Effect of Moderate to Severe Hepatic Steatosis on Vaccine Immunogenicity against Wild-Type and Mutant Virus and COVID-19 Infection among BNT162b2 Recipients.

BACKGROUND: We aimed to investigate the effect of non-alcoholic fatty liver disease (NAFLD) on BNT162b2 immunogenicity against wild-type SARS-CoV-2 and variants and infection outcome, as data are lacking. METHODS: Recipients of two doses of BNT162b2 were prospectively recruited. Outcomes of interest were seroconversion of neutralizing antibody by live virus microneutralization (vMN) to SARS-CoV-2 strains (wild-type, delta and omicron variants) at day 21, 56 and 180 after first dose. Exposure of interest was moderate-to-severe NAFLD (controlled attenuation parameter ≥ 268 dB/M on transient elastography). We calculated adjusted odds ratio (aOR) of infection with NAFLD by adjusting for age, sex, overweight/obesity, diabetes and antibiotic use. RESULTS: Of 259 BNT162b2 recipients (90 (34.7%) male; median age: 50.8 years (IQR: 43.6-57.8)), 68 (26.3%) had NAFLD. For wild type, there was no difference in seroconversion rate between NAFLD and control groups at day 21 (72.1% vs. 77.0%; p = 0.42), day 56 (100% vs. 100%) and day 180 (100% and 97.2%; p = 0.22), respectively. For the delta variant, there was no difference also at day 21 (25.0% vs. 29.5%; p = 0.70), day 56 (100% vs. 98.4%; p = 0.57) and day 180 (89.5% vs. 93.3%; p = 0.58), respectively. For the omicron variant, none achieved seroconversion at day 21 and 180. At day 56, there was no difference in seroconversion rate (15.0% vs. 18.0%; p = 0.76). NAFLD was not an independent risk factor of infection (aOR: 1.50; 95% CI: 0.68-3.24). CONCLUSIONS: NAFLD patients receiving two doses of BNT162b2 had good immunogenicity to wild-type SARS-CoV-2 and the delta variant but not the omicron variant, and they were not at higher risk of infection compared with controls.

Association between Recent Usage of Antibiotics and Immunogenicity within Six Months after COVID-19 Vaccination.

Background: Gut microbiota can be associated with COVID-19 vaccine immunogenicity. We investigated whether recent antibiotic use influences BNT162b2 vaccine immunogenicity. Methods: BNT162b2 recipients from three centers were prospectively recruited. Outcomes of interest were seroconversion of neutralising antibody (NAb) at day 21, 56 and 180 after first dose. We calculated the adjusted odds ratio (aOR) of seroconversion with antibiotic usage (defined as ever use of any antibiotics within six months before first dose of vaccine) by adjusting for covariates including age, sex, smoking, alcohol, and comorbidities. Results: Of 316 BNT162b2 recipients (100 [31.6%] male; median age: 50.1 [IQR: 40.0-57.0] years) recruited, 29 (9.2%) were antibiotic users. There was a trend of lower seroconversion rates in antibiotic users than non-users at day 21 (82.8% vs. 91.3%; p = 0.14) and day 56 (96.6% vs. 99.3%; p = 0.15), but not at day 180 (93.3% vs. 94.1%). A multivariate analysis showed that recent antibiotic usage was associated with a lower seroconversion rate at day 21 (aOR 0.26;95% CI: 0.08-0.96). Other factors associated with a lower seroconversion rate after first dose of the BNT162b2 vaccine included age ≥ 60 years (aOR: 0.34;95% CI: 0.13-0.95) and male sex (aOR: 0.14, 95% CI: 0.05-0.34). There were no significant factors associated with seroconversion after two doses of BNT16b2, including antibiotic use (aOR: 0.03;95% CI: 0.001-1.15). Conclusions: Recent antibiotic use may be associated with a lower seroconversion rate at day 21 (but not day 56 or 180) among BNT162b2 recipients. Further long-term follow-up data with a larger sample size is needed to reach a definite conclusion on how antibiotics influence immunogenicity and the durability of the vaccine response.

Timing of prior exposure to antibiotics and failure of Helicobacter pylori eradication: a population-based study.

BACKGROUND: The success rate of conventional Helicobacter pylori eradication therapy is declining, due to rising antibiotic resistance. OBJECTIVES: To determine the temporal effects of prior antibiotic exposure on eradication outcome. PATIENTS AND METHODS: This is a retrospective cohort study including all H. pylori-infected patients who received their first course of clarithromycin-containing triple therapy in 2003-18. Prior antibiotic exposures before H. pylori eradication therapy (up to 180 days, 1 year or 3 years) were retrieved. A logistic regression model was used to evaluate the association between different timings of previous antibiotic exposure, recent (within 30/60 days) or distant period, and the need for retreatment for H. pylori. RESULTS: A total of 120 787 H. pylori-infected patients were included. Prior exposure to any antibiotics within 180 days was associated with a higher risk of retreatment (OR 1.18, 95% CI 1.13-1.24) and the risk progressively increased with longer duration of antibiotic use. The results were consistent for prior exposure up to 1 year (OR 1.26, 95% CI 1.20-1.31) or 3 years (OR 1.30, 95% CI 1.25-1.35). However, when compared with those without prior antibiotic exposure, recent exposure (within 30 days) did not increase the risk of retreatment, which was consistent for analysis with prior antibiotic exposure up to 3 years. Notably, recent use of cephalosporins within 30/60 days and nitroimidazole within 30 days had significantly lower risks of retreatment. CONCLUSIONS: Any prior antibiotic exposure increased the risk of treatment failure of clarithromycin-containing triple therapy. Recent exposures to some classes of antibiotics may paradoxically increase treatment success.

Myopenia and Reduced Subcutaneous Adiposity in Children With Liver Disease Are Associated With Adverse Outcomes.

BACKGROUND: Sarcopenia is defined as reduced skeletal muscle mass (SMM) or myopenia and altered muscle function and physical performance. It is unknown whether myopenia in children with end-stage liver disease (ESLD) adversely impacts clinical outcomes. We hypothesized that myopenia was prevalent in children with ESLD and related to suboptimal nutrition intake contributing to gross motor and growth delay, increased hospitalization, and medical complications. METHODS: This retrospective study evaluated abdominal imaging (computed tomography/magnetic resonance imaging) for SMM (total, psoas, paraspinal, abdominal wall muscle; cm2 /height2 ) and adipose tissue (total, visceral, subcutaneous adipose tissue [SAT], ) determinations at the third and fourth lumbar vertebrates during liver transplantation (LTx) assessment. ESLD children (n = 30) were age- and gender-matched to healthy controls (n = 24). Myopenia was defined as SMM index z score <-2 and low SAT was defined as SAT index z-score <-1.5. Anthropometric, biochemical, and clinical data (hospitalization, complications, growth, neurodevelopment, energy/protein intake) were collected at LTx assessment, LTx, and post LTx (first hospitalization, 6 months, 12 months). RESULTS: Four distinct body composition phenotypes in children with ESLD were found: (1) myopenia with low SAT (17%;5 of 30), (2) myopenia (3%;1 of 30), (3) low SAT (20%;6 of 30), (4) normal muscle mass and SAT (60%;18 of 30). Myopenia with low SAT was prevalent in older (>2 years), male children and was associated with gross motor delay, reduced energy intake, and increased hospitalization and infections (total/viral/fungal). CONCLUSIONS: Myopenia, accompanied by low SAT in children with ESLD, is associated with adverse clinical outcomes. Rehabilitation strategies aimed at combating myopenia in children are important.

Deficits in Muscle Strength and Physical Performance Influence Physical Activity in Sarcopenic Children After Liver Transplantation.

Sarcopenia is a muscle disease characterized by reduced skeletal muscle mass (SMM), muscle strength, and physical performance. Reduced SMM has been identified in children after liver transplantation (LT), but no information related to muscle strength/physical performance or lifestyle factors contributing to sarcopenia is available. We hypothesized that sarcopenia, as determined by measures of SMM, muscle strength, and physical performance, is highly prevalent in children after LT and is related to poor diet quality (DQ) and physical inactivity. A cross-sectional study in post-LT children (n = 22) and age-matched healthy controls (n = 47) between the ages of 6 and 18 years examining body composition (dual energy X-ray absorptiometry and multiple skinfold), measures of muscle strength (handgrip, sit-to-stand, and push-ups), physical performance (6-minute walk test and stair climb test), diet (3-day food intake), and physical activity (accelerometer) was conducted. Low muscle strength/physical performance and SMM (SMM z scores ≤-1.5) were defined by values 2 standard deviations below the mean values for age- and sex-matched controls. Sarcopenia occurred in 36% of children who underwent LT, and they had significantly lower scores for muscle strength (sit-to-stand and push-up tests) and physical performance (stair climb test) than controls (P < 0.05). Deficits in physical performance in children with sarcopenia were predominantly revealed by longer stair climbing times (P = 0.03), with no differences in other muscle tests. Low SMM, muscle strength, and physical performance were associated with a lower amount of time spent in fairly and very active physical activity, but no associations with DQ were found. Sarcopenia is highly prevalent in children after LT and is related to lower moderate-to-vigorous physical activity. Development of effective rehabilitation strategies to treat sarcopenia are needed in post-LT children.

Pediatric Sarcopenia: A Paradigm in the Overall Definition of Malnutrition in Children?

BACKGROUND: Malnutrition is a common complication in children with chronic diseases. Sarcopenia is one component of malnutrition, characterized by reduced skeletal muscle mass (SMM) and muscle function. The presence of sarcopenia is associated with adverse outcomes in children. Although there is growing research interest in sarcopenia, no review has been done on this novel concept in pediatrics. The purpose of this review was to explore current evidence in sarcopenia with and without obesity and to evaluate the knowledge gaps in the assessment of childhood sarcopenia. METHODS: A total of 12 articles retrieved from PubMed or Web of Science databases were included. RESULTS: Limited studies have elucidated sarcopenia in pediatrics. Challenges in sarcopenia assessment include heterogeneity in definition and absence of standardized body composition methods used to measure SMM and muscle function tests. There is a lack of age-specific and gender-specific normative data for SMM, particularly in young children and infants. None of the studies incorporated muscle function assessment, causing potential bias and misclassification of sarcopenia. The research in childhood sarcopenia is also hampered by low study quality, limited number of outcomes-based research, and lack of longitudinal data. CONCLUSION: Consensus needs to be reached in methodological approaches in sarcopenia diagnosis, body composition measurements, and age-appropriate muscle function tests in pediatrics. Careful considerations on growth, neurocognitive status, and factors influencing development in various clinical populations are warranted. Early identification of sarcopenia is crucial to enable targeted treatment and prevention to be carried out across the pediatric clinical populations.

Sarcopenia in Chronic Liver Disease: Impact on Outcomes.

Malnutrition is a common complication in patients with end-stage liver disease (ESLD) awaiting liver transplantation (LT). Malnutrition and sarcopenia overlap in etiology and outcomes, with sarcopenia being defined as reduced skeletal muscle mass and muscle function. The purpose of this review was to identify the prevalence of sarcopenia with and without obesity in adults and children with ESLD and to assess the methodological considerations in sarcopenia diagnosis and the association of sarcopenia with pre- and post-LT outcomes. A total of 38 articles (35 adult and 3 pediatric articles) retrieved from PubMed or Web of Science databases were included. In adults, the prevalence rates of pre-LT sarcopenia, pre-LT sarcopenic obesity (SO), post-LT sarcopenia, and post-LT SO were 14%-78%, 2%-42%, 30%-100%, and 88%, respectively. Only 2 adult studies assessed muscle function in patients diagnosed with sarcopenia. The presence of pre-LT sarcopenia is associated with higher wait-list mortality, greater postoperative mortality, higher infection risk and postoperative complications, longer intensive care unit (ICU) stay, and ventilator dependency. The emerging pediatric data suggest that sarcopenia is prevalent in pre- and post-LT periods. In 1 pediatric study, sarcopenia was associated with poor growth, longer perioperative length of stay (total/ICU) and ventilator dependency, and increased rehospitalization in children after LT. In conclusion, there is a high prevalence of sarcopenia in adults and children with ESLD. Sarcopenia is associated with adverse clinical outcomes. The present review is limited by heterogeneity in the definition of sarcopenia and in the methodological approaches in assessing sarcopenia. Future studies are needed to standardize the sarcopenia diagnosis and muscle function assessment, particularly in the pediatric population, to enable early identification and treatment of sarcopenia in adults and children with ESLD.

Persistence of Sarcopenia After Pediatric Liver Transplantation Is Associated With Poorer Growth and Recurrent Hospital Admissions.

INTRODUCTION: Sarcopenia is prevalent in adults pre-liver transplantation (LTx) and post-LTx contributing to adverse outcomes. Little is known regarding the prevalence of sarcopenia in pediatric LTx recipients. This novel study examined sarcopenia prevalence and associations with post-LTx growth and healthcare utilization in pediatric LTx recipients. METHODS: We prospectively assessed body composition at annual clinical appointments in children (0.5-17 years; n = 58) by Dual-energy-X-ray absorptiometry (absolute/regional/percent fat mass [FM], fat-free mass [FFM], skeletal muscle mass [SMM]). Sarcopenia was defined as SMM z scores ≤2. Additional variables measured included age, gender, PELD, immunosuppressive therapies (dose/type), weight, weight-z, height, height-z, serum aspartate aminotransferase, alanine aminotransferase, γ-glutamyltransferase, albumin, total/conjugated bilirubin, prothrombin time, international normalized ratio, albumin, creatinine clearance, urea and creatinine at LTx assessment, LTx and annual clinic appointments. Healthcare variables studied included rejection (number/type/severity), length of in-patient stay (total, intensive care unit [ICU], emergency, readmission) and ventilator dependency. RESULTS: Sarcopenia occurred in 41% (n = 17) at 7.6 (± 3.1) years; with a mean time post-LTx of 1.1 ± 1.9 (1-8) years. Female children ≤9.8 years had a higher sarcopenia prevalence than children >9.8 years (83.1% vs 17.1%; p = 0.004). Sarcopenia was associated with lower weight velocity standard deviation scores, lower weight-z/height-z scores at 2-10 years post LTx, increased hospitalization (total, ICU, emergency and readmission) and ventilator dependency (p < 0.05), but not to rejection and/or corticosteroid therapy (p > 0.05). CONCLUSIONS: This is the first study demonstrating persistent sarcopenia associated with poorer growth and recurrent hospitalization in children post-LTx.