Bile acid malabsorption in HIV infected patients with chronic diarrhoea

Aims: To look for the presence of bile acid malabsorption in HIV infected patients with chronic diarrhoea and determine whether bile sequestering agents may have a role in palliating this common problem.
Methods: Nineteen HIV infected patients with chronic diarrhoea (duration >one month) poorly controlled on conventional treatment were investigated using the seven day retention of ⁷⁵seleno-23-homocholic acid taurine (SeHCAT) as a measure of bile acid loss from the enterohepatic circulation. Patients with evidence of bile acid malabsorption were offered cholestyramine.
Results: Sixteen (84%) had evidence of bile acid malabsorption (<15% retention at seven days). Ten of the 16 patients with bile acid malabsorption had terminal ileal biopsies -six had ileitis and four normal histology, suggesting that malabsorption is not always related to terminal ileitis. Thirteen patients with bile acid malabsorption have been treated with cholestyramine and 11 have reported a symptomatic response.
Conclusions: Bile acid malabsorption can be demonstrated in some cases of HIV associated chronic diarrhoea and we suggest a therapeutic trial of a bile sequestering agent in patients whose symptoms are not well controlled using conventional anti-diarrhoeal agents.     

Associations between FTO genotype and total energy and macronutrient intake in adults: a systematic review and meta‐analysis

Risk variants of fat mass and obesity‐associated (FTO) gene have been associated with increased obesity. However, the evidence for associations between FTO genotype and macronutrient intake has not been reviewed systematically. Our aim was to evaluate the potential associations between FTO genotype and intakes of total energy, fat, carbohydrate and protein. We undertook a systematic literature search in OVID MEDLINE, Scopus, EMBASE and Cochrane of associations between macronutrient intake and FTO genotype in adults. Beta coefficients and confidence intervals (CIs) were used for per allele comparisons. Random‐effect models assessed the pooled effect sizes. We identified 56 eligible studies reporting on 213,173 adults. For each copy of the FTO risk allele, individuals reported 6.46 kcal day^?1 (95% CI: 10.76, 2.16) lower total energy intake (P = 0.003). Total fat (P = 0.028) and protein (P = 0.006), but not carbohydrate intakes, were higher in those carrying the FTO risk allele. After adjustment for body weight, total energy intakes remained significantly lower in individuals with the FTO risk genotype (P = 0.028). The FTO risk allele is associated with a lower reported total energy intake and with altered patterns of macronutrient intake. Although significant, these differences are small and further research is needed to determine whether the associations are independent of dietary misreporting.     

Dietary intake and overweight and obesity among persons living with HIV in Atlanta Georgia

In the U.S., there has been a rise in overweight and obesity among persons living with HIV (PLWH). The aim of this study was to examine dietary intake and body mass index (BMI) in PLWH in Atlanta Georgia relative to the U.S. population. Dietary intake among PLWH was compared with recommended standards as well as estimated dietary intake for adults in the U.S. Over 31% of the study participants were overweight [BMI?=?25–29.9?kg/m²], and 33.1% obese [BMI?≥?30?kg/m²]. Results indicated significant dietary differences between participants in our sample and U.S. daily recommendations for adults as well as estimated intakes of the U.S. population. Both males and females consumed more percentage of energy from fat and less fiber as well as fruit and vegetables servings than what is recommended. Results suggest that overweight and obesity are an additional health burden to PLWH in our sample and that their daily dietary practices are not meeting the U.S. government-recommended nutritional standards.     

Helicobacter pylori infection and drugs malabsorption

Drug absorption represents an important factor affecting the efficacy of oral drug treatment.Gastric secretion and motility seem to be critical for drug absorption.A causal relationship between impaired absorption of orally administered drugs and Helicobacter pylori(H.pylori)infection has been proposed.Associations have been reported between poor bioavailability of l-thyroxine and l-dopa and H.pylori infection.According to the Maastricht Florence Consensus Report on the management of H.pylori infection,H.pylori treatment improves the bioavailability of both these drugs,whereas the direct clinical benefits to patients still await to be established.Less strong seems the association between H.pylori infection and other drugs malabsorption,such as delavirdine and ketoconazole.The exact mechanisms forming the basis of the relationship between H.pylori infection and impaired drugs absorption and/or bioavailability are not fully elucidated.H.pylori infection may trigger a chronic inflammation of the gastric mucosa,and impaired gastric acid secretion often follows.The reduction of acid secretion closely relates with the wideness and the severity of the damage and may affect drug absorption.This minireview focuses on the evidence of H.pylori infection associated with impaired drug absorption.     

Protein leverage and energy intake

Increased energy intakes are contributing to overweight and obesity. Growing evidence supports the role of protein appetite in driving excess intake when dietary protein is diluted (the protein leverage hypothesis). Understanding the interactions between dietary macronutrient balance and nutrient‐specific appetite systems will be required for designing dietary interventions that work with, rather than against, basic regulatory physiology. Data were collected from 38 published experimental trials measuring ad libitum intake in subjects confined to menus differing in macronutrient composition. Collectively, these trials encompassed considerable variation in percent protein (spanning 8–54% of total energy), carbohydrate (1.6–72%) and fat (11–66%). The data provide an opportunity to describe the individual and interactive effects of dietary protein, carbohydrate and fat on the control of total energy intake. Percent dietary protein was negatively associated with total energy intake (F = 6.9, P < 0.0001) irrespective of whether carbohydrate (F = 0, P = 0.7) or fat (F = 0, P = 0.5) were the diluents of protein. The analysis strongly supports a role for protein leverage in lean, overweight and obese humans. A better appreciation of the targets and regulatory priorities for protein, carbohydrate and fat intake will inform the design of effective and health‐promoting weight loss diets, food labelling policies, food production systems and regulatory frameworks.     

Helicobacter pylori infection and food-cobalamin malabsorption

Two entities of considerable recent interest,Helicobacter pylori infection of the stomach and food-cobalamin malabsorption, are each intimately associated with gastric abnormalities. A possible connection between the two entities thus suggested itself and prompted us to study 98 subjects with low serum cobalamin levels but normal Schilling test results and 17 controls with normal cobalamin levels. Food-cobalamin absorption was measured with the egg yolk-cobalamin absorption test (EYCAT) and was abnormal in 56 of the 115 subjects. IgG antibody toH. pylori was found in 78% of the 27 patients with severe food-cobalamin malabsorption (EYCAT <1.0% excretion), compared with only 45% of 29 subjects with mild malabsorption (EYCAT 1.0–1.99%) and 42% of 59 subjects with normal absorption (EYCAT 2.0%) (x²=9.52,P<0.01). Antibody-positive patients had lower EYCAT excretion values than those without antibody (2.03±1.83% vs 3.11±2.13%,t=2.913,P=0.005). While Hispanic patients tended to malabsorb food cobalamin more frequently than did white or black patients, and men were more often antibody-positive than women, race, sex, or age characteristics were not responsible for the significant association between serologic evidence ofH. pylori infection and severe malabsorption of food cobalamin. The association that we describe suggests that gastritis induced byH. pylori predisposes to a more severe form of food-cobalamin malabsorption, among its other effects on gastric status.This study was supported by grant DK-32640 from the National Institutes of Health, by the NIH National Center for Research Resources of the General Clinical Research Centers grant MO1 RR-43, by the Medical Research Service of the Department of Veterans Affairs, and by the Procter & Gamble Company.     

HIV reservoirs and the possibility of a cure for HIV infection

Recent studies demonstrate that suppressive therapy can drive HIV-1 RNA levels to less than 50 copies mL(-1) in patient plasma. Yet, ultrasensitive assays show that most patients continue to harbour low-level persistent viremia. Treatment intensification studies indicate that low-level viremia could arise from several different sources. These sources include: (i) long-lived HIV-infected cells that replicate and produce virus; (ii) ongoing replication cycles in cells located in sanctuary sites where drug levels are suboptimal; and/or (iii) proliferation of latently infected cells with regeneration of a stable reservoir of slowly dividing infected cells. A well-defined latent reservoir of HIV is memory CD4+ T-cells where latency is established when an activated CD4+ T-cell becomes infected by HIV, but transitions to a terminally differentiated memory cell before it is eliminated. This review examines the dynamics and possible reservoirs of persistent HIV in patients on suppressive therapy, the mechanisms promoting viral latency and strategies to purge latent viral reservoirs. The promising research described here takes a number of steps forward to seriously address HIV remission and/or eradication.     

Autoimmune polyglandular failure associated with malabsorption and gastric carcinoid tumour

Abstract. A 21-year-old female with autoimmune polyglandular failure (APG) manifested by insulin-dependent diabetes mellitus (IDDM), hypothyroidism and pernicious anaemia developed severe malabsorption due to exocrine pancreatic insufficiency. Supplemental pancreatic enzymes resulted in marked improvement of steatorrhea. There was also an incidental finding of gastric carcinoid tumour. We identified only 13 other patients in our institution with either type 2 or 3 APG, one of which had significant steatorrhoea. Another patient with IDDM, hypothyroidism and pernicious anaemia had an asymptomatic gastric carcinoid tumour. The possible mechanisms for malabsorption in APG are discussed.     

Dysplastic haemopoiesis following orthotopic liver transplantation: comparison with similar changes in HIV infection and primary myelodysplasia

Summary To validate scientifically our prior empiric observations that patients develop significant haemopoietic dysplasia following solid organ transplantation, we developed a quantitative lineage-specific scoring system to evaluate dysplastic features of bone marrow aspirates and core biopsies. We used this scoring system to compare retrospectively randomly selected bone marrow aspirates and core biopsies from 19 patients undergoing orthotopic liver transplantation (OLT), 21 with a known history of human immunodeficiency virus (HIV) infection, and 18 with primary or chemotherapy-related myelodysplastic syndromes (MDS). Our results show that the OLT patient group developed significant but milder haemopoietic dysplastic changes than the HIV or MDS groups, and that the MDS group developed more severe dysplasia of the myeloid lineage than the other groups. The possible roles for drugs and infectious agents in the pathophysiology of dysplastic changes are discussed.     

Testing children of mothers with HIV infection: experience in three south-west London HIV clinics

Objective

There are several reported cases of vertically infected children presenting with advanced HIV infection in the UK. The children of women with HIV infection are at increased risk of being infected. There are few data available on the number of such children that are yet to be tested for HIV. This study looked at the HIV testing status of children whose mothers attend HIV services at three south‐west London clinics.

Methods

Case notes of women attending the clinics from 1 January to 30 June 2009 were reviewed. When data were incomplete, women were prospectively interviewed.

Results

Case notes of 605 women were reviewed; 478 women had 1107 children. The majority of women (386; 81%) were of Black African ethnicity. Sixty‐one per cent (675 of 1107) of the children were known to have been tested for HIV. The children resident abroad were more likely to be untested compared with those resident in the UK; 186 of 255 (73%) vs. 246 of 852 (29%). A quarter (106 of 432) of the untested children were ≤18 years old; 49 (46%) of these were resident in the UK. The most common reason given by the mothers for not testing was a perceived ‘unlikely risk’.

Conclusions

A significant number of children at risk of vertically transmitted HIV infection, including 49 children ≤18 years and resident in the UK, were identified through this study. The mothers are being encouraged to have these children tested and a multidisciplinary team involving adult and paediatric HIV healthcare professionals has been set up to negotiate and facilitate testing.     

Interactions between HIV infection and other sexually transmitted diseases

Mechanisms and implications of the interaction between HIV and other STDs such as syphilis, Herpes simplex, Chlamydia and Neisseria gonorrhoeae infection are presented and relevant case reports and trials described.     

Burden of HIV among young transgender women: factors associated with HIV infection and HIV treatment engagement

Young transgender women (YTW) are disproportionately affected by HIV, however, little is known about the factors associated with HIV infection and treatment engagement. We examined correlates of HIV infection and the steps of the HIV treatment cascade, specifically, being aware of their HIV infection, linked to care, on ART, and adherent to ART. We analyzed the baseline data of Project LifeSkills, a randomized control trial of sexually active YTW recruited from Chicago, Illinois and Boston, Massachusetts. We conducted multivariable Poisson regressions to evaluate correlates of HIV infection and the steps of the HIV treatment cascade. Nearly a quarter (24.7%) of YTW were HIV-infected. Among HIV-infected YTW, 86.2% were aware of their HIV status, 72.3% were linked to care, 56.9% were on ART, and 46.2% were adherent to ART. Having avoided healthcare due to cost in the past 12 months and not having a primary care provider were associated with suboptimal engagement in HIV care. Our results suggest that improving linkage and retention in care by addressing financial barriers and improving access to primary care providers could significantly improve health outcomes of YTW as well as reduce forward transmission of HIV.     

Micronutrient interventions and HIV infection: a review of current evidence

OBJECTIVE: To review the current evidence on the role of micronutrient supplementation in HIV transmission and progression. METHOD: Literature review. RESULTS: The importance of micronutrients in the prevention and treatment of childhood infections is well known, and evidence is emerging that micronutrient interventions may also affect HIV transmission and progression. CONCLUSION: Interventions to improve micronutrient intake and status could contribute to a reduction in the magnitude and impact of the global HIV epidemic. However, more research is needed before specific recommendations can be made.     

Lactose malabsorption in the elderly: Role of small intestinal bacterial overgrowth

Objective. The prevalence of lactose malabsorption (LM) is increased in the elderly, although the mechanisms responsible are still a matter of speculation. The objective of this study was to investigate the possible roles of reduced functional small intestinal absorptive area, lactase deficiency and small intestinal bacterial overgrowth (SIBO). Material and methods. Twenty Caucasian (Anglo-Celtic), asymptomatic, well-nourished, elderly volunteers (median age 79 years, range 70–94 years) with no clinically apparent predisposition to SIBO underwent a 50 g lactose breath hydrogen test (LBHT) and mannitol absorption test, the latter as an index of functional small intestinal absorptive area. Those with LM additionally underwent bacteriological assessment of small intestinal secretions and mucosal biopsy, to assess the contribution of SIBO and lactase deficiency, respectively, to the pathogenesis of LM in individual cases. The prevalence of SIBO was also determined in elderly subjects without LM. Twenty asymptomatic younger subjects (median age 29 years, age range 18–35 years) served as controls. All subjects were “hydrogen producers” in response to lactulose. Results. LM was evident in 10/20 (50%) elderly subjects and 1/20 (5%) younger subjects (p=0.003). Mannitol absorption did not differ significantly in elderly and younger subjects or in elderly subjects with and without LM. SIBO was documented in 9/10 (90%) elderly subjects with LM; eradication was associated with resolution of LM. Lactase deficiency was evident in only one elderly subject with LM. SIBO was evident in 2/10 (20%) elderly subjects without LM (p=0.005 compared to those with LM). Lactulose breath hydrogen test identified only 2/11 (18%) elderly subjects with SIBO. Conclusions. Increased prevalence of LM in the elderly is mostly due to clinically non-apparent SIBO, rather than mucosal factors. The lactulose breath hydrogen test cannot be relied upon to identify elderly subjects with SIBO, even in those without an anatomical predisposition.     

Heterogeneity of gastric histology and function in food cobalamin malabsorption: absence of atrophic gastritis and achlorhydria in some patients with severe malabsorption

BACKGROUND: The common but incompletely understood entity of malabsorption of food bound cobalamin is generally presumed to arise from gastritis and/or achlorhydria. AIM: To conduct a systematic comparative examination of gastric histology and function. SUBJECTS: Nineteen volunteers, either healthy or with low cobalamin levels, were prospectively studied without prior knowledge of their absorption or gastric status. METHODS: All subjects underwent prospective assessment of food cobalamin absorption by the egg yolk cobalamin absorption test, endoscopy, histological grading of biopsies from six gastric sites, measurement of gastric secretory function, assay for serum gastrin and antiparietal cell antibodies, and direct tests for Helicobacter pylori infection. RESULTS: The six subjects with severe malabsorption (group I) had worse histological scores overall and lower acid and pepsin secretion than the eight subjects with normal absorption (group III) or the five subjects with mild malabsorption (group II). However, histological findings, and acid and pepsin secretion overlapped considerably between individual subjects in group I and group III. Two distinct subgroups of three subjects each emerged within group I. One subgroup (IA) had severe gastric atrophy and achlorhydria. The other subgroup (IB) had little atrophy and only mild hypochlorhydria; the gastric findings were indistinguishable from those in many subjects with normal absorption. Absorption improved in the two subjects in subgroup IB and in one subject in group II who received antibiotics, along with evidence of clearing of H pylori. None of the subjects in group IA responded to antibiotics. CONCLUSIONS: Food cobalamin malabsorption arises in at least two different gastric settings, one of which involves neither gastric atrophy nor achlorhydria. Malabsorption can respond to antibiotics, but only in some patients. Food cobalamin malabsorption is not always synonymous with atrophic gastritis and achlorhydria, and hypochlorhydria does not always guarantee food cobalamin malabsorption.