Background: Frailty is a predictor of disease progression in cirrhotic patients. Prehabilitation programs are helpful interventions to reduce frailty and worsening sarcopenia. Methods: This was a single-group, pre-post feasibility study of a 6-week home pedometer-monitored program with the goal of achieving a weekly compound 5%-10% step increase and thereby decreasing frailty in cirrhotic patients. A review of patients was performed 3 years after the intervention to assess clinical status and walking levels. Results: Sixty-three cirrhotic patients were recruited and 71% completed the study. At the end of week 6, mean steps per day had increased by 37% from 3,394 at baseline to 4,500 (p < 0.001), with a mean weekly compound increase of 6.4%. For study completers, the mean Fried frailty index (FFI) score improved from 2.64 at baseline to 2.24 at the end of the intervention (p = 0.007). Patients with Model of End-Stage Liver Disease-Sodium (MELD-Na) scores <15 had significantly improved mean FFI scores, from 2.74 to 2.26 (p = 0.007); those with scores >= 15 did not have significant improvement. At the 3-year follow-up, 18% of patients had died, 13% had undergone liver transplantation, and 37% self-reported that they were walking more than before the intervention. Conclusions: These findings suggest the 6-week home pedometer-monitored program is feasible but is best suited for cirrhotic patients whose disease has not advanced to levels where they are considered for transplantation, as indicated by MELD-Na scores >= 15.

Severe mental illness may affect health behaviors and outcomes during pandemics. Few studies have assessed whether people living with schizophrenia spectrum disorders (SSD) experienced adverse COVID-19 outcomes. In a population-based historical cohort study comprising members of a health maintenance organization, we included 1273 patients with SSD and 12,730 age- and sex-matched controls tested for SARS-CoV-2 between March 2020 and May 2022. We assessed the association between schizophrenia and hospitalization, hospital length-of-stay, 30-day, and one-year mortality, constructing multiple linear regression and logistic regression models adjusting for sociodemographic factors, BMI, smoking, number of comorbidities, and vaccinations. We also assessed whether vaccination modified the association between schizophrenia and mortality. Among patients with SSD, 477 (37.5

All major U.S. guidelines now validate average-risk colorectal cancer (CRC) screening at 45–49 years of age. We aimed to highlight the importance of promoting colonoscopy among younger populations as part of a comprehensive strategy to reduce the burden of CRC. Our study analyzed data from 235,782 colonoscopy reports of individuals, which were categorized into six age groups: 45–49 years, 50–54 years, 55–59 years, 60–64 years, 65–69 years, and 70–74 years. Parameters such as age, gender, histopathology of polyps, quantity of polyps, and polyp detection rate (PDR) were assessed. Our study shows a progressive increase in colonoscopy uptake among individuals aged 45–54. PDR increased significantly with age, from 25.7

BACKGROUND:The risk of thrombosis increases after SARS-CoV-2 infection. This study aimed to assess associations between pre-infection anticoagulant exposure and SARS-CoV-2 infection-related outcomes in a population-based cohort. METHODS:Members of the "Meuhedet" health maintenance organization aged >45 years who tested positive for SARS-CoV-2 infection (03/2020-04/2022) were followed. Pre-infection anticoagulant exposure (PAE) was defined as any anticoagulant therapy prescribed ≥1 month prior to SARS-CoV-2 testing. Univariate analyses, multivariable models adjusting for confounders, propensity-score matching, and an age-stratified analysis were performed to assess associations between PAE and hospitalization, intensive care unit (ICU) admission, 30-day and one-year mortality. RESULTS:Of the 127,801 patients included, 2951(2.3 %) had PAE. Comorbidities including ischemic heart disease, diabetes mellitus, hypertension, heart failure, and atrial fibrillation were more common among anticoagulant-exposed than unexposed individuals (p < 0.001). Patients with PAE experienced higher hospitalization (22.7 % vs 5.6 %), ICU admissions (1.9 % vs 0.5 %), 30-day and 1-year mortality rates (4.8 % vs. 0.6, and 8.8 % vs. 1.1 %, respectively), than unexposed individuals, but similar lengths-of-stay. In the multivariable analysis, PAE was independently associated only with hospitalizations (adjusted odds ratio (aOR) = 1.29 [95 % confidence interval (CI): 1.13-1.47]), whereas in the propensity-matched analysis, none of the outcomes differed significantly between the groups. However, in the stratum aged >75 years, 30-day and one-year mortality were significantly reduced in those with PAE (aOR = 0.68 [CI:0.48-0.97], and aOR = 0.73 [CI:0.55-0.97], respectively). CONCLUSION:SARS-CoV-2-infected individuals with prior exposure to anticoagulants have more comorbidities and experienced a higher incidence of hospitalization but not mortality compared to unexposed patients. Paradoxically, mortality risks decreased in the oldest stratum of anticoagulant-exposed individuals. Further research is required to assess mechanisms for this apparent protective effect.

Abstract Background Inflammatory bowel disease (IBD) is a state of excess inflammatory cytokines, including tumor necrosis α (TNF). Studies in human and animal models showed that TNF has an important role in pathophysiology of insulin resistance (1). While there is some evidence of a link between IBD and diabetes mellitus (DM) and that anti-TNF therapy is associated with better glucose levels in patients with IBD and DM (2), the potential for prevention of onset or impact of other advanced therapies has not been described. Methods We used the TriNetX global federated network to identify patients with IBD ≥18 years diagnosed with IBD between 2019 and 2024, and who were treated with advanced therapy within 2 years of that diagnosis. Patients who were diagnosed with DM prior or within 3 months of IBD diagnosis or treatment were excluded. The primary endpoint was a diagnosis of DM or a HgbA1C>6.5%. Patients were divided into two different cohorts: 1) patients treated with anti-TNF, and 2) patients treated with vedolizumab, IL23 inhibitors or JAK inhibitors, and never with anti-TNF. Patients were compared using a 1:1 propensity matching by race, gender, age, sociodemographic comorbidities, BMI, hypertension, long term use of steroids, ischemic heart disease, IBD subtype and past total or partial colectomy. A diagnosis of psoriasis was used as positive control outcome, and a diagnosis of upper respiratory tract infections (URTI) was used as negative control outcome. Results 43,372 patients with a new diagnosis of IBD were identified: 30,583 treated with anti TNF and 12,789 treated with other advanced therapies. Following propensity scored matching, 12,762 patients were in each balanced cohort. After a follow up of 3 years, patients treated with anti TNF had a 72.5% lower risk for subsequent diabetes (0.3% vs. 1.04% HR 0.275, 95% CI 0.174 -0.437, p<0.001), a higher risk of psoriasis (HR 1.35, 95% CI 1.074 - 1.694, p<0.001) but no significant difference of URTI (Figure 1). Conclusion Patients with IBD treated with anti-TNF have a significantly lower risk of developing diabetes compared to patients treated with other advanced therapies. The mechanisms and protective effect of anti-TNF therapy warrants further investigation. References 1.Knobler, Hilla MD; Zhornicky, Taiba MD; Sandler, Alex MD; Haran, Nurit PhD; Ashur, Yafa MD; Schattner, Ami MD. Tumor Necrosis Factor–α–Induced Insulin Resistance May Mediate The Hepatitis C Virus–Diabetes Association. American Journal of Gastroenterology 98(12):p 2751-2756, December 2003. | DOI: 10.1111/j.1572-0241.2003.08728.x 2.Malini Gupta-Ganguli, Kyle Cox, Blake Means, Ivan Gerling, Solomon S. Solomon; Does Therapy With Anti–TNF-α Improve Glucose Tolerance and Control in Patients With Type 2 Diabetes?. Diabetes Care 1 July 2011; 34 (7): e121–121. https://doi.org/10.2337/dc10-1334 Figure 1 - Risk of Clinical Outcomes in Patients with IBD Treated with anti-TNF vs. Other Advanced Therapies in Propensity Matched Cohorts (n=12,762 in each cohort)

AimsCOVID-19 infection may result in complications including congestive heart failure (CHF). It is vital to identify factors associated with CHF post COVID so as to improve outcomes. The aim of this study was to determine whether baseline low alanine transaminase (ALT) levels are associated with new diagnosis of CHF following infection with COVID-19.Methods and resultsThe study was a retrospective cohort study of patients in the Meuchedet Health Fund database. The analysis was performed on all subjects aged 18 years and older who tested positive for SARS-CoV-2 and had ALT levels measured prior to infection. Patients were excluded if diagnosed with congestive heart failure or cirrhosis prior to COVID-19, or if they died within 30 days of SARS-CoV-2 contraction. The study endpoint was a new diagnosis of CHF as recorded in the subject's electronic medical record.Results131,953 adult patients infected with COVID were included in the cohort. Of them, 205 patients (0.16%) were diagnosed with CHF following COVID-19 infection. The occurrence of CHF was significantly higher in the low ALT group (0.34% vs. 0.14%, p- value < 0.001). This difference was more prominent when analyzing patients aged 50 and older (1.4% vs. 0.35, p-value < 0.001). In a multivariate logistic regression, pre-morbid low ALT remained significantly associated with the occurrence of post COVID-19 CHF (OR—1.95, 95% CI −1.03 to 2.53).ConclusionsThis study demonstrates that low ALT levels prior to infection with COVID-19 is associated with a new diagnosis of CHF following infection. Patients with low ALT levels prior to COVID-19 infection should have cardiovascular complaints post COVID carefully assessed.

Abstract Background Diet is believed to modulate intestinal inflammation through its regulatory effects on the microbiota, gut immune system, and epithelial barrier function. Previous research, mostly based on questionnaires of food consumption, showed that high dietary intake of total fats, meat and processed food is associated with an increased risk of incident IBD, while plant-based , fiber rich-diet is associated with a reduced risk of incident IBD. Between the years 1998-2017, Vegans enlisted to the Israel Defense forces (IDF) were entitled to a special allowance. Strict requirements for confirmation of vegan status were followed. We assessed whether a vegan diet protect against incident IBD in a cohort of young Israeli adults. Methods A historical prospective cohort including all Israeli adolescents enlisted between 1998-2017. The data gathered included age, sex, body mass index (BMI), country of origin, general intelligence tests (GIT), socioeconomic status (SES), and incident IBD. A multivariate logistic regression model and 1:1 propensity score-matched cohorts were utilized to calculate the OR of developing IBD in vegans compared to controls. Results The study population consisted of 1,049,005 subjects, 630,536 (60%) males, and 5941 (0.57%) vegans. The median follow-up duration was 1046 days (IQR 727-1094). Vegans came from higher SES (6.3 vs. 5.9, p<0.001), were more likely to be of European descent (47.2% vs. 25.8%, p<0.001), and had higher GIT results (63.5 vs 52.6, P<0.001). Along the study period, 2039 (0.19%) subjects developed IBD , 17 among vegans (0.29%), and 2022 among controls (0.19%) (p=0.12). In both groups, the distribution of CD and UC cases was exactly the same, with 70% of cases being CD and 30% being UC. IBD patients were more likely to be male (64.3% vs. 60.1%, p<0.001), from European origins (39% vs. 25.9%, p<0.001), and a higher SES (6.15+- 1.54 vs. 5.94+-1,64, p<0.001). Based on a multivariate logistic regression controlling for sex, country of origin, BMI, GIT and SES, a vegan diet was not associated with a reduction in IBD incidence (OR 1.14, 95% CI 0.68-1.78). Analysis of a 1:1 propensity-score-matched cohort of subjects (n=5484) demonstrated no statistically significant differences between vegans and controls regarding IBD incidence (0.29 vs. 0.32%, p=0.87). An exploratory evaluation of the impact of vegan diet on endoscopic severity was performed only in CD patients and revealed a lower incidence of large ulcers in the vegan group (57%) compared to controls (79%). Conclusion In this nationwide cohort of young Israeli adults, a vegan diet was not associated with a reduction in the incidence of IBD. Endoscoppic disease severity might be milder among vegan CD patients. References Hou JK, Abraham B, El-Serag H. Dietary intake and risk of developing inflammatory bowel disease: a systematic review of the literature. Am J Gastroenterol. 2011;106(4):563-573. doi:10.1038/ajg.2011.44 Narula N, Wong ECL, Dehghan M, et al. Association of ultra-processed food intake with risk of inflammatory bowel disease: prospective cohort study. BMJ. 2021;374:n1554. Published 2021 Jul 14. doi:10.1136/bmj.n1554 Chen J, Wellens J, Kalla R, et al. Intake of Ultra-processed Foods Is Associated with an Increased Risk of Crohn's Disease: A Cross-sectional and Prospective Analysis of 187 154 Participants in the UK Biobank. J Crohns Colitis. 2023;17(4):535-552. doi:10.1093/ecco-jcc/jjac167

INTRODUCTION:Medication holidays in inflammatory bowel disease (IBD) offer a potential means to balance disease management, costs, and quality of life. This concept is increasingly relevant in light of the chronic nature of IBD, the cumulative side effects associated with long-term pharmacotherapy, and the evolving treatment landscape that now includes a large armamentarium of effective induction, maintenance, and rescue therapies paired with disease monitoring tools that enable early intervention. AREAS COVERED:This review critically examines the rationale, implementation, and risks of medication holidays in IBD. Recent evidence is reviewed to help guide the risks of relapse involved with cessation of therapy. The selection criteria for patients, the necessary monitoring protocols, and strategies for managing potential relapses are outlined. EXPERT OPINION:Despite the potential benefits, medication holidays in IBD involve significant risks and require careful patient selection and active management. Current research highlights a need for improved predictive models and a deeper understanding of patient-specific outcomes and consequences. The future of medication holidays will depend heavily on advancements in noninvasive monitoring technologies and more personalized approaches to therapy. Ultimately, establishing clearer guidelines for safely conducting medication holidays will be crucial in integrating this strategy into routine clinical practice.

Background: Sarcopenia is underdiagnosed in patients with inflammatory bowel disease (IBD). Low alanine transaminase (ALT) is associated with sarcopenia. We evaluated the association between low ALT and the presence of IBD and disease activity. Methods: Data were collected from a national Israeli health insurer cohort comprising 976,615 patients. Patients with a diagnosis of IBD were compared to healthy controls. After exclusion of patients with liver disease, ALT > 40 IU/L and age < 18, a total of 233,451 patients were included in the analysis. Low ALT was defined as <10 IU/L. Results: Low ALT was more common amongst patients with IBD than in healthy controls (7.76% vs. 5.7% p < 0.001). Low ALT was found in 148 (7.9%) of the patients with CD and 69 (6.9%) of the patients with UC. For CD, low ALT was associated with increased fecal calprotectin (FC) and CRP (223.00 μg/mg [63.45–631.50] vs. 98.50 [31.98–324.00], p < 0.001, 9.10 mg/L [3.22–19.32] vs. 3.20 [1.30–8.30], p < 0.001) and decreased albumin and hemoglobin (3.90 g/dL [3.60–4.20] vs. 4.30 [4.00–4.50], p < 0.001,12.20 g/dL [11.47–13.00] vs. 13.60 [12.60–14.70], p < 0.001). For UC, low ALT was associated with higher FC and CRP (226.50 μg/mg [143.00–537.00] vs. 107.00 [40.85–499.50], p = 0.057, 4.50 mg/L [1.90–11.62] vs. 2.30 [1.00–6.20], p < 0.001) and with lower albumin and hemoglobin (4.00 g/dL [3.62–4.18] vs. 4.30 [4.10–4.40], p < 0.001, 12.40 g/dL [11.60–13.20] vs. 13.60 [12.60–14.60], p < 0.001). These findings remained consistent following multivariate regression and in a propensity score-matched cohort. Conclusions: Low ALT is more common in patients with IBD and is associated with biochemical disease activity indices.

INTRODUCTION:Nonalcoholic Fatty Liver Disease (NAFLD) has become the leading cause of liver morbidity. The Mediterranean diet can improve NAFLD and may be offered as treatment. Intermittent fasting has been shown to improve aspects of the metabolic syndrome, but its effect on NAFLD is inconclusive.OBJECTIVES:A randomized - controlled study assessed the outcomes of the effect of the Mediterranean diet alone versus the Mediterranean diet in combination with intermittent fasting for 16 weeks in patients with NAFLD (1:2 ratio) and subsequent long term follow-up. Outcomes parameters included the response to treatment as measured by body mass index (height and weight), waist-hip ratio, and levels of steatosis and fibrosis as measured by transient elastography. In addition, satisfaction and compliance were assessed via questionnaires (ten-point Likert scale).RESULTS:Sixteen out of 40 recruited patients completed the study (69% men, mean age 45.8 ± 12.1 years, mean baseline BMI 33 ± 4.5), of which nine patients were included in the arm of diet in combination with intermittent fasting. The two groups were similar at baseline with regard to age, gender, height, weight, BMI, waist to hip ratio, and levels of steatosis and fibrosis. At the study end, a significant decrease was observed (p-value = 0.01) in the degree of steatosis from 316.4 ± 50.4 to 279 ± 35.7 DB/m. The improvement in steatosis was significant (p-value = 0.01) in the intermittent fasting group (an improvement of 13.8 ± 20.9%) as compared to the group without intermittent fasting (4.2 ± 20.9%, no statistical significance). The other physical outcome measures did not show a statistically significant change between values at the beginning of the study and study end (16 weeks). Participant questionnaires were completed at a mean follow-up of 1.6 ± 0.2 years and showed a high level (8.3 ± 1.69) of compliance at the beginning of the study in both groups. In addition, both study groups expressed a similar degree of difficulty in adhering to the assigned diet. By study end, participant adherence was significantly higher (p-value = 0.04) among the Mediterranean diet group alone (7 ± 2) as compared to the group in combination with intermittent fasting (4.9 ± 2). Furthermore, those in the Mediterranean diet alone group were more willing (9.7 ± 0.8) to continue the dietary treatment after completing the study as compared to the intermittent fasting group (6.4 ± 0.7) (p-value = 0.03). Study participants in both groups reported that their dietary treatment was overall beneficial (7.9 ± 2.2).CONCLUSIONS:This study, given the limitations of a small sample size, suggests that a Mediterranean diet in combination with intermittent fasting improves steatosis in NAFLD patients over the long term as compared to Mediterranean diet without time restricted eating.

Background and Aims: We retrospectively assessed the clinical Pfizer’s mRNA SARS-CoV-2 BNT162b2 vaccination outcomes and the serologic impact on liver transplant (LT) recipients. Patients and Methods: One hundred and sixty-seven LT cases followed between March 1, 2020 and September 25, 2021, and were stratified into two groups: (1) 37 LT recipients after SARS-CoV-2 infection before vaccine era and (2) 130 LT recipients vaccinated with 2 doses without earlier SARS-CoV-2 exposure. Serum SARS-CoV-2 spike immunoglobulins (anti-S) were assessed 7 days following vaccination (Liaison assay). Results: In addition to the 37 nonvaccinated cases (22.2% of total group) who experienced SARS-CoV-2 infection (34 symptomatic and 3 asymptomatic), another 8 vaccinated symptomatic recipients (4.8%) were infected (5 from the third and three from the fourth waves). Three of the 45 infected cases died (6.7%) before the vaccine program. Vaccinated group: of the 130 LT vaccinated recipients, 8 (6.2%) got infected postvaccination (added to the infected group) and were defined as clinical vaccine failure; 38 (29.2%) were serological vaccine failure (total failure 35.4%), and 64.6% cases were serological vaccine responders (anti-S≥19 AU/mL). Longer post-LT interval and lower consumption of immunosuppressants (steroids, FK506, and mycophenolate mofetil) correlated with favorable SARS-CoV-2 vaccine response. Mammalian target of rapamycin inhibitors improved vaccine outcomes associated with lower FK506 dosages and serum levels. Patients with anti-S levels <100 AU/mL risked losing serologic response or being infected with SARS-CoV-2. A booster dose achieved an effective serologic response in a third of failures and most responders, securing better and possibly longer protection. Conclusion: Pfizer’s BNT162b2 vaccine seems to lessen SARS-CoV-2 morbidity and mortality of LT recipients even with weak serological immunogenicity. Switching mycophenolate mofetil to mammalian target of rapamycin inhibitors might be effective before boosters in vaccine failure cases. A booster vaccine should be considered for nonresponders and low-responders after the second dose.

IntroductionFrailty is a known risk factor for many diseases, including COVID-19. However, many frail patients are undiagnosed as the diagnosis can be cumbersome. Alanine transaminase (ALT) is found not only in the liver but also in the muscle tissue, and multiple studies show that frail sarcopenic patients have lower ALT. Frail patients are at increased risk for severe COVID-19. We evaluated the association between pre-infection low ALT and the risk for severe COVID-19.MethodsWe collected data regarding all subjects tested for SARS-CoV-2 between 1 March 2020 and 31 December 2021 from a national state-mandatory HMO in Israel, serving more than 1.3 million patients. Clinical and laboratory data were collected, including ALT from the year prior to infection. Severe COVID-19 was defined either as death, ICU admission, or ≥10 hospitalization days. Patients with low ALT (ALT ≤ 10 IU/l) were compared with patients with normal ALT (11–40 IU/l). Patients younger than 18 years with a diagnosis of liver disease and with ALT > 40 IU/l were excluded.ResultsDuring the study period, 58,961 patients tested positive for SARS-CoV-2. The patients in the low ALT group were younger (40.53 vs. 42.73, p < 0.001), less likely to be males (12.3 vs. 38.7%, p < 0.001), and had lower BMI (25.97 vs. 27.15, p < 0.001). The patients in the low ALT group had higher mortality (2.36 vs. 0.57%, p < 0.001), more ICU hospitalizations (0.49 vs. 0.41%, p = 0.47), and more prolonged hospitalizations [2.63% (95% CI 2–3.2%) vs. 0.98% (95% CI 0.86–1.1%) p < 0.001]. In multivariate logistic regression analyses, low ALT was associated with an increased risk of severe COVID-19, with increased mortality (OR 1.88, 95% CI 1.37–2.56) and prolonged hospitalization (OR 1.78, 95% CI 1.33–2.35).ConclusionLow ALT level prior to infection is a significant risk factor for morbidity and mortality from COVID-19 infection. Further studies are warranted to address treatment options for this population.

In this study, we compared the failure rates of fosfomycin and nitrofurantoin for uncomplicated urinary tract infections. We used Meuhedet Health Services’ large database to collect data on all female patients, older than 18 years, who were prescribed either antibiotic during 2013–2018. Treatment failure was a composite endpoint of hospitalization, emergency-room visit, IV antibiotic treatment, or prescription of a different antibiotic, within seven days of the initial prescription. Reinfection was considered when one of these endpoints appeared 8–30 days following the initial prescription. We found 33,759 eligible patients. Treatment failure was more common in the fosfomycin group than the nitrofurantoin group (8.16% vs. 6.87%, p-value < 0.0001). However, reinfection rates were higher among patients who received nitrofurantoin (9.21% vs. 7.76%, p-value < 0.001). Among patients younger than 40 years, patients treated with nitrofurantoin had more reinfections (8.68% vs. 7.47%, p value = 0.024). Treatment failure rates were mildly higher in patients treated with fosfomycin, despite having less reinfections. We suggest that this effect is related to a shorter duration of treatment (one vs. five days) and encourage clinicians to be more patient before declaring fosfomycin failure and prescribing another antibiotic.

Background: SARS-CoV-2 vaccine responses that could harbor potential risks to chronic liver diseased patients.Aims: To assess immune response following Pfizer's SARS-CoV-2 vaccine in patients with different liver fibrosis severities of nonalcoholic fatty liver disease (NAFLD).Methods: Clinical and histological (NAS-score and fibrosis stage) characteristics of NAFLD patients before vaccine were correlated with serologic vaccine responses of two doses of the BNT162b2. Serum SARS-CoV-2 spike immunoglobulins (anti-S) were assessed on day seven following immunization (Liaison assay).Results: The mean-age of patients (n = 157) was 56.9 +/- 13.2 years (46.5 % males). 94.8 % had a positive response (anti-S levels >= 19 AU/ml). The anti-S cutoff of 200 AU/ml used to separate strong vs. weak responses. A strong response (anti-S titers >= 200 AU/ml) was observed in 93/157 (59.2 %) patients with a mean-age of 53.1 +/- 13.8 years (45.2 % males). A weak response (anti-S titers < 200 AU/ml) was observed in 64/157 (40.8 %) cases with a mean-age of 62.3 +/- 10.2 years (p < 0.0001). The strong response subgroup had lower metabolic comorbidities, including glucose hemostasis, hypertension, and dyslipidemia (p < 0.04). Moreover, the strong response subgroup had fibrosis stages F0-F2 (75.3 % vs. 56.3 %) and lower rates of advanced stages F3-F4 (24.7 % vs. 43.8 %). The F0-F2 subgroups had significantly higher rates of strong responses than the F3-F4 stages. The anti-S >= 200 and anti-S >= 400 AU/ml response achieved in 66 % and 36.8 % of the F0-F2 population was significantly higher than the 45.1 % (p = 0.006) and 23.5 % (p = 0.05) in the F3-F4 population, respectively. The Fib-4 calculations and Fibroscan evaluations were consistent with histologic fibrosis assessment.Conclusion: Advanced liver fibrosis (assessed by histology, Fib-4, or Fibroscan) is a risk factor for lower response to Pfizer's BNT162b2 vaccine, and patients should be prioritized for the vaccine booster against SARS-CoV-2.

Background and Aims: There is conflicting evidence regarding the association between proton pump inhibitors (PPI) and the risk of acquisition and severity of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.Aim: To evaluate the association between PPI exposure and infection and development of severe disease in patients infected with SARS-CoV2in a large population-based historical cohort.Methods: Data were extracted from a health maintenance organization database in Israel that insures over 1,200,000 individuals from across the country. All patients who underwent SARS-CoV-2 testing between March and November 2020 were included. Logistic regression and matched analyses were used to compare patients prescribed and exposed to PPIs to those not prescribed PPIs regarding SARS-CoV-2 positivity. In addition, among SARS-CoV-2 positive patients (n = 44,397) the likelihood of developing severe disease, defined by a composite endpoint of death, ICU admission and prolonged hospitalization, was compared in those exposed and not exposed to PPIs.Results: Among 255,355 adult patients who underwent SARS-CoV-2 testing by PCR, 44,397 (17.4%) were positive for SARS-CoV-2 and 12,066 (4.7%) patients were prescribed PPIs in the 3 months before testing. In a multivariable logistic regression model controlling for age, gender, smoking status, BMI, diabetes mellitus, hypertension, COPD, history of ischemic heart disease and fasting blood glucose (FBG) levels, no significant association was found between PPIs and SARS-CoV-2 positivity (p = 0.09 aOR 0.94, 95% CI – 0.88–1.01). Among SARS-CoV-2 positive patients, 910 (2%) had a severe infection. Multivariate logistic regression controlling for the abovementioned confounders, showed no such association between PPIs and severe COVID-19 (p = 0.28). Elevated FBG levels were significantly associated with both PPI exposure (p < 0.001) and severe COVID-19 infection (p < 0.001). These results were reinforced by a matched analysis (n = 655 pairs).Conclusion: PPIs are spuriously associated with severe COVID-19 due to the presence of elevated FBG as a confounder. Our study accounted for the FBG levels of patients and known risk factors for severe COVID-19 infection, which may be the reason for the discrepancy in prior studies. These results may aid in understanding potential confounders when evaluating potential associations of PPIs with other respiratory or viral diseases.

Abstract Background Sarcopenia is underdiagnosed in patients with Inflammatory bowel disease (IBD). Studies have shown that low alanine transaminase (ALT) levels are associated with sarcopenia. We evaluated the association of low ALT levels with the IBD diagnosis and activity. Methods Data of patients from state mandatory health maintenance organization in Israel was collected. Electronic medical records within the past two years included diagnosis, medications, blood and stool tests. Based on ICD9 coding, patients diagnosed with Ulcerative Colitis (UC) or Crohn’s disease (CD) were compared to healthy control group. Patients with ICD9 diagnosis of chronic liver disease, cirrhosis, and age <18 were not included. Serum ALT lower than, 15 was considered low. Results Our cohort consisted of, 348,454 patients, of them, 1780 patients with CD and, 916 with UC. Mean ALT was lower among patients with IBD than healthy controls (22.71 vs., 24.04, p-value<0.001). In multivariate logistic regression, controlling for age, sex, BMI, and smoking status, IBD was associated with low ALT levels (OR –, 1.25, 95% CI, 1.12–1.39, p-value<0.001) Of the CD patients, 392 (27.96%) were in the low ALT group. Patients in the low ALT group were younger (38.85 vs., 42.38 p- value<0.001), were less likely to be male (33.9% vs., 54.7%), had lower BMI (23.94 vs., 26.29 p – value<0.001). Fecal Calprotectin and CRP was higher in the low ALT group (601.25 vs., 282.33 p-value<0.001, 12.94 vs., 7.35 p value<0.001 respectively) while serum albumin was lower (4.12 vs., 4.28 p-value<0.001). Among patients with UC, 204 (30.13%), had low ALT. Patients in the low ALT group were slightly younger (46.92 vs., 49.65 p-value=0.06), less likely to be male, 22.5% vs., 52% p-value<0.001), had lower BMI (25 vs., 26.37 p-value=0.004). Patients with low ALT had higher CRP levels (12.92 vs., 6 p-value<0.001) and non-significantly higher fecal calprotectin levels (779.52 vs., 498.18 p-value, 0.16). Serum albumin was lower in the low ALT group (4.04 vs., 4.26 p value<0.001) In multivariate linear regression models, controlling for age, gender IBD subtype, and smoking status, low ALT was associated with elevated fecal calprotectin and CRP and lower albumin levels (p-value<0.001). Conclusion Patients with IBD have lower ALT levels than the general population. Among patients with IBD, low ALT is associated with active disease. Further studies are warranted to strengthen the association of low ALT with sarcopenia among patients with IBD.

The Pfizer‐BioNTech coronavirus disease 2019 (COVID‐19) vaccine has been offered to nonallergic ≥16‐year‐old Israeli adults since December 19, 2020. Data regarding factors associated with vaccine ineffectiveness are limited. The aim of this study is to assess the impact of hepatic fibrosis on the efficacy of the BioNTech vaccine. Serum severe acute respiratory syndrome coronavirus 2 spike immunoglobulins (S IgG) obtained at least 7 days following vaccination completion was correlated with the prevaccine calculated Fibrosis‐4 (FIB‐4) score among 719 employees in the Hadassah Medical Center, Jerusalem. Positive vaccine response (S IgG levels ≥ 19 AU/mL) was found in 708 of 719 individuals (98.5%). Vaccine failure (S IgG levels < 19) was found in 11 (1.5%); of these, 7 were immunosuppressed. Mean FIB‐4 available in 501 of 708 vaccine responders was 1.13 ± 0.66, mean age 51.4 ± 12.4 years (29.3% males), and mean S IgG titers 239.7 ± 86.1 AU/mL. Similar to the general population, 70.5% had normal FIB‐4 (<1.3), 26.8% undetermined FIB‐4 (1.3‐2.67), and 2.7% advanced FIB‐4 (>2.67). When divided into response subgroups, 158 of 501 individuals (30.1%) with IgG titers 19‐100 AU/mL had a mean FIB‐4 of 1.48 ± 0.82; 198 (39.5%) with IgG titers 101‐200 AU/mL had mean FIB‐4 of 1.22 ± 0.76; 83 (16.6%) with titers 201‐300 AU/mL had mean FIB‐4 of 1.04 ± 0.48; 38 (7.6%) individuals with IgG titers 301‐400 AU/ml had a mean FIB‐4 of 1.08 ± 0.63; and 121 (24.2%) with IgG titers >400 AU/mL had mean FIB‐4 of 1.18 ± 0.87. Increased FIB‐4, age, and male gender significantly correlated with lower postvaccine IgG titers (P < 0.001). FIB‐4 results were confirmed using FibroScan data displaying advanced fibrosis impact on weakened COVID‐19 vaccine response. Conclusion: Immune suppression, older age, male gender, and advanced chronic liver disease are risk factors for lower vaccine response. The FIB‐4 provides a simple tool to prioritize candidates for third‐dose vaccine booster.