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).

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.

NOTTO guidelines for vaccine-induced thrombotic thrombocytopenia in organ donation and transplantation

From the context of organ donation, COVID-19 vaccine-induced thrombotic thrombocytopenia (VITT) is important as there is an ethical dilemma in utilizing versus discarding organs from potential donors succumbing to VITT. This consensus statement is an attempt by the National Organ and Tissue Transplant Organization (NOTTO) apex technical committees, India, to formulate the guidelines for deceased organ donation and transplantation in relation to VITT to help in appropriate decision-making. VITT is a rare entity, but a meticulous approach should be taken by the organ procurement organization's (OPO) team in screening such cases. All such cases must be strictly notified to the national authorities (NOTTO) as a resource for data collection and ensuring compliance with protocols in the management of adverse events following immunization. Organs from any patient who developed thrombotic events up to 4 weeks after adenoviral vector-based vaccination should be considered to be linked to VITT and investigated appropriately. The viability of the organs must be thoroughly checked by the OPO, and the final decision in relation to organ use should be decided by the expert committee of the OPO team consisting of a virologist, a hematologist, and a treating team. Considering the organ shortage, in case of suspected/confirmed VITT, both clinicians and patients should consider the riskbenefit equation based on limited experience. An appropriate written informed consent of potential recipients and family members should be obtained before the transplantation of organs from suspected or proven VITT donors.

Challenges of CAD for thorax diseases including Covid-19 by using artificial intelligence

Artificial Intelligence(AI) is simulation of human intelligence in machines. It is programmed such that it can think as human and perform actions or take appropriate decision. In current covid-19 pandemic, its important to diagnosis more asymptomatic people to save their life. There various diseases related to thorax such as pneumonia, lung cancer, COPD(Chronic Obstructive Pulmonary Disease). Its leading death cause in world. Even fetus are also effected by pneumonia from birth times. The remote area people also can be saved by proper diagnosis on time by using CAD(Computer Assisted Detection). There is some challenges in training of algorithm in AI to give more accuracy. In this paper those issues such as class imbalance, multi task and data size are discussed with solutions for each problem. Different diseases, which look similar by radiologist can be detected in early stage. The pre-processing and finetuning of thorax x-ray is done before applying to CNN(convolutional neural network). Loss functions are calculated with proper weightage value. So that algorithm work even in small training set. © 2021 Author(s).

Optimal diagnostic tool for surveillance of oesophageal varices during COVID-19 pandemic.

AIM: To study the diagnostic accuracy and utility of triphasic abdominal computed tomography (CT) in the diagnosis and grading of oesophageal varices (OVs) as an alternative to endoscopy during the COVID-19 pandemic. MATERIALS AND METHODS: A prospective analysis was undertaken of retrospective data from cirrhotic patients who underwent oesophago-gastro-duodenoscopy (OGD) and a triphasic abdominal CT from January to December 2019. Endoscopists and radiologists provided their respective independent assessment of OV grading after being blinded to the clinical details. Performance of CT grading of OVs was compared with the reference standard endoscopic grading using weighted kappa (k). Non-invasive scores such, as aspartate transaminase (AST)-to-platelet ratio index (APRI), Fibrosis-4 (FIB-4) Index, platelet: spleen (PS) ratio were correlated between the two techniques. RESULTS: OV grading between endoscopists and radiologists showed 81.73% agreement (85 out of 104 patients) in the comparative analysis of 104 cirrhotic patients, of which no varices (57.1%, n=4), small (85.1%, n=23), medium (72.2%%, n=26), and large varices (94.1%, n=32) with a weighted k score of 0.88 (95% confidence interval 0.82-0.94). Overall, the sensitivity of CT in the diagnosis of no, small, medium, and large OVs was 66.6%, 79.3%, 89.6%, and 94.1%, respectively, with an area under the receiver operating curve (AUROC) score of 0.775, 0.887, 0.839, and 0.914. Performance of APRI, FIB-4, and PS ratio correlated well with the severity of OVs with no difference between OGD and CT grading. CONCLUSION: Triphasic abdominal CT can be an invaluable tool in the diagnosis and grading of OVs during the COVID-19 pandemic.

COVID-19 lockdown: impact on liver transplant recipients - a single centre survey

We conducted a short survey amongst liver transplant recipients to assess the impact and challenges faced during COVID-19 lockdown. Results were analysed using SPSS V 17.0. Chi-square test was utilized to compare variables between the two time periods. A P-value of <0.05 was considered statistically significant. We conducted a short survey amongst liver transplant recipients to assess the impact and challenges faced during COVID-19 lockdown. Results were analysed using SPSS V 17.0. Chi-square test was utilized to compare variables between the two time periods. Whereas, physical exercise (84.5[%] vs 71.4[%], P=0.04), occupation (53.6[%] vs 23.8[%], P=0.00), problems accessing pharmacy (2.4[%] vs 38.1[%], P=0.00), access to emergency doctors (95.2[%] vs 77.4[%], P=0.00), laboratory investigations (98.8[%] vs 46.4[%], P=0.00) and transplant centre (95.2[%] vs 78.6[%], P=0.00) were significantly affected during the lockdown period. Lockdown has significantly affected physical exercise of transplant recipients and the reasons were 'scared of COVID-19' and 'lack of space for exercise'. In patients who carried out physical exercise, the majority (68 patients) switched to indoor walking. Twenty-five (32.6[%]) patients reported a median 3 (1-5) kilograms weight gain in 3 weeks;75[%] of them gained more than 2 kilograms during the same period. Thirty-two (38.0[%]) patients reported difficult accessibility to pharmacy and commonly reported reasons were 'non-availability of immunosuppressive drugs' (17 patients) and 'lack of transport' (15 patients). Similarly, patients who were unable to carry out laboratory tests reasoned out 'accessibility and transport challenges. With accessibility to local emergency doctors and transplant centre most patients reported, 'no necessity at present'. WHO recommended measures of self-hygiene to reduce COVID-19, such as regular hand washing, wearing mask, social distancing was carried out by 82 (97.6[%]), 45 (53.6[%]) and 80 (95.2[%]), respectively. Interestingly only 23 (46.9[%]) were confined indoors during the lockdown period.