Sofosbuvir-velpatasvir in children 3-17 years old with hepatitis C virus infection.

BACKGROUND: The safety and efficacy of sofosbuvir-velpatasvir in children aged 3-17 years with chronic hepatitis C virus (HCV) infection of any genotype were evaluated. METHODS: In this Phase 2, multicenter, open-label study, patients received once daily for 12 weeks either sofosbuvir-velpatasvir 400/100 mg tablet (12-17 years), 200/50 mg low dose tablet or oral granules (3-11 years and ≥17 kg), or 150/37.5 mg oral granules (3-5 years and <17 kg). The efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Dose appropriateness was confirmed by intensive pharmacokinetics in each age group. FINDINGS: Among 216 patients treated, 76% had HCV genotype 1% and 12% had genotype 3. Rates of SVR12 were 83% (34/41) among 3-5-year-olds, 93% (68/73) among 6-11-year-olds, and 95% (97/102) among 12-17-year-olds. Only two patients experienced virologic failure. The most common adverse events were headache, fatigue, and nausea in 12-17-year-olds; vomiting, cough, and headache in 6-11-year-olds; and vomiting in 3-5-year-olds. Three patients discontinued treatment because of adverse events. Four patients had serious adverse events; all except auditory hallucination (n = 1) were considered unrelated to study drug. Exposures of sofosbuvir, its metabolite GS-331007, and velpatasvir were comparable to those in adults in prior Phase 2/3 studies. Population pharmacokinetic simulations supported weight-based dosing for children in this age range. INTERPRETATION: The pangenotypic regimen of sofosbuvir-velpatasvir is highly effective and safe in treating children 3-17 years with chronic HCV infection.

Neutralizing antibodies to interferon alfa arising during peginterferon therapy of chronic hepatitis B in children and adults: Results from the HBRN trials.

BACKGROUND: Peginterferon-α (PegIFNα) is of limited utility during immunotolerant (IT) or immune active (IA) phases of chronic hepatitis B infection but is being explored as part of new cure regimens. Low/absent levels of IFNα found in some treated patients are associated with limited/no virological responses. AIM: To determine if sera from participants inhibit IFNα activity and/or contain therapy-induced anti-IFNα antibodies. METHODS: Pre-, on- and post-treatment sera from 61 IT trial participants on PegIFNα/ entecavir therapy and 88 IA trial participants on PegIFNα/tenofovir therapy were screened for anti-IFNα antibodies by indirect ELISA. The neutralization capacity of antibodies was measured by pre-incubation of sera +/- recombinant-human IFNα (rhIFNα) added to Huh7 cells with measurement of interferon stimulated gene (ISG)-induction by qPCR. Correlations between serum-induced ISG inhibition, presence, and titer of anti-IFNα antibodies and virological responses were evaluated. RESULTS: Pre-incubation of on-treatment serum from 26 IT (43%) and 13 IA (15%) participants with rhIFNα markedly blunted ISG-induction in Huh7 cells. Degree of ISG-inhibition correlated with IFNα antibody titer (p<0.0001; r=0.87). On-treatment development of anti-IFNα neutralizing antibodies (nAbs) was associated with reduced qHBsAg and qHBeAg declines (p<0.05) and inhibited IFNα bioactivity to 240 weeks after PegIFNα cessation. Children developed anti-IFNα nAbs more frequently than adults (p=0.004) but nAbs in children had less impact on virological responses. CONCLUSIONS: The development of anti-IFNα nAbs during PegIFNα treatment diminishes responses to antiviral therapy. Understanding how and why anti-IFNα antibodies develop may allow for optimization of IFN-based therapy, which is critical given its renewed use in HBV-cure strategies.

Oral vancomycin is associated with improved inflammatory bowel disease clinical outcomes in primary sclerosing cholangitis-associated inflammatory bowel disease (PSC-IBD): A matched analysis from the Paediatric PSC Consortium.

BACKGROUND: Data on oral vancomycin for primary sclerosing cholangitis (PSC)-associated inflammatory bowel disease (IBD) are limited. AIMS: Using data from the Paediatric PSC Consortium, to examine the effect of vancomycin on IBD activity. METHODS: In this retrospective multi-centre cohort study, we matched vancomycin-treated and untreated patients (1:3) based on IBD duration at the time of primary outcome assessment. The primary outcome was Physician Global Assessment (PGA) of IBD clinical activity after 1 year (±6 months) of vancomycin. We used generalised estimating equations (GEE) to examine the association between vancomycin and PGA remission, adjusting for IBD type, severity and medication exposures. Secondary outcomes included serum labs and endoscopic remission (global rating of no activity) among those with available data and also analysed with GEE. RESULTS: 113 PSC-IBD patients received vancomycin (median age 12.7 years, 63% male). The matched cohort included 70 vancomycin-treated and 210 untreated patients. Vancomycin was associated with greater odds of IBD clinical remission (odds ratio [OR] 3.52, 95% CI 1.97-6.31; adjusted OR [aOR] 5.24, 95% CI 2.68-10.22). Benefit was maintained in sensitivity analyses restricted to non-transplanted patients and those with baseline moderate-severe PGA. Vancomycin was associated with increased odds of endoscopic remission (aOR 2.76, 95% CI 1.002-7.62; N = 101 with data), and with lower CRP (p = 0.03) and higher haemoglobin and albumin (both p < 0.01). CONCLUSION: Vancomycin was associated with greater odds of IBD clinical and endoscopic remission. Additional, preferably randomised, controlled studies are needed to characterise efficacy using objective markers of mucosal inflammation, and to examine safety and define optimal dosing.

SHINERS Study of Chloride Order-Disorder Phase Transition and Solvation of Cu(100).

Shell-isolated nanoparticle enhanced Raman spectroscopy (SHINERS) and density functional theory (DFT) are used to probe Cl- adsorption and the order-disorder phase transition associated with the c(2 × 2) Cl- adlayer on Cu(100) in acid media. A two-component ν(Cu-Cl) vibrational band centered near 260 ± 1 cm-1 is used to track the potential dependence of Cl- adsorption. The potential dependence of the dominant 260 cm-1 component tracks the coverage of the fluctional c(2 × 2) Cl- phase on terraces in good agreement with the normalized intensity of the c(2 × 2) superstructure rods in prior surface X-ray diffraction (SXRD) studies. As the c(2 × 2) Cl- coverage approaches saturation, a second ν(Cu-Cl) component mode emerges between 290 and 300 cm-1 that coincides with the onset and stiffening of step faceting where Cl- occupies the threefold hollow sites to stabilize the metal kink saturated Cu <100> step edge. The formation of the c(2 × 2) Cl- adlayer is accompanied by the strengthening of ν(O-H) stretching modes in the adjacent non-hydrogen-bonded water at 3600 cm-1 and an increase in hydronium concentration evident in the flanking H2O modes at 3100 cm-1. The polarization of the water molecules and enrichment of hydronium arise from the combination of Cl- anionic character and lateral templating provided by the c(2 × 2) adlayer, consistent with SXRD studies. At negative potentials, Cl- desorption occurs followed by development of a sulfate νs(S═O) band. Below -1.1 V vs Hg/HgSO4, a new 200 cm-1 mode emerges congruent with hydride formation and surface reconstruction reported in electrochemical scanning tunneling microscopy studies.

Event-free survival of maralixibat-treated patients with Alagille syndrome compared to a real-world cohort from GALA.

BACKGROUND AND AIMS: Alagille syndrome (ALGS) is characterized by chronic cholestasis with associated pruritus and extrahepatic anomalies. Maralixibat, an ileal bile acid transporter inhibitor, is an approved pharmacologic therapy for cholestatic pruritus in ALGS. Since long-term placebo-controlled studies are not feasible or ethical in children with rare diseases, a novel approach was taken comparing 6-year outcomes from maralixibat trials with an aligned and harmonized natural history cohort from the G lobal AL agille A lliance (GALA) study. APPROACH AND RESULTS: Maralixibat trials comprise 84 patients with ALGS with up to 6 years of treatment. GALA contains retrospective data from 1438 participants. GALA was filtered to align with key maralixibat eligibility criteria, yielding 469 participants. Serum bile acids could not be included in the GALA filtering criteria as these are not routinely performed in clinical practice. Index time was determined through maximum likelihood estimation in an effort to align the disease severity between the two cohorts with the initiation of maralixibat. Event-free survival, defined as the time to first event of manifestations of portal hypertension (variceal bleeding, ascites requiring therapy), surgical biliary diversion, liver transplant, or death, was analyzed by Cox proportional hazards methods. Sensitivity analyses and adjustments for covariates were applied. Age, total bilirubin, gamma-glutamyl transferase, and alanine aminotransferase were balanced between groups with no statistical differences. Event-free survival in the maralixibat cohort was significantly better than the GALA cohort (HR, 0.305; 95% CI, 0.189-0.491; p <0.0001). Multiple sensitivity and subgroup analyses (including serum bile acid availability) showed similar findings. CONCLUSIONS: This study demonstrates a novel application of a robust statistical method to evaluate outcomes in long-term intervention studies where placebo comparisons are not feasible, providing wide application for rare diseases. This comparison with real-world natural history data suggests that maralixibat improves event-free survival in patients with ALGS.

Change in Health-Related Quality of Life in Youth with Chronic Hepatitis B Living in North America: A 5-Year Cohort Study.

BACKGROUND: Greater hepatitis-related symptomology is associated with lower health-related quality-of-life (HRQoL) among untreated youth with chronic hepatitis B (CHB). How HRQoL changes over time in this population is unknown. METHODS: Children from 7 hepatology centers in North America positive for hepatitis B surface antigen, not taking anti-viral therapy, were enrolled in the Hepatitis B Research Network. A validated self-report HRQoL measure, the Child Health Questionnaire Child Report (CHQ-CF87), was completed annually by participants 10-17 years, with demographic variables, liver disease symptoms, and laboratory tests. Linear mixed-effects models were used to evaluate the 10 CHQ-CF87 subscale scores over 5 years among participants who completed the CHQ-CF87 at least twice. RESULTS: Participants (N = 174) completed the CHQ-CF87 a median of 4 times. Median age was 12 years (interquartile range: 10-14) at baseline; 60% were female, 79% Asian, and 47% adopted. The CHQ-CF87 subscale scores were high at baseline (median range: 75.4-100) and did not differ by time point, except for the Family Activities subscale (mean [95% CI]: 82.3 [79.8-84.8] at baseline; 90.8 [86.1-94.6] week 240). Most subscale scores lacked sufficient individual-level variability in change over time to evaluate predictors. Being White versus Asian predicted a more favorable change in Behavior (6.5 [95% CI: 2.0-11.0]). Older age predicted less favorable change in Mental Health (-0.8 [95% CI: -1.36 to -0.23] per year). Changes in liver enzymes and hepatitis B antigens, DNA, or symptom count were not related to changes in these subscale scores. CONCLUSION: HRQoL was generally good and consistent across 5 years in youth with CHB.

Quantifying the Effect of Guest Binding on Host Environment.

The environment around a host-guest complex is defined by intermolecular interactions between the complex, solvent molecules, and counterions. These interactions govern both the solubility of these complexes and the rates of reactions occurring within the host molecules and can be critical to catalytic and separation applications of host-guest systems. However, these interactions are challenging to detect using standard analytical chemistry techniques. Here, we quantify the hydration and ion pairing of a FeII4L4 coordination cage with a set of guest molecules having widely varying physicochemical properties. The impact of guest properties on host ion pairing and hydration was determined through microwave microfluidic measurements paired with principal component analysis (PCA). This analysis showed that introducing guest molecules into solution displaced counterions that were bound to the cage, and that the solvent solubility of the guest has the greatest impact on the solvent and ion-pairing dynamics surrounding the host. Specifically, we found that when we performed PCA of the measured equivalent circuit parameters and the solubility and dipole moment, we observed a high (>90%) explained variance for the first two principal components for each circuit parameter. We also observed that cage-counterion pairing is well-described by a single ion-pairing type, with a one-step reaction model independent of the type of cargo, and that the ion-pairing association constant is reduced for cargo with higher water solubility. Quantifying hydration and cage-counterion interactions is a critical step to building the next generation of design criteria for host-guest chemistries.

Improving Hepatitis B Screening at Family Health Centers Using Quality Improvement and Electronic Medical Record Tools.

Chronic hepatitis B viral (HBV) infection is associated with significant morbidity and mortality with endemic areas carrying most of the global burden of HBV disease. Current HBV screening rates in the United States are suboptimal. We aimed to improve HBV screening rates at regional family health centers serving high-risk refugee populations by 20% over 2 years. We used quality improvement (QI) methodology and implemented interventions providing electronic medical record (EMR)-enabled HBV screening tools within known clinical workflows. EMR tools captured country-of-origin data to identify persons from HBV-endemic regions with provision of a laboratory order set to ensure performance of appropriate HBV screening tests. The project was initiated prior to the COVID pandemic but continued during the pandemic with imposed social isolation measures. We nevertheless demonstrated 4 statistical process control chart shifts and achieved our QI smart aim. Further, we demonstrated a high HBV detection rate (8.2%-12.8%) among persons identified for screening.

Simulating dielectric spectra: A demonstration of the direct electric field method and a new model for the nonlinear dielectric response.

We demonstrate a method to compute the dielectric spectra of fluids in molecular dynamics (MD) by directly applying electric fields to the simulation. We obtain spectra from MD simulations with low magnitude electric fields (≈0.01 V/Å) in agreement with spectra from the fluctuation-dissipation method for water and acetonitrile. We examine this method's trade-off between noise at low field magnitudes and the nonlinearity of the response at higher field magnitudes. We then apply the Booth equation to describe the nonlinear response of both fluids at low frequency (0.1 GHz) and high field magnitude (up to 0.5 V/Å). We develop a model of the frequency-dependent nonlinear response by combining the Booth description of the static nonlinear dielectric response of fluids with the frequency-dependent linear dielectric response of the Debye model. We find good agreement between our model and the MD simulations of the nonlinear dielectric response for both acetonitrile and water.

Solvent effects determine the sign of the charges of maximum entropy and capacitance at silver electrodes.

Fully harnessing electrochemical interfaces for reactions requires a detailed understanding of solvent effects in the electrochemical double layer. Predicting the significant impact of solvents on entropic and electronic properties of electrochemical interfaces has remained an open challenge of computational electrochemistry. Using molecular dynamics simulations of silver-water and silver-acetonitrile interfaces, we show that switching the solvent changes the signs for both the charge of maximum capacitance (CMC) and charge of maximum entropy (CME). Contrasting the capacitance and CME behavior of these two interfaces, we demonstrate that the preferred orientation of the solvent molecule and the corresponding charge density determine the sign of the CMC and CME and, hence, the qualitatively different charge asymmetry of the electrochemical interface.

Biliary Atresia in Adolescence and Adult Life: Medical, Surgical and Psychological Aspects.

Prior to 1955, when Morio Kasai first performed the hepatic portoenterostomy procedure which now bears his name, Biliary atresia (BA) was a uniformly fatal disease. Both the Kasai procedure and liver transplantation have markedly improved the outlook for infants with this condition. Although long-term survival with native liver occurs in the minority, survival rates post liver transplantation are high. Most young people born with BA will now survive into adulthood but their ongoing requirements for health care will necessitate their transition from a family-centred paediatric service to a patient-centred adult service. Despite a rapid growth in transition services over recent years and progress in transitional care, transition from paediatric to adult services is still a risk for poor clinical and psychosocial outcomes and increased health care costs. Adult hepatologists should be aware of the clinical management and complications of biliary atresia and the long-term consequences of liver transplantation in childhood. Survivors of childhood illness require a different approach to that for young adults presenting after 18 years of age with careful consideration of their emotional, social, and sexual health. They need to understand the risks of non-adherence, both for clinic appointments and medication, as well as the implications for graft loss. Developing adequate transitional care for these young people is based on effective collaboration at the paediatric-adult interface and is a major challenge for paediatric and adult providers alike in the 21st century. This entails education for patients and adult physicians in order to familiarise them with the long-term complications, in particular for those surviving with their native liver and the timing of consideration of liver transplantation if required. This article focusses on the outcome for children with biliary atresia who survive into adolescence and adult life with considerations on their current management and prognosis.

Expression of HLA and Autoimmune Pathway Genes in Liver Biopsies of Young Subjects With Autoimmune Hepatitis Type 1.

OBJECTIVES: To test the hypothesis that autoimmune hepatitis (AIH type I) in young subjects is due to genetic differences in proinflammatory genes responding to viral triggers in patients and controls. METHODS: Intrahepatic gene expression was compared between AIH type I (n = 24, age 9-30 years) patients (hereafter referred to as the AIH group) and controls (n = 21, age 4-25 years). RNA sequencing was performed on complementary DNA (cDNA) libraries made from total RNA extracted from formalin-fixed paraffin-embedded (FFPE) liver biopsy samples. Gene expression levels were quantified, and differentially expressed genes were functionally analyzed. Pathway analysis was performed using the databases Kyoto Encyclopedia of Genes and Genomes (KEGG) and PANTHER. The remaining sequences were mapped to the RefSeq complete set of viral genomes. RESULTS: Differential gene analysis identified 181 genes that were significantly differentially expressed (136 upregulated in the AIH group). Autoimmune pathway genes such as CD19 and CD20 which are important in B cell regulation and maturation as well as, CD8 and LY9 , which are T-cell related, were upregulated in our AIH group. Genes implicated in AIH pathogenesis including CXCL10 , which is thought to be associated with AIH severity and progression, complement genes ( C1QA, C1QB , and C1QC ), and human leucocyte antigen ( HLA ) genes ( HLA-DRB1, HLA-DRA, HLA-B , and HLA-C ) were upregulated in samples from the AIH group. Specific viral etiologies were not found. CONCLUSIONS: Unbiased next-generation sequencing and differential gene expression analysis of the AIH group has not only added support for the role of B cells in the pathogenesis and treatment of AIH but also has introduced potential new therapeutic targets: CXCL10 (anti- CXCL10 ) and several complement system-related genes.

Improving the Accuracy of Atomistic Simulations of the Electrochemical Interface.

Atomistic simulation of the electrochemical double layer is an ambitious undertaking, requiring quantum mechanical description of electrons, phase space sampling of liquid electrolytes, and equilibration of electrolytes over nanosecond time scales. All models of electrochemistry make different trade-offs in the approximation of electrons and atomic configurations, from the extremes of classical molecular dynamics of a complete interface with point-charge atoms to correlated electronic structure methods of a single electrode configuration with no dynamics or electrolyte. Here, we review the spectrum of simulation techniques suitable for electrochemistry, focusing on the key approximations and accuracy considerations for each technique. We discuss promising approaches, such as enhanced sampling techniques for atomic configurations and computationally efficient beyond density functional theory (DFT) electronic methods, that will push electrochemical simulations beyond the present frontier.

Changes in serum hepatitis B surface and e antigen, interferon-inducible protein 10, and aminotransferase levels during combination therapy of immune-tolerant chronic hepatitis B.

BACKGROUND AND AIMS: Treatment of immune-tolerant (IT) children and adults with combined peginterferon alfa-2a and entecavir results in a decline in serum HBeAg and HBsAg concentrations but rarely results in loss of HBeAg or sustained off-treatment response. Factors associated with declines in these viral antigens during treatment remain unexplored. APPROACH AND RESULTS: We investigated the pattern of virologic and biochemical response in 86 participants (59 children, 27 adults) by serial quantitative measurement of HBsAg (qHBsAg), quantitative HBeAg (qHBeAg), HBV RNA, interferon-inducible protein (IP-10), IL-18, and alanine aminotransferase (ALT). Each individual had previously been treated with 8 weeks of entecavir followed by 40 weeks of combined peginteferon and entecavir. We defined the interrelationships between these parameters and virologic response measured as nadir declines from baseline for HBeAg and HBsAg. The patterns of HBsAg and HBeAg decline were similar in pediatric and adult participants. Higher levels of IP-10 were observed during treatment in participants with greater ALT elevations and greater reductions of qHBsAg and qHBeAg. Individuals with peak ALT values exceeding three times the upper limit of normal were significantly more likely to have >1 log10 decline in both viral antigens. HBV DNA became undetectable in 21 of 86 (24%) and HBV RNA in 4 of 77 (5%) during therapy, but both markers remained negative only in those who became HBsAg negative, all of whom also had ALT elevations. CONCLUSIONS: Induction of IP-10 during peginterferon treatment in adults and children in the IT phase of chronic HBV infection is associated with ALT elevations and decline in viral antigens, suggesting a degree of interferon-inducible viral control.

Interfacial water asymmetry at ideal electrochemical interfaces.

Controlling electrochemical reactivity requires a detailed understanding of the charging behavior and thermodynamics of the electrochemical interface. Experiments can independently probe the overall charge response of the electrochemical double layer by capacitance measurements and the thermodynamics of the inner layer with potential of maximum entropy measurements. Relating these properties by computational modeling of the electrochemical interface has so far been challenging due to the low accuracy of classical molecular dynamics (MD) for capacitance and the limited time and length scales of ab initio MD. Here, we combine large ensembles of long-time-scale classical MD simulations with charge response from electronic density functional theory to predict the potential-dependent capacitance of a family of ideal aqueous electrochemical interfaces with different peak capacitances. We show that while the potential of maximum capacitance varies, this entire family exhibits an electrode charge of maximum capacitance (CMC) between -2.9 and -2.2 µC/cm2, regardless of the details in the electronic response. Simulated heating of the same interfaces reveals that the entropy peaks at a charge of maximum entropy (CME) of -5.1 ± 0.6 µC/cm2, in agreement with experimental findings for metallic electrodes. The CME and CMC both indicate asymmetric response of interfacial water that is stronger for negatively charged electrodes, while the difference between CME and CMC illustrates the richness in behavior of even the ideal electrochemical interface.

The Inflammatory Cytokine Profile Associated With Liver Damage Is Broader and Stronger in Patients With Chronic Hepatitis B Compared to Patients With Acute Hepatitis B.

Liver damage in hepatitis B is immune driven and correlates with inflammatory markers in patient serum. There is no comparison of these markers to determine if inflammatory profiles are distinct to different types of liver damage across patients at different stages of disease. We measured 25 inflammatory markers in patients with acute hepatitis B and chronic hepatitis B with hepatitis B e antigen seroconversion and chronic patients stopping nucleoside analogue therapy. Myeloid markers dominated the inflammatory profile in all stages of hepatitis B. More inflammatory markers were detectable in chronic patients, including elevated concentrations of cytotoxic effectors Fas ligand, TRAIL, and TNF-α.

Survival Benefit of Split-Liver Transplantation for Pediatric and Adult Candidates.

Patient and graft survival are similar following whole-liver transplantations (WLTs) versus split-liver transplantations (SLTs) among pediatric and adult recipients, yet SLTs are rarely used. We sought to determine the survival benefit associated with accepting a splittable graft offer for SLT versus declining and waiting for a subsequent offer using 2010 to 2018 Scientific Registry of Transplant Recipients (SRTR) data on 928 pediatric and 1814 adult liver transplantation candidates who were ever offered a splittable graft. We compared eventual mortality, regardless of subsequent transplants, between those patients who accepted versus declined a split liver offer with adjustments for Pediatric End-Stage Liver Disease/Model for End-Stage Liver Disease (MELD) scores, diagnosis, and weight among pediatric candidates and matching for MELD score, height, and offer among adult candidates. Among pediatric candidates ≤7 kg, split liver offer acceptance versus decline was associated with a 63% reduction in mortality (adjusted hazard ratio [aHR], 0.17 0.370.80 [P = 0.01]; 93.1% versus 84.0% 1-year survival after decision). Within 1 year of decline for those ≤7 kg, 6.4% died and 31.1% received a WLT. Among pediatric candidates >7 kg, there was no significant difference associated with acceptance of a split liver offer (aHR, 0.63 1.071.82 [P = 0.81]; 91.7% versus 94.4% 1-year survival after decision). Within 1 year of decline for those >7 kg, 1.8% died and 45.8% received a WLT. Among adult candidates, split liver offer acceptance was associated with a 43% reduction in mortality (aHR, 0.39 0.570.83 [P = 0.005]; 92.2% versus 84.4% 1-year survival after decision). Within 1 year of decline for adult candidates, 7.9% died and 39.3% received a WLT. Accepting split liver offers for SLT could significantly improve survival for small children and adults on the waiting list.

Compressive Stress and Charge Redistribution during CO Adsorption onto Pt.

The change in surface stress associated with the adsorption and oxidative stripping of carbon monoxide (CO) on (111)-textured Pt is examined using the wafer curvature method in 0.1 mol/L KHCO3 electrolyte. The curvature of the Pt cantilever electrode was monitored as a function of potential in both CO-free and CO-saturated electrolytes. Although CO adsorbs as a neutral molecule, significant compressive stress, up to -1.3 N/m, is induced in the Pt. The magnitude of the stress change correlates directly with the CO coverage and, within the detection limits of the stress measurement, is elastically reversible. Density functional theory calculations of a CO-bound Pt surface indicate that charge redistribution from the first atomic layer of Pt to subsurface layers accounts for the observed compressive stress induced by the charge neutral adsorption of CO. A better understanding of adsorbate-induced surface stress is critical for the development of material platforms for sensing and catalysis.