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In subjects with CHC resulting from G1-HCV, IR and overt diabetes are major determinants of advanced fibrosis, regardless of the degree of steatosis, mainly in the presence of severe necroinflammation.

SUMMARY Background

SUMMARY BackgroundMetabolic factors have been associated with liver damage in patients with non-alcoholic fatty liver disease (NAFLD).

SUMMARY BackgroundLiver stiffness measurement (LSM) using transient elastography (TE) is used to stage fibrosis in patients with liver disease, diagnostic reliability and the factors affecting its performance in patients with non-alcoholic fatty liver disease (NAFLD) are incompletely understood.

There are contrasting results in studies of cardiovascular risk in patients with genotype 1 chronic hepatitis C (G1 CHC). We evaluated the prevalence of carotid atherosclerosis compared with a control population in order to assess the potential association between atherosclerosis, host and viral factors, and liver histological features. In all, 174 consecutive biopsy-proven G1 CHC patients were evaluated by anthropometric and metabolic measurements and 174 patients attending an outpatient cardiology unit were used as controls. Intima-media thickness (IMT) and carotid plaques, defined as focal thickening of >1.3 mm at the level of common carotid, were evaluated using ultrasonography. All G1 CHC biopsies were scored by one pathologist for staging and grading, and graded for steatosis. Carotid plaques were found in 73 (41.9%) G1 CHC patients compared with 40 (22.9%) control patients (P < 0.001). Similarly, G1 CHC patients had a greater IMT compared with control patients (1.04 6 0.21 versus 0.90 6 0.16; P < 0.001). Multivariate logistic regression analysis showed that older age (odds ratio [OR] 1.047, 95% confidence interval [CI]: 1.014-1.082, P 5 0.005), and severe hepatic fibrosis (OR 2.177, 95% CI: 1.043-4.542, P 5 0.03), were independently linked to the presence of carotid plaques. In patients 55 years, 15/67 cases with F0-F2 fibrosis (22.3%) had carotid plaques, compared with 11/21 (52.3%) with F3-F4 fibrosis (P 5 0.008). By contrast, in patients >55 years the prevalence of carotid plaques was similar in those with or without severe fibrosis (25/43, 58.1% versus 22/43, 51.1%; P 5 0.51). Conclusion: Severe hepatic fibrosis is associated with a high risk of early carotid atherosclerosis in G1 CHC patients. (HEPATOLOGY 2012;55:1317-1323

Metabolic factors have been associated with liver damage in patients with genotype 1 chronic hepatitis C (G1 CHC). We tested visceral adiposity index (VAI), a new marker of adipose dysfunction in G1 CHC, patients to assess its association with host and viral factors and its link to both histological findings and sustained virological response (SVR). Two hundred thirtysix consecutive G1 CHC patients were evaluated by way of liver biopsy and anthropometric and metabolic measurements, including insulin resistance (IR), homeostasis model assessment (HOMA), and VAI using waist circumference, body mass index, triglycerides, and highdensity lipoprotein cholesterol. All biopsies were scored by one pathologist for staging and grading and graded for steatosis, which was considered moderate to severe if !30%. Multiple linear regression analysis revealed that VAI score was independently associated with higher HOMA score (P 5 0.009), log10 hepatitis C virus RNA levels (P 5 0.01), necroinflammatory activity (P 5 0.04), and steatosis (P 5 0.04). Multiple logistic regression analysis revealed that IR (OR 3.879, 95% CI 1.727-8.713, P 5 0.001), higher VAI score (OR 1.472, 95% CI 1.051-2.062, P 5 0.02), and fibrosis (OR 2.255, 95% CI 1.349-3.768, P 5 0.002) were linked to steatosis !30%. Logistic regression analysis revealed that older age (OR 1.030, 95% CI 1.002-1.059, P 5 0.03), higher VAI score (OR 1.618, 95% CI 1.001-2.617, P 5 0.04), and fibrosis (OR 2.608, 95% CI 1.565-4.345, P < 0.001) were independently associated with moderate to severe necroinflammatory activity. No independent associations were found between VAI score and both fibrosis and SVR. Conclusion: In G1 CHC patients, higher VAI score is independently associated with both steatosis and necroinflammatory activity and has a direct correlation with viral load. (HEPATOLOGY 2010;52:1543-1552

BACKGROUND. BRAFV600E mutation and p27kip1 expression have been introduced as novel indicators that may predict prognosis in different tumors, as well as in papillary thyroid carcinomas. METHODS. Tissue samples from 214 consecutive patients who underwent total or near‐total thyroidectomy with histological diagnosis of papillary thyroid carcinoma (PTC) ≤1 cm were analyzed for BRAFV600E mutation by a real‐time, allele‐specific amplification and for p27kip1 expression by immunohistochemistry. RESULTS. The BRAFV600E mutation was detected in 88 of the tumors examined, with significant differences between groups with and without lymph node (LN) metastases; the mean age of patients with BRAFV600E mutation was significantly higher than that of patients without mutations. A significant association was found between low p27Kip1 protein expression and multifocality, bilaterality, and extrathyroidal extension, in addition to LN metastasis. In 42 cases with LN metastases, 23 harbored the BRAFV600E mutation in the metastatic tumor and presented a wider diameter of the largest metastatic area, a higher number of involved LNs, and a higher percentage of metastatic lesions with extracapsular extension of LN (ECE‐LN). A significantly lower mean value of p27Kip1 was observed in LNs harboring the BRAFV600E mutation and in ECE‐LN; an inverse correlation was found between p27Kip1 and the number of metastatic LNs, as well as the diameter of the largest metastatic area in LN. CONCLUSIONS. The authors' data suggested that BRAFV600E mutation and p27Kip1 down‐regulation in cancer cells of PTC ≤1 cm may be factors that facilitate tumor‐cell growth and progression once these are seeded in the LNs. Cancer 2007. © 2007 American Cancer Society.