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.

Curcumin, Silybin Phytosome(®) and α-R-Lipoic Acid Mitigate Chronic Hepatitis in Rat by Inhibiting Oxidative Stress and Inflammatory Cytokines Production.

Chronic hepatitis is recognized as a worldwide health problem that gradually progresses towards cirrhosis and hepatocellular carcinoma. Despite the large number of experiments using animal models for allergic hepatitis, it is still difficult to produce a picture of chronic hepatitis. Therefore, this study was conducted to introduce an animal model approximating to the mechanism of chronicity in human hepatitis. The study also aimed to examine the hepatoprotective effects of curcumin, silybin phytosome(®) and α-R-lipoic acid against thioacetamide (TAA)-induced chronic hepatitis in rat model. TAA was administered intraperitoneally at a dose of 200 mg/kg three times weekly for 4 weeks. At the end of this period, a group of rats was killed to assess the development of chronic hepatitis in comparison with their respective control group. TAA administration was then discontinued, and the remaining animals were subsequently allocated into four groups. Group 1 was left untreated, whereas groups 2-4 were allowed to receive daily oral doses of curcumin, silybin phytosome(®) or α-R-lipoic acid, respectively, for 7 weeks. Increases in hepatic levels of malondialdehyde associated with TAA administration were inhibited in groups receiving supplements. Furthermore, glutathione depletion, collagen deposition, macrophage activation and nuclear factor κappa-B expression as well as tumour necrosis factor-α and interleukin-6 levels were significantly decreased in response to supplements administration. Serological analysis of liver function and liver histopathological examination reinforced the results. The above evidence collectively indicates that the antioxidant and anti-inflammatory activities of curcumin, silybin phytosome(®) and α-R-lipoic acid may confer therapeutic efficacy against chronic hepatitis.

[Clinical observation on auxiliary treatment with suanzaoren decoction for chronic severe hepatitis].

OBJECTIVE: To investigate the curative effect and safety of auxiliary treatment with Suanzaoren Decoction (SZRD) on patients with chronic severe hepatitis (CSH). METHODS: Sixty patients, with the diagnosis in accordance with the diagnostic criterion of CSH, were assigned to the treated group and the control group, 30 in each group. Patients in the control group were treated with comprehensive therapy including symptomatic supportive treatment, anti-infective therapy and artificial liver plasmapheresis etc., while those in the treated group were orally taken SZRD additionally. Patients' condition of sleeping and changes of total bilirubin (TBIL), prothrombin activity (PTA), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) were observed before and after treatment, and the adverse reactions were observed as well. RESULTS: The sleeping status were significantly improved in the treated group after treatment, and the serum levels of TBIL, TNF-alpha and IL-1 were significantly decreased. The improvement rate was 66.7% (20/30) and significantly higher than that (40.0%, 12/30) in the control group. CONCLUSION: SZRD can significantly improve the sleeping status of CSH patients, alleviate the hepato-cellular injury by inflammatory cytokines and without obvious adverse reaction.

Hepatoprotective activity of Psidium guajava Linn. leaf extract.

The study was designed to evaluate the hepatoprotective activity of P. guajava in acute experimental liver injury induced by carbon tetrachloride, paracetamol or thioacetamide and chronic liver damage induced by carbon tetrachloride. The effects observed were compared with a known hepatoprotective agent, silymarin. In the acute liver damage induced by different hepatotoxins, P. guajava leaf extracts (250 and 500mg/kg, po) significantly reduced the elevated serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and bilirubin. The higher dose of the extract (500 mg/kg, po) prevented the increase in liver weight when compared to hepatoxin treated control, while the lower dose was ineffective except in the paracetamol induced liver damage. In the chronic liver injury induced by carbon tetrachloride, the higher dose (500 mg/kg, po) of P. guajava leaf extract was found to be more effective than the lower dose (250 mg/kg, po). Histological examination of the liver tissues supported the hepatoprotection. It is concluded that the aqueous extract of leaves of guava plant possesses good hepatoprotective activity.

Clinical pathological study of treatment of chronic hepatitis with hyperbaric oxygenation.

OBJECTIVE: To detect the feasibility and theoretic basis for treatment with hyperbaric oxygenation (HBO) in chronic hepatitis and to compare the changes in hepatic function, immunity, pathologic morphology, ultrastructure and HBV in hepatic tissues before and after treatment. METHODS: Sixty cases of chronic hepatitis were randomly selected and divided into two groups: the experiment (n = 30) and control groups (n = 30). Patients in the experimental group were treated with HBO for 6 courses. Patients in the control group were treated for 60 days with the usual drugs used in the clinic. The function and bloodstream graph of liver were examined and liver biopsies were made before and after treatments. Routine paraffin sections were stained with HE and observed under the light microscope. Ultra thin slides from paraformaldehyde and glutaraldehyde fixed liver tissue were stained with lead citrate and observed with the transmission electric microscope. HBsAg and HBcAg in liver of the experimental group were detected with ABC immunohistochemistry method before and after treatment. RESULTS: For the experimental group, ALT, SB, gamma-GT, AKP, IgG, and IgM in blood and the degeneration and necrosis of hepatocytes were remarkably decreased (P < 0.05 ), the mean contractive wave of bloodstream in liver and the bloodstream in right ramus of janitrix were remarkably increased (P < 0.05), and the swelling of mitochondria, increase of lysosomes, generation of Kupffer cells, infiltration of lymphocytes in portal area and capillary generation were all remarkably all eviated (P < 0.05) after treatment with HBO. There were significant differences between the experimental and control groups after treatment with different methods (P < 0.05). For patients in the experimental group, the fibrosis and fat-storing cells in the liver were not reduced (P > 0.05), and the expression of HBsAg and HBcAg in liver was not weakened (P < 0.05) after treatment. CONCLUSIONS: Treatment with HBO for chronic hepatitis was effective and recommendable, but it could not reverse liver fibrosis. However, it might be able to delay or prevent the liver from fibrosis, so it might be more effective at the early and middle stages of chronic hepatitis. HBO could not inhibit the HB virus. So we consider that treatment with HBO should be simultaneous with anti HBV therapy.

Adult syncytial giant cell chronic hepatitis due to herbal remedy.

Syncytial giant cell hepatitis is an uncommon form of chronic hepatitis in adults, although it has been reported in association with viral infection (including HCV and HIV infection), drug reactions and autoimmune disorders. We here report a very unusual case of giant cell chronic hepatitis in a 26-old-woman, who had been taking a herbal remedy (ISABGOL) for chronic constipation. The presence of viral and metabolic diseases has been excluded; an autoimmune etiology was very unlikely as the autoimmunity test remained negative during the year of follow-up and the total disease score normalized (from 13 to 8) without corticosteroid treatment. The causative role of the herbal remedy was further supported by the spontaneous and dramatic clinical, biochemical and histologic improvement observed following its withdrawal, despite the absence of any treatment.

Pathological changes in cobalt-supplemented and non-supplemented twin lambs in relation to blood concentrations of methylmalonic acid and homocysteine.

In a controlled field study of three years' duration we evaluated the effect of cobalt supplementation on pathological changes in cobalt/vitamin B12-deficient Texel twin lambs grazing the same cobalt-deficient pasture. Semi-quantitative evaluation of the histopathology of liver and brain was done on 44 sets of twins. Pathological changes were related to blood concentrations of vitamin B12, methylmalonic acid, and homocysteine. Lesions were mainly confined to the liver and brain. Acute hepatic changes were characterized by steatosis, hepatocytic degeneration, and single cell necrosis. Chronic changes consisted of bile duct proliferation, the presence of ceroid containing macrophages, and fibrosis in the portal triads. Many non-supplemented lambs showed polymicrocavitation and Alzheimer type II reaction in the brain. Polioencephalomalacia was observed in three non-supplemented lambs but was regarded as a secondary lesion. Our results indicate that the main lesions found in cobalt/vitamin B12-deficient lambs are acute and chronic hepatitis. These lesions were associated with low concentrations of vitamin B12 and high concentrations of methylmalonic acid and homocysteine in the blood. The liver lesions were also associated with polymicrocavitation of the brain, probably as morphological evidence of hepatoencephalopathy.

[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.

Chronic hepatitis induced by Jin Bu Huan.

BACKGROUND/AIMS: Jin Bu Huan and other Chinese herbal products are widely taken remedies. They have been developed as a natural alternative to traditional drugs in the treatment of various ailments. Their ability to induce several side effects such as acute hepatitis has already been described. We report a case of chronic hepatic damage following administration of Jin Bu Huan Anodyne tablets. METHODS: The patient, a 49-year-old man, developed biochemical signs of liver damage 2 months after beginning Jin Bu Huan intake (3 tablets/daily) including biopsy-proven chronic hepatitis with moderate fibrosis. Virological, autoimmune, metabolic or other hepatotoxic causes were excluded. Liver function impairment was resolved by discontinuing Jin Bu Huan intake. CONCLUSIONS: This case reinforces the already known hepatotoxicity of this product and should make us think more about the uncontrolled use of alternative products.

[Comparison of pre- and post-treatmental hepatohistology with heavy dosage of Paeonia rubra on chronic active hepatitis caused liver fibrosis].

No report has been found on comparison of pre- and post-treatmental liver biopsies for chronic active hepatitis (CAH) caused liver fibrosis. The aim of this paper was to study the effects of a heavy dosage of Radix Paeoniae rubra to the reabsorptive action of liver collagen fibres. The patients were suffering from CAH or CAH with liver cirrhosis confirmed by liver biopsies. By the end of 3 months, the second liver biopsy was carried out. The results showed that among 4 patients with liver cirrhosis, the false lobules disappeared; and that 6 patients with CAH only, the interlobular collagen fibres of 4 patients were completely reabsorbed. The effective rate reached 77.8%. It was concluded that a heavy dosage of Paeonia rubra was effective in arresting the development of liver fibrosis, and in promoting the reabsorption of collagen fibres.

[Characteristics of clinical pathology and changes of liver function in blood stasis syndrome in liver diseases].

The experimental study on 30 patients of the Blood Stasis Syndrome of liver diseases was discussed in this paper. Two characteristics were found. One was the pathological feature which manifested as follows: (1) DIAGNOSIS: the Blood Stasis Syndrome of liver disease was mainly diagnosed in the chronic active hepatitis and the early stage of cirrhosis of liver, while that of non-Blood Stasis was mainly observed in the chronic persistent hepatitis (P less than 0.01); (2) Pathological change: The histological changes such as piecemeal necrosis, bridging necrosis, the destruction of limiting plate, eosinophilic change, etc. It was more obvious in the Blood Stasis group than that with non-Blood Stasis Syndrome (P less than 0.01), (3) The manifestation of Blood Stasis Syndrome was not in parallel with the severity of the liver disease. The another characteristic was the changes of liver function, which expressed more markedly in the Blood Stasis group with higher level of SGPT, lower ratio of A/G and increased globulin, they were more obvious than that in non-Blood Stasis group (P less than 0.01).