HIV infection and cancer in the era of highly active antiretroviral therapy (Review)

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Relation of epicardial fat and alanine aminotransferase in subjects with increased visceral fat

Background: Increased visceral adipose tissue (VAT) is a risk factor for an unfavorable cardio-metabolic profile and fatty liver. Individuals with human immunodeficiency virus (HIV) on highly active antiretroviral therapy (HAART) can be associated with metabolic syndrome (MS) and higher visceral fat. However, the potential link between cardiac adiposity, emerging index of visceral adiposity, and fatty liver is still unexplored. Objective: To evaluate whether echocardiographic epicardial adipose tissue, index of cardiac adiposity, could be related to serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity, surrogate markers of fatty liver, in HIV-infected patients with (HIV+MS+) and without HAART-associated MS (HIV+MS-). Methods and Procedures: This was a cross-sectional observational study on 57 HIV+MS+ patients, 52 HIV+MS- and 57 HIV-negative subjects with MS (HIV-MS+), as control group. Epicardial fat thickness and intra-abdominal VAT were obtained by echocardiography and magnetic resonance imaging (MRI), respectively. Serum ALT and AST activity, plasma adiponectin levels, and MS biochemical parameters were measured. Results: Echocardiographic epicardial fat thickness was correlated with MRI-VAT (r = 0.83, P < 0.01), AST/ALT ratio (r = 0.77, P < 0.01), ALT (r = 0.58, P < 0.01), AST (r = 0.56, P < 0.01), and adiponectin (r = -0.45, P < 0.01) in HIV+MS+. MRI-VAT and AST/ALT ratio were the best correlates of epicardial fat thickness (r(2) = 0.45, P < 0.01). Discussion: This study shows for the first time a clear relationship of epicardial fat, index of cardiac and visceral adiposity, and serum ALT and AST activity, markers of fatty liver, in subjects with increased visceral adiposity and cardio-metabolic risk. This correlation seems to be independent of overall adiposity and rather function of excess visceral adiposity

position paper per un programma di eliminazione della epatite c nella popolazione a rischio dei consumatori di sostanze e dei detenuti

The data recently published in scientific literature identify in substance abuse the most important risk factor for the transmission of HCV. Another population at risk is represented by detainees, mainly because most of them have a history of substance use. Treatment of the population at risk (substance users and detainees) must become a priority for health systems both to ensure fairness of access to care and to achieve the public health goal of eliminating HCV. The programs to take charge should be multi-disciplinary, flexible, tailored, evidence-based, disseminated homogeneously throughout the national territory, and supported by procedures and guidelines including harm reduction actions, as suggested by the WHO

Short versus standard treatment with pegylated interferon alfa-2A plus ribavirin in patients with hepatitis C virus genotype 2 or 3: the cleo trial

<p>Abstract</p> <p>Background</p> <p>In patients with chronic hepatitis C virus (HCV) genotype 2 or 3, 24 weeks' treatment with pegylated interferon alfa (PEG-IFN-alpha) and ribavirin induces a sustained virological response (SVR) in almost 80% of cases. Evidence suggests that a similar response rate may be obtained with shorter treatment periods, especially in patients with a rapid virological response (RVR). The aim of this study was to compare the efficacy of 12 or 24 weeks of treatment in patients with chronic HCV genotype 2 or 3 and to identify patients suitable for 12 weeks treatment.</p> <p>Methods</p> <p>Two hundred and ten patients received PEG-IFN-alpha-2a (180 ug/week) and ribavirin (800-1200 mg/day) for 4 weeks. Patients with a RVR (HCV RNA not detectable) were randomized (1:1) to either 12 (group A1) or 24 (group A2) weeks of combination therapy. Patients without a RVR continued with 24-weeks' combination therapy (group B). HCV RNA was monitored at weeks 4, 8, 12, and 24, and at week 24 post-treatment.</p> <p>Results</p> <p>At study end, end of treatment response (ETR) was observed in 62 (86%) patients of group A1 and in 55 (77%) patients of group A2 (p < 0.05) Relapse rate was 3% each in groups A1 and A2, and 6% in group B. Among patients with a HCVRNA test 24 weeks after the end of treatment, SVR was observed in 60 (83%) of group A1 patients and in 53 (75%) of group A2 patients. Rapid virological response, low baseline HCV RNA levels, elevated alanine aminotransferase levels and low fibrosis score, were the strongest covariates associated with SVR, independent of HCV genotype. No baseline characteristic was associated with relapse.</p> <p>Conclusion</p> <p>In HCV patients with genotype 2 or 3, 12-week combination therapy is as efficacious as 24-week therapy and several independent covariates were predictive of SVR.</p> <p>Trial registration</p> <p>Trial number ISRCTN29259563</p

Edge reductions in cyclically k-connected cubic graphs

AbstractThis paper examines edge reductions in cyclically k-connected cubic graphs, focusing on when they preserve the cyclic k-connectedness. For a cyclically k-connected cubic graph G, we denote by Nk(G) the set of edges whose reduction gives a cubic graph which is not cyclically k-connected. With the exception of three graphs, Nk(G) consists of the edges in independent k-edge cuts. For this reason we examine the properties and interactions between independent k-edge cuts in cyclically k-connected cubic graphs. These results lead to an understanding of the structure of G[Nk]. For every k, we prove that G[Nk] is a forest with at least k trees if G is a cyclically k-connected cubic graph with girth at least k + 1 and Nk ≠ ⊘. Let fk(ν) be the smallest integer such that |Nk(G)| ≤ fk(ν) for all cyclically k-connected cubic graphs G on ν vertices. For all cyclically 3-connected cubic graphs G such that 6 ≤ ν(G) and N3 ≠ ⊘, we prove that G[N3] is a forest with at least three trees. We determine f3 and state a characterization of the extremal graphs. We define a very restricted subset N4b of N4 and prove that if N4g = N4 − N4b ≠ ⊘, then G[N4g] is a forest with at least four trees. We determine f4 and state a characterization of the extremal graphs. There exist cyclically 5-connected cubic graphs such that E(G) = N5(G), for every ν such that 10 ≤ ν and 16 ≠ ν. We characterize these graphs. Let gk(ν) be the smallest integer such that |Nk(G)| ≤ gk(ν) for all cyclically k-connected cubic graphs G with ν vertices and girth at least k + 1. For k ∈ {3, 4, 5}, we determine gk and state a characterization of the extremal graphs

Long term nucleotide and nucleoside analogs treatment in chronic hepatitis B HBeAg negative genotype D patients and risk for hepatocellular carcinoma

Background and rationale of the study. Effect of Long-term nucleoside/nucleotide (NUC) on hepatocellular carcinoma (HCC) incidence in a population of HBeAg-negative genotype D patients has not been adequately studied in real-life cohorts. Our aim was to evaluate the impact of liver fibrosis and other variables on HCC incidence in this population of patients. Of 745 patients with chronic hepatitis B (CHB), 306 HBeAg-negative genotype D were selected and included in this study. All patients received treatment with NUC for at least 18 months. Patients with CHB or compensated cirrhosis were included. Patients with HCC diagnosed before or during the first 18 months of NUC therapy were excluded. Results. HCC was diagnosed in 2 CHB patients (1.0%) and 23 cirrhosis patients (20%) (OR = 24.41, 95% CI 5.40 < OR < 153.2; p < 0.0001). Multivariate analysis revealed that HCC risk was independently associated with age ≥ 60 years (OR = 6.45, 95% CI 1.22 to 34.0; p = 0.02) and liver cirrhosis (OR = 12.1, 95% CI 1.39 to 106.2; p = 0.02), but not with virological response (VR), and previous resistance to NUC, or rescue therapy. Multivariate analysis in cirrhosis patients revealed that only age ≥ 60 years was an independent risk factor associated with HCC (p = 0.003). Conclusions. Liver cirrhosis and age ≥ 60 years are the stronger risk factors for HCC in genotype D HBeAgnegative patients. Previous resistance to NUC in patients that achieved a VR after rescue therapy was not a predictive factor regarding HCC. VR does not appear to significantly reduce the overall incidence of HCC when a patient has already progressed to liver cirrhosis

Human immunodeficiency virus & cardiovascular risk

Highly active antiretroviral therapy (HAART) significantly changed the prevalence of the cardiovascular manifestations of human immunodeficiency virus (HIV)/AIDS. In developed countries, a 30 per cent reduction in the prevalence of cardiomyopathy and pericardial effusion was observed, possibly related to a reduction of opportunistic infections and myocarditis. In developing countries, however, where the availablity of HAART is limited, and the pathogenic impact of nutritional factors is significant, a 32 per cent increase was seen in the prevalence of cardiomyopathy and related high mortality rate from congestive heart failure. Also, some HAART regimens in developed countries, especially those including protease inhibitors, may cause, in a high proportion of HIV-infected patients, a lipodystrophy syndrome that is associated with an increased risk of cardiovascular events related to a process of accelerated atherosclerosis. Careful cardiac screening is warranted for patients who are being evaluated for, or who are receiving HAART regimens, particularly for those with known underlying cardiovascular risk factors, according to the most recent clinical guidelines

Epicardial fat thickness and nonalcoholic fatty liver disease in obese subjects

Objective: Ectopic fat accumulation within the heart and the liver are linked to an increased cardiovascular risk. Ultrasound-measured cardiac and liver steatosis are easily accessible markers of intra-organ ectopic fat accumulation. The hypothesis that echocardiographic epicardial fat thickness is independently associated with nonalcoholic fatty liver disease (NAFLD) in obese subjects is tested. Design and Methods: Sixty-two obese (BMI > 30 kg m(-2)) subjects with ultrasonographic evidence of NAFLD and 62 control obese subjects without history or signs of NAFLD underwent echocardiographic epicardial fat thickness measurement. Results: Epicardial fat thickness was significantly higher (P < 0.01) in obese subjects with NAFLD when compared to those without NAFLD. Epicardial fat thickness was significantly higher (9.7 +/- 0.2 vs. 8 +/- 0.7 mm, P < 0.01) in subjects with severe (ultrasound score 3) than those with moderate (score 2) liver steatosis. Among waist circumference and BMI, epicardial fat thickness resulted in the best independent correlate of liver steatosis (R-2 = 0.77, P < 0.001). Conclusions: Our study suggests that epicardial fat is a good predictor of liver steatosis in obese subjects. Echocardiographic epicardial fat predicts ultrasound-measured fatty liver better than BMI or waist circumferences does. Patients with severe fatty liver infiltration presented with the highest amount of cardiac fat accumulation