High‐sensitivity C‐reactive protein,disease activity,and cardiovascular risk factors in systemic lupus erythematosus

Objective

To study the level of high‐sensitivity C‐reactive protein (hsCRP) and its relationship with disease activity, damage, and cardiovascular risk factors in patients with systemic lupus erythematosus (SLE).

Methods

Consecutive patients who fulfilled ≥4 American College of Rheumatology criteria for SLE who did not have a concurrent infection were recruited. Blood was assayed for hsCRP level, and disease activity, organ damage of SLE, and cardiovascular risk factors were assessed. Linear regression analyses were performed for the relationship between hsCRP levels, SLE activity, damage, and cardiovascular risk factors.

Results

In total, 289 patients were studied (94% women, mean ± SD age 39.0 ± 13.1 years, and mean ± SD SLE duration 7.8 ± 6.7 years). The mean ± SD Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score was 4.9 ± 5.6 and clinically active SLE was present in 122 patients (42%). The mean ± SD hsCRP level was 4.87 ± 12.7 mg/liter, and 28 patients with active SLE (23%) had an undetectable hsCRP level (<0.3 mg/liter). The linear regression analyses revealed a significant correlation between hsCRP level and musculoskeletal disease (β = 0.21), hematologic disease (β = 0.19), active serositis (β = 0.46), and clinical SLEDAI score (β = 0.24) after adjusting for age, sex, body mass index, serum creatinine, and the use of various medications (P < 0.005 for all). hsCRP levels correlated significantly with anti–double‐stranded DNA titer (β = 0.33, P < 0.001) but did not correlate with complement C3 (β = ?0.07, P = 0.26). An hsCRP level >3 mg/liter was significantly associated with male sex, long‐term smoking, diabetes mellitus, a higher atherogenic index, and a history of arterial thrombosis. hsCRP levels correlated significantly with pulmonary and endocrine damage scores.

Conclusion

hsCRP was detectable in 77% of SLE patients with clinically active disease and correlated with SLEDAI scores, particularly in serositis and in the musculoskeletal and hematologic systems. Elevated hsCRP levels in SLE were associated with certain cardiovascular risk factors and a history of arterial thromboembolism.

     

Insulin resistance, inflammation, and vascular disease in nondiabetic predialysis chronic kidney disease patients

Background:

Chronic kidney disease (CKD) is associated with high cardiovascular morbidity and mortality, which is not fully explained by traditional risk factors; hence, the interest in nontraditional risk factors such as inflammation and insulin resistance (IR). Though IR is shown in nondiabetic CKD, its association with vascular disease and inflammation in this population is unknown, and is what this study aims to investigate.

Hypothesis:

IR and inflammation are related to vascular disease in nondiabetic predialysis CKD patients.

Methods:

We studied carotid‐artery intima‐media thickness (IMT) and endothelial function (brachial artery flow mediated dilation [FMD]) in 35 nondiabetic predialysis patients with stage 3–5 CKD and 35 age‐ and gender‐matched controls. Insulin resistance was measured using the homeostasis model assessment for insulin resistance score (HOMA‐IR), inflammation by high‐sensitivity CRP (hsCRP), and their relationship with FMD and IMT.

Results:

Patients with CKD showed reduced FMD (3.34 ± 2.14% vs 5.27 ± 1.78%, P<0.001) and increased IMT (0.78 ± 0.22 mm vs 0.64 ± 0.16 mm, P = 0.003) compared with controls. The CKD patients had a higher HOMA‐IR (2.20 ± 1.08 vs 1.13 ± 0.64, P<0.001) and hsCRP (3.25 ± 5.47 mg/L vs 1.10 ± 1.85 mg/L [median ± interquartile range], P = 0.02). In the study population, HOMA‐IR was directly related to hsCRP. After adjusting for traditional risk factors, high HOMA‐IR and hsCRP were significantly related to decreased FMD (adjusted β = ? 0.44, 95% confidence interval [CI]: ? 1.55 to ? 0.08, P = 0.003 and adjusted β = ? 0.51, 95% CI: ? 0.51 to ? 0.15, P = 0.001) and increased IMT (adjusted β = 0.62, 95% CI: 0.54–1.90, P = 0.001 and adjusted β = 0.43, 95% CI: 0.08–0.57, P = 0.011), respectively.

Conclusions:

Subjects with systemic inflammation were more insulin‐resistant, and in nondiabetic predialysis CKD, IR and systemic inflammation were independently associated with endothelial dysfunction and atherosclerosis. © 2011 Wiley Periodicals, Inc. Dr. Debasish Banerjee and Dr. Alejandro Recio‐Mayoral are joint first authors. This study has been supported by grants awarded by the Spanish Society of Cardiology to Dr. A. Recio‐Mayoral and by the St. George's Charitable Foundation to Dr. D. Banerjee. The authors have no other funding, financial relationships, or conflicts of interest to disclose.

     

The relationship between self‐report and performance‐related measures: Questioning the content validity of timed tests

Objective

To examine the determinants of the modest correlation between self‐report and performance‐related measures in patients with osteoarthritis of the hip or knee.

Methods

Measures included the Lower Extremity Functional Scale (LEFS), the self paced walk, timed up‐and‐go, and stair test. Each performance measure consisted of 3 domains: time, pain (visual analog scale), and exertion (Borg scale). Activity specificity was assessed by examining correlations between the LEFS with single activity and multiple activity time scores. Domain specificity was examined by comparing correlations between the LEFS and single and multiple domain scores. The impact of measurement error was considered.

Results

Increasing the number of activity time scores had no effect. Forming a composite performance score based on time, pain, and exertion substantially increased the correlation from 0.44 (composite timed score) to 0.59 (pooled domain and activity score) (P = 0.009).

Conclusion

Performance scores based on time alone appear to inadequately represent the breadth of health concepts associated with functional status.

     

Health‐related quality of life in juvenile‐onset systemic lupus erythematosus and its relationship to disease activity and damage

Objective

To assess the health‐related quality of life (HRQL) of patients with juvenile‐onset systemic lupus erythematosus (JSLE) and its relationship with disease activity and accumulated damage.

Methods

In this cross‐sectional study, HRQL was assessed using the Child Health Questionnaire (CHQ), disease activity using the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and accumulated damage using the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI).

Results

A total of 297 patients were included. The mean ± SD physical and psychosocial summary scores of the CHQ were 40.2 ± 15.0 and 44.8 ± 10.7, respectively. The most impaired CHQ subscales were global health, general health perceptions, and parent impact–emotional. The SLEDAI score was significantly correlated with both the physical summary score (r = ?0.29, P < 0.0001) and psychosocial summary score (r = ?0.25, P < 0.0001), whereas the SDI score was significantly correlated only with the physical summary score (r = ?0.23, P = 0.0001).

Conclusion

We found that patients with JSLE have significant impairment of their HRQL, particularly in the physical domain. HRQL may be affected by both disease activity and accumulated damage, particularly in the renal, central nervous, and musculoskeletal systems.

     

Polymorphism at position −308 of the tumor necrosis factor α gene influences outcome of infliximab therapy in rheumatoid arthritis

Objective

To test whether the G‐to‐A polymorphism at position −308 in the promoter of the tumor necrosis factor α (TNFα) gene influences response to infliximab therapy in patients with rheumatoid arthritis (RA).

Methods

We genotyped 59 RA patients by polymerase chain reaction and subdivided them into two groups: those with the A/A or A/G genotype and those with the G/G genotype. We compared the groups' clinical responses to infliximab treatment after 22 weeks, using the Disease Activity Score in 28 joints (DAS28).

Results

We found that 42% of patients in the A/A and A/G group and 81% of patients in the G/G group had improvement of at least 1.2 in the DAS28 score (P = 0.0086). The average improvement in the DAS28 score was 1.24 in the A/A and A/G patients and 2.29 in the G/G patients (P = 0.029).

Conclusion

These data suggest that patients with a TNFα −308G/G genotype are better infliximab responders than are patients with A/A or A/G genotypes. TNFα −308 genotyping may be a useful tool for predicting response to infliximab treatment.

     

Gabapentin in the treatment of fibromyalgia: A randomized,double‐blind,placebo‐controlled,multicenter trial

Objective

To assess the efficacy and safety of gabapentin in patients with fibromyalgia.

Methods

A 12‐week, randomized, double‐blind study was designed to compare gabapentin (1,200–2,400 mg/day) (n = 75 patients) with placebo (n = 75 patients) for efficacy and safety in treating pain associated with fibromyalgia. The primary outcome measure was the Brief Pain Inventory (BPI) average pain severity score (range 0–10, where 0 = no pain and 10 = pain as bad as you can imagine). Response to treatment was defined as a reduction of ≥30% in this score. The primary analysis of efficacy for continuous variables was a longitudinal analysis of the intent‐to‐treat sample, with treatment‐by‐time interaction as the measure of effect.

Results

Gabapentin‐treated patients displayed a significantly greater improvement in the BPI average pain severity score (P = 0.015; estimated difference between groups at week 12 = −0.92 [95% confidence interval −1.75, −0.71]). A significantly greater proportion of gabapentin‐treated patients compared with placebo‐treated patients achieved response at end point (51% versus 31%; P = 0.014). Gabapentin compared with placebo also significantly improved the BPI average pain interference score, the Fibromyalgia Impact Questionnaire total score, the Clinical Global Impression of Severity, the Patient Global Impression of Improvement, the Medical Outcomes Study (MOS) Sleep Problems Index, and the MOS Short Form 36 vitality score, but not the mean tender point pain threshold or the Montgomery Asberg Depression Rating Scale. Gabapentin was generally well tolerated.

Conclusion

Gabapentin (1,200–2,400 mg/day) is safe and efficacious for the treatment of pain and other symptoms associated with fibromyalgia.

     

Intraarticular injection of anakinra in osteoarthritis of the knee: A multicenter,randomized, double‐blind,placebo‐controlled study

Objective

To evaluate the clinical response, safety, and tolerability of a single intraarticular injection of anakinra in patients with symptomatic osteoarthritis (OA) of the knee.

Methods

Patients with OA of the knee were enrolled in a multicenter, double‐blind, placebo‐controlled study and randomized 2:1:2 to receive a single intraarticular injection of placebo, anakinra 50 mg, or anakinra 150 mg in their symptomatic knee. Patients were evaluated for 12 weeks postinjection. The primary end point was the change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score from baseline to week 4. Safety assessments included the evaluation of adverse events (AEs), laboratory tests, and vital signs. Pharmacokinetic parameters were assessed in a subset of patients.

Results

Of 170 patients who enrolled, 160 (94%) completed the study. The mean improvements from baseline to week 4 in the WOMAC score were not statistically different between the placebo group and the patients who received 50 mg of anakinra (P = 0.67) or 150 mg of anakinra (P = 0.77). Anakinra was well tolerated. No withdrawals due to AEs or serious AEs, and no serious infections or deaths were reported. No clinically significant trends were noted in laboratory values or vital signs. Pharmacokinetic parameters demonstrated that the mean terminal half‐life of anakinra in serum after intraarticular injection was ∼4 hours.

Conclusion

Anakinra was well tolerated as a single 50‐mg or 150‐mg intraarticular injection in patients with OA of the knee. However, anakinra was not associated with improvements in OA symptoms compared with placebo.

     

Association of functional outcome with both personal‐ and area‐level socioeconomic inequalities in patients with inflammatory polyarthritis

Objective

To describe the relationship between baseline area‐ and person‐level social inequalities and functional disability at 3 years in patients with early inflammatory polyarthritis (IP).

Methods

A total of 1,393 patients with new‐onset IP were recruited and allocated an Index of Multiple Deprivation (IMD) 2004 score based on their area of residence, and a social class based on baseline self‐reported occupation. Differences in the Health Assessment Questionnaire (HAQ) score at baseline and 3 years by IMD or social class were tested. The mean 3‐year change in HAQ score was compared by IMD and social class, and interactions between these measures examined.

Results

Patients from more deprived areas had poorer 3‐year HAQ outcome than those from less deprived areas (P = 0.019, adjusted for baseline HAQ score, age, sex, and symptom duration). The mean difference in HAQ change was most notable between the most deprived (IMD4) and least deprived areas (IMD1) (0.22; 95% confidence interval [95% CI] 0.11, 0.34). There was also a significant difference in HAQ score change between patients of the highest (SCI and II) and lowest social class (SCIV and V) (0.11; 95% CI 0.02, 0.20). For the mean (95% CI) 3‐year change in HAQ score, a significant interaction exists between IMD score and social class and their association with HAQ scores (P = 0.001) to modify outcome: IMD1/SC I and II ?0.23 (95% CI ?0.40, ?0.06) versus IMD 4/SC IV and V 0.15 (95% CI ?0.05, 0.34).

Conclusion

Person‐ and area‐level inequalities combine to modify outcome for rheumatoid arthritis. A person's social circumstance and residential environment have independent effects on outcome and are not just alternative measures of the same exposure.

     

Sleep disturbances and neurobehavioral functioning in children with and without juvenile idiopathic arthritis

Objective

To compare sleep disturbances and neurobehavioral function in children with juvenile idiopathic arthritis (JIA) to age‐ and sex‐matched control children.

Methods

Children (n = 116) ages 6–11 years with (n = 70) and without (n = 46) JIA and their parents participated. Parents completed questionnaires on sleep habits, sleep behavior, and school competence of their children; children completed computerized neurobehavioral performance tests.

Results

Compared to control children, children with JIA had a statistically significant (P < 0.001) greater mean overall sleep disturbance score and higher scores on 6 of 8 subscales (all P < 0.03) of the Children's Sleep Habits Questionnaire (CSHQ). There were no group differences on neurobehavioral performance test scores. However, regardless of group, children with an overall CSHQ score above an established cutoff for clinically significant sleep disturbances had slower mean simple reaction time (t = ?2.2, P < 0.03) and mean 5‐choice reaction time (t = ?2.3, P < 0.02) compared to those below the cutoff score. The CHSQ overall sleep disturbance score predicted reaction time (P < 0.009) after controlling for age, intelligence quotient, medication, and group.

Conclusion

Children with JIA have more parent‐reported sleep disturbances, but performed as well as control children on a series of standardized computer tests of neurobehavioral performance. Children with more disturbed sleep had slower reaction times.

     

Validity of self‐administered quality of well‐being scale in musculoskeletal disease

Objective

To evaluate the self‐administered Quality of Well‐Being (QWB‐SA) Scale for patients with rheumatic diseases.

Methods

Family medicine patients (n = 562) and rheumatology patients (n = 334) were assessed using the following tools: QWB‐SA, Health Assessment Questionnaire (HAQ), Arthritis Impact Measurement Scales (AIMS), and Rapid Assessment of Disease Activity in Rheumatology (RADAR).

Results

Patients with arthritis had significantly lower QWB‐SA scores and significantly higher HAQ scores than family medicine patients with and without adjustment for covariates. The QWB‐SA was significantly associated with quartiles from the RADAR, AIMS, and HAQ, providing evidence for the validity of the generic measure in patients with arthritis. Discriminant function analysis was used to create an arthritis‐specific scoring system for the QWB‐SA. Analyses demonstrated systematic relationships between the Quality of Well‐Being arthritis composite and the disease‐specific RADAR, AIMS, and HAQ.

Conclusions

Evidence supports the validity of the QWB‐SA for patients with rheumatic diseases. QWB‐SA items can be used to calculate an arthritis‐specific score. The QWB‐SA can be used to gain generic information for cost‐utility analysis and disease‐specific outcomes information for patients with arthritis.

     

Quality of well‐being in older people with osteoarthritis

Objective

To examine the sensitivity of the Quality of Well‐Being Scale (QWB) as a measure of health‐related quality of life (HRQOL) in people with osteoarthritis (OA).

Methods

The QWB was administered, along with the Arthritis Impact Measurement Scale (AIMS) and other health measures. Health care utilization data were also obtained.

Results

People with OA had a mean QWB score of 0.643. The QWB scores were significantly correlated with total AIMS scores, self‐rated health status, health care costs, depression scores, and most AIMS subscales. In addition, changes in QWB scores after 1 year were significantly correlated with changes in total AIMS scores and some AIMS subscales.

Conclusion

The QWB appears to be a useful and sensitive generic, utility‐based measure of HRQOL in people with OA.

     

Prevalent vertebral fractures among children initiating glucocorticoid therapy for the treatment of rheumatic disorders

Objective

Vertebral fractures are an under‐recognized problem in children with inflammatory disorders. We studied spine health among 134 children (87 girls) with rheumatic conditions (median age 10 years) within 30 days of initiating glucocorticoid therapy.

Methods

Children were categorized as follows: juvenile dermatomyositis (n = 30), juvenile idiopathic arthritis (n = 28), systemic lupus erythematosus and related conditions (n = 26), systemic arthritis (n = 22), systemic vasculitis (n = 16), and other conditions (n = 12). Thoracolumbar spine radiograph and dual x‐ray absorptiometry for lumbar spine (L‐spine) areal bone mineral density (BMD) were performed within 30 days of glucocorticoid initiation. Genant semiquantitative grading was used for vertebral morphometry. Second metacarpal morphometry was carried out on a hand radiograph. Clinical factors including disease and physical activity, calcium and vitamin D intake, cumulative glucocorticoid dose, underlying diagnosis, L‐spine BMD Z score, and back pain were analyzed for association with vertebral fracture.

Results

Thirteen vertebral fractures were noted in 9 children (7%). Of these, 6 patients had a single vertebral fracture and 3 had 2–3 fractures. Fractures were clustered in the mid‐thoracic region (69%). Three vertebral fractures (23%) were moderate (grade 2); the others were mild (grade 1). For the entire cohort, mean ± SD L‐spine BMD Z score was significantly different from zero (?0.55 ± 1.2, P < 0.001) despite a mean height Z score that was similar to the healthy average (0.02 ± 1.0, P = 0.825). Back pain was highly associated with increased odds for fracture (odds ratio 10.6 [95% confidence interval 2.1–53.8], P = 0.004).

Conclusion

In pediatric rheumatic conditions, vertebral fractures can be present prior to prolonged glucocorticoid exposure.

     

Alcohol consumption and markers of inflammation in women with preclinical rheumatoid arthritis

Objective

To examine the association between alcohol consumption and markers of inflammation in preclinical rheumatoid arthritis (RA).

Methods

We studied 174 incident RA cases with stored blood collected 1–16 years prior to RA symptoms (preclinical RA), from the Nurses' Health Study. Alcohol intake was measured using a detailed food frequency questionnaire administered every 4 years, prior to blood collection. Plasma was tested for biomarkers of inflammation, including high‐sensitivity C‐reactive protein (hsCRP), anti–cyclic citrullinated peptide (anti‐CCP) antibodies, interleukin‐6 (IL‐6), and soluble tumor necrosis factor receptor II (sTNFRII). Generalized additive models were used to identify structure in the relationship between each biomarker and cumulative average alcohol intake. Then general linear models were used for multivariable adjusted analyses with appropriate polynomial terms of alcohol consumption.

Results

After controlling for age at blood collection, smoking, parity and duration of breastfeeding, menopausal status, oral contraceptive use, body mass index, and the time between blood collection and RA onset, we found that the daily alcohol consumption showed a U‐shaped association with IL‐6 levels in RA patients, prior to symptoms. We also found an inverse relationship between alcohol intake and sTNFRII levels, but no associations with hsCRP or anti‐CCP levels.

Conclusion

These results demonstrate an association between alcohol consumption and markers of inflammation, including IL‐6 and sTNFRII, in RA patients, prior to the occurrence of symptoms.

     

Anaerobic exercise capacity in patients with juvenile‐onset idiopathic inflammatory myopathies

Objective

To 1) report the feasibility of an “all‐out” 30‐second cycling exercise test (Wingate Anaerobic Exercise Test [WAnT]) in juvenile‐onset idiopathic inflammatory myopathy (JIIM) patients, 2) describe the anaerobic exercise capacity in juvenile dermatomyositis patients, and 3) determine if the anaerobic exercise capacity could be related to disease duration or disease phase.

Methods

Twenty patients (age 14.13 ± 5.4 years) with JIIM participated in this study. All patients were able to perform the WAnT without adverse events.

Results

Comparison with healthy controls revealed a ?29.3 ± 26.58% (P = 0.001) and ?27.6 ± 25.7% (P = 0.002) impairment in mean power and peak power on the WAnT, respectively. The WAnT correlated with disease phase and with knee extensor muscle strength.

Conclusion

The WAnT might be a valuable adjunct next to other assessment tools in the followup of JIIM patients.

     

sE‐selectin for stratifying outcome in rheumatoid arthritis

Objectives

To determine the usefulness of sE‐selectin as a marker for early diagnosis and stratification of rheumatoid arthritis.

Methods

We investigated several markers of disease activity, including circulating adhesion molecules and other standard laboratory tests, in a 2–3 year followup analysis of patients with rheumatoid arthritis.

Results

The mean ± SD levels of sE‐selectin (91.68 ± 31.8 ng/ml versus 49.83 ± 14.76 ng/ml) and rheumatoid factor (375.7 ± 394.4 U versus 44.66 ± 37.63 U) were strongly elevated in severe (n = 15) versus mild (n = 7) courses of disease. Statistical calculation of mean and standard deviation revealed that sE‐selectin represents a highly significant marker for the presence of persistent and aggressive disease over time, regardless of therapeutic intervention and observation time points (P = 0.0004). Notably, regression analysis identified constant values for all parameters analyzed and, therefore, a stable course of the disease could be predicted from the beginning.

Conclusion

sE‐selectin appears to be a powerful marker to predict the severity of rheumatoid arthritis.

     

Treatment of polyarteritis nodosa and microscopic polyangiitis with poor prognosis factors: A prospective trial comparing glucocorticoids and six or twelve cyclophosphamide pulses in sixty‐five patients

Objective

Because the optimal cyclophosphamide (CY) treatment duration for severe polyarteritis nodosa (PAN) without virus infection and microscopic polyangiitis (MPA) has not been established, we conducted a trial to compare the effectiveness of 6 versus 12 CY pulses given in combination with corticosteroids (CS).

Methods

Sixty‐five (18 PAN, 47 MPA) previously untreated patients were randomized to receive 12 (n = 34) or 6 (n = 31) CY pulses combined with CS. PAN and MPA were histologically proven or met ACR criteria. All patients presented ≥1 factor of severity according to the five factor score (FFS). CY pulses were administered every 2 weeks for 1 month, then every 4 weeks. The end point of the study was the number of events (relapses and/or deaths) occurring in each group, analyzed according to an intention‐to‐treat strategy. The outcome was evaluated by Cox proportional hazards analysis.

Results

The baseline characteristics were similar for both groups. The mean (± SD) followup was 32 ± 21 months. Survival analysis showed a significantly lower relapse probability (P = 0.02; hazards ratio [HR] = 0.34) and higher event‐free survival (P = 0.02, HR = 0.44) for the 12 CY‐pulse group while the mortality rates were not significantly different (P = 0.47).

Conclusion

These results suggest that 6 CY pulses are less effective than 12 CY pulses to treat severe PAN and MPA, particularly with respect to the risk of relapses.

     

Role of CA-125 in identification of right ventricular failure in chronic obstructive pulmonary disease

Background:

Chronic obstructive pulmonary disease (COPD) is a progressive and debilitating disease. Cor pulmonale, characterized by right ventricular (RV) failure, can severely influence prognosis in these patients. Hence, early recognition might be important for tailoring therapy. An old biomarker, CA‐125, seems to be associated with the right heart. We aimed to show the relationship between CA‐125 levels and RV failure in patients with COPD.

Hypothesis:

CA‐125 might be a useful biomarker in identification of RV failure in patients with COPD.

Methods:

Forty patients with recent exacerbation of COPD were enrolled into the study. Another 40 age‐ and sex‐matched individuals were enrolled for comparison. Levels of CA‐125 were measured in the patients during the hospital stay. The COPD patients underwent echocardiographic study on the same day. Right‐ventricular parameters were evaluated, and RV failure was identified via transthoracic echocardiography.

Results:

Patients with COPD had significantly higher CA‐125 levels compared with controls (median 33.94 U/mL vs 9.76 U/mL, respectively; P < 0.001). Levels of CA‐125 were correlated with systolic pulmonary artery pressure (r = 0.550, P < 0.001), tricuspid annular plane systolic excursion (r = ? 0.496, P = 0.001), and tricuspid lateral annulus S velocity (r = ? 0.549, P = 0.002). High CA‐125 levels, obtained in hospitalized patients with COPD before echocardiography, enabled identification of RV failure with a sensitivity of 89.5% and specificity of 85.7%.

Conclusions:

The CA‐125 biomarker can be used to identify COPD patients with RV failure. © 2011 Wiley Periodicals, Inc. The authors have no funding, financial relationships, or conflicts of interest to disclose.

     

Persistently normal alanine aminotransferase levels in HIV/HCV-coinfected patients: the role of steatosis

Objective

The frequency and significance of, and liver biopsy findings associated with, a persistently normal alanine aminotransferase (ALT) level in HIV/hepatitis C virus (HCV)‐coinfected patients are poorly characterized. We analysed factors associated with persistently normal ALT levels, defined as at least three consecutive normal ALT values over a 6‐month period, in a group of 381 HIV/HCV‐coinfected patients.

Methods

Patients were categorized into two groups according to ALT values: group 1, patients with persistently normal ALT levels; and group 2, patients with elevated ALT values. Possible interactions with host factors, HIV and HCV viral factors, antiretroviral treatment and histological features were examined.

Results

Thirty‐six patients (9.4%) had persistently normal ALT levels. None of the 36 patients had cirrhosis. Seven patients (19.4%) had a METAVIR fibrosis score of F3. In multivariate analysis, a lower mean METAVIR inflammation score [odds ratio (OR) 0.50, 95% confidence interval (CI) 0.28–0.89; P=0.017], the absence of steatosis (OR 0.43, 95% CI 0.20–0.90; P=0.026) and HCV genotype 4 infection (OR 2.81, 95% CI 1.15–6.68; P=0.023) were associated with persistently normal ALT levels.

Conclusion

The slower progression of chronic hepatitis in patients with persistently normal ALT levels could be related, in part, to a lower frequency of steatosis

     

Assessment of atherosclerotic risk factors and endothelial function in children and young adults with pediatric‐onset systemic lupus erythematosus

Objective

To characterize atherosclerotic risk factors and endothelial function in pediatric‐onset systemic lupus erythematosus (SLE).

Methods

Lipoproteins, oxidized state, and autoantibodies to oxidized low‐density lipoprotein (Ox‐LDL) were assessed. Endothelial function was evaluated using brachial artery reactivity.

Results

Thirty‐three SLE patients and 30 controls were studied. SLE subjects had significantly decreased mean high‐density lipoprotein (HDL) cholesterol (41 mg/dl versus 51 mg/dl; P = 0.002) and apolipoprotein A‐I (97 mg/dl versus 199 mg/dl; P = 0.0004). There was no difference between groups in markers of oxidized state (including nitric oxide metabolites, isoprostanes, and Ox‐LDL) or in endothelial function. However, SLE subjects had increased median anti‐Ox‐LDL IgG (2,480 relative light units [RLU] versus 1,567 RLU; P = 0.0007) and IgG immune complexes with LDL (4,222 RLU versus 2,868 RLU; P = 0.002).

Conclusion

Pediatric SLE patients had significantly decreased levels of HDL cholesterol and apolipoprotein A‐I and elevated titers of autoantibodies to Ox‐LDL. Despite these atherosclerotic risk factors, SLE patients had normal measures of oxidized state and endothelial function.