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.

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.

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.

Calcium absorption in elderly subjects on high- and low-fiber diets: effect of gastric acidity.

In vitro studies suggest that the effect of fiber in inhibiting calcium absorption is pH dependent. In nine normal, elderly control subjects and eight elderly subjects with achlorhydria, 47Ca was ingested with three test meals: a low-fiber meal (0.5 g dietary fiber), a high-fiber meal (10.5 g), and a high-fiber meal with 120 mL of 0.1 mol HC/L. In control subjects calcium retention, measured in a whole-body counter, was 25.7 +/- 4.0% (mean +/- SD) with the low-fiber meal, 19.1 +/- 1.9% with the high-fiber meal (P less than 0.002 vs low fiber), and 18.9 +/- 3.3% with the high-fiber-plus-acid meal (P less than 0.002 vs low fiber, NS vs high fiber). Calcium absorption in achlorhydric subjects was not different from control subjects: 26.2 +/- 8.0% with low fiber, 19.6 +/- 4.1% with high fiber (P less than 0.04 vs low fiber), and 21.0 +/- 5.8% with high fiber plus acid (P less than 0.04 vs low fiber, NS vs high fiber). We conclude that, in humans, the reduction in calcium absorption with high fiber intake is unaffected by gastric pH.

Interactions between nutrition and infection with human immunodeficiency virus.

Nutritional status is severely compromised in persons infected with the human immunodeficiency virus (HIV). One or a combination of several disease-related factors can contribute to substantial weight loss and malnutrition, accelerating the downhill course of the disease. Efforts to prevent weight loss should include early intervention aimed at appetite stimulation, nutritional supplementation with high-calorie, high-protein oral supplements, and diagnosis and treatment of underlying infections and malabsorption. Although enteral or parenteral feedings may be warranted, these forms of nutritional support pose special problems in HIV-infected persons, and the ultimate benefits of these measures are not yet clear. The recent use of pharmacologic agents to stimulate appetite or improve body composition shows promise, but more research is needed before these drugs can be widely recommended as adjuncts to therapy. In general, unproven remedies should be avoided, as their risks may well outweigh their benefits.

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.

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.

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.

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.

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.

Treatment of primary biliary cirrhosis with low-dose weekly methotrexate.

Nine women with symptomatic precirrhotic primary biliary cirrhosis have been treated with oral pulse methotrexate, 15 mg/wk, for 12-34 months. Three women had pruritus, two fatigue, and four pruritus and fatigue. Itching disappeared and fatigue lessened or disappeared in all within 4-11 months after starting methotrexate. All who itched were able to discontinue cholestyramine (five) or antihistamines (two). Biochemical tests of liver function improved in all patients and then worsened in three when methotrexate was discontinued or the dose lowered. Mean serum alkaline phosphatase decreased from 471 to 171 U/L (P less than 0.01), serum bilirubin from 0.99 to 0.59 mg/dL (P less than 0.05), and serum alanine aminotransferase from 132 to 61 U/L (P = 0.02), and serum cholesterol fell from 265 to 213 mg/dL (NS). The decrease in serum cholesterol was significant, P = 0.05, if data were used just from the six women whose baseline serum cholesterol levels were elevated. Serum albumin remained normal in all. The serum bilirubin levels became normal in three of four patients with elevated levels. The serum alkaline phosphatase levels became normal in four patients and the alanine aminotransferase levels in three. Liver histology improved in five patients and was stable in the remaining four based on a quantitative evaluation of coded liver biopsy specimens. The improvement in histology was primarily due to decreased portal inflammation and bile duct injury. The titer of antimitochondrial antibody decreased in seven patients. The data suggest that methotrexate may be effective treatment for precirrhotic primary biliary cirrhosis. Controlled trials are needed to evaluate long-term efficacy and toxicity.

Treatment of primary sclerosing cholangitis with oral methotrexate.

Ten patients with well-documented primary sclerosing cholangitis who had no signs of portal hypertension or liver failure were treated with oral pulse methotrexate for at least 1 yr. The methotrexate dose averaged 15 mg/wk (0.2 mg/kg/wk). All six patients who were symptomatic became asymptomatic within 1-5 months of starting methotrexate. Biochemical tests of liver function improved in all patients. The alkaline phosphatase value decreased from a mean (+/-SD) of 373 +/- 210 IU to 140 +/- 77 IU (p = 0.0008), the mean alanine aminotransferase (ALT) from 115 +/- 74 to 76 +/- 79 U/L (p = 0.005), and the mean aspartate aminotransferase (AST) value from 88 +/- 37 to 57 +/- 40 U/L (p = 0.007). The improvement in mean bilirubin (1.19 +/- 1.41 to 0.67 +/- 0.25 mg/dl) was not statistically significant. Serum albumin remained normal (3.97 +/- 0.46 to 4.22 +/- 0.36 g/dl). Nine patients had a repeat liver biopsy after 1 yr of methotrexate therapy. Six of the nine showed histologic improvement with a reduction in inflammation. The other three liver biopsies were unchanged. Repeat cholangiograms were done in six patients. Two showed improvement. In one of the two, who had early disease, the cholangiogram became normal, and the liver biopsy was markedly improved. The other four cholangiograms showed no progression of disease. No toxicity was detected in these 10 patients. These results suggest that low-dose oral methotrexate therapy is effective in primary sclerosing cholangitis if treatment is begun before signs of portal hypertension or liver failure occur.

A double-blind controlled trial of oral-pulse methotrexate therapy in the treatment of primary sclerosing cholangitis.

BACKGROUND/AIMS: Primary sclerosing cholangitis (PSC) is a progressive disease with no accepted effective treatment. Because methotrexate was associated with clinical and histological improvement in two men with PSC, we conducted a prospective trial of methotrexate in PSC. METHODS: A prospective placebo-controlled, double-blind trial of methotrexate in PSC was performed. Twenty-four patients with PSC were randomized to receive methotrexate or placebo for a 2-year period. Seven of 12 taking methotrexate and five taking placebo had cirrhosis. Serial liver biopsies, endoscopic retrograde cholangiopancreatography (ERCP), and biochemical tests of liver function were followed. RESULTS: There were no significant changes in liver histological results, ERCP findings, tests of liver function (other than alkaline phosphatase), or outcome between the two groups. Mean alkaline phosphatase levels decreased by 152 IU in the methotrexate group and increased by 30 IU in the placebo group (P = 0.032). Patients taking methotrexate were more likely to reduce or discontinue cholestyramine than patients taking placebo. CONCLUSIONS: This study does not support efficacy for methotrexate in the treatment of PSC. On the basis of this study, the empiric use of methotrexate in patients with PSC is not recommended. However, methotrexate is being further evaluated in patients with precirrhotic PSC.

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.

Hepatic copper content is normal in early primary biliary cirrhosis and primary sclerosing cholangitis.

In previous studies, the majority of patients with the cholestatic liver diseases, primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC), had increased hepatic copper (Cu) levels even in early stages of disease. We prospectively measured hepatic copper content by atomic absorption spectrophotometry in 55 patients with PBC, 6 patients with PSC, and 29 patients with other chronic noncholestatic liver diseases. Hepatic Cu content was normal in 22/61 (36%) of patients with PBC or PSC; 18 of the 22 did not have cirrhosis (82%). Hepatic Cu content increased with increasing stage of disease (r = 0.61, P < 0.001) and was positively correlated with serum total bilirubin (r = 0.6, P < 0.0001) and alkaline phosphatase (r = 0.5, P < 0.001). All patients with stage I and II disease had hepatic Cu < 150 micrograms/g dry weight, and all patients with hepatic Cu > 150 micrograms/g dry weight had stage III and IV disease. Hepatic Cu content is normal in early PBC and PSC. Copper accumulation in the liver in these cholestatic liver diseases is secondary to cholestasis rather than a primary phenomenon.

The nuclear family: Correspondence in cognitive and affective reactions to the threat of nuclear war among older adolescents and their parents.

In order to assess the relationship between family members' cognitive and affective responses to nuclear war issues, 317 college students and their parents (n=559) independently completed a multifaceted questionnaire that included items concerning personal reactions, predictions, opinions, and attitudes about nuclear war. Results revealed a negligible relationship between the responses of college students and their parents, although the level of concordance between mothers and fathers was somewhat greater. Moreover, parents and students were relatively poor at predicting each others' nuclear threat attitudes, and the strength with which an attitude was endorsed did not enhance its predictability. Results are discussed with regard to heterogeneity in attitudinal and affective reactions within families, and with regard to the idea that infrequent communication concerning nuclear war issues may be occurring.