A STAT4 variant increases liver fibrosis risk in Caucasian patients with chronic hepatitis B.

BACKGROUND: Host genetic modifiers of the natural history of chronic hepatitis B (CHB) remain poorly understood. Recently, a genome-wide association study (GWAS)-identified polymorphism in the STAT4 gene that contributes to the risk for hepatocellular carcinoma (HCC) was shown to be associated with the full spectrum of hepatitis B virus (HBV) outcomes in Asian patients. However, the functional mechanisms for this effect are unknown and the role of the variant in modulating HBV disease in Caucasians has not been investigated. AIMS: To determine whether STAT4 genetic variation is associated with liver injury in Caucasian patients with CHB and to investigate potential mechanisms mediating this effect. METHODS: STAT4 rs7574865 was genotyped in 1085 subjects (830 with CHB and 255 healthy controls). STAT4 expression in liver, PBMCs and NK cells, STAT4 phosphorylation and secretion of interferon-gamma (IFN-γ) according to STAT4 genetic variation was examined. RESULTS: STAT4 rs7574865 genotype was independently associated with hepatic inflammation (OR: 1.42, 95% CI: 1.07-2.06, P = 0.02) and advanced fibrosis (OR: 1.83, 95% CI: 1.19-2.83, P = 0.006). The minor allele frequency of rs7574865 was significantly lower than that in healthy controls. rs7574865 GG risk carriers expressed lower levels of STAT4 in liver, PBMCs and in NK cells, while NK cells from patients with the risk genotype had impaired STAT4 phosphorylation following stimulation with IL-12/IL-18 and a reduction in secretion of IFN-γ. CONCLUSION: Genetic susceptibility to HBV persistence, hepatic inflammation and fibrosis in Caucasians associates with STAT4 rs7574865 variant. Downstream effects on NK cell function through STAT4 phosphorylation-dependent IFN-γ production likely contribute to these effects.

The antiviral role of zinc and metallothioneins in hepatitis C infection.

Metallothioneins (MTs) are small, cysteine-rich proteins characterized by a high affinity for monovalent and divalent cations, such as copper and zinc. Of the four known MT isoforms, only, members of the MT 1 and 2 subfamilies are widely expressed, acting as metal chaperones whose primary role is to mediate intracellular zinc homoeostasis. Metallothioneins are potently induced by heavy metals and other sources of oxidative stress where they facilitate metal binding and detoxification as well as free radical scavenging. Metallothionein expression is well documented in the context of viral infection; however, it remains uncertain whether MTs possess specific antiviral roles or whether induction is merely a consequence of cellular stress. To better understand the role of MTs following hepatitis C virus (HCV) infection, we examined MT expression and localization in vitro and in vivo and used a siRNA knockdown approach to ascertain their antiviral efficacy. We confirmed HCV-driven MT induction in vitro and demonstrated MT accumulation in the nucleus of HCV-infected hepatocytes by immunofluorescence. Using a pan-MT siRNA to knock down all members of the MT1 and MT2 subfamilies, we demonstrate that they are mildly antiviral against the JFH1 strain of HCV in vitro (~1.4 fold increase in viral RNA, P < .05). Furthermore, the antiviral effect of zinc treatment against HCV in vitro was mediated through MT induction (P < .05). Our data suggest a potential benefit of using zinc as a low-cost adjunct to current HCV antiviral therapies and suggest that zinc may facilitate the antiviral role of MTs against other viruses.

IFNL3/4 genotype is associated with altered immune cell populations in peripheral blood in chronic hepatitis C infection.

Single-nucleotide polymorphisms near the interferon lambda 3 (IFNL3) gene predict outcomes to infection and anti-viral treatment in hepatitis C virus (HCV) infection. To identify IFNL3 genotype effects on peripheral blood, we collected phenotype data on 400 patients with genotype 1 chronic hepatitis C (CHC). The IFNL3 responder genotype predicted significantly lower white blood cells (WBCs), as well as lower absolute numbers of monocytes, neutrophils and lymphocytes for both rs8099917 and rs12979860. We sought to define the WBC subsets driving this association using flow cytometry of 67 untreated CHC individuals. Genotype-associated differences were seen in the ratio of CD4CD45RO+ to CD4CD45RO-; CD8CD45RO+ to CD8CD45RO-, NK CD56 dim to bright and monocyte numbers and percentages. Whole blood expression levels of IFNL3, IFNLR1 (interferon lambda receptor 1), IFNLR1-mem (a membrane-associated receptor), IFNLR1-sol (a truncated soluble receptor), MxA and T- and NK (natural killer) cell transcription factors TBX21, GATA3, RORC, FOXP3 and EOMES in two subjects were also determined. CHC patients demonstrated endogenous IFN activation with higher levels of MxA, IFNLR1, IFNLR1-mem and IFNLR1-sol, and IFNL3 genotype-associated differences in transcription factors. Taken together, these data provide evidence of an IFNL3 genotype association with differences in monocyte, T- and NK cell levels in the peripheral blood of patients with CHC. This could underpin genotype associations with spontaneous and treatment-induced HCV clearance and hepatic necroinflammation.

Vancomycin-associated drug reaction with eosinophilia and systemic symptoms syndrome.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare but potentially life-threatening multi-system disorder characterised by the delayed onset of fever, rash and internal organ involvement following the administration of a drug. We report three definite cases of vancomycin-associated DRESS syndrome occurring and review the literature regarding this syndrome.

Hepatic metallothionein expression in chronic hepatitis C virus infection is IFNL3 genotype-dependent.

The IFNL3 genotype predicts the clearance of hepatitis C virus (HCV), spontaneously and with interferon (IFN)-based therapy. The responder genotype is associated with lower expression of interferon stimulated genes (ISGs) in liver biopsies from chronic hepatitis C patients. However, ISGs represent many interacting molecular pathways, and we hypothesised that the IFNL3 genotype may produce a characteristic pattern of ISG expression explaining the effect of genotype on viral clearance. For the first time, we identified an association between a cluster of ISGs, the metallothioneins (MTs) and IFNL3 genotype. Importantly, MTs were significantly upregulated (in contrast to most other ISGs) in HCV-infected liver biopsies of rs8099917 responders. An association between lower fibrosis scores and higher MT levels was demonstrated underlying clinical relevance of this association. As expected, overall ISGs were significantly downregulated in biopsies from subjects with the IFNL3 rs8099917 responder genotype (P=2.38 × 10(-7)). Peripheral blood analysis revealed paradoxical and not previously described findings with upregulation of ISGs seen in the responder genotype (P=1.00 × 10(-4)). The higher MT expression in responders may contribute to their improved viral clearance and MT-inducing agents may be useful adjuncts to therapy for HCV. Upregulation of immune cell ISGs in responders may also contribute to the IFNL3 genotype effect.

Minimum phosphorus requirement of one-cycle and two-cycle (molted) hens.

In experiment 1 (one cycle), hens were fed diets containing 0.10, 0.115, 0.125, 0.135, 0.15, or 0.45% available P (AP) from 40 to 56 wk of age, with the last diet being a positive control. Egg production, egg mass, and BW were reduced (P < 0.05) by all lower AP levels except 0.15% AP when compared with the 0.45% AP treatment. In the second experiment (two cycles with a molt), hens were initially fed diets containing 0.10, 0.12, 0.14, 0.16, 0.18, 0.20, or 0.45% AP from 21 to 63 wk of age. Diets containing 0.10, 0.12, and 0.14% AP were terminated at 35, 39, and 50 wk, respectively, due to low egg production and increased mortality. Hens fed 0.16% AP also had significantly lower production performance than hens fed 0.45% AP during the first cycle. Hens on the 0.16 to 0.45% AP treatments were induced molted at 64 wk of age by 10 d of feed removal. The hens were then returned to the same AP layer diet they had been fed from 21 to 63 wk. For the 68 to 108 wk postmolt second-cycle period, hens fed the 0.16 to 0.20% AP diets (166 to 209 mg/d) had significantly lower egg production, egg mass, and feed efficiency than hens fed 0.45% AP. The results of our study indicated that first-cycle hens required approximately 0.18% AP or 198 mg AP/hen per day, and molted hens in their second cycle had a requirement that was greater than 0.20% AP or 209 mg AP/hen per day.

Effect of soybean variety and processing on growth performance of young chicks and pigs.

The objective of this study was to determine whether soybeans without the Kunitz trypsin inhibitor and lectins could be fed effectively to young chicks and pigs. Specifically, we compared the growth performance of chicks and pigs fed diets containing modified soybeans: Kunitz trypsin inhibitor-free (KF), lectin-free (LF), lectin and Kunitz trypsin inhibitor-free (LFKF), conventional soybeans (CSB), and commercially obtained, dehulled, solvent-extracted soybean meal (SBM). A 7-d chick experiment was conducted to evaluate the nutritional value of CSB, KF, LF, LFKF, and SBM. The experiment was conducted as a completely randomized design, with four replicates, five treatments, and six male chicks per pen (n = 120). The five treatments consisted of 23% CP dextrose-soybean-based diets containing KF, LF, LFKF, CSB, or SBM as the source of dietary protein. A 28-d pig experiment was conducted to evaluate the nutritional value of CSB, LF, LFKF, and SBM. Pens of four pigs were assigned randomly to a control, corn-SBM, or one of six corn-soybean diets containing raw or extruded soybean varieties as a 2 x 3 factorial arrangement of treatments in a randomized complete block design with five blocks per treatment (n = 140). Chicks fed diets containing any of the raw soybean varieties gained less weight (P < 0.05) than chicks fed SBM (22.81 g/d for SBM vs. 14.17 g/d for the raw soybeans combined). Among the raw soybean treatments, there was a greater effect on growth performance (P < 0.05) by removing both lectins and Kunitz trypsin inhibitor (ADG of 16.56 g for LFKF) than by removing each antinutritional factor separately (ADG of 14.38 and 14.11 g for KF and LF, respectively). Pig growth performance was different (P < 0.001) for SBM (ADG of 409 g) and all the varieties when extruded (ADG of 450 g for CSB, 417 g for LF, and 408 g for LFKF) compared with the raw soybean treatments (ADG of 101 g for CSB, 165 g for LF, and 266 g for LFKF). Among the raw soybean treatments, growth performance improved (P = 0.003) as the antinutritional factor, lectin, was removed from the soybean and improved further (P = 0.045) when both lectins and Kunitz trypsin inhibitor were removed. The growth-inhibiting effect of feeding modified soybeans to young animals was more detrimental for pigs than for chicks in our experiments. Soybeans without the Kunitz trypsin inhibitor and lectins cannot be fed successfully to young chicks and pigs without heating.

Impact of galactose, lactose, and Grobiotic-B70 on growth performance and energy utilization when fed to broiler chicks.

Three chick assays were conducted to determine the effect of increasing dietary galactose (GAL), lactose (LAC), and Grobiotic-B70, a LAC fermentation product, on growth performance, toxicity, and energy utilization when fed to commercial broiler chicks. One-day-old male commercial broiler chicks were randomly assigned to treatments in each assay. In all assays, a 22% CP corn-soybean meal-dextrose basal diet containing a growth-promoting antibiotic (Bacitracin methylene disalicylate) was fed. In assay 1, GAL was added at 2, 4, 6, 10, or 15%. In assay 2, Grobiotic-B70 was added at 5%. In assay 3, GAL, LAC, and Grobiotic-B70 were each added at 2, 4, and 6%. All additions were made in place of dextrose, and diets were fed from 0 to 20 or 21 d of age. In assay 1, the 15% GAL treatment resulted in high mortality (27%) by d 3 and was terminated. The 10% GAL treatment also resulted in increased mortality, most of which occurred during the 7-to-14-d period. Inclusion of 2 and 4% GAL resulted in an improvement (P < 0.05) in growth compared to the basal diet. Inclusion of 2, 4, 6, and 10% GAL resulted in a significant linear decrease in MEn (r2 = 0.85). In chick assay 2, 5% Grobiotic-B70 increased growth during the first 2 wk. In chick assay 3, 6% Grobiotic increased weight gain (P < 0.05) from 0 to 14 d, and addition of 2 or 4% GAL, 2 or 4% LAC, and 4 or 6% Grobiotic-B70 increased weight gain (P < 0.08) from 0 to 21 d. Our results indicate that levels of 10 to 15% GAL are toxic. In contrast, low levels of GAL and Grobiotic-B70, and possibly LAC, may increase growth of commercial broiler chicks.

Efficacy of high available phosphorus corn in laying hen diets.

Our objective was to determine if high available phosphorus corn would provide sufficient available phosphorus (AP) to laying hens fed corn-soybean meal diets from 57 to 69 wk of age. Six replications of 12 Dekalb Sigma Leghorn hens were fed a normal yellow dent (YD) corn-soybean meal diet or high available phosphorus (HAP) corn-soybean meal diet without and with 0.04% supplemental inorganic P. The unsupplemented YD diet was calculated to contain 17% CP, 3.8% Ca, and 0.10% AP, and the unsupplemented HAP diet contained 17% CP, 3.8% Ca, and 0.16% AP. In addition, a positive control, YD diet (17% CP, 3.8% Ca, 0.45% AP) was also fed. The HAP corn was directly substituted for YD on a weight basis, and the amount of soybean meal was kept constant in all diets. Egg production, hen body weight, egg weight, egg mass, feed consumption, and feed efficiency were measured. The YD and the YD + 0.04% P treatments were terminated at 61 and 65 wk of age, respectively, due to severe depressions in egg production. Egg production and egg mass for hens fed HAP diets were not different (P > 0.05) from those of hens fed the 0.45% AP diet; however, hens fed the unsupplemented HAP diet did have lower hen body weights and feed intake (P < 0.05) compared to hens fed the positive control diet. Our results indicate that HAP corn contains more available P than normal YD corn and that hens can be fed HAP corn-soybean meal diets containing little or no P supplementation with only minimal effects on production performance.

Evaluation of nonfeed removal methods for molting programs.

An experiment was conducted using 336 White Leghorn hens (60 wk of age) randomly assigned to one of four treatments that consisted of feed removal for 4 or 10 d or no feed removal with ad libitum access to 95% corn or 95% wheat middlings molt diets that contained supplemental minerals and vitamins. At the end of the 4- or 10-d feed removal period, hens on these treatments were provided with the corn molt diet for 24 or 18 d, respectively. Hens on the corn or wheat middlings treatments were fed the diets for 28 d. At d 28, hens on all treatments were fed a corn-soybean meal (16% CP) layer diet for 40 wk (64 to 104 wk of age). Both feed removal and the wheat middlings treatments resulted in total cessation of egg production within 8 d. Egg production of hens fed the corn molt diet had decreased to 3% by d 28. Body weight loss for hens fed the corn or wheat middlings diet was approximately 15 and 8% at d 28, respectively. Hens fed the wheat middlings diet returned to production slightly faster than hens on the other treatments. Postmolt egg production and egg mass (wk 5 to 44) were generally higher for the wheat middlings and 10-d feed removal treatments than for the corn or 4-d feed removal treatments. There were no consistent differences in mortality, egg weight, egg specific gravity, feed efficiency, and layer feed consumption among treatments. This research indicates that diets with high corn or wheat middlings, particularly wheat middlings, are effective nonfeed removal methods for molting hens.

Phytase effects on amino acid digestibility in molted laying hens.

Two hundred sixteen previously molted Dekalb Delta Leghorn laying hens (78 wk of age) were utilized to determine the effect of phytase on the ileal digestibility of amino acids. The hens were randomly arranged in a 3 x 2 factorial to evaluate three diet types that were corn-soybean meal (C-SBM), C-SBM-meat and bone meal (C-SBM-MBM), and C-SBM-wheat middlings (C-SBM-WM) and two levels of phytase (0 or 300 U/kg of diet). Each treatment was administered to four replicates of nine hens per replicate. Hens were fed the experimental diets for 21 d, and daily egg production and feed intake were recorded. After 21 d, the hens were euthanized, and ileal contents were collected for amino acid and digestible energy determination. Egg production of the hens did not differ among the treatments (P > 0.05). A significant interaction between diet type and phytase level for Ala, Gly, Leu, and Met was observed. The interaction resulted because phytase numerically increased amino acid digestibilities for the C-SBM-MBM and C-SBM-WM diets, but phytase addition numerically decreased the amino acid digestibilities for the C-SBM diet. Diet type had a significant effect on digesibilites of most amino acids. The latter effect was due primarily to lower amino acid digestibilities for the C-SBM-MBM diet than the C-SBM-WM diet. Phytase had no significant affect on digestibility of any amino acid. Ieal digestible energy was significantly affected by diet type but not by phytase. In conclusion, diet type had a significant effect on apparent ileal amino acid digestibility and digestible energy, but phytase had no consistent effect.

Efficacy of phytase for increasing protein efficiency ratio values of feed ingredients.

Data previously reported in several studies have suggested that phytase improves amino acid digestibility in chicks. It was the objective of the current study to determine if phytase would increase the protein efficiency ratio (PER) values (g weight gain per g protein intake) for several feed ingredients fed to chicks. Six experiments were conducted and ingredients evaluated were casein, soybean meal, canola meal, cottonseed meal, peanut meal, wheat middlings, wheat bran, rice bran, defatted rice bran, meat and bone meal, and corn gluten meal. Casein was evaluated to serve as a phytate-free control ingredient. Each feedstuff was analyzed for CP and included in cornstarch:dextrose diets as the only source of protein to provide 10% dietary protein in Experiments 1 to 5 or 18% dietary protein (soybean meal) in Experiment 6. Dietary Ca and nonphytate P levels were varied among experiments and ranged from 0.95 to 1.5% Ca and 0.35 to 0.675% nonphytate P. The test ingredient diets were fed with 0 or 1,200 units of phytase/kg to New Hampshire x Columbian chicks from 8 to 17 or 20 d of age. The PER values varied greatly among ingredients, ranging from 1.4 for corn gluten meal to 4.2 for canola meal. Phytase addition had no significant effect (P > 0.10) on PER values for any of the ingredients evaluated, except for an increase for casein in one experiment. The results indicated that 1,200 U of phytase/kg did not significantly increase protein utilization of several feed ingredients as assessed by a PER chick growth assay.

Early postmolt performance of laying hens fed a low-protein corn molt diet supplemented with spent hen meal.

We used a total of 504 commercial Single Comb White Leghorn hens (69 and 65 wk of age) in each of two experiments, and hens were induced to molt by feed withdrawal only. Feed withdrawal lasted for 12 and 11 d, and hens lost 26 and 25%, body weight in Experiments 1 and 2, respectively. All hens were then weighed, and seven replicate groups of 12 hens each were assigned to molt diet treatments. In Experiment 1, diets consisted of a corn basal diet (7.9% CP) or corn basal diet supplemented with 7.5 or 10% spent hen meal (SHM) each from two different sources. In Experiment 2, the corn basal diet or this diet supplemented with 5 or 10% SHM alone or 5% SHM plus Met, Lys, and Trp was evaluated. A molt diet of 16% CP corn-soybean meal was used as a positive control in both experiments. Molt diets were fed for 15 d in both experiments, at which time all hens were fed a 16% CP layer diet. Performance was measured for 8 wk following the beginning of feeding the layer diet. Feeding the low-protein corn molt diet supplemented with 5 to 10% SHM improved early postmolt egg production performance and body weight gain compared with hens fed the corn basal diet alone. The 7.5 and 10% SHM diets yielded early postmolt performance that was not significantly different (P > 0.05) from that of hens fed the high-protein (16% CP) diet. Supplementing the 5% SHM diet with amino acids generally did not significantly improve performance. The present study thus indicates that improved early postmolt performance may be achieved by supplementation of a low-protein corn molt diet with 5 to 10% SHM.

Multi-drug resistant Pseudomonas aeruginosa outbreak in a burns unit--an infection control study.

A newly introduced, multi-drug resistant (MDR) strain of Pseudomonas aeruginosa was isolated from four patients admitted to the Concord Hospital Burns Unit (BU) between December 1997 and March 1998. It was the cause of recurrent episodes of bacteraemia in two. This strain was resistant in vitro to gentamicin, piperacillin and ciprofloxacin. The isolates were confirmed as a clonal strain by pulse field gel electrophoresis (PFGE). Multiple environmental swabs were taken to search for an environmental reservoir, but no source was identified. Random cultures of staff members' hands failed to demonstrate ongoing carriage. In the absence of a demonstrable point source for the outbreak, direct cross-transmission patient to patient, via transient staff hand contamination, was the most likely route of infection. Following study commencement no new cases of infection with the MDR strain were detected. It would appear that the infection cycle has been interrupted, and the outbreak terminated following the discharge of the last infected patient from the BU. Contamination of a neutral detergent in the BU with Klebsiella oxytoca was detected incidentally during environmental surveillance. A potential hospital-wide outbreak was averted.

Nutritional evaluation of low phytate and high protein corns.

Three chick experiments and two cecectomized rooster experiments were conducted to determine P bioavailability and amino acid (AA) digestibility in two low phytate corns (LP), a high protein corn (HP), and a corn containing both low phytate and high protein content (HP/LP) compared with conventional corn (CONV). From 8 to 20 or 21 d of age, 1-wk-old New Hampshire x Columbian chicks were fed a cornstarch-dextrose-soybean meal (SBM) basal diet containing 0.10% available P or the basal diet supplemented with two concentrations of P (0.05 or 0.06% and 0.10 or 0.12%) from KH2PO4 or two concentrations of the corns (20 or 21% and 40 or 42%). Bioavailability of P based on tibia bone ash was much higher for LP than for CONV; values ranged from 21 to 40% for CONV and from 59 to 95% for LP. Digestibility of AA in cecectomized roosters indicated no significant differences (P > 0.05) between CONV and HP in the first rooster experiment. Digestibilities of eight AA, including lysine, methionine, and arginine, in LP and HP/LP were higher (P < 0.05) than those in CONV in the second rooster experiment. The results of this study indicated that the P in LP was two to three times more bioavailable than the P in CONV and that the digestibilities of AA in HP/LP were equal to or higher than those in CONV.

Protein dispersibility index as an indicator of adequately processed soybean meal.

Three chick assays (8 to 17 or 21 d) were conducted to evaluate protein dispersibility index (PDI) as an indicator of minimum adequate heat processing of soybean meal compared with the urease index and protein solubility in 0.2% KOH. Solvent-extracted soyflakes (SF) were subjected to various autoclaving times at 121 C and 105 kPa and were included in 23% CP dextrose-SF diets or 20% CP corn-SF-corn gluten meal diets. Autoclaving times in Chick Assays 1, 2, and 3 were 0 to 36 min, 0 to 30 min, and 0 to 12 min, respectively. Body weight gains and gain-to-feed ratios increased (P < 0.05) with increased SF heating time (0 to 18 min in Chick Assay 1, 0 to 10 min in Chick Assay 2, and 0 to 9 min in Chick Assay 3), with no additional improvement for longer autoclaving times. Urease index values (pH increase) were high initially and at the shorter autoclaving times (1.65 to 2.4), and then decreased suddenly to 0.3 or below as autoclaving time increased in two of the three chick assays. The KOH protein solubility values generally decreased as autoclaving time increased, but the responses were often inconsistent. Protein dispersibility index displayed the most consistent responses to heating time: it decreased from above 70% to generally below 30% as autoclaving time increased from 0 to 30 or 36 min (mean r2 from linear regression of PDI on autoclaving time was 0.92 for the three chick assays). The latter responses were particularly evident for the heating times, which yielded the greatest changes in chick growth performance. These results suggest that PDI is a more consistent and sensitive indicator of minimum adequate heat processing of soybean meal than urease index or protein solubility in KOH.

Effect of presolvent extraction processing method on the nutritional value of soybean meal for chicks.

This study evaluated the effect of extruding or expander processing prior to solvent extraction on the nutritional value of soybean meal (SBM). Three samples of SBM containing 100% nonexpander SBM, 100% expander SBM, or a mixture of nonexpander and expander SBM were obtained from a commercial plant. An experiment was conducted using Peterson x Hubbard commercial male broiler chicks fed 20% CP corn-SBM-corn gluten meal diets from 8 to 21 d of age. The experiment had a 3 x 2 x 2 factorial design, with three SBM types, two levels of Met + Cys (0.77 and 0.90%), and two levels of Lys (0.95 and 1.20%). Processing method had no effect on the amino acid concentration or protein solubility of the SBM. Dietary treatment had no significant effect on chick weight gain or feed intake. Feed efficiency was significantly improved (P < 0.05) by Met and Lys supplementation, but SBM processing method had no significant effect. The results of this study indicate that presolvent processing method (expander or nonexpander) had no significant effect on the nutritional value of SBM for broiler chicks.

Citric acid does not improve phosphorus utilization in laying hens fed a corn-soybean meal diet.

Data previously obtained from our laboratory have indicated that citric acid was very effective at improving phytate-P utilization in chicks fed a P-deficient corn-soybean meal (SBM) diet. The objective of the current study was to determine if citric acid would have similar effects in a commercial strain of Single Comb White Leghorn laying hens (n = 432) fed a corn-SBM diet containing 0.10% available P (AP). Dietary treatments were a corn-SBM basal diet (0.10% AP, 3.8% Ca, and 17% CP) supplemented with 0, 1, 2, 3, or 4% citric acid and a positive control diet containing 0.45% AP. Each of the six dietary treatments were fed to six replicate groups of 12 hens from 22 to 40 wk of age. No significant differences in performance were observed among treatments during the first 4 wk of the experiment. Hen-day egg production, feed consumption, feed efficiency, and egg yield were subsequently depressed in hens fed 0, 1, 2, 3, or 4% citric acid compared with hens fed 0.45% AP. The results of this study indicate that citric acid does not improve the utilization of dietary P in laying hens fed a corn-SBM diet containing 3.8% Ca.