Study on Antibodies to Liver Antigens in Chinese Patients with Different Liver Diseases

Autoimmune liver diseases include autoimmune hepatitis(AIH), primary biliary cirrhosis (PBC) and primary scle rosing cholangitis (PSC). The examination of autoimmuneantibodies is important to diagnose these kinds of diseases.But up to the present, due to the limited knowledge of au toantigens and immature method of examination, especiallyof some autoantibodies which are not only present in au toimmune diseases but found in 10% 15% of the patientswith viral hepatitis or other immune…     

Bacteriophage Prevents Alcoholic Liver Disease

<正>Alcoholic hepatitis is a severe alcohol-associated liver disease with minimal treatment options. A recent study by Duan et al. uncovers that the exotoxin-secreting gut bacterium Enterococcus faecalis is a critical contributor to alcoholic hepatitis. This bacterium can now be eliminated with a bacteriophage, suggesting a new way to treat this life-threatening disease.     

Taurine Reduces Liver Damage in Non-Alcoholic Fatty Liver Disease Model in Rats by Down-Regulating IL-9 and Tumor Growth Factor TGF-β

Bulletin of Experimental Biology and Medicine - The study employed a rat model to examine the effects of taurine (Tau) on prevention and therapy of non-alcoholic fatty liver disease (NAFLD). In...     

High-Carbohydrate Diet Selectively Induces Tumor Necrosis Factor-α Production in Mice Liver

Obesity may represent a state of chronic low-grade inflammation associated with infiltration of adipose tissue by inflammatory cells. Tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1/JE), two important inflammatory cytokines, have been shown to be regulated according to changes in body adiposity. In this study on Swiss mice, we compared the influences of long-term high-carbohydrate (HC) or high-fat (HF) diet on adiposity, glucose tolerance, and secretion of TNF-α and MCP-1/JE by adipose tissue and liver. For 8 weeks, male Swiss mice (7–8 weeks) were fed either standard laboratory rodent diet (control group), HC diet (64% carbohydrate, 19% protein, and 11% fat), or HF diet (45% carbohydrate, 17% protein, and 38% fat), with the latter two diets having no fiber. Oral glucose tolerance test, triacylglycerol (TAG) plasma concentration, and systemic or tissue levels of the two proinflammatory cytokines were determined. Body weight increased by approximately 20% in mice fed the experimental diets compared with mice fed the control diet. Systemically, the hypercaloric diets induced hyperglycemia with impairment in glucose tolerance, elevated circulating TAG levels, and increased plasma concentrations of TNF-α and MCP-1/JE. In the target organs (adipose tissue and liver), both diets increased MCP-1/JE levels. However, the HC diet, but not the HF diet, was able to increase TNF-α concentration in the liver. These results have shown that the nature of nutrients influences the type of proinflammatory cytokines in target organs and may contribute to the comorbidities of obesity.     

IDO-Competent-DCs Induced by IFN-γ Attenuate Acute Rejection in rat Liver Transplantation

Purpose

We established a stable rat model of liver transplantation using Sprague-Dawley rats and Wistar rats in order to investigate the role of the IDO gene in acute rejection after rat liver transplantation.

Methods

IDO gene expression and IDO enzyme activity were quantified in liver syngeneic grafts and allografts using microdialysis-HPLC. Liver allografts were evaluated for IDO expression by histopathology. We measured liver function-related biomarkers in liver allografts which were re-infused with untreated or IFN-γ-treated dendritic cells (DCs).

Results

We found a significant increase in IDO gene expression and IDO enzyme activity in liver allografts compared the sham and syngeneic graft groups. There was a significant correlation between the number of IDO-positive cells and severity of acute rejection. IDO gene expression and enzyme activity was upregulated in the IFN-γ-treated DC group within 7 days after transplantation compared to the untreated DC group and survival rates were significantly improved.

Conclusions

Our results suggested that IDO gene expression correlates with the severity of acute rejection and that IFN-γ-induced IDO-positive DCs may attenuate acute rejection and catalyze local tryptophan metabolism via IDO enzyme expression, leading to immune tolerance after liver transplantation.     

Liver Repopulation and Carcinogenesis: Two Sides of the Same Coin?

Liver repopulation by transplanted normal hepatocytes has been described in a number of experimental settings. Extensive repopulation can also occur from the selective proliferation of endogenous normal hepatocytes, both in experimental animals and in the human liver. This review highlights the intriguing association between clinical and experimental conditions related to liver repopulation and an increased risk for development of hepatocellular carcinoma. It is suggested that any microenvironment that is able to sustain the clonal growth of normal transplanted (or endogenous) hepatocytes is also geared to select for the emergence of rare resistant cells with an altered phenotype. Whereas the first pathway leads to liver repopulation with normal histology, the latter results in the growth of focal proliferative lesions and carries an increased risk of neoplastic disease. The implications of this association are discussed, both in terms of pathogenetic significance and possible therapeutic exploitation.     

Hepatocellular Calcification in Severe Ischemia–Reperfusion Injury in a Liver Allograft

Ischemia–reperfusion injury (IR) of solid organ allografts is a consequence of ischemia resulting from disruption of blood flow during organ harvest and transportation. Histologically, this manifests as variable necrosis in a pattern similar to that seen in systemic hypoperfusion. Calcification of hepatocytes has been rarely observed in ischemic injury due to systemic shock and in two cases of severe IR, both of which were associated with graft loss and death. The authors present another case of dystrophic calcification within hepatocytes occurring in a liver allograft affected by severe IR. Biochemical stains revealed that the mineralized material was calcium phosphate (likely hydroxyapatite). By electron microscopy, the hepatocyte cytoplasm was filled with variably calcified vacuoles, a subset of which likely represented swollen mitochondria. When encountered in hepatic allograft biopsies, hepatocellular calcification is associated with ischemic injury and a poor prognosis.     

Murine CD5+, CD8+ Normal Fetal Liver Cells Enhance an Immune Response: Benzo(α) Pyrene-Exposed CD5+ Fetal Liver Cells are Inhibitors

The effects of 150 ug benzo(α)pyrene/gm body weight given intraperitoneally to the pregnant mouse at mid-gestation leads to long-lasting (> 18 months post-birth) immune deficiency in the progeny. Although the progeny are immunodeficient their T cell subsets induced marked enhancement and/or inhibition of cell proliferation in an immune response. Earlier we saw a striking increase (up to 7-fold) in CD8⁺ cells in the 18 day gestation liver of benzo(α)pyrene-exposed fetuses. We hypothesized that immune deficiency in carcinogen-exposed progeny could be attributed to an increase in classical CD8⁺ suppressor T-cells. Surprisingly, however, we found that CD8⁺ and CD5⁺ (Lyt 1⁺) cells of normal fetal liver enhance cell proliferation in an immune response. However, liver CD5⁺ cells from benzo(α)pyrene-exposed fetuses led to a dramatic reduction of the enhancing effect. Thus, as a novel finding, it appears that the profile of CD5⁺ cells, under the ontogenic influence of benzo(α)pyrene, transforms from cells that normally augment cell proliferation in an immune response to cells that are inhibitors. On the other hand the functional status of CD8⁺ cells is not affected. This change in physiological status of CD5⁺ cells may have important implications on T and B cell interactions, and the role of CD5⁺cells in T cell receptor signaling.     

Is Non-Alcoholic Fatty Liver Disease Less Frequent among Women with Prader-Willi Syndrome?

ObjectivePatients with Prader-Willi syndrome (PWS) have been hypothesized to be at lower risk of non-alcoholic fatty liver disease (NAFLD) because of higher insulin sensitivity. However, PWS patients have a peculiar body composition, i.e. higher fat mass and lower fat-free mass, which may confound such associations. We evaluated whether NAFLD is less frequent in PWS than in non-PWS women matched on percent body fat (PBF).MethodsPBF was measured by dual-energy X-ray absorptiometry. Liver fat was assessed by ultrasonography. Insulin sensitivity and beta-cell function were evaluated by oral glucose tolerance testing. Coarsened exact matching (CEM) was used to match PWS and non-PWS women on PBF. General and generalized linear models taking CEM into account were used to perform comparisons between PWS and non-PWS women.Results20 women with PWS were matched to 27 women without PWS on the basis of PBF (mean 53 vs. 54%, p = 0.6). Insulin sensitivity and beta-cell function were similar in the two groups. However, the prevalence of NAFLD was 25% in PWS versus 59% in non-PWS women (p = 0.04).ConclusionNAFLD is less frequent in PWS than in non-PWS women but this finding is not associated with higher insulin sensitivity.Key Words: Prader-Willi syndrome, Obesity, Body composition, Dual energy X-ray absorptiometry, Insulin resistance     

Liver transplantation: is it possible in HIV/HCV co-infected patients?

The prognosis of HIV infection has been modified by antiretroviral therapy. However, the morbidity and the mortality of HCV co-infection increase and may be a major problem of health service. Up to now co-infected patients are excluded of transplantation due to complexity, the ethical aspects, the immunodeficiency and the co-infection. This study tries to estimate the feasibility in this population. Between December 1999 and March 2002, seven patients were transplanted. The average of CD4 was 332/ml; the viral load was <50 copies/ml. Before transplantation, no patient had experienced opportunist infection and all patients received antiretroviral therapy adapted to their history. The average follow-up is of 14 months: one patient died 3 months after transplantation, the other one presented a candida in oesophagus, the average of CD4 was 280/ml, and viral load was <50 copies/ml in five patients. A relapse of HVC was observed in all patients. Interferon/rivabirine therapy was proposed for four patients. Every patient received tacrolimus and corticoids. HAART were modified four times for toxicity and one time for virological failure. We observed two cases of transient renal insufficiency, two cases of diabetes, two cases of pancreatitis, and abnormalities of the respiratory mitochondrial chain in four patients. Finally, liver transplantation in HIV-HCV co-infected patients seems to be feasible when strict criteria of selection are taken into account. This still experimental strategy requires a multidisciplinary partnership.     

Liver inflammation and regeneration: two distinct biological phenomena or parallel pathophysiologic processes?

The anatomic localization and unique vasculature of the liver, along with its cell properties, make this organ an efficient line of defense against blood-borne infections, either systemic or arising in the abdomen. Liver cells can modify the host immune response by releasing immunomodulatory molecules, interacting with cells of the immune system and acting as scavengers for inflammatory mediators. However, these defensive functions do not protect the liver itself from the severe injury that may be caused by pathogens, toxins or pollutant xenobiotics. Therefore, the mammalian liver has developed a unique adaptation in the form of an astonishing regenerative capability. The complexity of regeneration requires a well-orchestrated system to control this process. Growing evidence suggest the importance of immune mechanisms as a part of this system. It seems likely that the mechanisms that serve to eliminate infections (and may simultaneously cause liver injury) are also active in restoring the structural and functional integrity of the damaged liver.     

Dose-Dependent Effect of α-Tocopherol on Activity of Xenobiotic Metabolizing Enzymes in Rat Liver

Oral treatment with -tocopherol for 4 days dose-dependently increased the content of cytochrome P450 (CYP), catalytic activities of CYP1A1, CYP1A2, CYP2B1, CYP2C, and activity of NADPH-cytochrome-P450 reductase in the liver of male rats, but did not change activity of glutathione S-transferase. These results suggest that -tocopherol induced the enzymes of phase I of xenobiotic metabolism, including CYP1 and CYP2 families involved in the metabolism of drugs and procarcinogenes.