Pre-existing chronic liver disease is associated with poor outcome in patients with SARS-CoV2 infection

COVID-19 is characterized by predominant respiratory and gastrointestinal symptoms. Liver enzymes derangement is seen in 15-55% of the patients. Cirrhosis is characterized by immune dysregulation, leading to concerns that these patients may be at increased risk of complications following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients with metabolic dysfunction-associated fatty liver (MAFLD) had shown a 4-sixfold increase in severity of COVID-19, and its severity and mortality increased in patients with higher fibrosis scores. Patients with chronic liver disease had shown that cirrhosis is an independent predictor of severity of COVID-19 with increased hospitalization and mortality. An international European registry study included 756 patients with chronic liver disease from 29 countries reports high mortality in patients with cirrhosis (32%). Data of 228 patients collected from 13 Asian countries on patients with CLD, known or newly diagnosed, with confirmed COVID-19 (APCOLIS study) showed that SARSCoV- 2 infection produces acute liver injury in 43% of CLD patients without cirrhosis. Additionally, 20% of compensated cirrhosis patients develop either ACLF or acute decompensation. In decompensated cirrhotics, the liver injury was progressive in 57% of patients, with 43% mortality. Patients with CLD and associated diabetes and obesity had a worse outcome. Liver related complications were seen in nearly half of the decompensated cirrhotics, which were of greater severity and with higher mortality. Increase in Child Turcotte Pugh (CTP) score and model for end-stage liver disease (MELD) score increases the mortality in these patients. In a subsequent study of 532 patients from 17 Asian countries was obtained with 121 cases of cirrhosis. An APCOLIS risk score was developed, which included presence of comorbidity, low platelet count, AKI, HE and respiratory failure predicts poor outcome and an APCOLIS score of 34 gave a sensitivity and specificity of 79.3%, PPV of 54.8% and NPV of 92.4% and predicted higher mortality (54.8% vs 7.6%, OR = 14.3 [95 CI 5.3-41.2], p<0.001) in cirrhosis patients with Covid-19. The APCOLIS score is helpful in triaging and prognostication of cirrhotics with Coivd-19. The impact of COVID-19 on patients with cirrhosis due to non-alcoholic fatty liver disease (NASH-CLD) was separately studied in 177 NASH-CLD patients. Obese patients with diabetes and hypertension had a higher prevalence of symptomatic COVID. Presence of diabetes [HR 2.27], fraility [HR 2.68], leucocyte counts [HR 1.69] and COVID-19 were independent predictors of worsening liver functions in patients with NASH-CLD. Severity of Covid in Cirrhosis could also be assessed by measuring ICAM1 the Intercellular Adhesion Molecule, an indicator of Endothelial Injury Marker. in Cirrhosis with Covid 19 Immunosuppression should be reduced prophylactically in patients with autoimmune liver disease and post-transplantation with no COVID-19. Hydroxychloroquine and remdesivir are found to be safe in limited studies in a patient with cirrhosis and COVID-19. And is safe in cirrhosis patients. However, flare of AIH has been reported in AIH patients. For hepatologists, cirrhosis with COVID-19 is a pertinent issue as the present pandemic cause severe disease in patients with chronic liver disease leading to more hospitalization and decompensation.

Low Serum Albumin at Admission Is Associated with Mortality among Inpatients with Cirrhosis: A Multi-National Experience

Background: MELD and Child-Pugh scores have traditionally been used as prognostic indicators in patients with cirrhosis. Albumin infusions in outpatients have been associated with improved outcomes, but not in transplant waitlisted patients or inpatients. This aim of this study was to assess whether low serum albumin (sAlb) on admission alone is a poor prognostic indicator among cirrhotic inpatients from a new multi-national cohort. Method(s): The CLEARED study is a global study that enrolled consecutive non-electively admitted inpatients without organ transplant or COVID-19 from 6 continents. Admission demographics, medical history, laboratory data, inpatient course, death/hospice transfer and mortality at 30 days post-discharge were recorded. Patients were divided into 3 groups: sAlb <28gm/L(A), sAlb >=28 but <35gm/L (B), and sAlb>=35gm/L (C) were compared. Multi-variable logistic regression was performed using inpatient mortality and overall 30-day mortality as outcomes. Result(s): 2429 patients were enrolled from 21 countries worldwide. The distribution was A:49%, B:39%, C:12%. Gp A patients were significantly younger (54yrs vs. 57yrs vs 58yrs p<0.0001) but with similar gender distribution, and higher MELD-Na score of 25 vs. 20 vs. 17 (p<0.0001). Gp A patients were more likely to have alcohol as etiology of cirrhosis (49% vs. 45% vs 38%, p=0.004), and were more likely to have either infection (27% vs. 18% vs. 13%, p<0.0001), HE (39% vs. 33% vs. 23%, p=0.005) or fluid related issues as a reason for admission (p<0.0001). More patients in Gp A received albumin infusion during their hospital stay (120gm vs. 100gm vs. 100gm p=0.0004), mostly for the indications of AKI (47% vs. 49% vs. 47%, p=0.79) and performance of large volume paracentesis (44% vs. 42% vs. 41%, p=0.80), followed by bacterial peritonitis indication (22% vs. 17% vs. 11%, p=0.01). Group A patients had longer hospital stays (9 days vs. 8 days vs. 7 days (p<0.001), but similar ICU transfer (23% vs. 22% vs. 20%, p=0.55). group A patients were more likely to die while inpatients (19% vs. 11% vs. 5%, p<0.0001), or by 30 days post-discharge (29% vs. 20% vs. 9%, p<0.0001). Table shows the admission variables associated with a poor outcome. Conclusion(s): Hypoalbuminemia is extremely common among admitted cirrhotic patients, with sAlb of <28gm/L occurring in almost half. Together with MELD-Na score and infection at admission, a low sAlb is associated with a poor outcome in these patients. Future studies will need to validate these findings and to assess whether albumin infusions will improve the outcome of these patients. (Figure Presented).

Differences in Mortality Rates in Inpatients with Cirrhosis Depends on the Low, Middle or High Income Country Location: Multi-National Cleared Consortium Experience

Background: Although cirrhosis is a major cause of mortality worldwide, there could be disparities in outcomes. This needs a global consortium to study disparities in inpatient cirrhosis care Aim: Define the impact of location in prediction of outcomes in inpts with cirrhosis. Method(s): CLEARED prospectively enrolled non-electively admitted cirrhosis pts without COVID from all continents. To ensure equity, we allowed only 50 pts/site. Admission details, cirrhosis history, inpatient & 30-day course were recorded. World bank classification of low/low middle income (LMI), upper middle (UMI) & High income (HI) were used. Cirrhosis details, inpatient & 30-day outcomes were compared between groups. Multi-variable regression was performed using inpatient & 30-day mortality as outcomes. Result(s): 2758 pts from 21 countries from all continents, including Africa & Australia, were included.727 were L/LMI, 1050 UMI & 981 pts were from HICs. More men & younger pts were in LMI. Cirrhosis details: More pts in HI gp had 6M hospitalizations & infections, HE & ascites while prior variceal bleeding was higher in LMI . Prior HCC & transplant listings were lower in LMI but similar in UMI/HI. Alcohol & NASH was highest in HI. Viral hepatitis & cryptogenic were highest in UMI.Admissions: Admission MELD was highest in LMI. LMI pts were admitted more for GI Bleed, HE, & DILI, while anasarca & HBV flares were higher in UMI. Higher SBP (36% vs 24% vs 21% p<0.0001) & lowest skin/soft-tissue infections were in LMI (5% vs 5% vs 10% p=0.008);rest were similar. Nosocomial infections, driven by UTI were highest in LMI & HI pts (15% vs 14% vs 11% UMI, p=0.03). Admission diuretics, PPIs, Lactulose & statins were highest & antivirals lower in HI. SBP prophylaxis & rifaximin were highest in LMI pts. Outcome(s): More LMI pts needed ICU & had more organ failures (Fig B). Discharge MELD was highest in LMI. In-hospital mortality was highest & transplant lowest in LMI. This extended to 30-day mortality & transplant in LMI patients vs HI pts.Regression: In-hospital mortality was linked with age, infections, MELD & being in a LMI/UMI vs HIC while being on a transplant list, diabetes, & SBP prophylaxis were protective (Fig C). 30-day mortality predicted by age, ascites, HCC, discharge MELD, organ failures, LMI/UMI vs HIC but rifaximin was protective(Fig D). In-hospital transplant was higher with high MELD, admission rifaximin & listed pts &lower in LMI (OR 0.26) & UMI (OR 0.22) & age. 30-day transplant was higher in those with hyponatremia, ascites & HRS, on the list & on rifaximin and lower in LMI (OR 0.24) & UMI (OR 0.59) vs HI. Conclusion(s): In a global study of inpatients with cirrhosis, there were major differences in outcomes. Not being in a high-income country significantly increased the risk of inpatient and 30-day mortality independent of demographics, medications, in-hospital course, and cirrhosis severity likely due to disparities in access to transplant, which should be accounted for in global models. (Figure Presented).

Comparative analysis of acute on chronic liver failure related to herbs and anti-tubercular drugs

Objectives: Liver injury precipitated by drugs and herbal medicines( DHMs) can have variable presentations and outcomes. In Indian subcontinent, drug induced liver injury due to Anti-tubercular drugs( ATDs) and inadvertent herbs induced liver injury (HILI) are common. Comparative natural history and outcome of acute-onchronic liver failure(ACLF) due to common DHMs is largely unknown. Materials and Methods: Consecutive in-patients with ACLF precipitated by herbs or ATDs(year 2010-2021) were compared for baseline clinical profile, disease severity, histological features and organ failures. Treatment outcomes and predictors of in-hospital mortality were also analyzed. Results: 529 patients presented with ACLF related to HILI(ACLF-H, n = 430) and ATDs(ACLF-D, n = 99) [Mean Age-47.6 - 14 years, mean MELD score and HVPG were 29.1 - 5.4 and 15.5 - 3.4 mmHg respectively]. 61.4% patients had underlying histological cirrhosis. 21.2% patients had additional superadded acute insult [severe alcoholic hepatitis(n = 66), acute hepatitis E or A(n = 24/15)]. Twelve percent ACLF-H patients presented with clinical cholestasis, autoimmune hepatitis(n = 18) and hypersensitivity reactions(n = 4). Most common recognizable agent associated with ACLF-H was Tinospora cordifolia (n = 35,8.1%), inadvertently used in Indian households during the COVID-19 pandemics. Patients with ACLF-H as compared to ACLF-D had higher male preponderance (70.9% vs. 54.5%;p-0.002) and peripheral eosinophilia (6.4% vs. 1%;p-0.03), clinical cholestasis (19.6% vs 10.8%;p-0.05) and acute kidney injury (44.4% vs. 28.3%;p-0.003) at presentation. Use of plasma exchange(18.5%) had no impact on outcomes. None of the patients underwent liver transplantation. In-hospital mortality(19.2%) was higher in ACLF-D compared to HILI ACLF-H (31.3% vs. 17.2%;p-0.002). Presence of AKI [HR:5.5 (95%CI:2.78 to 11.1)], hepatic encephalopathy[HR:4.4(95%CI:1.76 to 11)] and pneumonia[ HR:7.2(95%CI: 3.59 to 14.65)] were independent predictors of mortality. Conclusion: Herbs and anti-tubercular drugs are common precipitants of ACLF in India and have high in-hospital mortality resulting from sepsis and organ(s) failure. In the absence of specific treatment options, prevention and early and careful monitoring of liver functions is of utmost importance.

CLEARED Global consortium results highlight regional variation and need for equity in inpatient outcomes in hospitalized patients with Chronic Liver Disease

Background and aims: A global study with equitable participation for cirrhosis and chronic liver disease (CLD) outcomes is needed. We initiated the Chronic Liver disease Evolution And Registry for Events and Decompensation (CLEARED) study to provide this global perspective. Aim to evaluate determinants of inpatient mortality and organ dysfunction in a multi-center worldwide study. Method: We prospectively enrolled pts with CLD/Cirrhosis >18 years without organ transplant or COVID-19 who were admitted non-electively. To maintain equity in outcome analysis, a maximum of 50 pts/site were allowed. Data for admission variables, hospital course, and inpatient outcomes (ICU, death, organ dysfunction [ODF]) were recorded. This was analyzed for death and ODs using significant variables on admission and including World Bank classification of low/middle-income countries (LMIC). A model for in-hospital mortality for all variables during the hospital course, including ODs) was analyzed. Results: 1383 pts (55 ± 13 yrs, 64% men, 39% White, 30% Asian, 10% Hispanic, 9% Black, 12% other) were enrolled from 49 centers (Fig A). 39% were from high-income while the rest were from LMICs. Admission MELDNa 23 (6–40) with history in past 6 months of hospitalizations 51%, infections 25%, HE 32%, AKI 23%, prior LVP 15%, hydrothorax 8% and HCC 4%. Leading etiologies were Alcohol 46% then NASH 23%, HCV 11% and HBV 13%. Most were on lactulose 52%, diuretics 53%, PPI 49% and statins 11%, SBP prophylaxis 16%, beta-blockers 35% and rifaximin 31%. 90% were admitted for liver-related reasons;GI bleed 30%, HE 34%, AKI 33%, electrolyte issues 30%, anasarca 24% and 25% admission infections. In-hospital course: Median LOS was 7 (1–140) days with 25% needing ICU. 15% died in hospital, 3% were transplanted, 46% developed AKI,15% grade 3–4 HE, 14% shock, 13% nosocomial infections and 13% needed ventilation. Logistic Regression: Fig B shows that liver-related/unrelated factors on admission which predicted in-hospital mortality and development of organ dysfunction with MELDNa and Infections being common among all models. Nosocomial infections and organ dysfunctions predicted mortality when all variables were considered. High-income countries had better mortality outcomes likely due to transplant and ICU availability. AUCs were >0.75 (Figure Presented) Conclusion: In this worldwide equitable experience, admission cirrhosis severity and infections are associated with inpatient outcomes, which are greater in low-income settings. Liver-related and unrelated factors and regional variations are important in defining critical care goals and outcome models in inpatients with cirrhosis.

SARS-CoV-2 Lineage Tracking, and Evolving Trends Seen during Three Consecutive Peaks of Infection in Delhi, India: a Clinico-Genomic Study.

Since its advent, the pandemic has caused havoc in multiple waves due partly to amplified transmissibility and immune escape to vaccines. Delhi, India also witnessed brutal multiple peaks causing exponential rise in cases. Here we had retrospectively investigated clade variation, emergence of new lineages and varied clinical characteristics during those three peaks in order to understand the trajectory of the ongoing pandemic. In this study, a total of 123,378 samples were collected for a time span of 14 months (1 June 2020 to 3 August 2021) encompassing three different peaks in Delhi. A subset of 747 samples was processed for sequencing. Complete clinical and demographic details of all the enrolled cases were also collected. We detected 26 lineages across three peaks nonuniformly from 612 quality passed samples. The first peak was driven by diverse early variants, while the second one by B.1.36 and B.1.617.2, unlike third peak caused entirely by B.1.617.2. A total of 18,316 mutations with median of 34 were reported. Majority of mutations were present in less than 1% of samples. Differences in clinical characteristics across three peaks was also reported. To be ahead of the frequently changing course of the ongoing pandemic, it is of utmost importance that novel lineages be tracked continuously. Prioritized sequencing of sudden local outburst and community hot spots must be done to swiftly detect a novel mutation/lineage of potential clinical importance. IMPORTANCE Genome surveillance of the Delhi data provides a more detailed picture of diverse circulating lineages. The added value that the current study provides by clinical details of the patients is of importance. We looked at the shifting patterns of lineages, clinical characteristics and mutation types and mutation load during each successive infection surge in Delhi. The importance of widespread genomic surveillance cannot be stressed enough to timely detect new variants so that appropriate policies can be immediately implemented upon to help control the infection spread. The entire idea of genomic surveillance is to arm us with the clues as to how the novel mutations and/or variants can prove to be more transmissible and/or fatal. In India, the densely populated cities have an added concern of the huge burden that even the milder variants of the virus combined with co-morbidity can have on the community/primary health care centers.

Prolonged detection of sars cov2 rna in extracellular vesicles in nasal swab rt-pcr negative patients

Background: There is a prolonged RT-PCR positivity seen in COVID-19 infected patients up to 2-3 months.It is assumed that this virus is usually non-infective but there are hardly any study on the reactivation of this virus within the respiratory tract. We aim to investigate the presence of viral particles inside Extracellular vesicles (EV) and its role in underlying liver disease patients. Methods: SARS CoV2 nasal and throat swab RT-PCR positive n=64 {n=12(18.7%) chronic liver disease (CLD);n=52 (81.3%) non-liver disease} n=5 RT PCR negative subjects (HC) were studied. SARS CoV2 patients were also followed up for day(d) 7 and 14. Nasal swab [collected in viral transport media (VTM)] and plasma samples were investigated at each time point. Extracellular vesicles were isolated using differential ultracentrifugation. SARS CoV2 RNA was measured using qRT-PCR by Altona Real Star kit. Cellular origin of EV was confirmed using epithelial cells (Epcam+ CK19+ CDh1+), endothelial cells (CD31+CD45-), hepatocytes (ASGPR+) surface markers by Flow cytometry. Results: The COVID19 patients {Mean age 54±23 years;41 males} were having severity between moderate to severe. In patients with cirrhosis, the most common aetiology of liver disease was alcohol (MELD 22±8). In baseline RT-PCR positive patients, SARS-CoV2 RNA inside the EV was present in 53/64 (82%) patients with comparable viral load between VTM and EV (mean 1CT - 0.033±0.005 vs. 1CT- 0.029±0.014, p=ns). On follow-up at day 7, of the 24 patients negative for COVID19, 10 (41%) had persistence of virus in the EV (1CT - 0.028±0.004) and on day 14, 14 of 40 (35%) negative RT-PCR had EVs with SARS CoV2 RNA (1CT - 0.028±0.06). The mean viral load decreased at day7 and day14 in EV from baseline (p=0.008;0.002 respectively). The probability of detecting SARS-CoV2 in EVs in the VTM negative patients was significantly (p=0.001) greater { relative risk ratio 2.25 (95% of CI 1.08 to 4.67;p=0.02, odds ratio 28.1(95% of CI -1.27 to 619.9;p=0.03)}.SARS-CoV2 RNA otherwise undetectable in plasma, was found to be positive in EV in 12.5% of COVID19 positive patients. Interestingly, significantly prolonged and high viral load was found in EV at day 14 in CLD-COVID19 patients compared to COVID19 alone (p=0.002). The high cellular injury was seen in CLDCOVID19 infected patients with significant high levels of EV associated with epithelial cells and hepatocytes than COVID19 alone (p=0.004;0.001). Conclusion: Identification of SARS-CoV2 RNA in EV, in RT-PCR negative patients indicates persistence of infection for and likely recurrence of the infection. It is suggestive of another route of transmission as EV harbour SARS CoV2 RNA. EV associated RNA may determine the ongoing inflammation and clinical course of subjects with undetectable SARS-CoV2 virus and this may also have relevance in management of chronic liver disease patients.

Limited usage of prednisolone: Severe alcoholic hepatitis beyond steroids, a path to be explored!

Background: Steroids are mainstay of treatment in severe alcoholic hepatitis and steroid ineligibility is major cause of mortality, specially in the absence of transplant option. There is paucity of data on the proportion and causes of steroid ineligibility, and the natural history and outcome in such patients.This data would help in planning alternative therapeutic strategies.We aimed to study the factors responsible for steroid ineligibility and clinical course of these patients. Methods: Consecutive patients of SAH admitted to the Institute of Liver and Biliary Sciences, between April 2017 to February 2021 were screened for steroid eligibility. All patients who left against medical advice or had likelihood of death within 24 hours of admission, were excluded. The criteria for ineligibility were MDF >90,Acute kidney injury, sepsis, extrahepatic organ failures or severe comorbidities. The patients who developed an event in the hospital or were discharged were followed for 90days survival. Results: Altogether,522 patients were admitted with SAH,138(26.4%) were steroid eligible and 384(73.6%) were ineligible(figure 1).The main reasons for steroid ineligibility were: one or more organ failures in 179(46.7%) patient, with 37(9.6%), 71(18.4%), 28(7.2%) and 43(11.1%) patients having 4,3,2 and 1 organ failures respectively. Specifically, 28.3%(109) patients had AKI, 31.8% (122) had respiratory failure, 33.5% (129) had circulatory failure, 39.3%(159) had grade 3 or more encephalopathy. In addition, 32(8.3%) patients had a DF of >90, 27(7.0%) patients had recent upper GI bleed,25/384(6.5%) had superadded acute viral hepatitis ,20(5.2%) patients had severe alcohol withdrawal and 7(1.8%) had SBP. 15(4%) patients were not given steroid due to spontaneous reduction in mDF to <32 after admission. Further, 42(10.9%) patients were either found to spontaneously improve during the period of evaluation and hence were not taken up for steroid therapy. 37(9.6%) patients were not given steroids due urinary infection, continuous fever, cellulitis, mild COVID and active tuberculosis. The overall survival in the steroid ineligible cohort at day 90 was 54.4%, while the 28 day survival was 58.5%. On multivariate Analysis the presence of any organ failure, Age, albumin, AARC score, Presence of variceal bleed increase the risk of mortality (table1). 42 patients had spontaneously resolving jaundice were not given steroids, out of them 6 patients were readmitted and required the therapy. None of them died on follow up at day 90. Twenty patients had alcohol withdrawal at presentation;6 of them subsequently received steroids. Conclusion: Almost two-third patients with SAH are not eligible to receive steroids and carry a high 90 days mortality. The age, albumin, AARC score, variceal bleed and presence of organ failure predict mortality in steroid non exposed SAH patients. RCT's are needed for comparing various therapies used in such patients. .

Study of efficacy, immune response and safety of chadox1 ncov- 19/covishield vaccine in liver transplant recipients from tertiary care centre in india

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is not associated with an increased mortality in liver transplant (LT) recipients;however, they are at high-risk of severe COVID-19 complications. The efficacy or safety of COVID-19 vaccines have not been described in LT recipients and immunogenicity of vaccines against COVID-19 may be lower in liver transplant recipients as age, lower glomerular filtration rate, and enhanced immunesuppression are predictors of poor response to vaccination. We studied the safety and immunogenicity of ChAdOx1 nCoV- 19/Covishield vaccine in LT recipients. Methods: We enrolled 15 LT recipients, two doses of ChAdOx1 nCoV- 19/Covishield vaccine were administered at an interval of 4-6 weeks. To assess the immune response, samples were collected at baseline, 28 days then 14 days after second dose to measure the SARS Cov2 S1 anti-spike total antibody (IgG, IgM and IgA), S1 Anti-spike RBD IgG and Surrogate neuralization assay were done. Adverse events following immunization (AEFI) and breakthrough infections were documented. Results: Of the 15 patients enrolled, mean age was 55 years (IQR 46-76), with male predominance (86.7%), median duration after transplant was 1611 days (IQR 630- 3931). Blood group B was most common (53.3%), followed by 0 (20%), A and ab (26.6%). 3 LT recipients had prior infection 8 months before and 3 developed breakthrough infection after first dose which were mild. Baseline antibodies were positive in 5, suggesting asymptomatic infection in 2 patients. 2 patients not mounting an IgG response even 14 days after 2nd dose were non-responders, 7 seroconverted to medium level antibodies (6.31-12.3 S/CO) and 1 developed a high antibody response (18.6 S/CO). Neutralizing antibodies were present in 66.6% of the cases. No serious AEFI were reported, mild diarrhoea and fever were reported in 1 case each. Conclusion: This is the first study on immune response and safety of ChAdOx1 nCoV- 19/Covishield vaccine in LT recipients. Vaccine was well tolerated with no serious adverse event in LT recipients and even single dose gave protection against serious disease. Protective immune response was seen in two third of the patients. One third had no or inadequate immune response making them vulnerable to risk of serious SARS CoV2 infection.

Graft injury and neutrophil lymphocyte ratio predicts the severity and survival due to COVID 19 among liver transplant recipients - Multicentre results from apcolis-lt study

Background: Liver Transplant recipients have an increased susceptibility to SARS CoV2 infection with a possible more severe disease course. There is paucity of data of SARSCoV2 infection in this cohort from Asia. We report on the data of an on-going APCOLIS-1 (APASL Liver Injury Spectrum, APCOLIS) registry with the aim to define the profile, risk factors for severity and predictors of survival among the liver transplant recipients. Methods: In a multinational study, data was recorded between April 2020 to May 2021 across 13 countries in Asia. The data was compiled on a survey monkey under the APASL COVID-19 study task force [NCT04345640]. We performed multivariate logistic regression to identify independent predictors of severity and all cause mortality among the liver transplant (LT) recipients suffering from COVID-19. Results: Altogether, 130 LT recipients were enrolled [mean age 53 ± 12 years, median post-transplant period, 54 months (range 2-77 months)]. Majority (92, 71% ) of the patients had undergone live-donor transplant. Severe COVID was seen in 21/130 (16%) and 17/130 (13%) required ICU care. COVID related organ failures (OF) were seen in 17 patients (13%), predominantly as respiratory (16/21, 76.2%) followed by renal (9/21, 42.8%) and circulatory (5/21, 23.8%) with ventilatory requirement in 12/21 (57.1%) of the severe cases. Among the baseline parameters age [HR=1.08, 95CI 1.01-1.16, p=0.03], presentation with dyspnea [HR=6.34, 95CI 1.78-22.9, p=0.004] and Neutrophil to Lymphocyte ratio (NLR) [HR=1.08, 95CI 1.01-1.17, p=0.04] independently predicted a severe course of the COVID-19 among LT recipients. The baseline NLR of 8.47 ± 1.45 peaked to 17.94 ± 3.68 in median of 15 days (range 1-37) among severe cases [p<0.001] indicating rapid progression of disease. Age above 55 years increased the disease severity with AUROC of 0.78, sensitivity of 72.7% and specificity of 74.8%. Time from LT, immunosuppression dosage or presence of co-morbidities did not influence the outcome. Graft dysfunction was seen in 21/130 (16%);predominantly as acute cellular rejection in 13/130 (10%) and graft failure 7/130 (5%). The all cause mortality was 8% (11/130). Among non-survivors, the baseline NLR of 4.88 ± 1.63 increased to a peak value of 25.14 ± 5.49 [p<0.001] i.e 5 folds. The baseline NLR [HR=1.17, 95CI 1.03-1.34, p=0.02], development of graft injury [HR=27.21, 95CI 2.55-290., p=0.006] and COVID related OF [ HR=21.87, 95CI 2.39-203.85, p=0.007] independently predicted mortality due to SARSCoV2 infection. Conclusion: COVID-19 infection precipitates a severe disease course in one fifth of the liver transplant recipients, leading to graft dysfunction and early mortality. LT recipients above 55 years of age, presenting with dyspnea and high NLR need to be specifically watched for a progressive disease course. Dynamic NLR determination can help in early stratification and referral to a specialized liver unit to improve outcomes.

Profile of sars cov2 infection among liver transplant recipients across asia pacific

Background: COVID-19 among liver transplant (LT) recipients varies with symptoms, severity, time from LT and with treatment from region to region. Here-with we report the clinical presentation, spectrum of disease and outcome from the Asia Pacific region. Methods: In this multinational study, data was recorded between April 2020 to May 2021 across 13 countries in Asia. The data was compiled on survey monkey under the APASL COVID-19 study task force [NCT04345640]. Severity of COVID infection was defined as per WHO guidelines. We analysed symptoms, demography, treatment, clinical course and treatment among LT patients with COVID-19. Results: Among a total 130 LT patients, males were 117 with mean age of 53±12 years and majority were live donor transplant (92,71%). The most common etiology of liver disease was ethanol (37, 28%) followed by NASH (28,22%) and cryptogenic(21,16%). Median post LT period was 54 months. Co-morbidity was present in 101 patients (78%), the most common being obesity (61,47%),followed by Diabetes (56,43%) and hypertension(30,23%). The presenting complaints were fever(82%), cough(61%), dyspnoea(29%) and diarrhoea(7%);8% were asymptomatic. Respiratory distress was seen in 29 (22%) cases;17 received only oxygen and 12 needed ventilator support. Prior to illness, only CNI was used as immunosuppressant in 30% (39), CNI & MMF in 31% (40) and in another 31% (40) mTOR inhibitors alone or with a CNI and triple regimen in 9%. During COVID, only low dose steroid was used in 50% (64), low dose CNI in mild to moderate ( 32%,41), complete avoidance of MMF in 4% cases where as low dose CNI and MMF in 16% (20) patients. Immunosuppression reintroduction done in 68% to pre-COVID dose and 28% were maintained on low dose CNI with steroids with close monitoring of LFT and pre-COVID dose was restarted after 14 days of recovery .4% had graft dysfunction leading to early augmentation of immunosuppression. Any antiviral was received by 36%, convalescent plasma by 26% and immunomodulators like tocilizumab or bevacizumab in 13%. Home care offered to 46% cases while those admitted, 41% were managed in ward only and 13% needed ICU admission. Graft function was unaffected in majority (109, 84%) but Acute Cellular Rejection was noted in 10% cases and DILI or other causes in 6%. Liver injury in the form of raised transaminases or bilirubin was noted in 19% at hospital stay and in 40% at presentation. Severe COVID was in 16% (21) cases with mortality in 8% (11). Conclusion: Compared to general population post-LT patients have an increased mortality due to COVID. Home based care could be feasible in only half of the patients.

Psychosocial difficulties and quality of life in liver transplant recipients during the COVID-19 pandemic

Background: The pandemic of COVID-19 devastated the global community, not only related to illnes but also the other domains i e physical, mental and social aspect too The liver transplant recepients, who supposed to be vulnerable and also need close monitoring as well as support must have been affected The aim of this study was to identify the anxiety, psychosocial difficulties and post-transplant quality of life during the COVID-19 pandemic Methods: A cross-sectional survey was conducted on Liver transplant recipients with informed consent through questionnaire circulated to them The structured questionnaire includes clinical and demographic variables, psychosocial difficulties during COVID-19 pandemic and by using the COVID-19 anxiety scale and Post-Transplant Quality of life questionnaire (pTQOL- 32 item for last 4 weeks) Results: A total of 109 patients completed the study questionnaire The mean age of the participants was 50 49 (± 11 08) years with 88% being males;and a median duration from transplant was 52 37 months The majority had a Live donor liver transplant (79 8%) from a family member Almost all (99 1 %) were on regular follow up and treatment prior to the pandemic Only 57% could able to maintain planned hospital visit, 7 3% couldn't be able to attend the hospital as desired by the treating unit where as 16 5% had fear of COVID-19 infection upon hospital visit and 26 6% opted for tele-consultation during this period Upto 88% could not pursue their regular activities, 39 % could not continue the routine exercise and physiotherapy due to imposed restrictions The economic impact was noted with 3.7% find difficulties for supporting the drug expenses and about 7 3% managed by the immmusuprresants and curtailing the other supportives During this peroid 4 6% had a deranged liver function test requring immeduate attention and 1 patient had COVID-19 The COVID anxiety was not much, but the median psychosocial difficulty score was 18 and mean total pLTQ score was 41 75 (± 33 76) , suggesting the stress of SARS CoV2 on daily life Conclusion: The COVID-19 pandemic had a toll on post liver transplant recepients in terms of significant psychosocial difficulties and poor quality life This in addition to physical and medical conditions needs worth attention Awareness campaigns and comprehensive is an unmet need for a holistic care of this previledged cohort.

COVID-19 and gastroenterology: clinical insights and recommendations for gastroenterology care providers.

While the COVID-19 pandemic evolves, we are beginning to understand the role the gastrointestinal tract plays in the disease and the impact of the infection on the care of patients with gastrointestinal (GI) and liver diseases. We review the data and understanding around the virus related to the digestive tract, impact of the pandemic on delivery of GI services and daily gastroenterology clinical practice, and the effects on patients with pre-existing GI diseases.