Occult Hepatitis B Virus Infection in Hyperlipidemia Patients.

Chronic hepatitis B virus (HBV) infection is associated with lower prevalence of hyperlipidemia (HLP). However, occult HBV infection (OBI) in HLP patients has not yet been explored. OBI is defined as the presence of detectable HBV DNA in serum or liver tissue but undetectable HBV surface antigen in serum. In this study, 1,036 HLP patients and 1,134 replacement blood donor controls were recruited. Among them, 252 HLP patients and 255 blood donors with antibody to HBV core positive were selected and analyzed. HBV DNA was confirmed by nucleic acid testing assays, and nucleotide mutations were analyzed. OBI was detected in 9.5% (24/252) of HLP patients and 2.4% (6/255) of blood donors, respectively (P < 0.001). In HLP population, 41.7% of OBI and 13.6% of non-OBI carriers were associated with daily alcohol consuming > 30 g/day (P < 0.01), while in control population those rates were not statistically different between OBI and non-OBI carriers (P > 0.05). Viral load of OBI in HLP patients was higher than that of OBI in blood donors (P < 0.05), which was a positive correlation between total cholesterol and HBV viral load levels (r = 0.474 P = 0.019). HBV vaccination rate was found significantly lower in OBI HLP patients than that in non-OBI HLP patients (P < 0.01). Importantly, mutations were found in basic core promoter region of HBV among OBI HLP patients. In conclusion, the frequency of OBI is significantly higher in HLP patients, especially those patients with heavy daily alcohol consumption.

Evaluación del potencial hipolipemiante de Cymbopogon citratus S. en un modelo de hiperlipidemia aguda / Evaluation of hypolipidemic potential of Cymbopogon citratus S. in a model of acute hyperlipidemia

Se realizó un estudio farmacológico en el Departamento de Investigaciones Experimentales de laUnidad de Toxicología Experimental Villa Clara, para evaluar el efecto hipolipemiante de la especieCymbopogon citratus S. (caña santa), en un modelo de hiperlipidemia aguda inducida conpoloxamer 407, detergente no iónico. Se emplearon ratones machos C57BL/6J, el extracto fueevaluado en dosis de 400 mg/kg (grupo V) y 600mg/kg (grupo VI). Se formaron seis gruposexperimentales: el grupo I correspondió al control negativo, el II al grupo control de hiperlipidemia,el III y IV a grupos controles de sinvastatina y ácido nicotínico y los grupos V y VI a las dosisevaluadas del extracto de Cymbopogon citratus S. Se efectuó la caracterización fitoquímica delextracto hidroalcohólico; además, se evaluaron signos clínicos de toxicidad, la concentración plasmática de colesterol total, triacilglicéridos y lipoproteínas de muy baja densidad. El tamizajefitoquímico corroboró la presencia de compuestos reductores, alcaloides y taninos, y se observógran concentración de flavonoides y triterpenos. Las variables colesterol, triacilglicéridos ylipoproteínas de muy baja densidad para los grupos V y VI mostraron diferencias significativasrespecto al grupo control de hiperlipidemia (II), y se comportaron de manera similar a los gruposcontroles de sinvastatina (III) y ácido nicotínico (IV). Se concluye que el extracto de caña santa enlas dosis de estudio en el modelo de hiperlipidemia aguda presenta actividad hipolipemiante(AU)

A pharmacological study was conducted at the Department of Experimental Researches of theExperimental Toxicology Unit from Villa Clara, to evaluate the lipid-lowering effect of the speciesCymbopogon citrates S. (lemongrass) in a model of acute hyperlipidemia induced by poloxamer407, non-ionic detergent. C57BL/6J male mice were used; the extract was evaluated in doses of400mg/kg and 600mg/kg (group V and VI respectively). Six experimental groups were formed:group I corresponded to the negative control, II to control group of hyperlipidemia, III and IV tocontrol groups of sinvastatin and nicotinic acid, as well as, group V and VI corresponded to theevaluated doses of Cymbopogon citratus S extract. Phytochemical characterization ofhydroalcoholic extract was done; there were also evaluated clinical signs of toxicity, the plasmaconcentration of total cholesterol, triacylglycerol (TAG) and very low- density lipoprotein (VLDL).The phytochemical screening confirmed the presence of reducing compounds, alkaloids andtannins, showing great concentration of flavonoids and triterpenes. Cholesterol, TAG and VLDLvariables for groups V and VI showed significant differences with respect to control group ofhyperlipidemia (II), and behaved similarly to the control groups of sinvastatin (III) and nicotinic acid(IV). As a conclusion, the Cymbopogon citrates S. extract at the doses studied in the model of acutehyperlipidemia presents hypolipidemic activity(AU)

Factors related to HIV-associated neurocognitive impairment differ with age.

Over 50% of HIV-infected (HIV+) persons are expected to be over age 50 by 2015. The pathogenic effects of HIV, particularly in cases of long-term infection, may intersect with those of age-related illnesses and prolonged exposure to combined antiretroviral therapy (cART). One potential outcome is an increased prevalence of neurocognitive impairment in older HIV+ individuals, as well as an altered presentation of HIV-associated neurocognitive disorders (HANDs). In this study, we employed stepwise regression to examine 24 features sometimes associated with HAND in 40 older (55-73 years of age) and 30 younger (32-50 years of age) HIV+, cART-treated participants without significant central nervous system confounds. The features most effective in generating a true assessment of the likelihood of HAND diagnosis differed between older and younger cohorts, with the younger cohort containing features associated with drug abuse that were correlated to HAND and the older cohort containing features that were associated with lipid disorders mildly associated with HAND. As the HIV-infected population grows and the demographics of the epidemic change, it is increasingly important to re-evaluate features associated with neurocognitive impairment. Here, we have identified features, routinely collected in primary care settings, that provide more accurate diagnostic value than a neurocognitive screening measure among younger and older HIV individuals.

Human cytomegalovirus-IgM seropositivity is not associated with atherogenic alterations of lipid profiles and inflammatory status in ischemic stroke patients: a preliminary study.

BACKGROUND: Past exposure to human cytomegalovirus has been suggested to participate in the pathogenetic events associated with atherosclerotic lesion establishment and progression. However, whether ongoing human cytomegalovirus infection is related to plaque instability, and subsequent acute cerebral ischemia, is relatively unknown. The purpose of this study was to evaluate the potential relationships between active human cytomegalovirus infection and ischemic stroke, especially in regard to metabolism and inflammation. METHODS: Ninety-nine acute ischemic stroke patients, associated with large artery atherosclerosis, were divided into two groups based on the presence or absence of human cytomegalovirus immunoglobulin M (IgM) (human cytomegalovirus-IgM-positive/human cytomegalovirus-IgM-negative = 33:66). Baseline clinical characteristics, inflammatory factors, and biochemical assessments were compared in both groups. Then, all patients and human cytomegalovirus-IgM-positive patients were divided into quartiles according to their high-sensitivity C-reactive protein levels, respectively, and risk factors were compared. Finally, correlations between inflammatory factors (high-sensitivity C-reactive protein and white blood cell count) and other atherosclerosis risk factors in both human cytomegalovirus-IgM-positive and -negative subjects were evaluated. RESULTS: An association between human cytomegalovirus-IgM seropositivity and atherogenic modification of metabolism and inflammatory status were not found in this study. Both age and white blood cell count increased across quartiles of high-sensitivity C-reactive protein in all subjects (P = 0.001), while age and low-density lipoprotein cholesterol increased across quartiles of high-sensitivity C-reactive protein in the human cytomegalovirus-IgM-positive group (P = 0.02 and 0.007, respectively). Multivariate linear regression analysis showed that high-sensitivity C-reactive protein was associated with age in human cytomegalovirus-IgM-positive group (P = 0.002), while no other factor was associated with white blood cell count in these subjects. CONCLUSION: Our study provided no evidence for the direct implication of active systemic human cytomegalovirus infection, represented by human cytomegalovirus-IgM positivity, in the pathogenesis of acute ischemic strokes, particularly those involving plaque instability and metabolic disorders.

Outcomes of switch to atazanavir-containing combination antiretroviral therapy in HIV-1-infected patients with hyperlipidemia.

BACKGROUND: Prolonged exposure to combination antiretroviral therapy (CART) may result in hyperlipidemia and other metabolic complications. This study aimed to evaluate the clinical, virologic, and immunologic outcomes in HIV-infected patients with hyperlipidemia whose CART was switched to atazanavir-containing antiretroviral regimens. METHODS: In this 48-week prospective, observational study that was conducted at designated hospitals for HIV care in Taiwan, HIV-infected patients aged 18 years or older who had developed hyperlipidemia after receiving CART that did not contain atazanavir were enrolled. Antiretroviral regimens were switched to regimens containing two nucleoside reverse-transcriptase inhibitors plus atazanavir 400 mg once daily or atazanavir 300 mg boosted with ritonavir 100 mg once daily. The lipid profiles, including total triglycerides, total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, CD4+ lymphocyte counts, and plasma HIV RNA load were determined every 3 months. RESULTS: Sixty-six patients with hyperlipidemia were enrolled. At the end of the study, triglyceride levels declined by 49.0% (p = 0.0002) and total cholesterol levels by 18.1% from baseline (p < 0.0001), whereas there were no significant changes observed for low-density lipoprotein- and high-density lipoprotein-cholesterol levels. Mean CD4 lymphocyte count increased from 465 cells/µL at baseline to 498 cells/µL at the end of the study, whereas the proportion of patients with undetectable plasma HIV RNA load increased from 73.1% to 81.7%. The regimens were well tolerated. CONCLUSIONS: Switch to atazanavir-containing regimens that were well tolerated resulted in significant improvement of hyperlipidemia and maintenance of clinical, immunologic, and virologic responses to CART.

Prevalence and treatment of hyperlipidemia in patients with chronic hepatitis C infection.

BACKGROUND: Patients with chronic hepatitis C (HCV) infection can also have hyperlipidemia. Glucose intolerance has been associated with HCV infection and treating hyperlipidemia in this and other high-risk groups is warranted. We hypothesized that hyperlipidemia is common in patients with hepatitis C and that it is under-treated for fear of worsening liver function. DESIGN: From the Stratton Veterans Affairs Medical Center computerized database, we collected information on patients with HCV infection enrolled in hepatology clinic. We collected information on age, sex, duration of HCV infection, concomitant diagnoses, medications they were on, laboratory values including hepatic function, glucose, and lipid levels. We collected information on the lipid levels and various cardiovascular risk factors. METHODS: This is a retrospective study involving record review. We analyzed the data collected from the records for prevalence of high cholesterol (as defined by the National Cholesterol Education Program) and for prevalence of various cardiovascular risk factors. We analyzed prevalence of treatment of hyperlipidemia in various risk groups. In the patients who were treated for hyperlipidemia, we collected information on any worsening hepatic function that led to treatment discontinuation. RESULTS: Six hundred and twenty-eight (70.5%) out of 891 patients with hepatitis C had hyperlipidemia. Of the 628 patients who had hyperlipidemia, 81 (12.7%) had positive antibody and RNA not tested; 162 (25.4%) had positive antibody but negative RNA testing; and 385 (61.3%) had positive testing for viral RNA. Two hundred and eighty-four (45.2%) of 628 patients with hyperlipidemia were eligible for treatment to lower it. Of 146 patients with hyperlipidemia and diabetes mellitus or arterial disease who were qualified for treatment (LDL >99), 95 (65.1%) were treated with lipid-lowering medication. Of 148 patients with hyperlipidemia and without diabetes or arterial disease who were qualified for treatment, 64 (43.3%) were treated with lipid-lowering medication. CONCLUSION: A high prevalence of hyperlipidemia in patients infected with HCV is observed. Prevalence is highest among those who are positive for viral RNA. About half the patients with hyperlipidemia were eligible for treatment with drugs to lower it. Treatment of hyperlipidemia with medication though surprisingly common could improve.

Mitigation of antiretroviral-induced hyperlipidemia by hepatitis C virus co-infection.

BACKGROUND: Hyperlipidemia is a recognized complication of HIV antiretroviral therapy. The interactions between HIV, hepatitis C virus (HCV), antiretroviral agents and lipids are not well understood. METHODS: We evaluated the lipid data of patients receiving antiretroviral therapy at the Ottawa Hospital Immunodeficiency Clinic between January 1996 and June 2005 using a clinic database. RESULTS: A total of 357 HIV-mono-infected and 115 HIV/HCV-co-infected patients were evaluated. The mean changes in total cholesterol (mmol/l) from baseline to months 6 and 12 were 1.00 and 1.24 in HIV mono-infection, and 0.19 (P < 0.001) and 0.01 (P < 0.001) in HIV/HCV, respectively. Metabolic complications including hypercholesterolemia resulted in the interruption of HAART in HIV mono-infection (8%), but not in those with HIV/HCV (< 1%; P < 0.001). Eight per cent of HIV-mono-infected and no co-infected patients initiated lipid-lowering therapy while on their initial course of HAART (P < 0.001). Total cholesterol increased by 0.85 mmol/l in HIV/HCV-co-infected recipients of interferon-based HCV treatment achieving a sustained virological response (SVR), but did not change in those who did not achieve a SVR. CONCLUSION: HCV co-infection appears to confer a degree of protection from HAART-related lipid complications. The mechanism of this finding deserves evaluation. The implications of this observation for long-term cardiovascular disease risk remains a pressing issue.

Effects of bezafibrate in patients with chronic hepatitis C virus infection: combination with interferon and ribavirin.

An association of hepatitis C virus (HCV) with low-density lipoproteins (LDL) in serum of patients with chronic hepatitis C (CHC) has been suggested. We conducted a prospective study in CHC patients complicated with hyperlipidaemia, to examine whether bezafibrate, which is commonly used for treatment of hyperlipidaemia, reduces serum HCV-RNA titre and improves liver dysfunction. Fifteen patients received daily oral bezafibrate treatment (400 mg/day) for 8 weeks, and its effects on serum lipids, transaminases, HCV-RNA titres, and HCV-RNA titres bound to LDL were evaluated. Fifteen untreated patients with CHC and hyperlipidaemia were used as controls. The mean serum alanine aminotransferase levels and HCV-RNA titres significantly decreased at the end of bezafibrate therapy in the treated group (105 +/- 34 to 80 +/- 32 IU/L, P = 0.02 and 2.23 +/- 2.71 to 1.78 +/- 2.38 x 10(7) copies/mL, P < 0.01 respectively), but no changes were observed in the control group. Serum HCV-RNA titres bound to LDL, as quantified by immunoprecipitation using anti-LDL antibody, also decreased in all 15 treated patients [5.55 +/- 6.59 to 1.07 +/- 1.58 x 10(6) copies/ml, P < 0.01 (mean reduction rate was -78.5 +/- 17.0%)]. Sucrose density-gradient ultracentrifugation study revealed that HCV-RNA-decreased density fractions after the bezafibrate were identical to LDL-density fractions (1.015-1.062 g/mL). Eight CHC patients were treated with bezafibrate, interferon, and ribavirin triple therapy for 32 weeks, and four patients achieved sustained virological response to therapy. This pilot study provides further evidence of an association between HCV and LDL in serum and suggests the potential usefulness of bezafibrate as an anti-HCV reagent for the treatment of CHC patients.

Clinical impact of HIV-related lipodystrophy and metabolic abnormalities on cardiovascular disease.

Metabolic complications and altered fat distribution associated with HIV infection and antiretroviral therapy may lead to accelerated coronary artery disease (CAD). The high prevalence of multiple cardiovascular risk factors in a significant number of HIV patients is a cause for concern in both patients and physicians. Non-invasive strategies to measure subclinical CAD have been inconclusive. Long-term studies are underway to determine cardiac event rates, intervention strategies and consequences for the clinical management of HIV disease. In the present paper, we summarize the most prevalent risk factors in individuals with HIV infection receiving highly active antiretroviral therapy by focusing on the clinical implications of metabolic abnormalities and HIV-related lipodystrophy on CAD.

Increased serum interferon alpha in HIV-1 associated lipodystrophy syndrome.

BACKGROUND: A syndrome of lipodystrophy (LD) associated with peripheral lipoatrophy and central/visceral adiposity has been reported in HIV-1-infected patients treated by combined antiretroviral therapy (ART). Lipid metabolism is partly regulated by both steroid hormones and cytokines and we have previously reported that dyslipidaemia in LD-positive men is correlated to an increase in cortisol : DHEA ratio (Christeff et al., AIDS 1999;13:2251). In this study we questioned whether it is also related to cytokine perturbations. MATERIALS AND METHODS: A cross-sectional study was performed on 42 HIV-1-positive men on ART, 27 of whom had symptoms of LD, defined by computed tomography scan. Serum cytokines (IFN-alpha, TNF-alpha, sTNF-RI, sTNF-RII, IL-6, IL-1beta and IL-2) and lipids [cholesterol, triglycerides (TG) and their subclasses], and apolipoproteins (Apo), were determined. RESULTS: Serum IFN-alpha was markedly increased in LD-positive compared with LD-negative men and controls. IL-6 and TNF-alpha concentrations were also significantly elevated in HIV-positive men compared to controls but the levels of these cytokines did not differ between the two groups of patients. A significant positive correlation was found between accumulation of IFN-alpha and increased levels of cholesterol, TG, VLDL cholesterol, VLDL TG, ApoB and ApoB-ApoA1 ratio. A multivariate forward-performed analysis revealed that IFN-alpha is the best marker for lipid perturbations associated to LD, followed by insulin and cortisol : DHEA ratio. CONCLUSIONS: This study demonstrates an association between serum IFN-alpha and lipid alterations in LD-positive men. The concomittant action of IFN-alpha and cortisol : DHEA ratio is probably one of the mechanisms responsible for hyperlipidaemia in LD syndrome.

HIV-associated lipodystrophy: description, pathogenesis, and molecular pathways.

HIV-infected individuals taking antiretroviral medications may experience changes in body shape and metabolism, commonly known as HIV-associated lipodystrophy (HIVLD). In vitro and in vivo research have revealed numerous effects of both protease inhibitors and nucleoside reverse transcriptase inhibitors on the function of various organs--most importantly adipose tissue, liver, and muscle. The metabolic abnormalities could result in an increased risk of cardiovascular disease in this vulnerable and relatively young population. Treatment strategies, normally successful in the general population, have generally been less effective in this group of people, in which the detrimental effects of the antiretroviral medications are ongoing.

Antiretroviral therapy-associated hyperlipidaemia in HIV disease.

Widespread utilization of highly active antiretroviral therapy (HAART) for HIV-infection, primarily protease inhibitors in combination with nucleoside analogue reverse transcriptase inhibitors, has recently led to a sustained reduction in the morbidity and mortality of this disease. However, administration of HAART is frequently associated with the development of lipid disorders. The severity and prevalence of dyslipidaemia vary, depending on the type of HAART, nutritional status, HIV disease stage, and concomitant presence of lipodystrophy and insulin resistance (two additional adverse effects of HAART). The mechanism that is responsible for HAART-associated dyslipidaemia remains incompletely understood. Recent data indicate that this effect may be, at least in part, accounted for by protease inhibitor-mediated inhibition of the proteasome activity and accumulation of the active portion of sterol regulatory element-binding protein-1c in liver cells and adipocytes. Whether lipid disorders in HIV-infected patients receiving HAART translate into an increased cardiovascular risk, and the indications for lipid-lowering interventions in this population, remain to be established.