Loss of trefoil factor 1 inhibits biliary regeneration but accelerates the hepatic differentiation of progenitor cells in mice.

Although the regeneration of the adult liver depends on hepatic progenitor cells (HPCs), many uncertainties regarding hepatic regeneration in the injured liver remain. Trefoil factor family 1 (TFF1), a secretory protein predominantly expressed in the gastrointestinal tract, is responsible for mucosal restitution. Here, we investigated the role of TFF1 in liver regeneration using a mouse model of hepatic injury (choline-deficient ethionine-supplemented diet and carbon tetrachloride administration) and genetically engineered mice (TFF1 knockout (TFF1-/-)). Immunohistochemistry analysis of human liver samples revealed TFF1 expression in the hepatocytes close to ductular reaction and the regenerating biliary epithelium in injured liver. The number of cytokeratin 19 (CK19)-positive bile ducts was significantly decreased in the TFF1-/- mice after liver injury. Notch pathway in the TFF1-/- mice was also downregulated. HPCs in the control mice differentiated into biliary cells (CK19+/SRY HMG box 9 (SOX9)+) more frequently. In contrast, HPCs in the TFF1-/- mice more frequently differentiated into a hepatic lineage (alpha fetoprotein+/SOX9+) after acute liver damage. Hepatocyte proliferation was upregulated, and the liver weight was increased in TFF1-/- mice in response to chronic liver damage. Thus, TFF1 is responsible for liver regeneration after liver injury by promoting HPC differentiation into a biliary lineage and inhibiting HPC differentiation into a hepatic lineage.

Metabolic characterization of hepatocellular carcinoma using nontargeted tissue metabolomics.

Hepatocellular carcinoma has a poor prognosis due to its rapid development and early metastasis. In this report, we characterized the metabolic features of hepatocellular carcinoma using a nontargeted metabolic profiling strategy based on liquid chromatography-mass spectrometry. Fifty pairs of liver cancer samples and matched normal tissues were collected from patients having hepatocellular carcinoma, including tumor tissues, adjacent noncancerous tissues, and distal noncancerous tissues, and 105 metabolites were filtered and identified from the tissue metabolome. The principal metabolic alternations in HCC tumors included elevated glycolysis, gluconeogenesis, and ß-oxidation with reduced tricarboxylic acid cycle and Δ-12 desaturase. Furthermore, increased levels of glutathione and other antioxidative molecules, together with decreased levels of inflammatory-related polyunsaturated fatty acids and phospholipase A2, were observed. Differential metabolite levels in tissues were tested in 298 serum specimens from patients with chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Betaine and propionylcarnitine were confirmed to confer good diagnostic potential to distinguish hepatocellular carcinoma from chronic hepatitis and cirrhosis. External validation of cirrhosis and hepatocellular carcinoma serum specimens further showed that this combination biomarker is useful for diagnosis of hepatocellular carcinoma with a supplementary role to α-fetoprotein.

[Rationale for using essential phospholipids in chronic diseases of the liver: the dynamics of electric and viscoelastic parameters of erythrocytes].

Under supervision there were 38 men (age from 36 till 57 years) with diffuse hepatic diseases (DHD) in stadia of hepatitis, 27--in dynamics of treatment of essential phospholipids. Is experimentally established: structure-functional erythrocyte characteristics by methods of dielectrophoresis, thin-layer chromatography correlate with lipid and phospholipid composition of red cell membranes. The low level of phospholipids in erythrocyte membranes and direction of changes in their fractional composition in the DHD is the basis for the use of essential phospholipids. Against the background of therapy noted a significant increase in amplitude of deformation, polarizability, capacity, speed of movement of red blood cells to the electrodes and lower levels of generalized indicators of viscosity, rigidity, electrical conductivity, index of aggregation and destruction.

[Correction of glutamine metabolism impairments in the operated liver with chronic hepatitis by hyperbaric oxygen].

Application of hyperbaric oxygenation (HBO, 3 ata, 1 session for 50 min per day) during the first three days after liver resection (LR, 15-20% from the organ mass) in animals with chronic toxic hepatitis (CCl4, 50%, 0,1 ml/per 100 g of body mass, subcutaneously, once in 2 days, 65 days) eliminates a deficit of glutamine and glutamate in an operated liver and prevents accumulation of the endogenic toxin, ammonia, caused by combined effects of CCl4 and LR. Thus hyperbaric oxygen modulates the effect of the LR on the activity of key enzymes of the glutamine metabolism in liver: glutamine synthetases (GS) and phosphate-dependent glutaminases (PDG). HBO enhanced and prolonged the LR effect of the GS activity and restricted analogous changes in PDG during an early (3 day) postoperative period and promoted a delayed transient stimulation in the late (7 day) postoperative period. In contrast to non-oxygenated animals with LR this was not accompanied by accumulation of ammonia and the decrease in glutamine concentration in the liver.

Frequency and pattern of Chinese herbal medicine prescriptions for chronic hepatitis in Taiwan.

ETHNOPHARMACOLOGICAL RELEVANCE: Chinese herbal medicine (CHM) has been commonly used in treating liver diseases in Asian countries. AIM OF STUDY: To conduct a large-scale pharmacoepidemiological study and evaluate the frequency and pattern of CHM prescriptions in treating chronic hepatitis. MATERIALS AND METHODS: We obtained the database of traditional Chinese medicine outpatient claims from the national health insurance in Taiwan for the whole 2002. Patients with chronic hepatitis were identified by the corresponding diagnosis of International Classification of Disease among claimed visiting files. Corresponding prescription files were analyzed, and association rule were applied to evaluate the co-prescription of CHM in treating chronic hepatitis. RESULTS: Among the 91,080 subjects treated by CHM for chronic hepatitis, the peak age was in the 40 s, followed by 30 s and 50 s. Male/female ratio was 2.07:1. Long-dan-xie-gan-tang and Saliva miltiorrhiza (Dan-shen) were the most commonly prescribed Chinese herbal formula and single herbal drug, respectively. The most common two-drug prescription was Jia-wei-xia-yao-san plus Saliva miltiorrhiza, and the most common three-drug prescription was Jia-wei-xia-yao-san plus Saliva miltiorrhiza and Artemisia capillaries (Yin-chen-hao). CONCLUSIONS: This study showed the utilization pattern of Chinese herbal drugs or formulae in treating chronic hepatitis. Further researches and clinical trials are needed to evaluate the efficacy of these Chinese herbs or its ingredients in treating chronic hepatitis.

Effects of selenium on peripheral blood mononuclear cell membrane fluidity, interleukin-2 production and interleukin-2 receptor expression in patients with chronic hepatitis.

AIM: To study the effect of selenium on peripheral blood mononuclear cell (PBMC) membrane fluidity and immune function in patients with chronic hepatitis. METHODS: PBMCs were pretreated with selenium (1.156x10(-7) mol/L) for 6 h in vitro or extracted directly from patients after administration of selenium-yeast continuously for 8-12 wk (200 microg/d), and then exposed to Con-A for 48 h. The membrane fluidity, interleukin-2 (IL-2) production and interleukin-2 receptor (IL-2R) expression in PBMCs and malondialdehyde (MDA) concentration in medium and lipid peroxide (LPO) in plasma were determined. RESULTS: The PBMC membrane fluidity, IL-2 production and IL-2R expression in patients with chronic hepatitis were significantly lower than those in healthy blood donators (particle adhesive degree R, 0.17+/-0.01 vs 0.14+/-0.01, P<0.01; IL-2, 40.26+/-9.55 vs 72.96+/-11.36, P<0.01; IL-2R, 31.05+/-5.09 vs 60.58+/-10.56, P<0.01), and the MDA concentration in medium in patients with chronic hepatitis was significantly higher than that in healthy blood donators (1.44+/-0.08 vs 0.93+/-0.08, P<0.01). Both in vitro and in vivo administration of selenium could reverse the above parameters. CONCLUSION: Supplement of selenium can suppress lipid peroxidation, and improve PBMC membrane fluidity and immune function in patients with chronic hepatitis.

[The joint use of prednisolone and phospholipid-containing hepatoprotectors in experimental chronic hepatitis]. / Sovmestnoe primenenie prednizolona i gepatoprotektorov, soderzhashchikh fosfolipidy, pri éksperimental'nom khronicheskom gepatite.

In chronic CCl4-hepatitis in rats phospholipid-containing hepatoprotectors, essentiale and eplir differ in their influence on the therapeutic effect of prednisolone; essentiale does not change the antiproliferative effect of the glucocorticoid and weakens its membrane-stabilizing effect, eplir increases these therapeutic effects of prednisolone. Besides, eplir, in distinction from essentiale, reduces lipid accumulation in the liver and hypoproteinemia which are induced by prednisolone.

Relationship of 31P MR spectroscopy to the histopathological grading of chronic hepatitis and response to therapy.

PURPOSE: In vivo phosphorus-31 MR spectroscopy (31P MRS) was performed in the human liver in order to investigate the relation between: the ratios of phosphorus metabolites in the liver; the histopathological grading of chronic hepatitis; and the response to therapy. MATERIAL AND METHODS: Hepatic 31P MRS using the DRESS method (depth-resolved surface-coil spectroscopy) was carried out in 45 patients with chronic viral hepatitis or autoimmune hepatitis, and in 16 control subjects. We measured the ratios of the peak areas of phosphomonoesters (PME), inorganic phosphate (Pi), or phosphodiesters (PDE) to the peak area of beta-adenosine triphosphate (ATP). RESULTS: The PDE/ATP ratio of patients with chronic hepatitis or liver cirrhosis was lower than that of control subjects (liver cirrhosis = 0.74; chronic active hepatitis = 1.13-1.21; normal = 1.43); only a small difference was found in the PME/ATP and Pi/ATP ratios. There was no correlation between the spectra and histopathological grading or response to therapy, but the response to therapy was poor when a reduced PDE/ATP ratio was present. CONCLUSION: The PDE/ATP ratio measured by 31P MRS makes it possible to identify the transition of chronic active hepatitis into liver cirrhosis with a poor response to therapy.

Amount and composition of bone minerals in chronic liver disease.

Alterations in bone mineral are a common complication of chronic liver disease. The aim of the current study was to assess bone mineral status in patients with chronic liver disease not treated with corticosteroids and to investigate any possible correlation with the histological stage of liver disease. Bone mineral status in 27 patient with chronic active hepatitis, and 17 with active cirrhosis was compared to that of matched controls. Partial body neutron activation analysis was applied for measuring hand bone phosphorus, single-photon absorptiometry for measuring forearm bone mineral content, and dual-energy x-ray absorptiometry for measuring spinal bone mineral density. These noninvasive measurements were supplemented with data obtained by high resolution radiography and biochemistry. Decreased metacarpal cortical thickness was found in five patients, all in the cirrhotic group. In addition, both mean intact parathyroid hormone and 25-hydroxyvitamin D levels were reduced in this group of patients. The mean values of the quantities assessed by the in vivo techniques in patients in the early stages of the hepatic disease did not differ statistically from those of matched normal controls. On the contrary, these quantities were reduced by 9% in the patients at the late stages relative to controls. In conclusion, only the late stages of liver disease are associated with an increased risk of fractures.

[Clinical and experimental observations of buzhong yiqi decoction in the treatment of chronic hepatitis B].

A clinical observation of Buzhong Yiqi decoction (BZYQD) and Western medicine was used on a matched control in treating chronic hepatitis B. The result showed that BZYQD was significantly better than the Western medicine in improving clinical symptoms and signs, the liver function and serological test of hepatitis B antigen-antibody system (HBAg-Ab system), P < 0.05. In order to explore the therapeutical mechanism of BZYQD, the study of the effects of which on synthesis of hepatic DNA, RNA and protein in mice were performed too. The results showed that BZYQD had marked promotive effects on the synthesis of hepatic DNA, RNA and protein. It was considered that the mechanism of anti-hepatitis effects might related to the enhancing protein synthesis in liver, promoting the repairs of the damaged liver tissue and improving the defense function of organism as a whole.

Serial P-31 MR spectroscopy after fructose infusion in patients with chronic hepatitis.

Serial changes in phosphorus metabolites after intravenous administration of fructose were compared between five healthy volunteers and five patients with chronic hepatitis by means of phosphorus-31 magnetic resonance (MR) spectroscopy. P-31 spectra were obtained every 5 minutes after intravenous drip infusion of 20% fructose at a dose of 0.5 g/kg of body weight. In the healthy volunteers, phosphomonoesters (PME) increased to 338% +/- 76% of the preadministration value at 15-20 minutes. Inorganic phosphate (Pi) was depleted in the first 15 minutes, then rebounded to 260% +/- 67% of the initial value. beta-adenosine triphosphate decreased to less than 50% of its initial value and then gradually recovered. In patients with chronic hepatitis, the increase of PME at 15-20 minutes (151% +/- 49% of the preadministration value) was significantly less than that in healthy volunteers (P less than .05). In addition, the rebound of Pi at 35-40 minutes (126% +/- 42%) was significantly less than that in healthy volunteers (P less than .05). In conclusion, P-31 MR spectroscopy with fructose administration is valuable in the functional evaluation of diffuse liver diseases.

Assessment of nutritional status of patients with end-stage liver disease undergoing liver transplantation.

Nutritional assessment factors (including dietary history, anthropometric and biochemical measurements, and evaluation of immunocompetence) were retrospectively reviewed in 74 patients undergoing an initial liver transplantation procedure. The patients were subdivided into four categories on the basis of type of liver disease: chronic active hepatitis (N = 24), primary sclerosing cholangitis (N = 22), primary biliary cirrhosis (N = 20), and acute or subacute hepatitis (N = 8). Our nutritional assessment data indicated that malnutrition was present preoperatively in all liver transplantation groups but that each group had distinct characteristics. The group with primary biliary cirrhosis seemed to have the best hepatic synthetic function despite extreme wasting of muscle and fat. On the basis of all criteria, the group with acute hepatitis was the most malnourished of the various disease groups. Aggressive nutritional support, which includes adequate intake of nutrients and supplementation of vitamins and trace minerals, should be encouraged for all potential liver transplant patients.

[Effect of polyunsaturated phosphatidylcholine and vitamin B complex on the metabolism of selenium homotaurocholic acid in patients with chronic liver disease]. / Azione della fosfatidilcolina polinsatura (EPL) + complesso vitaminico B sul metabolismo del SeHCAT in pazienti con epatopatia cronica.

SeHCAT, a synthetic homologue of thaurocolic acid, may be used to examine the dynamics of enterohepatic circulation. A greater retention of SeHCAT may be attributed to a defective hepatic clearance and to a partial redistribution of the biliary acid pool outside the enterohepatic circle. This method has been applied to 20 patients affected with chronic hepatic disorders. The percentage of retention of SeHCAT in normal subjects was 19-20 on average. The hepatopathic patient has an average SeHCAT retention of 54%. After treatment with polyunsaturated phosphatidylcholine (EPL) plus vitamin B complex i.v., the percentage of SeHCAT retention was significantly less than 31% (P less than 0.001). It can be hypothesized that the drug determines an improvement of the enterohepatic circle (acting on the hepatic clearance) in patients with chronic hepatic disorders as shown by the reduction of the percentage of SeHCAT retention noticed.