Diabetes pattern on the 75 g oral glucose tolerance test is a risk factor for hepatocellular carcinoma in patients with hepatitis C virus
Patients with hepatitis C virus (HCV) frequently show glucose intolerance. Diabetes mellitus (DM) has been proposed to be a risk factor for hepatocellular carcinoma (HCC).
The aim of this study is to clarify the influence of glucose intolerance as evaluated by the 75 g oral glucose tolerance test (OGTT) on hepatocarcinogenesis in patients with HCV.
This study was carried out in a cohort of 197 patients with HCV who had not been previously diagnosed as having DM. All patients underwent the 75 g OGTT at entry. They were also screened for HCC and, thereafter, the rate of hepatocarcinogenesis was compared between the patients with and without glucose intolerance.
Based on the results of the 75 g OGTT, 125 (63%) had normal glucose tolerance (NGT), 49 (25%) had impaired glucose tolerance (IGT) and 23 (12%) had the DM pattern. HCC occurred more frequently in patients with the DM pattern than in patients with either NGT or IGT. Even in patients without advanced liver fibrosis, HCC was more frequently observed in patients with DM than in patients with NGT. A multiple logistic regression analysis showed advanced liver fibrosis, the DM pattern on the 75 g OGTT, an older age and gamma-glutamyltransferase to all be independent risk factors related to hepatocarcinogenesis.
A DM pattern on the 75 g OGTT was thus found to be associated with hepatocarcinogenesis and the 75 g OGTT is considered to be useful for identifying this risk factor for HCC in patients with HCV.
Available from: Hui-Ying Rao
- "Among these, nine studies were performed in one hospital, and two studies were multicenter trials (11 hospitals). Eight studies provided respective data on diabetes mellitus (DM) or pre-diabetes – and other three studies reported total data on DM and pre-diabetes –.Only one study  reported data in patients co-infected with HIV. "
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ABSTRACT: There is a significant association between effects of interferon-alpha treatment and the risk of developing hyperglycemia in patients with chronic hepatitis C virus (HCV) infection. The objective of this systematic review and meta-analysis on the basis of published observational studies was to estimate risk of hyperglycemia in chronic HCV patients who had acquired sustained virological responses (SVR) compared to those without SVR.
We identified eligible studies by searching the relevant databases, including PubMed, Embase, and Google, for papers published between January 1990 and April 2011. The selection of eligible papers was carried out using a scoring system based on guidelines and inclusion criteria that were established before the articles were identified. Heterogeneity across studies was determined and the meta-analysis was performed following standard guidelines.
Eleven eligible studies provided data of the incidence of hyperglycemia in chronic hepatitis C patients with SVR in comparison with patients without these conditions. The results demonstrated that SVR was associated with a lower risk of hyperglycemia (odds ratio = 0.497, 95% confidence interval 0.421-0.587, p<0.001), and there was no evidence of any substantial between-study heterogeneity (I(2) = 24.4%, p>0.1). Results of meta-regression showed patients with different baseline glucose (normal vs. abnormal) and patients with co-infected HIV (presence vs. absence) as the sources of low heterogeneity (p<0.15).The lowest risk of hyperglycemia was described in patients with normal glucose baseline (OR = 0.402, 95%CI 0.297-0.543, p<0.001). This is the first systematic review and meta-analysis performed to examine the association between SVR and risk of hyperglycemia in patients with HCV infection. Our meta-analysis suggests that SVR reduce the risk of developing glucose abnormalities, especially in patients with normal glucose baseline.
Available from: Markus Krupp
- "Besides our data several clinical reports support a synergism between Diabetes mellitus and cancer development. Konishi I et al. reported a correlation between a diabetic pattern of the 75 g oral glucose tolerance test OGTT and hepatocarcinogenesis and considered it a significant risk factor for hepatocellular carcinoma (HCC) in patients with hepatitis C virus . Also Huo et al. found that Diabetes mellitus independently predicts decreased survival in HCC patients . "
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ABSTRACT: Cancer cells are characterized by massive dysegulation of physiological cell functions with considerable disruption of transcriptional regulation. Genome-wide transcriptome profiling can be utilized for early detection and molecular classification of cancers. Accurate discrimination of functionally different tumor types may help to guide selection of targeted therapy in translational research. Concise grouping of tumor types in cancer maps according to their molecular profile may further be helpful for the development of new therapeutic modalities or open new avenues for already established therapies.
Complete available human tumor data of the Stanford Microarray Database was downloaded and filtered for relevance, adequacy and reliability. A total of 649 tumor samples from more than 1400 experiments and 58 different tissues were analyzed. Next, a method to score deregulation of KEGG pathway maps in different tumor entities was established, which was then used to convert hundreds of gene expression profiles into corresponding tumor-specific pathway activity profiles. Based on the latter, we defined a measure for functional similarity between tumor entities, which yielded to phylogeny of tumors.
We provide a comprehensive, easy-to-interpret functional cancer map that characterizes tumor types with respect to their biological and functional behavior. Consistently, multiple pathways commonly associated with tumor progression were revealed as common features in the majority of the tumors. However, several pathways previously not linked to carcinogenesis were identified in multiple cancers suggesting an essential role of these pathways in cancer biology. Among these pathways were 'ECM-receptor interaction', 'Complement and Coagulation cascades', and 'PPAR signaling pathway'.
The functional cancer map provides a systematic view on molecular similarities across different cancers by comparing tumors on the level of pathway activity. This work resulted in identification of novel superimposed functional pathways potentially linked to cancer biology. Therefore, our work may serve as a starting point for rationalizing combination of tumor therapeutics as well as for expanding the application of well-established targeted tumor therapies.
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ABSTRACT: Clinical progression of chronic hepatitis C depends on several cofactors, which also have a negative affect on the rate of response to interferon-alpha-based therapy. Given the current worldwide prevalence of the metabolic syndrome, the impact of obesity and insulin resistance, and of their histopathological correlate, hepatic steatosis, on the natural history and management of chronic hepatitis C is undoubtedly very important. We will review some of the current knowledge on the clinical consequences of overweight/obesity, steatosis and insulin resistance on chronic hepatitis C, and discuss how this issue may be dealt with in clinical practice.
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