in the perfused liver of liver-injury rats were similar to the values (3.78 +/- 0.66 micrograms/g/30 min, 191 +/- 31 ng/g/30 min, and 5.0 +/- 1.0%) in control rats, whereas the release of T3 (12.7 +/- 3.2 ng/g/30 min) in the effluent in injured livers was significantly (P less than 0.05) lower than that (16.9 +/- 3.0 ng/g/30 min) in control livers. We concluded that in CCl4-induced liver-injury rats, the low serum T3 level may partly be due to the decreased release of T3 from liver cells after conversion of T4 to T3 rather than to a decreased conversion of T4 to T3.

Alanine Transaminase↗

PubMed2005

Growth hormone regulates the expression of hepatocyte nuclear factor-3 gamma and other liver-enriched transcription factors in the bovine liver.

Growth hormone (GH) regulates the expression of many genes in the liver, and for some genes this regulation may be mediated through liver-enriched transcription factors (LETFs). As part of the long-term goal to investigate the role of LETFs in GH regulation of gene expression in the liver, in this study we determined the effect of GH administration on the expression of 10 LETFs, including hepatocyte nuclear factor (HNF)-1alpha, HNF-1beta, HNF-3alpha, HNF-3beta, HNF-3gamma, HNF-4alpha, HNF-6, CCAAT/enhancer-binding protein (C/EBP) alpha, C/EBPbeta, and albumin D-element binding protein (DBP) in the bovine liver. Eighteen non-lactating and non-pregnant Angus cows were assigned randomly to three groups (n=6 per group) and each cow received a single intramuscular injection of 500 mg slow-release recombinant bovine GH. Liver biopsy samples were taken from group 1 cows 6 h after GH administration, from group 2 cows 24 h after GH administration, and from group 3 cows 1 week after GH administration. Liver biopsies were also collected from group 3 cows 1 day before GH administration, serving as pre-GH controls. The LETF mRNAs in these liver samples were quantified using ribonuclease protection assays with probes generated from bovine LETF cDNAs cloned by standard reverse transcription-polymerase chain reaction. The levels of HNF-3gamma and HNF-6 mRNAs were higher (P< 0.05) in the cows 24 h and 1 week after GH administration than in the untreated cows or the cows 6 h after GH administration. The levels of HNF-4alpha mRNA were higher (P< 0.05) in the cows 1 week after GH administration than in the other three groups of cows. The levels of C/EBPalpha mRNA were higher (P< 0.05) in the cows 24 h after GH administration than in the untreated cows or the cows 6 h after GH administration. The levels of HNF-3alpha mRNA were higher (P< 0.05) in the cows 6 h after GH administration but were lower (P< 0.05) in the cows 24 h or 1 week after GH administration compared with those in the untreated cows. The levels of DBP mRNA were higher (P< 0.05) in the cows 6 h after GH administration but were lower (P< 0.05) in the cows 24 h after GH administration compared with those in the untreated cows. The levels of HNF-1alpha, HNF-3alpha, and C/EBPbeta mRNAs were not different (P>0.05) between groups. The expression of HNF-1beta mRNA was not detectable. Thus, the expression of six LETFs including HNF-3gamma , HNF-3beta, HNF-4alpha, HNF-6, C/EBPalpha, and DBP mRNAs in the bovine liver is regulated by GH, and these six LETFs may play a role in mediating GH regulation of gene expression in the liver. Among the 10 LETFs, the response of HNF-3gamma to GH is most significant. Cloning and sequencing the promoter region of this gene revealed multiple putative binding elements for signal transducers and activators of transcription 5 (STAT5), suggesting that GH regulation of HNF-3gamma expression in the liver may be mediated through direct binding of STAT5 to the HNF-3gamma promoter.

Animals↗

PubMed1995

Estimates of zinc and iron bioavailability in pork liver and the effect of sex of pig on the bioavailability of copper in pork liver fed to male and female chicks.

Four chick experiments were conducted to investigate possible explanations for why Cu bioavailability in pork liver is zero. One possible explanation was that pork liver contains compounds, such as Zn, that directly or indirectly inhibit Cu utilization. It has also been suggested that sex differences may influence Cu bioavailability. The effect of freeze-dried (FD) pork liver from gilts vs barrows was first examined. Neither FD gilt liver nor FD barrow liver provided any bioavailable Cu to chicks. The effect of sex of the chicks used in the assay (i.e., male chicks vs female chicks) was also examined, but there were no sex-dependent differences (P > .10) in the slopes of the standard curve generated by added Cu from CuSO4 or in the responses to added FD pork liver. Based on bone Zn uptake, Zn bioavailability in FD barrow liver and FD gilt liver was not different (P > .04) from that in ZnSO4, but Fe bioavailability (hemoglobin repletion assay) was approximately 40% (P < .05) of that in FeSO4 in both FD gilt liver and FD barrow liver.

Animal Feed↗

PubMed1978

Lipid metabolism in laying hens. The relationship of plasma lipids and liver fatty acid synthetase activity to changes in liver composition.

Plasma and liver samples were taken from a random sample of caged commercial hybrid layer hens which had been in egg production for fifteen months. The concentration of plasma and liver lipids and the activity of liver fatty acid synthetase (FAS) were measured in laying hens with liver weight of 20 to 53 g. Liver total lipid, water, non-lipid, and cytosolic fractions, which are the four major liver components, increased linearly with respect to wet liver weight. FAS activity increased with all liver components. Accumulation of lipid in the liver did not inhibit FAS activity. Total cholesterol, free cholesterol, esterified cholesterol, triglycerides, and phosphorous were measured on each plasma sample. Multiple regression analysis showed that all plasma lipids, except cholesterol esters, were related cubically with increasing wet liver weight and cytosolic protein.

Animals↗

PubMedDate not supplied

Correlation of 14C-griseofulvin metabolism in rat liver microsomes, isolated perfused rat livers, and in rats with bile duct cannulas.

The metabolism of 14C-griseofulvin has been compared in rat liver microsomes, isolated perfused rat livers, and rats with bile duct cannulas. In all three preparations, 4-desmethylgriseofulvin and 6-desmethylgriseofulvin were the major metabolites. The ratio of total 4-desmethylgriseofulvin to 6-desmethylgriseofulvin formed was 1.20, 0.89, and 1.01 in liver microsomes, isolated perfused livers, and rats with bile duct cannulas, respectively. After a 7-min incubation with liver microsomes, most (96%) of the griseofulvin remained unchanged. Only small amounts of 4-desmethylgriseofulvin (1.26%) of dose) and 6-desmethylgriseofulvin (1.05% of dose) were formed. In isolated perfused liver, most of the drug (59% of dose) was excreted into bile within 4 hr, primarily as 4-desmethylgriseofulvin (24% of dose) and 6-methylgriseofulvin (24% of dose). In animals with bile duct cannulas, 65% of the dose was excreted into bile and 18% of the dose into urine within 4 hours. In bile, 32% of the dose was excreted as 4-desmethylgriseofulvin and 20% of the dose as 6-desmethylgriseofulvin, whereas in urine the drug was excreated predominantly as 6-desmethylgriseofulvin (13% of dose) with only a small amount of 4-desmethylgriseofulvin (1% of dose), during the first 4 hr. These results show that there is good correlation in the metabolic fate of 14C-griseofulvin in the liver microsomes, isolated perfused liver, and rats with bile duct cannulas. In addition to the similar ratio of 4-desmethylgriseofulvin to 6-desmethylgriseofulvin, there is also an agreement in the extent of metabolism and biliary excretion in isolated perfused liver and in rats with bile duct cannulas, which suggests that the isolated perfused liver is an important technique for studying drug metabolism in animals.

Animals↗

PubMed2003

Preoperative right portal vein embolization in patients with metastatic liver disease. Metastatic liver volumes after RPVE.

PURPOSE: To quantify liver metastases and future remnant liver (FRL) volumes in patients who underwent right portal vein embolization (RPVE) and to evaluate the effects of this procedure on metastase growth. MATERIAL AND METHODS: Nine patients with liver metastases from primary colon (n = 5), rectal lesions (n = 1) and carcinoid tumors (n = 3) underwent spiral CT to evaluate the ratio of the non-tumorous parenchymal volume of the resected liver to that of the whole liver volume (R2). Hand tracing was used to isolate the entire liver, the resected liver and metastase volumes. All patients with R2 > 60% underwent RPVE. RESULTS: FRL exhibited a 101-336 cm3 (average 241 cm3) increase in volume 1 month after RPVE. One patient refused surgery for 2 months and before surgery the increase in volume of the FRL was similar to that of other patients (180.64 cm3). Percent metastases volume from colorectal carcinoma in embolized liver parenchyma increased from 62.4% to 138.4% at 1 month and to 562% at 2 months after RPVE. Metastase volume from carcinoid tumors was unchanged. CONCLUSION: One month after RPVE, hypertrophy of the FRL is evident. In the embolized liver, there was a progressive increase in metastase volume from colorectal carcinoma while metastase volume from carcinoid tumor was unchanged in embolized and non-embolized liver.

Adult↗

PubMed2004

[Influence of liver lesions and vitamin K1 on bleeding after liver biopsy in patients with chronic renal failure].

OBJECTIVE: To investigate the influence of liver lesions and vitamin K1 on bleeding after liver biopsy in patients with chronic renal failure and hepatitis virus infection. METHODS: Ninety-two renal transplant recipients on hemodialysis with hepatitis B or C virus infection received percutaneous liver biopsy. The severities of liver inflammation and fibrosis were evaluated by semi-quantitative technique. Thirty-four patients were given intramuscular injection of vitamin K1 before liver biopsy at the dose of 10 mg twice daily for 3 days. RESULTS: The total incidence of bleeding after liver biopsy was 12.0% (11/92) in these patients, and the use of vitamin K1 did not significantly influence the incidence of bleeding, nor did the degree of liver lesions. CONCLUSIONS: Bleeding occurred with a relatively high incidence after liver biopsy in patients with chronic renal failure and hepatitis virus B or C infection; vitamin K1 before liver biopsy could not reduce the incidence of bleeding, which is not correlated with the degree of liver lesions.

Biopsy↗

PubMed2005

[Three cases of multiple colorectal liver metastases responding to hepatic arterial infusion chemotherapy undergoing liver resection].

We encountered three cases of multiple liver metastases of colorectal cancer treated with hepatic resection after hepatic arterial infusion. Case 1: A 55-year-old female underwent sigmoidectomy for sigmoid colon cancer and six liver metastases. After responding postoperatively to hepatic arterial infusion chemotherapy (HIA), she underwent resection of liver metastases. Case 2: A 66-year-old man underwent colectomy and hepatic resection for cecal colon cancer and liver metastasis. Multiple liver metastases appeared six months after the operation. HIA resulted in a complete response. Liver metastases recurred twice and liver resection was performed each time. Case 3: A 52-year-old female underwent partial resection of colon and liver for ascending colon cancer and multiple liver metastases. After she responded postoperatively to HIA and systemic chemotherapy, the patient underwent resection of liver metastases. Case 1 has lung metastases at this writing. The other two patients are alive and well, and have been free from recurrence as of 4 years after operation.

Aged↗

PubMed2005

[Differentiation of bone marrow derived Thy-1+ beta2M- cells into liver cells in AA induced liver injury micro-environment].

OBJECTIVE: To investigate the differentiation of bone marrow derived Thy-1+ beta2M- cells (BDTCs) into liver cells in allyl alcohol (AA) induced liver injury micro-environment. METHODS: BDTCs of male F344 rats were isolated by two-step magnetic separation system (MACS) technique, and infused intraportally into female recipients after labeling with PKH26. Thirty recipients were divided randomly into 3 groups: (1) AA-injured liver + BDTCs infusion, (2) normal liver + BDTCs infusion and (3) AA-injured liver + NS infusion (control). Blood biochemical examination, fluorescence labeled cellular localization, Y-chromosome sry gene in-situ hybridization and immunohistochemistry were carried out to evaluate BDTCs distribution, differentiation and proliferation in recipients's livers after different intervals. RESULTS: Fluoromicroscopy and in situ hybridization suggested that BDTCs of donors were interspersed in pieces and cords among the necro-periportals induced by AA; immunohistochemistry indicated that those implanted cells expressed OV-6, AFP, CK19 and albumin successively, while positive cells were hardly seen in the normal liver + BDTCs infusion group. Compared with the controls, the blood biochemical restitution was more rapid in group (1), (9.8 d +/- 3.1 d vs. 13.7 d +/- 4.2 d). CONCLUSION: The injury micro-environment induced by AA facilitates BDTCs integration with hepatic cell plates and differentiation into mature liver cells. BDTCs differentiation into liver cells might accelerate endogenous liver cell regeneration and reparation.

Animals↗

PubMed1995

Transcription factor and liver-specific mRNA expression in facultative epithelial progenitor cells of liver and pancreas.

The pattern of mRNA expression for liver-specific proteins and liver-enriched transcription factors was studied in two models of facultative gut epithelial progenitor cells activation: D-galactosamine (GalN)-induced liver injury and dietary copper depletion leading to pancreatic acinar atrophy. After 5 weeks of copper deficiency (CuD), pancreatic acini of Fischer 344 rats underwent atrophy, associated with intense proliferation of small duct-like cells with oval-shaped nuclei. These cells resemble morphologically epithelial progenitor cells of the liver that proliferate after GalN administration. Activated pancreatic epithelial cells express mRNAs for liver-specific genes normally expressed in fetal liver, including alpha-fetoprotein, albumin, alpha-1 antitrypsin, glucose-6-phosphatase, and others, but not genes that are turned on after birth such as serine dehydratase, tyrosine aminotransferase, and multidrug resistance gene-1b. They express mRNAs for liver-enriched transcription factors including HNF-1 alpha, HNF-3 beta and gamma, HNF-4, and members of the CCAAT-enhancer binding protein (C/EBP) family. The only mRNA for a liver-enriched transcription factor not detected in the pancreas of CuD animals was HNF-3 alpha. Expression of HNF-3 alpha, beta, and gamma, and C/EBP-beta mRNA was highly activated in proliferating liver epithelial cells on days 2 and 3 after GalN injury. Increased expression of C/EBP-delta was observed first in the liver on day 1 after GalN administration and in the pancreas at 4 weeks after initiating CuD. We suggest that C/EBP-delta could be involved in the initial activation of epithelial progenitor cells and that HNF-3 alpha, beta, and gamma, and C/EBP-beta might participate in their maturation. We conclude further that pancreatic epithelial progenitor cells undertake differentiation through the hepatocyte lineage but cannot complete the differentiation program within the pancreatic milieu.

Animals↗

PubMed1995

[Fulminant liver failure before and after introduction of liver transplantation at Rikshospitalet].

The impact of liver transplantation on the survival in fulminant hepatic failure was evaluated in a retrospective study including 87 patients admitted to Rigshospitalet over a three and a half year period before and a three and a half year period after the Danish liver transplantation programme was started. The number of admissions increased by 178% in the second period. Fifty-two percent of the patients had acetaminophen induced liver failure, which over the last seven years has become the most common cause of severe acute liver disease in Denmark. In about half of the patients high volume plasmapheresis was used as liver-assist either alone or in combination with liver transplantation. Three patients in grade 4 hepatic coma (one with Hepatitis B, two with acetaminophen intoxication) were withdrawn from the waiting list for emergency liver transplantation after high volume plasmapheresis due to recovery. In patients with an estimated survival chance of less than 5-10% liver transplantation was performed with a survival rate of 60%. The survival rate for the non-liver transplanted patients was 49% in the same period compared to 30% in the three and a half year period before liver transplantation started.

Acetaminophen↗

PubMedDate not supplied

Resectional liver surgery in metastatic liver disease.

BACKGROUND/AIMS: To increase resectability rate and decrease intra-hepatic recurrence of metastatic liver disease of patients suffering from secondary liver tumors. Metastatic liver disease remains challenging and life threatening. At the time of diagnosis only 10% of patients are amenable to liver resection and of those 60-70% will develop recurrence in the residual liver 16 to 24 months following liver resection METHODOLOGY: Seventy patients out of a total number of 305 seen between November 1991 and May 1998, underwent combined liver resection followed by adjuvant locoregional targeted immunochemotherapy. Patients were divided in two groups. Group A (n=32) had uni-lobular localization of their disease and group B (n=38) had bi-lobular spread of the disease, but tumor occupied was less than 70% of liver surface. All had hepatic resection followed by adjuvant immuno-chemotherapy. RESULTS: Group A (n=32) had a 5 year survival of 75% with 8 patients alive more than 6 years and a mean survival for alive and dead patients of 50 months. Group B (n=38) had a mean survival of 40 months with 6 patients alive longer than 5 years. CONCLUSIONS: Liver resection combined with adjuvant immuno-chemotherapy enhances overall long-term survival in both patients with limited and advanced metastatic liver disease, and is recommended as a promising therapeutical alternative.

Adult↗

PubMed2005

Effects of artificial liver support system on patients with acute or chronic liver failure.

AIMS: Acute on chronic liver failure (AoCLF) is associated with a high mortality rate. Artificial liver support system (ALSS) is useful to bridge patients with liver failure to liver transplantation or to regenerate their own livers. The aims of this prospective study were to investigate the effects of ALSS on clinical manifestations, liver function, and 30-day survival to probe the factors related to mortality in patients with AoCLF. METHODS: In this study, 338 enrolled patients with AoCLF who received ALSS treatment for 1 to 8 sessions, were compared with 312 patients treated with conventional medications. RESULTS: Clinical manifestations and liver functions were significantly improved, namely, decreased levels of serum transaminases, total bilirubin, and bile acid, as well as increased levels of serum albumin following ALSS treatment. The 30-day survival rates of the patients who received ALSS versus controls were 47.9% versus 34.6%, respectively (P = .01). The MELD score and the stage of hepatic encephalopathy were highly associated with mortality (P < .001), but the sessions of ALSS showed a positive relation to the 30-day survival (P < .05). CONCLUSIONS: ALSS appears to be efficacious and safe for the treatment of patients with AoCLF. Both model for end-stage liver disease (MELD) score and hepatic encephalopathy are useful to predict the mortality of patients.

Adolescent↗