Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Basal serum growth hormone (GH) levels are elevated and insulin-like growth factor 1 (IGF-1) concentrations in serum are suppressed in patients with chronic liver disease. The aim of this study was to measure the urinary GH (U-GH) excretion and IGF-1 concentrations in patients with cirrhosis and to correlate these both to clinical and biochemical characteristics and survival rate. Urinary GH excretion, IGF-1, and other biochemical parameters were measured in 36 patients with alcoholic cirrhosis, while in the control group of 34 healthy individuals only U-GH excretion was measured. U-GH excretion was significantly higher in patients than in the healthy controls (p < 0.00001), and increased with deteriorating liver function assessed by modified Child-Turcotte score (p < 0.01). The highest U-GH excretions were found in patients with hepatic encephalopathy (p < 0.003). IGF-1 levels were reduced in cirrhosis and correlated with liver function (p < 0.001). Serum IGF-1 concentrations below 3.1 nmol/l were associated with a poor prognosis (p < 0.004). The elevated U-GH in patients with alcoholic cirrhosis may reflect high serum levels of GH due to increased pituitary secretion or decreased hepatic degradation of GH. In addition, the IGF-1 levels reflect the degree of hepatic insufficiency and, thus, seem to provide new prognostic information.
 ...
PMID:Urinary growth hormone (U-GH) excretion and serum insulin-like growth factor 1 (IGF-1) in patients with alcoholic cirrhosis. 831 59

Many studies on cirrhotic patients have shown that insulin-like growth factor 1 (IGF-1) plasma levels are related to the severity of liver dysfunction. This result suggests that IGF-1 is probably useful for monitoring liver function in the perioperative course of orthotopic liver transplantation (OLT). Growth hormone (GH), IGF-1 plasma levels, and routine liver function tests were measured in 15 adult cirrhotic patients undergoing OLT. Measurements were made at the beginning of the operation; during OLT; 24 hours after reperfusion; and in the morning on days 7, 30, and 90. Twenty age-matched healthy volunteers with normal liver function served as controls. The study group had significantly higher GH levels and lower IGF-1 levels in the preoperative period compared with the controls. All patients achieved a complete functional hepatic recovery 1 month after OLT, although in 6 of them, the graft had an initial poor function (Group-IPF). GH and IGF-1 levels achieved near normal range within 1 week after OLT, and they had no significant correlations with other routine biochemistry tests in this period. IGF-1 levels in Group-IPF rose more slowly than in the group with a normal recovery of graft function. Surprisingly, 24 hours after reperfusion, IGF-1 levels were higher in Group-IPF than in the group with normal graft function. In conclusion, the severe GH/IGF-1 axis impairment found in patients with end-stage cirrhosis reverted very rapidly in the first days after successful OLT. Such a quick, postoperative modulation of IGF-1 plasma level by the graft suggests that this hormone has the potential to become one of the early indicators of post-OLT liver function recovery.
 ...
PMID:Growth hormone/insulin-like growth factor 1 axis recovery after liver transplantation: a preliminary prospective study. 1510 63

Proliferation and differentiation of satellite cells are critical in the regeneration of atrophied muscle following immobilization and aging. We hypothesized that impaired satellite cell function is responsible for the atrophy of skeletal muscle also seen in cirrhosis. Myostatin and insulin-like growth factor 1 (IGF1) have been identified to be positive and negative regulators, respectively, of satellite cell function. Using a rat model of cirrhosis [portacaval anastamosis (PCA)] and sham-operated controls, we examined the expression of myostatin, its receptor activinR2b, and its downstream messenger cyclin-dependent kinase inhibitor p21 (CDKI p21) as well as IGF1 and its receptor in the gastrocnemius muscle. Expression of PCNA, a marker of proliferation, and myogenic regulatory factors (myoD, myf5, and myogenin), markers of differentiation of satellite cells, were also measured. Real- time PCR for mRNA and Western blot assay for protein quantification were performed. PCA rats had lower body weight and gastrocnemius weight compared with sham animals (P < 0.05). PCNA and myogenic regulatory factors were lower in PCA rats (P < 0.05). Myostatin, activinR2b, and CDKI p21 were higher in the PCA animals (P < 0.05). The expression of IGF1 and its receptor was lower in liver and skeletal muscle of PCA animals (P < 0.05). These data suggest that skeletal muscle atrophy seen in the portacaval shunted rats is a consequence of impaired satellite cell proliferation and differentiation mediated, in part, by higher myostatin and lower IGF1 expression.
 ...
PMID:Skeletal muscle atrophy is associated with an increased expression of myostatin and impaired satellite cell function in the portacaval anastamosis rat. 1525 63

The liver is the major organ for the metabolism of homocysteine (Hcy) and production of insulin-like growth factor 1 (IGF-1). Hcy metabolism and IGF-1 synthesis may be impaired in chronic liver diseases. The study investigated the regulatory effect of a Chinese herbal suppository, Vitalliver, on Hcy and IGF-1, as well as their relationship in patients with hepatitis B infection. Forty patients with chronic hepatitis B virus (HBV) infection without cirrhosis, 25 males and 15 females, were observed for changes in Hcy and IGF-1 after the administration of Vitalliver (one nightly) for a period of 3 months. Serum levels of Hcy, IGF-1 and IGFBP-3 were measured at baseline, and at 1 month and 3 months after treatment. Vitalliver reduced Hcy levels significantly (p = 0.001) from 9.7 +/- 2.8 to 9.0 +/- 2.1 micromol/L after treatment of 3 months. Furthermore, the IGF-1 levels increased significantly (p < 0.001) from 170.2 +/- 81.8 to 212.8 +/- 80.9 ng/mL at 1 month and 187.5 +/- 72.3 ng/mL at 3 months (p = 0.001) after treatment. In conclusion, it is speculated Vitalliver may have a self-regulatory effect on the release of IGF-1 in HBV patients without liver cirrhosis.
 ...
PMID:The effects of a Chinese medicinal suppository (Vitalliver) on insulin-like growth factor 1 and homocysteine in patients with hepatitis B infection. 1617 69

The natural history of Non Alcoholic Fatty Liver Disease (NAFLD) is difficult to assess, but there is mounting evidence that patients with NAFLD may eventually develop cirrhosis and hepatocellular carcinoma (HCC). Retrospective, case-control studies have shown that features suggestive of Non Alcoholic SteatoHepatitis (NASH) are more frequent in HepatoCellular Carcinoma (HCC) complicating cryptogenic cirrhosis than in matched HCC patients with known etiology. In the only available prospective cohort study, there is the absence of HCC as a complication of NASH-associated cirrhosis after a mean follow up of 7 years (median 5 years). However prospective NASH studies are too short to exclude late complications. In fact the average lenght of cirrhosis before the diagnosis of HCC was 16 years. The prevalence of risk factors associated with NASH can account for the increasing incidence of cryptogenic cirrhosis and subsequent HCC. Obesity and diabetes per se are significantly associated with the development of HCC. In particular diabetes was found to be a risk factor for HCC independent of age, gender, and race. Chronic hyperinsulinaemia and insulin-like growth factor 1 (IGF-1) might be involved in hepato-carcinogenesis. Exposure to physiological insulin concentrations stimulate proliferation of human and rat hepatoma cell line. Changes in the expression pattern of IGF-system components has been observed in patients with HCC, in human hepatoma cell lines and in their conditioned culture medium.
 ...
PMID:Steatosis and hepatocellular carcinoma risk. 1623 92

The growth hormone (GH)-insulin-like growth factor 1 (IGF-1) axis is impaired in liver cirrhosis. We determined the effects of GH and IGF-1 treatments in gastrectomized rats with thioacetamide-induced cirrhosis. GH did not increase hepatic IGF-1-mRNA, plasma IGF-1 or the tissue, i.e. gastrocnemius muscle IGF-1 level. IGF-1 administration increased plasma IGF-1 without increasing hepatic IGF-1-mRNA. GH and IGF-1 independently decreased postoperative urinary nitrogen excretion. We conclude that both GH and IGF-1 improve postoperative nitrogen metabolism. Furthermore, GH may exert its anabolic effects directly and/or via actions mediated by IGF-1 production, other than in the liver and in the skeletal muscle, in the setting of cirrhosis.
 ...
PMID:Effects of growth hormone and insulin-like growth factor 1 (IGF-1 ) on hepatic IGF-1-mRNA, plasma IGF-1 and nitrogen excretion in gastrectomized rats with liver cirrhosis. 1684 65

Bone marrow endothelial cells (BMECs) are important components of the hematopoietic microenvironment in bone marrow, and they can secrete several types of cytokines to regulate the functions of hematopoietic stem/progenitor cells. To date, it is unknown whether BMECs undergo functional changes and lead to hematopoietic abnormalities in cases of liver cirrhosis (LC). In the present study, whole genome microarray analysis was carried out to detect differentially expressed genes in human BMECs treated for 48 h with medium supplemented with 20% pooled sera from 26 patients with LC or 10 healthy volunteers as the control group. A total of 1,106 upregulated genes and 766 downregulated genes were identified. In Gene Ontology analysis, the most significant categories of genes were revealed. A large number of the upregulated genes were involved in processes, such as cell-cell adhesion, apoptosis and cellular response to stimuli and the downregulated genes were involved in the negative regulation of secretion, angiogenesis, blood vessel development and cell growth. Pathway analysis revealed that the upregulated genes were either cell adhesion molecules or parts of the apoptotic signaling pathway and the downregulated genes were involved in the Wnt signaling pathway and MAPK signaling pathway. These were the pathways with the highest enrichment scores. The results of apoptosis assays revealed that the humoral inhibitors in the sera of patients with LC induced the apoptosis of BMECs, which confirmed the accuracy of bioinformatic analysis. Moreover, we screened and verified 21 differentially expressed cytokine genes [transforming growth factor (TGF)B1, tumor necrosis factor (TNF)B, TNF receptor superfamily, member 11b (TNFRSF11B), TNF (ligand) superfamily, member 13b (TNFSF13B), interleukin (IL)1A, IL6, IL11, IL17C, IL24, family with sequence similarity 3, member B (FAM3B), Fas ligand (FASLG), matrix metallopeptidase (MMP)3, MMP15, vitronectin (VTN), insulin-like growth factor 1 (IGF1), fibroblast growth factor 22 (FGF22), slit homolog 2 (Drosophila) (SLIT2), thrombospondin (THBS)2, THBS3, chemokine (C-C motif) ligand 28 (CCL28) and macrophage stimulating 1 (MST1)] from 97 cytokine genes in BMECs treated with serum from patients with LC. The results from our study demonstrate that the humoral inhibitors in the sera of patients with LC induce the dysfunction and abnormal cytokine secretion by BMECs, which may be a novel mechanism responsible for hematological abnormalities in patients with LC.
 ...
PMID:Whole genome expression profiling and screening for differentially expressed cytokine genes in human bone marrow endothelial cells treated with humoral inhibitors in liver cirrhosis. 2404 11

Objective Growth hormone (GH) deficiency has recently been reported as a cause of nonalcoholic fatty liver disease (NAFLD), and GH supplementation has been shown to improve the histology of NAFLD. The aim of the present study was to clarify the relationship between the histological severity of NAFLD and production of the GH/insulin-like growth factor 1 (IGF-1) axis. Methods A total of 222 Japanese patients with liver biopsy-confirmed NAFLD and 55 patients with hepatitis C virus (HCV)-related chronic liver disease (CLD) were enrolled in the present study. The serum levels of GH, IGF-1, and IGF-binding protein 3 (IGFBP-3) were measured and their relationships with the histological severity of liver disease were assessed. To exclude age- and sex-related differences, the IGF-1 standard deviation score (IGF-1:SDS) was determined for each patient. Results With respect to the stage of fibrosis in patients with NAFLD, the serum GH levels were higher and the serum IGFBP-3 levels and IGF-1:SDSs were lower in patients with cirrhosis (grade F4 fibrosis) than in patients grade F1-F3 fibrosis; moreover, these differences were statistically significant (all p<0.01). The GH, IGF-1, and IGFBP-3 levels were not correlated with fibrosis in patients with HCV-related CLD. Furthermore, the GH levels were lower and the IGFBP-3 levels were significantly higher in patients with severe steatosis (S3) than in patients with mild to moderate steatosis (S1-S2) (p<0.05). Conclusion Increased GH levels and decreased IGF-1 and IGFBP-3 levels might contribute to the progression of NAFLD. The GH/IGF-1 axis may be important in the development of NAFLD, but not in patients with HCV-related CLD.
 ...
PMID:The Relationship between the Growth Hormone/Insulin-like Growth Factor System and the Histological Features of Nonalcoholic Fatty Liver Disease. 2825 Feb 90

Non-alcoholic fatty liver disease (NAFLD) is a chronic progressive liver disorder that begins with simple hepatic steatosis and progresses to non-alcoholic steatohepatitis, fibrosis, cirrhosis, and even liver cancer. As the global prevalence of NAFLD rises, it is increasingly important that we understand its pathogenesis and develop effective therapies for this chronic disease. Forkhead box O (FOXO) transcription factors are key downstream regulators in the insulin/insulin-like growth factor 1 (IGF1) signaling pathway, and have been implicated in a range of cellular functions including the regulation of glucose, triglyceride, and cholesterol homeostasis. The role of FOXOs in the modulation of immune response and inflammation is complex, with reports of both pro- and anti-inflammatory effects. FOXOs are reported to protect against hepatic fibrosis by inhibiting proliferation and transdifferentiation of hepatic stellate cells. Mice that are deficient in hepatic FOXOs are more susceptible to non-alcoholic steatohepatitis than wild-type controls. In summary, FOXOs play a critical role in maintaining metabolic and cellular homeostasis in the liver, and dysregulation of FOXOs may be involved in NAFLD development.
 ...
PMID:FOXO transcription factors in non-alcoholic fatty liver disease. 3003 12

Liver cirrhosis (LC) is a major cause of secondary sarcopenia. Sarcopenia makes the prognosis worse; thus, novel therapeutic options for sarcopenia in patients with LC are urgently required as they are currently limited. In this retrospective study, 158 patients with LC were screened, and 35 of those patients who were treated with L-carnitine for more than 6 months and for whom skeletal muscle mass changes could be evaluated by computer tomography were enrolled. Of the 158 patients, 79 patients who did not receive L-carnitine supplementation served as controls. Cases and controls were propensity score matched for age, sex, presence of hepatocellular carcinoma, and branched chain amino acid administration, and changes in skeletal muscle mass and clinical data were compared. The 35 patients who received L-carnitine supplementation and 35 propensity score-matched patients who did not receive carnitine supplementation comprised the final enrollment. Compared with control patients, patients who received L-carnitine had significantly worse liver function, which is associated with rapid progress of skeletal muscle depletion. However, loss of skeletal muscle mass was significantly suppressed in patients receiving L-carnitine, and a significant effect was observed in patient subgroups stratified by age, sex, presence of hepatocellular carcinoma, and branched chain amino acid administration. The change ratios of most laboratory data, including vitamin D and insulin-like growth factor 1 levels, were similar in the two groups, but ammonia levels were significantly less in those receiving L-carnitine. However, even in patients receiving L-carnitine but not showing an ammonia decrease, loss of skeletal muscle was significantly suppressed. Conclusion: L-carnitine suppresses loss of skeletal muscle mass and may therefore be a novel therapeutic option for sarcopenia in patients with LC. (Hepatology Communications 2018; 00:000-000).
 ...
PMID:L-Carnitine Suppresses Loss of Skeletal Muscle Mass in Patients With Liver Cirrhosis. 3009 2


1 2 Next >>