BACKGROUND:Frailty adversely affects post-transplant outcomes in chronic liver disease (CLD). This study evaluated the feasibility and the impact of preoperative supervised aerobic and resistance exercises (SARE) on frailty and outcomes after living donor liver transplantation (LDLT). METHODS:This single-centre randomized controlled trial assigned the LDLT recipients to standard medical therapy (SMT) or SARE+SMT for 4 weeks pre-LDLT. Liver Frailty Index (LFI), Short Physical Performance Battery (SPPB), pulmonary function tests (PFTs) and postoperative outcomes were compared. RESULTS:Sixty patients, [54 (90%) males, 26 (43.33%) alcoholic liver disease, 18 (30%) NASH, median MELDNa of 22 (19-27) and CTP A 5 (8.33%), B 22 (36.67%), C 33 (55%) were randomised (30/group)]. Baseline parameters, LFI and SPPB were comparable. At enrolment, 46(76.67%) were pre-frail, 7(11.67%) frail and 53(88.33%) were sarcopenic. Seven(11.66%) patients died during workup, four lost to follow-up and 49 underwent LDLT. In SARE arm, 40% patients attended ≥5 exercise sessions. No adverse events occurred; recurrent admissions were hinderance to study adherence. Adjusted analysis showed similar LFI (p=0.92), SPPB (p=0.71) and PFT between groups. A borderline improvement in NIV discontinuation (p=0.05) and earlier chair and bipedal ambulation (p=0.10 and p=0.09, respectively) was observed with SARE. Significant correlations were observed for POD30 LFI [MV duration- r=0.56 (p=0.00), NIV duration- r=0.509 (p=0.00), hospital stay- r=0.547 (p=0.00) and ICU stay- r=0.563 (p=0.00)], with similar statistically significant correlations for POD14 and POD30 LFI, SPPB and PFTs. CONCLUSIONS:Preoperative SARE is safe and feasible in high MELD/ Child patients. LFI, SPPB, PFT, and postoperative outcomes were comparable between groups. SARE showed borderline improvement in ambulation and NIV discontinuation. Better LFI, SPPB, PFTs predicted improved clinical outcomes.

Sepsis remains a global health burden associated with significant morbidity and mortality. Bacteria are known to be the predominant pathogens in sepsis; however, viral etiologies in sepsis are still under diagnosed. Respiratory viral pathogens have been previously linked to sepsis, but the knowledge of incidence, disease burden and mortality of viral-induced sepsis remains limited. This study aimed at understanding the role of respiratory viral infections in the causation of sepsis in liver disease patients. In this retrospective study, the clinical records of liver disease patients with influenza-like illness, whose requests for respiratory viral testing were received from January 2019 to December 2022, were reviewed. Respiratory viruses were identified using FilmArray 2.0 respiratory panel (BioFire Diagnostics, Utah, USA). Of 1391 patients tested, a respiratory viral etiology was detected in 23

Background: Very limited literature on the clinical course of COVID-19 among liver transplant recipients (LT) is available from India. The present study aimed to evaluate the clinical and mutational profile of SARS-CoV-2 among LT. Methodology: This was a retrospective study including LT cases in whom SARS-CoV-2 RT-PCR testing was requested between April 2020 and December 2022. Detailed mutational analysis was performed by comparing LT COVID-19 positive study group i.e. LT-CoV(+) with two control groups. One including COVID-19 positive with underlying chronic liver disease (CLD) i.e. CLD-CoV(+) and other including COVID-19 positive outpatients without any underlying LD i.e. NLD-CoV(+) Results: Among 213 cases, 48 (22.5 %) were positive [LT-CoV(+)] and the remaining 165 (77.5 %) were negative [LT-CoV(-)] for SARS-CoV-2. Of these, 49 % had mild, 14 % moderate and 37 % had severe COVID-19. Mortality was recorded in 11 (23 %) cases, the majority being non-vaccinated. Severe COVID-19 with intensive care requirement was significantly higher among recipients with >5 years since transplant compared to recipients with <= 5 years (p = 0.02). Among 40 samples subjected to whole genome sequencing, 19 (47.5 %) were Delta, 15 (37.5 %) Omicron, and 6 (15 %) were other variants. COVID-19 severity was significantly higher in LT-CoV(+/D) with no significant difference in mortality (p = 0.122). No significant differences in mutational load and in fraction of deleterious mutations were observed between LT-/CLD-/NLD-CoV(+) groups for either Delta or Omicron. Conclusion: An overall fatality rate of 23 % was recorded among LT recipients. Longer duration since transplant was associated with severe clinical course. However, no significant difference in mutation load between studied groups was observed.

Aim and background:Respiratory viral infections (RVIs) cause significant hospitalizations every year. Also, RVIs caused by either influenza or noninfluenza group of viruses can have adverse outcomes, especially among immunosuppressed patients. Regular and timely supervision is needed for accurate etiological identification, to prevent inappropriate use of antibiotics in patients with nonbacterial etiology. This study aimed to identify the spectrum of RVIs and clinical characteristics among liver disease patients with influenza-like illness (ILI).Materials and methods:In this study, medical records of patients with ILI, whose requests for respiratory viral testing came from September 2016 to December 2022 were retrospectively reviewed. Respiratory viruses were identified using FilmArray 2.0 respiratory panel (BioFire Diagnostics, USA).Results:Of the 1,577 liver disease patients with ILI, the overall prevalence of RVI was 28% (n = 449). Infection by noninfluenza viruses (NIVs) was detected in 329 patients (73%), higher than those infected with influenza viruses. In multivariable logistic regression analysis, female gender [odds ratio (OR): 2.5, 95% confidence interval (CI): 1.5-4.2], infection with influenza B (OR: 3.3, 95% CI: 1.09-9.9) and decompensated cirrhosis (OR: 3.9, 95% CI: 1.7-8.5) were independent risk factors for mortality. Regarding seasonality, influenza peaked in monsoons and winters, whereas NIVs circulated throughout the year.Conclusion:Overall, this study adds new knowledge regarding the incidence of RVI and the distribution of respiratory viral etiologies among liver disease patients with ILI. The findings highlight that female gender, decompensated cirrhosis, and influenza B infection are independently associated with poor clinical outcomes. Early etiological identification of viral causes of ILI could aid in an enhanced understanding of the prevalence of ILI and the timely management of the patients.Clinical significance:Respiratory viral infections can cause severe illness in individuals with underlying liver disease. Accurate diagnosis and risk stratification is crucial in mitigating the adverse health effects.How to cite this article:Samal J, Prabhakar T, Prasad M, et al. Prevalence and Predictors for Respiratory Viral Infections among Liver Disease Patients. Euroasian J Hepato-Gastroenterol 2023;13(2):108-114.

BACKGROUND & AIMS:Hepatopulmonary syndrome (HPS) is characterised by a defect in arterial oxygenation induced by pulmonary vascular dilatation in patients with liver disease. Fingolimod, a sphingosine-1-phosphate (S1P) receptor modulator, suppresses vasodilation by reducing nitric oxide (NO) production. We investigated the role of S1P in patients with HPS and the role of fingolimod as a therapeutic option in an experimental model of HPS.METHODS:Patients with cirrhosis with HPS (n = 44) and without HPS (n = 89) and 25 healthy controls were studied. Plasma levels of S1P, NO, and markers of systemic inflammation were studied. In a murine model of common bile duct ligation (CBDL), variations in pulmonary vasculature, arterial oxygenation, liver fibrosis, and inflammation were estimated before and after administration of S1P and fingolimod.RESULTS:Log of plasma S1P levels was significantly lower in patients with HPS than in those without HPS (3.1 ± 1.4 vs. 4.6 ± 0.2; p <0.001) and more so in severe intrapulmonary shunting than in mild and moderate intrapulmonary shunting (p <0.001). Plasma tumour necrosis factor-α (76.5 [30.3-91.6] vs. 52.9 [25.2-82.8]; p = 0.02) and NO (152.9 ± 41.2 vs. 79.2 ± 29.2; p = 0.001) levels were higher in patients with HPS than in those without HPS. An increase in Th17 (p <0.001) and T regulatory cells (p <0.001) was observed; the latter inversely correlated with plasma S1P levels. In the CBDL HPS model, fingolimod restored pulmonary vascular injury by increasing the arterial blood gas exchange and reducing systemic and pulmonary inflammation, resulting in improved survival (p = 0.02). Compared with vehicle treatment, fingolimod reduced portal pressure (p <0.05) and hepatic fibrosis and improved hepatocyte proliferation. It also induced apoptotic death in hepatic stellate cells and reduced collagen formation.CONCLUSIONS:Plasma S1P levels are low in patients with HPS and even more so in severe cases. Fingolimod, by improving pulmonary vascular tone and oxygenation, improves survival in a murine CBDL HPS model.IMPACT AND IMPLICATIONS:A low level of plasma sphingosine-1-phosphate (S1P) is associated with severe pulmonary vascular shunting, and hence, it can serve as a marker of disease severity in patients with hepatopulmonary syndrome (HPS). Fingolimod, a functional agonist of S1P, reduces hepatic inflammation, improves vascular tone, and thus retards the progression of fibrosis in a preclinical animal model of HPS. Fingolimod is being proposed as a potential novel therapy for management of patients with HPS.

Background & Aims: Endothelial injury and dysfunction play a detrimental role in the pathogenesis of infections. Endothelium-related molecules have been reported as potential diagnostic and/or prognostic biomarkers of infection. The prognostic value of these biomarkers in patients with cirrhosis and infections remains elusive. Methods: In this study, we investigated the performance of key soluble endothelial injury biomarkers, including intercellular adhesion molecule 1 (ICAM1), von Willebrand factor (vWF), vascular endothelial growth factor receptor 1 (VEGFR1), and angiopoietin 1 and 2 (Ang1, 2) as mortality predictors in patients with cirrhosis and severe COVID-19 or bacterial sepsis. Results: A total of 66 hospitalized patients (admitted to the COVID-19 ward or liver intensive care unit [ICU]) were included. Twenty-two patients had COVID-19 alone, while 20 patients had cirrhosis plus COVID-19. Twenty-four patients had cirrhosis plus bacterial sepsis. Among patients with cirrhosis, the most common aetiology of liver disease was alcohol. ICAM1 was increased (p = 0.003) while VEGFR1 (p <0.0001) and Ang1 (p <0.0001) were reduced in patients with COVID-19 and cirrhosis, compared to patients with COVID-19 alone. Endothelial biomarker levels did not differ significantly between patients with cirrhosis and severe COVID-19 or bacterial sepsis in the ICU. In these patients, ICAM1 levels significantly and independently predicted mortality (hazard ratio 3.24; 95% CI 1.19-8.86) along with model for end-stage liver disease (MELD) score, renal and coagulation failures. The AUC for ICAM1 was 0.74, MELD was 0.60 and combined ICAM1 and MELD was 0.70. ICAM1 also positively correlated with the composite organ failure scores recorded 3-5 days post ICU admission (CLIF-OF and SOFA) in this subgroup of patients. Conclusion: The study indicates that in patients with cirrhosis, elevated plasma ICAM1 serves as an independent predictor of severe COVID-19-or sepsis-associated 28-day mortality. Lay summary: Bacterial sepsis and COVID-19 lead to increased mortality in patients with cirrhosis. In this study, we demonstrate that high plasma levels of ICAM1, an endothelial injury biomarker, is one of the important factors predicting mortality in critically ill cirrhotic patients with severe COVID-19 or bacterial sepsis. (C) 2021 The Author(s). Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL).

RATIONALE:Obstructive sleep apnea (OSA) is often seen among obese individuals and the obesity has a linear association with MAFLD. The contribution of chronic intermittent nocturnal hypoxia of OSA and association of MAFLD with OSA is an unmet need. The present study aimed to determine the etiology, impact and association of OSA severity and nocturnal hypoxemia among patients ofChronic liver disease (CLD). METHODS:In this study, analysis of the medical records and clinical details of the patients of CLD who had undergone polysomnography were analyzed after appropriate inclusion in study as per inclusion and exclusion criteria. After assessing the eligibility criteria, a total of 78 patients were included in the final analysis. Nocturnal hypoxemia was gauged from the baseline oxygen saturation record of study. Presence and severity of OSA were graded as per American Academy of Sleep Medicine (AASM) criteria. The primary objective of the study was to determine the association between OSA severity and nocturnal hypoxemia to the presence of Non-alcoholic Fatty Liver Disease (NAFLD). Secondary objectives were to assess the association of OSA severity and extent of nocturnal hypoxemia to the BMI and to determine the proportions of NAFLD subjects with OSA. RESULTS:A total of 78 patients were screened, of which only 11 (14.1%) were female. Out of these, 56 (71.8%) were classified to MAFLD group while 22 (28.2%) were to the non-MAFLD group. The patients in MAFLD group with mean age of 56.02 years were older as compared to non-MAFLD with mean age of 51.05 years but that was not statistically different. Patients were categorized into MAFLD (n = 56) and non-MAFLD, representing other etiologies of CLD (n = 22; ethanol, chronic Hepatitis B virus (HBV), chronic Hepatitis C virus (HCV), cryptogenic, Non-cirrhosis portal fibrosis (NCPF), Primary sclerosing cholangitis (PSC), Autoimmune hepatitis (AIH), sarcoidosis, Wilson's disease). The mean BMI was significantly higher in MAFLD in comparison to non-MAFLD (34.51 ± 8.79 vs. 25.47 ± 5.75; P = 0.000) and also the median AHI of MAFLD group was significantly higher than the non-MAFLD 4.95 {(1.85, 25.47) vs. 0.85 (0.30, 2.72) (P value < 0.000)} [Table 1]. Among the desaturation indices, the number of desaturations >3% {median of 122.50 (75.00, 241.25) vs. 63.00 (13.75, 158.00), P value 0.009} and average desaturation {mean of (5.04 ± 2.16) vs. (3.78 ± 1.226)%, P value 0.002} were significantly higher in MAFLD versus non-MAFLD group [Table 2]. The AHI and all desaturation parameters, although not statistically significant, were worst in Child B [Table 3]. CONCLUSION:MAFLD patients have higher prevalence and greater severity of OSA and worse nocturnal desaturation parameters as compared to non-MAFLD patients. OSA is independent of obesity among patients of CLD, but prevalent among NAFLD group. Further prospective studies are needed among MAFLD and OSA patients to elucidate the mechanism linking pathophysiology of OSA-MAFLD and guide therapy.

The severe acute respiratory syndrome corona virus-2 (referred to as SARS CoV2) pandemic had a great impact on public life in general as well as on populations with pre-existing disease and co-morbidities. Liver transplant and immunosuppressant medication predisposes to more severe disease and is often associated with poor outcome. The clinical features, disease course, treatment and process of modulating the immunosuppression is challenging. Here, we describe the clinical presentation, treatment and outcomes in six liver transplant recipients. Out of those six patients, three had mild, one had moderate and one had severe COVID-19, and one was asymptomatic. The immunosuppression minimization or withdrawal was done based upon the clinical severity. Consideration of tocilizumab and/o convalescent plasma as well as antivirals i.e. remdesvir done in severe cases. The routine practice of prophylactic anticoagulation, consideration of repurposed drugs (i.e. teicoplanin and doxycycline), and watchful monitoring of asymptomatic recipients helped to achieve an uneventful recovery.

Background: An increased covid-19 mortality has been reported in patients with liver cirrhosis. Given a significant association of endothelial damage with both liver disease and covid-19 severity, we investigated key endothelial injury markers in covid-19 patients with and without cirrhosis. Methods: A cross-sectional study with PCR-confirmed moderate/severe covid-19 hospitalized patients with and without cirrhosis was performed. Cirrhosis patients with bacterial sepsis were also recruited. Soluble plasma bio-markers of endothelial cell injury, including intercellular adhesion molecule 1 (ICAM1), von Willebrand Factor (vWF) antigen, vascular endothelial growth factor receptor 1 (vegfr1), angiopoietin 1 and 2 (Ang1, 2) were measured. Findings: A total of 56 hospitalized patients were included belonging to patients in moderate covid-19 category [covid-19 with liver cirrhosis (n=6); covid-19 without liver cirrhosis (n=8)] and severe covid-19 category [covid-19 with liver cirrhosis (n=10); severe covid-19 without liver cirrhosis (n=15)]. 17 patients were with liver cirrhosis plus bacterial sepsis. ICAM1 levels were increased (p=0.04) while vegfr1 (p<0.0001) and Ang1 (p<0.0001) were reduced in covid-19 patients with cirrhosis, as compared to that in covid-19 patients alone. On univariate logistic regression, ICAM1 (OR=9.81, 95%CI 11.69-155.9, p=0.03) and Ang2 levels (OR=3.72, 95%CI 1.29-21.92, p=0.04) predicted mortality in covid-19 patients with cirrhosis. Among severe covid-19, patients with covid-19 alone had a 28-day mortality of 76.7%, covid-19 plus cirrhosis had 48% while patients with cirrhosis had 23.8%. Endothelial injury biomarkers between cirrhosis patients with sepsis and those with covid-19 did not differ significantly. In cirrhosis patients with severe covid-19 and sepsis analysed together, elevated ICAM1 levels (OR=15, 95% CI 0.2-1380, P<0.05) and MELD score (OR=1.11, 95%CI=1.0-1.26, P<0.03) appeared to be significantly associated with mortality. For these patients, the area under the curve for ICAM1 was 0.721, while that of the MELD score was 0.621. An ICAM1 value higher than 182,150 pg/ml and MELD more than 31.5 was associated with higher mortality in liver cirrhosis patients with covid-19 and sepsis (ICAM1: HR: 5.65, 95% CI 2.16-14.83, p<0.01; MELD:HR: 1.09, 95% CI 1.02-1.16, p< 0.05). Interpretation: The study indicates that in patients with liver cirrhosis, altered levels of endothelial injury markers may be associated with a higher covid-19 and sepsis associated in-hospital mortality. Both elevated ICAM1 and MELD would serve as valuable predictors of covid-19 and sepsis associated mortality in cirrhosis patients. Funding: The study was funded by research funds from the Institute of liver and biliary Sciences (ILBS).Declaration of Interests: All authors declare no competing interestsEthics Approval Statement: The institutional review board approved this study (Ethics protocol no IEC/2020/82/NA01).

There are apprehensions among healthcare worker (HCWs) about COVID-19. The HCWs have been given hydroxychloroquine (HCQ) chemo-prophylaxis for seven weeks as per Government of India guidelines. To assess the apprehensions among HCWs about COVID-19 and to document accessibility, adherence and side effects related to HCQ prophylaxis in HCWs. A longitudinal follow up study was conducted in a tertiary care hospital. HCQ was given in the dose of 400 mg twice on day one, and then 400 mg weekly for seven weeks. 391 HCWs were interviewed using semi structured questionnaire. 62.2% HCWs expressed perceived danger posted by COVID-19 infection. Doctors (54%) showed least acceptance and paramedics (88%) showed highest acceptance to chemo-prophylaxis. 17.5% participants developed at least one of the side effects to HCQ. Females and nursing profession were significantly associated with adverse effects. Common side effects were gastro-intestinal symptoms, headache and abnormal mood change. Most of these were mild, not requiring any intervention. Gender, professions and perceived threat of COVID-19 were significantly associated with acceptance and adherence to HCQ prophylaxis. Two third of HCWs had perceived danger due to COVID-19. Three fourth of the HCWs accepted chemo-prophylaxis and four out of five who accepted had complete adherence to prophylaxis schedule. One out of five had developed at least one of side effects; however, most of these were mild not requiring any intervention.

CONTEXT:Control of COVID-19 has now become a critical issue for public health. Many ecological factors are proven to influence the transmission and survival of the virus. However, the association between different climatic factors and spread and mortality due to COVID-19 is unknown.AIM:To determine the association of different climatic factors with the spread and mortality due to COVID-19 during January 2020 to May 2020.METHODS AND MATERIAL:The climatic indicators included in the study were duration of sunshine, average minimum temperature, and average maximum temperature, with cumulative confirmed cases, deceased, and recovered cases. The data was performed for 138 different countries of the world, from January 2020 to May 2020.STATISTICAL ANALYSIS USED:Spearman's correlation analysis was used to assess the correlation between temperature and the spread and mortality of COVID-19 cases. Both univariate and multivariate analysis was performed for cumulative and month-wise analysis, using SPSS software.RESULTS:Average maximum temperature and sunshine duration were significantly associated with COVID-19 confirmed cases, deceased, and recovered. For every 1° increase in average temperature, the confirmed, deceased, and recovered cases decreased by 2047 (P = 0.03), 157 (P = 0.016), and 743 (P = 0.005) individuals. The association remained significant even after adjusting for environmental as well as non-environmental variables. Average sunshine duration was inversely correlated with an increase in daily new cases (r = - 2261) and deaths (r = - 0.2985).CONCLUSION:Higher average temperature and longer sunshine duration are strongly associated with COVID-19 cases and deaths in 138 countries.