The association of HIV viral load with indirect markers of liver injury.

This study assessed the association of HIV RNA with indirect markers of liver injury including FIB-4 index, liver enzymes and platelet counts in a high-risk Hispanic population. The data were derived from a prospective study that included 138 HIV/hepatitis C (HCV)-coinfected and 68 HIV-infected participants without hepatitis C or B co-infection (mono-infected). In unadjusted analyses, detectable HIV viral load (vs undetectable, <400 copies/mL) was associated with a 40% greater odds (OR 1.4, 95% CI: 1.1-1.9, P = 0.016) of FIB-4 > 1.45 in the HIV/HCV-coinfected group and 70% greater odds of FIB-4 > 1.45 (OR 1.7, 95% CI: 1.0-2.8; P = 0.046) in the HIV-mono-infected group. In multivariable analyses, a 1 log(10) increase in HIV RNA was associated with a median increase in FIB-4 of 12% in the HIV/HCV-coinfected group and 11% in the HIV-mono-infected group (P < 0.0001). Among the HIV/HCV-coinfected group, the elevating effect of HIV RNA on FIB-4 was strongest at low CD4 counts (P = 0.0037). Among the HIV-mono-infected group, the association between HIV RNA and FIB-4 was independent of CD4 cell counts. HIV RNA was associated with alterations in both liver enzymes and platelet counts. HIV antiretroviral therapy was not associated with any measure of liver injury examined. This study suggests that HIV may have direct, injurious effects on the liver and that HIV viral load should be considered when these indirect markers are used to assess liver function.

Role of acquired immune deficiency syndrome-defining conditions in human immunodeficiency virus-associated wasting.

To evaluate the contribution of acquired immune deficiency syndrome-defining conditions (ADCs) in human immunodeficiency virus (HIV)-associated wasting, we analyzed longitudinal data from 671 participants in a nutrition and HIV cohort study. Data on ADCs, height, and weight were collected at baseline and during 6 monthly study visits. The frequency of ADCs decreased over time, but the relative risk (RR) of wasting (decrease in body mass index [BMI] to <20 kg/m(2)) increased with a history of >1 ADC; the RR of wasting increased 1.3-fold with each additional historical ADC. Any ADC during the 6 months prior to a study visit was associated with a decrease in BMI to <20 kg/m(2). The risk of wasting increased 2.7-fold with each additional recent ADC. These risks were not altered when adjusted for socioeconomic status, CD4 cell count, energy intake, or baseline BMI. Although ADCs contribute to the development of wasting, their contribution is relatively small.

Changes in lean body mass and total body weight are weakly associated with physical functioning in patients with HIV infection.

CONTEXT: For clinicians managing weight loss in patients with HIV, it would be useful to understand how changes in lean body mass (LBM) effect physical functioning, and whether LBM is more strongly related to physical functioning than total body weight (TBW). OBJECTIVE: To determine the relationship of changes in LBM and changes in total body weight (TBW) to changes in self-reported physical functioning in men and women with HIV infection. METHODS: Study design was longitudinal analysis of 1474 patient-intervals (each interval was approximately 6 months long) in 486 persons. Patients were participants in Nutrition for Healthy Living, a cohort study of HIV positive persons in Massachusetts and Rhode Island. The main outcome measure was change in self-reported physical functioning. RESULTS: Of the 1,474 intervals, 1,165 were contributed by men and 309 by women. The mean CD4 count for the 1,474 intervals was 383 cells/ micro L. In men, 5 kg changes in LBM and TBW were associated with 2.2 (95% confidence interval, 0.9, 3.4, P= 0.001) and 2.6 (95% confidence interval, 1.3, 3.9, P= 0.0002) point changes in physical functioning (on a 100-point scale), respectively, after adjusting for covariates. The relationships of changes in LBM and TBW to changes in physical functioning were linear. In women, there were no significant relationships between changes in LBM or TBW to changes in physical functioning. CONCLUSIONS: In this longitudinal analysis of relatively healthy persons with HIV infection, changes in LBM and TBW were significantly related to changes in physical functioning in men, but the magnitude of the relationship was small. In women, changes in LBM and TBW were not related to changes in physical functioning. Our data suggest that it is not necessary to measure body composition (lean and fat compartments) to understand the impact of changes in weight on physical functioning - it is sufficient to follow total body weight.

Weight and body composition in a cohort of HIV-positive men and women.

OBJECTIVE: At issue is whether weight loss in HIV infection is a cachectic process, characterised by loss of lean body mass with conservation of fat, or a process of starvation. We present data on body composition from 516 persons at different stages of HIV infection as determined by CD4 counts. DESIGN: Cross-sectional analyses of body composition in relation to CD4 count. SETTING: The baseline data from a prospective cohort study of outcomes in HIV/AIDS in relation to nutritional status in Boston, Massachusetts, USA. SUBJECTS: : The first 516 subjects with HIV/AIDS to enroll in the study. RESULTS: Differences in weight in relation to CD4 counts were present only at CD4 counts of 600 or less (slope below : 1.9 kg per 100 CD4 cells, On average, 68% of the difference in weight over CD4 counts was fat (slope: 1.3 kg fat per 100 CD4 cells, CONCLUSIONS: This cross-sectional analysis suggests that weight loss consists principally of fat loss in those persons with adequate fat stores. This observation will need to be confirmed in longitudinal analyses.

Nutrition in the era of highly active antiretroviral therapy.

Despite tremendous advances in treatment, persons with human immunodeficiency virus (HIV) infection commonly experience a variety of nutritional problems, such as weight loss, fat redistribution, and obesity. We discuss basic dietary and metabolic problems as they pertain to persons with HIV infection and provide practical suggestions for their management. In all persons, changes in weight are caused by disruptions of energy balance, which can be disturbed by alterations in energy intake (effective ingestion of calories), energy expenditure (use of calories), or both. Factors that contribute to the disturbance of energy balance are discussed in the context of HIV infection. Management of weight loss and weight gain may then be directed at the affected components of energy balance. This information is intended to raise health care providers' attention to nutrition in their patients, including monitoring of weight, dietary issues, and relevant symptoms, and to encourage liaisons with experienced dietitians and exercise trainers.

Endoscopic ultrasound of the upper gastrointestinal tract.

Endoscopic ultrasound (EUS) is an evolving technique used by gastroenterologists to examine lesions that are located either within or adjacent to the walls of the upper gastrointestinal (GI) tract; this topic is relatively unknown to most radiologists. Proper use of this modality is benefited by a cooperative effort between gastroenterologists and radiologists specializing in ultrasound and cross-sectional imaging. This article informs radiologists of the applications of this procedure. Most patients are examined with EUS after a biopsy of a mucosal tumor has been performed. A smaller number are performed to evaluate submucosal masses or when pancreatic disease is suspected but not diagnosed. The examinations can be performed either with dedicated flexible echoendoscopes or with catheter-based probes passed through a conventional endoscope. The exact location of abnormalities associated with the upper GI tract can be observed. Known anatomic landmarks are sought. Abnormalities of structures outside the upper GI tract will occasionally be found during these examinations. The specific layers of the walls of the gut are examined, and the T and N-classification of upper GI tumors can be determined accurately. The performance of an EUS examination requires advanced skills, and in many medical centers, it is the imaging modality of choice to stage cancers, to evaluate submucosal masses, and to investigate both malignant and benign pancreaticobiliary disease. Endoscopic ultrasound is sensitive but not specific, and biopsy is necessary to establish a diagnosis. Therapeutic applications of EUS are evolving. Specialized applications with catheter-based probes are also being developed.

Body composition and dietary intake in relation to drug abuse in a cohort of HIV-positive persons.

We examined the relationships between drug abuse, weight, body composition, and dietary intake in persons infected with HIV in a cross-sectional analysis of baseline data from a longitudinal study of nutritional status and HIV. Body composition was measured by bioelectrical impedance analysis. Dietary data were collected by 3-day food records or 24-hour recalls. We analyzed data from 39 current intravenous drug users (IVDU), 103 past intravenous drug users (past-IVDU), 239 users of nonintravenous drugs (users-NIVD), and 61 nonusers (reference category). In the men, there were no differences in weight, body mass index (BMI), or body composition among the drug-use groups. In the women, there was a trend to lower weight and BMI across the drug use categories: IVDU women had lower average weight (-13.7 kg; p = .006), BMI (-5.6 units; p = .003) and less fat mass than non-users (-9.8 kg; p = .0001). In women, drug users had higher weight-adjusted energy intakes than nonusers, whereas in the men both drug using groups, NIVD and IVDU, had higher energy intakes than nonusers. These data suggest that intravenous drug-abuse is associated with lower weight and fat mass in women with HIV infection despite adequate self-reported energy intake.

Weight loss and wasting remain common complications in individuals infected with human immunodeficiency virus in the era of highly active antiretroviral therapy.

It has been postulated that the use of highly active antiretroviral therapy (HAART) would reduce the occurrence of human immunodeficiency virus (HIV)-associated weight loss and wasting. To test this assumption, we evaluated, by means of longitudinal analysis, a prospective cohort of 469 HIV-infected individuals enrolled in a study of the impact of HIV on nutrition. Overall, 156 individuals in the cohort (33.5%) met at least 1 of these definitions of wasting. Furthermore, 58% of the cohort (289 patients) lost >1.5 kg of weight in a 6-month period between any 2 study visits. More than 50% of the cohort was receiving HAART at the time that they met 1 of the definitions of wasting; with regard to the occurrence of wasting; no differences were related to therapy.

Relation of lean body mass to health-related quality of life in persons with HIV.

OBJECTIVE: To determine the nature and strength of the relation between lean body mass and measures of health-related quality-of-living (HRQL) including physical functioning in men and women with HIV. DESIGN: Cross-sectional analysis using 619 patients with HIV infection from two cities in the northeastern United States. MAIN OUTCOME MEASURES: Lean body mass (LBM) was assessed by bioimpedance analysis (BIA). Physical functioning, general health perceptions, energy/fatigue, and number of days spent in bed in the last month were determined by patient self-report. RESULTS: Data from 450 men and 169 women were analyzed. Mean age was 39 years, 37.6% were nonwhite, and mean CD4 counts were 352 cells/ml. In multivariable models, higher LBM was significantly associated with better physical functioning in men but not in women. In men, a 10-kg increment in LBM was associated with a 3.7 point (95% confidence interval [CI], 0.19-7.2) increment in physical functioning (0-100 scale). In similar analyses, higher LBM was significantly associated with better general health perceptions (10-kg increment in LBM associated with a 4.8 point [95% CI, 1.4-8.1] increment in general health perceptions), and fewer days in bed in the last month (10-kg increment in LBM associated with 0.9 [95% CI, -1.8-0] fewer days in bed). Lean body mass was not independently associated with energy/fatigue. CONCLUSIONS: In this diverse population of persons with HIV, LBM was significantly related to physical functioning and other measures of HQRL in men, but not in women. In men, the relation was linear but relatively weak. These data have potential implications for assessing the clinical impact of interventions aimed at increasing LBM. Even in men, increases in LBM in the ranges that are currently achievable may produce relatively small improvements in physical functioning and other measures of HRQL.

Diarrhea and abnormalities of gastrointestinal function in a cohort of men and women with HIV infection.

OBJECTIVE: The aim of this study was to determine the prevalence of gastrointestinal dysfunction in the era of improved treatment of HIV infection. METHODS: Gastrointestinal function was studied cross-sectionally in 671 persons with HIV. Absorptive function was measured by a 25-g D-xylose test, a Sudan-III stain for fecal fat on a 100-g fat diet, and serum levels of micronutrients. RESULTS: Eighty-eight percent had at least one abnormality of gastrointestinal function: 47.7% had low D-xylose absorption; 40.3% had a history of liver disease; 38.9% had diarrhea; 28.3% had chronic diarrhea; 22.5% had borderline or low serum vitamin B12 levels; 12.2% had stool pathogens; and 7.2% were hypoalbuminemic. Men were more likely to have low D-xylose absorption, diarrhea, and stool pathogens than women. Intravenous drug users (IVDUs) were more likely to have a history of liver disease and hypoalbuminemia. However, borderline or low vitamin B12 levels were less frequent in IVDUs; they tended to have less diarrhea and a lower prevalence of stool pathogens. Despite less history of liver disease, 14.1% of women were hypoalbuminemic. Differences in patterns of gastrointestinal dysfunction are unlikely to be due to severity of immunosuppression as abnormalities were seen in all risk groups with CD4 >200 cells/mm3. D-xylose absorption below 30 mg/dl, current diarrhea, and borderline levels of vitamin B12 were associated with advanced immunosuppression. CONCLUSIONS: Abnormalities of gastrointestinal function are common in the current era of HIV treatment, appear early in the course of HIV infection, and in the absence of diarrhea. Gender and IVDU are important determinants of the type and frequency of gastrointestinal abnormalities.

Bioelectrical impedance methods in clinical research: a follow-up to the NIH Technology Assessment Conference.

In 1994, the National Institutes of Health (NIH) convened a Technology Assessment Conference "to provide physicians with a responsible assessment of bioelectrical impedance analysis (BIA) technology for body composition measurement." In 1997, Serono Symposia USA, Inc., organized an invited panel of scientists and clinicians, with extensive research and clinical experience with BIA, to provide an update. Panel members presented reviews based on their own work and published studies for the intervening years. Updates were provided on the single and multifrequency BIA methods and models; continued clinical research experiences; efforts toward establishing population reference norms; and the feasibility of establishing guidelines for potential diagnostic use of BIA in a clinical setting. This report provides a summary of the panel's findings including a consensus on several technical and clinical issues related to the research use of BIA, and those areas that are still in need of additional study.

Elevated resting energy expenditure among HIV-seropositive persons receiving highly active antiretroviral therapy.

OBJECTIVES: To ascertain the relationships between resting energy expenditure (REE), HIV RNA in plasma, and highly active antiretroviral therapy (HAART). DESIGN: Cross-sectional analysis using data of a large cohort study of nutrition in relation to HIV disease. METHODS: HIV RNA in plasma, REE, fat-free mass (FFM), and medication regimens were assessed at 530 visits among 372 participants in a cohort study of HIV-seropositive men and women. RESULTS: HIV RNA in plasma was directly correlated with REE. After adjustment for FFM, age, CD4 cell count and HAART use, there was an increase in REE of 90 kJ/day per log10 copies/ml increase in HIV RNA [95% confidence interval (CI) 16-164; P = 0.02). HAART use had an independent effect on REE. In patients reporting HAART use, adjusted REE was 339 kJ/day higher than in those not reporting HAART use (95% CI 177-501; P = 0.0001). CONCLUSIONS: Viral load and HAART appear to exert independent effects on REE. Although HAART may decrease metabolic rate by lowering viral burden, it appears to increase metabolic demands through some mechanism(s) independent of its effect on viral burden. This may result in elevated REE despite control of viral replication.

The effect of protease inhibitors on weight and body composition in HIV-infected patients.

OBJECTIVES: To determine the nutritional changes that occur in HIV-infected patients receiving protease inhibitor (PI) therapy and to determine the effects of PI treatment on physical functioning and health perceptions in patients with HIV infection. DESIGN: Longitudinal data analysis of 38 patients from a large Nutrition and HIV cohort. METHODS: Patients were included if they had started PI therapy after enrollment in the cohort, if they had taken the drug for at least 4 months without interruption and if data on weight, body composition and viral loads were available. RESULTS: Mean person-months of follow-up was 8.1 months before and 12.2 months after PI treatment. Weight (1.54 kg, P < 0.0001), body mass index (0.50 kg/m2, P < 0.0001), physical functioning (8.52 points, P = 0.0006) and current health perception (6.7 points, P = 0.01) increased significantly, and the daily caloric intake increase was close to significance (915.5 kJ/day, P = 0.06), after treatment with PI. Lean body mass did not change. Patients who responded to PI therapy with decreased viral load (n = 28) had significantly greater weight gain per month than non-responders. CONCLUSIONS: PI therapy of HIV infection is associated with weight gain and improvement in quality of life indices. The weight gain is mainly in fat mass, with no change in lean body mass (skeletal muscle). Optimal therapy of HIV-infected patients with weight loss may require highly active antiretroviral therapy combined with an anabolic stimulus such as exercise, anabolic steroids or human growth hormone.

Endoscopic ultrasound. Diagnostic and therapeutic uses.

Endoscopic ultrasound (EUS) is an emerging technique that can be used to visualize lesions in or adjacent to the gastrointestinal tract. We performed a review of current indications and capabilities of endoscopic ultrasound. EUS provides diagnostic information on submucosal lesions of the gastrointestinal tract. It is the most accurate method for local staging of esophageal and rectal cancer. It appears to be more sensitive in detecting common bile duct stones than endoscopic retrograde cholangiopancreatography. Furthermore, its use avoids the risk of pancreatitis. Lesions deep to the gastrointestinal tract, such as mediastinal nodes or pancreatic lesions, can be biopsied through the EUS endoscope. New therapeutic uses of EUS include aid in endoscopic drainage of pancreatic pseudocysts and celiac axis neurolysis for the treatment of pain from pancreatic cancer. EUS offers many new diagnostic capabilities to visualize and biopsy lesions in or adjacent to the gastrointestinal tract. Therapeutic uses are also emerging for this new technique.

Evaluation of abnormal liver function in pregnancy.

Liver disease in pregnancy may present in a subtle or dramatic fashion. An approach using the pattern of liver function abnormalities, time of gestation, and constellation of symptoms will narrow the diagnostic possibilities. Diagnostic tests, including serology, ultrasonography of the hepatobiliary tree, and liver biopsy, can make a definitive diagnosis.

Acute fatty liver of pregnancy in triplet gestation.

BACKGROUND: Acute fatty liver is reported to be more common in twin than in singleton pregnancies. We report three cases of biopsy-proven acute fatty liver in triplet gestations. CASES: In all three cases of acute fatty liver complicating triplet pregnancies, the presenting features were vague abdominal complaints with elevated hepatic aminotransferase levels. A liver biopsy was performed in each case, and cesareans were performed immediately after the diagnosis was confirmed histologically. Clinical resolution occurred in all cases, and all infants did well in the neonatal period. CONCLUSION: Patients with triplet gestations should be monitored closely for the early signs of acute fatty liver. Triplet gestations may contribute to the onset of acute fatty liver by further stressing the fatty acid oxidation capabilities of the susceptible woman.

Utility of hepatic iron index in American patients with hereditary hemochromatosis: a multicenter study.

BACKGROUND & AIMS: A hepatic iron index (hepatic iron concentration divided by age) of more than 1.9 has been proposed as useful to identify patients with homozygous hereditary hemochromatosis (HHC). There are limited data on the diagnostic use of the hepatic iron index in patients with HHC in the United States. This study evaluated the hepatic iron index in the diagnosis of HHC in a multicenter U.S. study. METHODS: Hepatic iron concentration was measured in 509 patients undergoing liver biopsy. The diagnosis of HHC was made using clinical, biochemical, and histopathologic criteria. RESULTS: Fifty-five patients met criteria for HHC; hepatic iron index was > 1.9 in 51 of 55 (93%) patients with HHC but in none of 454 patients with other liver diseases; hepatic iron concentration was > 71 mumol/g dry weight in 54 of 55 patients with HHC but only 1 of the other 454 patients. CONCLUSIONS: A hepatic iron index of > or = 1.9 can identify most U.S. patients with HHC but is < or = 1.9 in 7%. A "threshold" hepatic iron concentration of 71 mumol/g can almost always distinguish patients with HHC from patients with other liver diseases and may be a useful adjunct to the hepatic iron index in the diagnosis of HHC in the diverse U.S. population.

Methotrexate treatment of idiopathic granulomatous hepatitis.

OBJECTIVE: To test the efficacy and safety of low-dose oral pulse methotrexate therapy in patients with idiopathic granulomatous hepatitis who had complications of, did not respond to, or refused glucocorticoid therapy. DESIGN: Prospective case study. SETTING: Academic medical center hospital. PATIENTS: Seven patients with biopsy-proven, idiopathic granulomatous hepatitis who could not tolerate or were unresponsive to glucocorticoid therapy. INTERVENTION: Low-dose oral pulse methotrexate, 15 mg/wk. MEASUREMENTS: Temperature, symptoms, dose of concurrent glucocorticoids, biochemical tests of liver function, side effects of methotrexate, and assessment of liver biopsy specimens. RESULTS: All six febrile patients became afebrile within 3 months of starting methotrexate. Fatigue and anorexia improved in all patients. Glucocorticoid therapy was successfully discontinued within 6 months of starting methotrexate in four patients receiving prednisone at entry. Liver biopsy specimens were obtained again after methotrexate therapy and showed absence of granulomas in four of four patients. The minimum effective dose of methotrexate was 0.20 mg/kg body weight per week. No serious adverse effects and no failures to respond to methotrexate therapy were noted in this group of patients. In three patients, methotrexate therapy has been successfully tapered without signs or symptoms of recurrent disease. CONCLUSIONS: Low-dose oral pulse methotrexate was effective in treating patients with granulomatous hepatitis.