LABORATORY PARAMETERS ASSOCIATED WITH CODIV-19 CYTOKINE STORM DEVELOPMENT

BackgroundSince the end of 2019, physicians became more and more familiar with SARS-CoV-2 infection and the variety of forms in which it may present and evolve. There have been a lot of studies trying to understand and predict why some patients develop a dysregulation of the immune response, with an exaggerated release of pro-inflammatory cytokines, called cytokine storm (1–4). There is scarce evidence in Romania regarding this aspect.ObjectivesThis study aims to verify the correlation between some laboratory parameters and the development of cytokine storm in SARS-CoV-2 infection in a cohort of over 200 patients admitted in a tertiary hospital from Romania, hoping that early identification of these risk factors of progression to a severe form of the disease can bring considerable benefit to patient care.MethodsThis is an analytical, observational, case-control study which includes 219 patients (all COVID-19 hospitalized patients on the Internal Medicine 3 department of Colentina Clinical Hospital, Bucharest, from 01 March 2020 to 1 April 2021). A series of data were collected, the laboratory parameters being the most important, including: albumin, lymphocyte (percentage), neutrophil (absolute value), aspartate aminotransferase, alanine aminotransferase, D-dimers, lactate dehydrogenase (LDH), anionic gap, chloremia, potassium and the BUN:creatinine ratio (BUN - blood urea nitrogen). The laboratory parameters used for the statistical analysis represent the average values of the first 7 days of hospitalization for those who did not develop cytokine storm, respectively until the day of its development, for the others. Patients were classified into these groups, those who developed cytokine storm, respectively those who did not have this complication taking into account the clinical and paraclinical criteria (impairment of respiratory function, elevations of certain markers 2-3 times above the upper limit of normal, those who died as a result of SARS-CoV-2 infection). Then Binary Univariate Logistic Regression was applied in order to verify the individual impact of every laboratory parameter on cytokine storm development. Furthermore, all laboratory parameters were subsequently included in the multivariate analysis, using the backward selection technique to achieve a model as predictive as possible.ResultsWe mention that the analysis of demographic data was previously performed, showing no statistically significant relationship between patient gender, age or comorbidities (history of neoplasm, lung diseases, cardiac pathology, obesity, type II diabetes and hypertension) and their evolution to cytokine storm. After performing binary univariate logistic regression we concluded that 8 of the 13 laboratory analyzes have had a significant change between groups (ferritin, PCR, albumin, Lymphocyte, Neutrophils, TGO, LDH, BUN:creatinine ratio). Only 150 patients were then included in the multivariate analysis. After the analysis, some of the variables lost their statistical significance, the final model including C-reactive protein, neutrophilia, LDH, ferritin and the BUN:creatinine ratio. This model correctly predicts the development of cytokine storm in 88% of cases.ConclusionHigh C-reactive protein, neutrophilia, LDH, ferritin and the BUN:creatinine ratio are risk factors for cytokine storm development and should be monitored in all COVID-19 patients in order to predict their evolution.References[1]Pedersen SF et all. SARS-CoV-2: A storm is raging[2]Mehta P et al. COVID-19: consider cytokine storm syndromes and immunosuppression[3]Hu B et al. The cytokine storm and COVID-19.[4]Caricchio R et al. Preliminary predictive criteria for COVID-19 cytokine stormAcknowledgements:NIL.Disclosure of InterestsNone Declared.

SWITCHING FROM IL-6R ANTAGONISTS TO OLOKIZUMAB, A DIRECT IL-6 INHIBITOR

BackgroundOlokizumab (OKZ), an IL-6 ligand inhibitor in doses of 64 mg every two weeks (q2w) or every 4 weeks (q4w) demonstrated significant improvements in signs and symptoms of RA. Due to lack of availability of the IL-6 receptor antagonists tocilizumab and sarilumab in the pandemic COVID-19 situation, RA patients (pts) were switched to OKZ as a registered drug in Russia in 2022.ObjectivesTo investigate safety and efficacy of OKZ after switching from an IL-6 receptor inhibitor in clinical practice.MethodsThis retrospective cohort study included available efficacy and safety data of OKZ in pts with RA after switching from tocilizumab (IV or SC) or sarilumab (SC) from 11 of participating centers.Efficacy assessments and routine biochemical data were analyzed using descriptive statistics – mean with standard deviation for continuous parameters and absolute and relative frequency for binary variables. AE were reported by participating centers according to pt's files. The statistical significance of data of the analyzed variable at a particular visit compared with previous visits or with the Switch visit was determined using paired t-test. Fisher's exact test or chi-square test was used to compare the proportion of pts with improvement/no change and worsening. All tests were 2-tailed, and a p-value <0.050 was considered statistically significant. As this is an observational study, the statistical criteria have not been pre-specified and therefore the data presented cannot be considered definitive but should be confirmed in future analyses.ResultsEfficacy and safety results were collected for 110 RA pts with a mean age of 47.8 (15.7) years, including 87 (79.1%) women. 77 (70.0%) pts were RF/ACPA positive. Mean RA duration was 13.1 (8.9) years and mean duration of treatment with an IL-6 receptor antagonist was 47.8 (30.0) months. Mean interval before switching was 54.7 (35.4) days with the main reason of unavailable IL6-R antagonist. Pts were treated with OKZ 64 mg q4w SC.Before initiation of OKZ, an increase of DAS28-CRP was observed due to a prolonged period after the last injection of the IL-6R inhibitor from 2.8 to 3.1 weeks in 32 pts on monotherapy who were transferred to OKZ faster (on average after 41.6 (23.8) days), and from 2.7 to 3.3 weeks in 73 pts on concomitant sDMARDs (60.0 (38.0) days). DAS28-CRP was improved to 2.8 on the second OKZ visit (S+1) in both groups. Response to OKZ was maintained over a period of 2 months with no difference between pts previously receiving an IL-6 R antagonist. Of note, lower disease activity based on DAS28-CRP of 2.5 and 2.6 was achieved after 8 weeks (S+2) of OKZ therapy compared to the previous IL-6R inhibitors treatment S-1 visit (P less 0.05) (Figure 1).Figure 1.Mean DAS28CRP over time, M(SD)[Figure omitted. See PDF]Abbreviation: S-2 and S-1 last visits before switching– S+1 and S+2 visits after switching,Treatment emergent AE occurred in 7 (6.4%) pts, the most common AE in 3 pts (2.7%) included arthralgia of hands and feet and transient leukopenia in 2 (1.8%) pts.Serious AE were reported by 1 (0.9%) pt (exacerbation of herpes infection that led to treatment discontinuation). No deaths were reported. There were no apparent differences in safety and efficacy outcomes between pts on OKZ monotherapy compared to combined treatment with csDMARDs. Only one pt was switched back to tocilizumab when it became available.Table 1.Summary of treatment emergent adverse events (safety population)NOKZ 64 mg q4w with MTX N=78OKZ 64 mg q4w monotherapy N=32Any AE51 carpal canal syndromeAny serious AE10Any AE leading to discontinuation of study drug10Any death00Any AE of special interest10Infections10Laboratory abnormalitiesHyperbilirubin-emiaALT, AST elevation less than 3 ULNALT, alanine transaminase;AST, aspartate transaminase;ULN, upper limit of normalConclusionIn pts with RA responding to an IL-6R antagonist, switching to OKZ was safe and well tolerated in clinical practice. The treatment response was maintained and in some pts disease activity moderately decreased in compariso to baseline level both in OKZ mono and combination therapy.Reference[1]J.Smolen, N Engl J Med 2022;387:715-726AcknowledgementsI have acknowledgements to Vinogradova I.B., Anoshenkova O.N., Antipova O.V., Baranov A.A., Bogdanova E.A., Grabovetskaya Y.Y., Ilivanova E.P.,Kalyagin A.N., Kushnir I.N., Lapkina N.A. Mokrousova M.V., Nesmeyanova O.B., Nikitina N.V., Shesternya P.A. and Yudina N.V.Disclosure of InterestsEugen Feist Consultant of: Abbvie, Eli Lilly, Galapagos, Medac, Novartis, Sanofi, Sobi, R-Pharm, Grant/research support from: Eli Lilly, Novartis, Pfizer, Evgeny Nasonov Consultant of: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer.

The Spectrum of COVID-19-Induced Liver Injury in Various Age and Risk Groups.

Coronavirus disease 2019 (COVID-19) has inflicted significant mortality and morbidity worldwide since the virus was first detected towards the end of 2019. Though it primarily affects the respiratory system, COVID-19 has been shown to have a multisystem effect. There have been literature on liver injury associated with COVID-19 in general but liver injury specific to certain risk and age groups needs to be looked into. Thus, we aim to discuss the liver injury associated with COVID-19 in various age and risk groups and revisit pathophysiology, biochemical markers and their correlation with outcomes, and current management recommendations.

Evaluation of De Ritis (AST/ALT), ALP/ALT, and AST/ALP ratios as prognostic factors in patients with acute ischemic stroke.

BACKGROUND: Stroke is one of the leading causes of disability worldwide. Recently, stroke prognosis estimation has received much attention. This study investigates the prognostic role of aspartate transaminase/alanine transaminase (De Ritis, AAR), alkaline phosphatase/alanine transaminase (ALP/ALT), and aspartate transaminase/alkaline phosphatase (AST/ALP) ratios in acute ischemic stroke (AIS). METHODS: This retrospective cohort study involved patients who experienced their first-ever AIS between September 2019 and June 2021. Clinical and laboratory data were collected within the first 24 hours after admission. Functional and mortality outcomes were evaluated 90 days after hospital discharge in clinical follow-up. Functional outcome was assessed by a modified Rankin Scale (mRS). The correlation between the laboratory data and study outcomes was evaluated using univariate analysis. In addition, regression models were developed to evaluate the predictive role of AST/ALP, ALP/ALT, and AAR ratios on the study outcomes. RESULTS: Two hundred seventy-seven patients (mean age 69.10 ± 13.55, 53.1% female) were included. According to univariate analysis, there was a weak association between 3-months mRS, and both AST/ALT (r = 0.222, P < 0.001), and AST/ALP (r = 0.164, P = 0.008). Subsequently, higher levels of these ratios and absolute values of AST, ALT, and ALP were reported in deceased patients. Based on regression models adjusted with co-variable (age, gender, underlying disease, and history of smoking) AST/ALT and AST/ALP ratios had a significant independent association with 3-month mRS (CI:1.37-4.52, p = 0.003, and CI: 4.45-11,547.32, p = 0.007, respectively) and mortality (CI: 0.17-1.06, adjusted R2 = 0.21, p = 0.007, and CI: 0.10-2.91, p = 0.035, adjusted R2 = 0.20, respectively). CONCLUSIONS: Elevated AST/ALP and AAR ratios at admission were correlated with poorer outcomes at 3 months in patients with first-ever AIS. Prospective studies in larger cohorts are required to confirm our findings and to evaluate further whether the AST/ALP and De Ritis ratios may represent a useful tool for determining the prognosis of AIS patients.

Outcome of children on the UK national prioritised paediatric registration tier

P69 Table 1Demographic and transplant data for all 14 prioritised patientsPatient/Sex Centre Age at registration (yrs) Primary liver disease Registered prior to Prioritisation Indication of Prioritization LT Waiting time on prioritised tier/Time on list prior to prioritisation 1/M 1 0 CDG Yes Acute decompensation with presence of encephalopathy Yes/LLS 5/27 2/M 2 1 Cryptogenic Cirrhosis Yes CLD with nodular lesions s/o HCC Yes/LLS 16/48 3/F 1 15 AILD Yes Chronic rejection Yes/whole liver 3/4 4/M 2 0 Biliary Atresia Yes PTLD/HAT/Sepsis Yes/LLS 14/71 5/F 2 4 IFALD No Coagulopathy with active bleeding/Renal impairment Yes/LLS 15/820 6/F 2 0 Biliary Atresia Yes Acute decompensation due to portal hypertension Yes/LLS 37/405 7/M 2 10 NSC Yes Decompensated chronic liver disease/Renal impairment Yes/reduced R lobe 4/7 8/M 3 8 PFIC3 Yes Acute decompensation of Chronic liver disease Yes/LLS 6/51 9/F 1 0 Other (Hepatoblastoma) Intestinal Tx prioritized Acute decompensation of Chronic liver disease Yes/LLS 11/ 10/F 2 0 Biliary atresia Yes Decompensated Chronic Liver Disease with Severe Coagulopathy Yes/LLS 10/120 11/M 1 0 Biliary atresia (Hepatoblastoma) Yes Acute decompensation of Chronic liver disease Yes/LLS 9/4 12/F 3 0 Biliary atresia Yes Acute decompensation of Chronic liver disease Yes/LLS 12/323 13/F 1 17 Hepatic Artery thrombosis Yes Hepatic Artery thrombosis Yes/whole liver 2/ 14/F 2 0 Biliary atresia Yes Acute decompensation of Chronic liver disease Suspended 12/65 PFIC3;Progressive Familial Intrahepatic Cholestasis type 3, LT;Liver transplantation, HCC;Hepatocellular Carcinoma NSC;Neonatal Sclerosing Cholangitis, CDG;Congenital Disorder of Glycosylation, AILD;Autoimmune Liver Disease, IFALD;Intestinal Failure Associated Liver Disease,PTLD;Center 1-Kings;Center2-Birmingham;Center3-Leeds.ConclusionThe national paediatric prioritization tier, introduced during the COVID19 pandemic, has been a pivotal initiative for the UK paediatric LT program, showcasing national collaboration. All patients underwent a LT successfully within a short time from prioritization with 100% patient and graft survival. The intention is to maintain this prioritized paediatric tier beyond the pandemic.

Ivermectin-Induced Liver Injury when Used as Self-Medication in SARS-CoV-2 Infection: An International Journal of Medical Toxicology and Drug Experience

Introduction: In the context of the global health emergency due to SARS-CoV-2 pandemic, ivermectin has been repurposed in some Latin American countries to treat COVID-19;in these countries its use as self-medication has been frequent (1). Ivermectin-induced liver injury, though extremely rare(2,3), had been previously described even before the COVID-19 pandemic Objective: To characterize clinical features of liver injury associated with ivermectin when used as self-medication for treating COVID-19. Methods: Clinical records of those patients diagnosed with severe COVID-19 at the Emergency Room in Rebagliati Hospital in Lima, Peru, during March 2021, were carefully revised. To establish diagnosis of drug-induced liver injury (DILI) and causality assessment, the criteria of DILI-Expert Working Group and the Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method (CIOMS/RUCAM), respectively, were used Results: Out of 327 patients identified, 38 took ivermectin as selfmedication (11%);of those 38, five were diagnosed with liver injury presumably related to that medication (13.2%). The mean age of those patients who developed the condition was 49.3 (12.3) [men, 4;woman, 1]. The mean (standard deviation) of Tomographic Severity Score (TSS), C-reactive protein, ferritin levels, Lymphocyte count and D-dimer were 52.2% (22.6), 13.8 (12.2) mg/dl, 1325.375 (239.7072) ng/ml, 2.0 (2.0) K/pl and 0.9 (0.7) pg/ml. The patients had no identified risk factors, but two;one patient had type I diabetes mellitus, and other, obesity. Mean daily ivermectin dose, duration, and total ivermectin dose were 32.9 (21.8) mg/day, 2.6 (0.6) days, and 89.6 (71.4) mg, respectively. As an average, liver injury occurred 11 (3.8) days after the start of treatment, none developed jaundice. Mean levels of alanine aminotransferase, alkaline phosphatase, gammaglutamyltransferase were increased 8 (4.4), 1.66 (0.9), 10.9 (5.0) times above the upper limit of normal. Two patients presented a hepatocellular pattern, 2 mixed and 1 cholestatic. All cases were mild and recovered. As for causality assessment, 4 cases were considered as possible, and one, as highly probable. Conclusion: Given its widespread use in some countries, ivermectininduced liver injury requires further pharmacovigilance studies when used for treating COVID-19.

Hepatic Disorders in Adults Associated with the Use of Ivermectin for SARS-CoV-2 Infection: A Pharmacovigilance Study in VigiBase: An International Journal of Medical Toxicology and Drug Experience

Introduction: In the face of the global health emergency due to SARS-CoV-2, Ivermectin has been, among other drugs, repurposed in some Latin American countries to treat COVID-19 [1]. Studies are needed on the safety of Ivermectin for this new indication. VigiBase is the WHO pharmacovigilance database that registers all Individual Case Safety Reports (ICSRs) from more than 130 countries. Objective: To review in VigiBase the reports of serious hepatic disorders in adults associated with the use of Ivermectin for COVID19. Methods: We extracted, in men or women aged > 18 years between 1 January 2020 and 7 march 2021, all ICSRs registered as serious associated with the use of ivermectin, and established the prevalence of serious hepatic disorders when Ivermectin was indicated for COVID-19 Results: During the study period, there were 1,393 ICSRs in VigiBase associated with Ivermectin, of which 60 (4.3%) were registered as serious;in 25 of those, Ivermectin had been used for COVID-19. Out of those 25, five reported serious cases of hepatic disorders (hepatitis, hepatocellular injury, cholestasis, increased alanine aminotransferase and aspartate aminotransferase, abnormal liver function test). Three patients were male and overall mean age was 59.2 ± 9.7 years. Ivermectin was administered during a mean of 2.5 ± 2.4 days, and the mean daily dose was 14.3 ± 2.9 mg. Two patients simultaneously received other drugs (Remdesivir, Hydroxychloroquine, Azithromycin). Two patients had concurrent conditions (strongyloidiasis, diabetes mellitus). Only in 2 patients liver enzyme data were reported. In all patients the evolution was favorable after stopping the drug (de-challenge), and no patient was re-exposed (rechallenge). Causality analysis was reported in 3 cases, qualifying as possible or probable. Conclusion: The safety of the use of Ivermectin should be studied more exhaustively, especially as regards the probability of hepatic disorders when used for COVID-19

Safety Profile of Antiviral Therapies for the Early Treatment/ Prevention of COVID-19: Analysis of the International Pharmacovigilance Database VigiBase: An International Journal of Medical Toxicology and Drug Experience

Introduction: After many months from the COVID-19 pandemic beginning, several anti-spike monoclonal antibodies (mAbs) and, more recently, other antiviral drugs for COVID-19 treatment in non-hospitalized patients have been marketed. Specifically, those drugs are indicated for SARS-CoV-2 infection early treatment in outpatient adults at high risk of developing severe COVID-19 [1]. Objective: To evaluate the post-marketing safety profile of antivirals drugs used for early COVID-19 treatment, using the World Health Organization global spontaneous reporting database (VigiBase). Methods: From VigiBase we identified all the individual case safety reports (ICSRs) of marketed mAbs (regdanvimab, sotrovimab, casirivimab/imdevimab, bamlanivimab/etesevimab and, specifically for COVID-19 prevention in immunocompromised patients, tixagevimab/cilgavimab) and other antiviral therapies for COVID-19 early treatment (remdesivir, nirmatrelvir/ritonavir, molnupiravir). We performed a descriptive analysis of ICSRs recorded in VigiBase of patients' demographics (age, sex, continent of origin) type of reporter, adverse drug reactions (ADRs) (Preferred Term level) and the Important Medical Events (IMEs), from their marketing date to May 4, 2022. In addition, we conducted a disproportional analysis using Reporting Odds Ratio (ROR), along with 95% confidence intervals (CIs), by comparing the frequency of ADRs (System Organ Class level) for each drug of interest with distribution of all ADRs from the whole database, excluding vaccines, reported in the same period. Results: Overall, up to 4th May,2022, 15,437 ICSRs of anti-spike mAbs (casirivimab/imdevimab: 27.2%;bamlanivimab/etesevimab: 7.3%;sotrovimab 3.3%;tixagevimab/cilgavimab 2.7% regdanvimab: 0.2%) and other antivirals (remdesivir: 54.5%;nirmatrelvir/ritonavir: 4.3%;molnupiravir 0.5%) from VigiBase were retrieved. ICSRs mainly involved females and 45-64 years old. The percentage of ICSRs that included IMEs was 32.4%. Overall, the most frequently reported ADRs were infusion-related reaction for both casirivimab/imdevimab (20.1%) and bamlanivimab/etesevimab (19.3%), pyrexia for regdanvimab (30.0%) and sotrovimab (8.1%), increased alanine aminotransferase for remdesivir (13.3%), dysgeusia for nirmatrelvir/ritonavir (39.5%), and diarrhoea for molnupiravir (18.8%). Overall, statistically significant RORs were observed for "Investigations" with remdesivir (N = 3163;ROR: 5.56;95% CI 5.32-5.81), "Gastrointestinal disorders" for molnupiravir (N = 178;ROR: 3.43;95% CI 2.82-4.17) and "Vascular disorders" for sotrovimab (N = 51;ROR: 2.07;95% CI 1.55-2.76). Conclusion: This study shows that the safety profile of anti-spike mAbs and other newly marketed antiviral therapies for the early treatment of COVID-19 is overall favourable. The most frequently reported ADRs in VigiBase are in line with those reported in the pivotal trials and Summary of Product Characteristics for all investigated antiviral drugs. The disproportional analysis identified some potential signals requiring further investigation.

Hypoxia and R-factor: predictors of abnormal lft in covid-19

IDDF2022-ABS-0170 Table 1Demographics, comorbidities, laboratory investigations and clinical outcomes of COVID-19 patients stratified by ALT All (n=163) Status of ALT P-value¶ Characteristics Abnormal (n=50) Normal (n=113) Age in years, median (IQR) 56 (43–65) 60 (50–67) 55 (37–64) 0.022 Gender, n (%) 0.124 Male 96 (58.9) 34 (68.0) 62 (54.9) Female 67 (41.1) 16 (32.0) 51 (45.1) Ethnic group, n (%) 0.520 Chinese 98 (60.1) 34 (68.0) 64 (56.6) Malay 18 (11.0) 4 (8.0) 14 (12.4) Indian 20 (12.3) 6 (12.0) 14 (12.4) Others 27 (16.6) 6 (12.0) 21 (18.6) Comorbidities, n (%) Diabetes 32 (19.6) 13 (26.0) 19 (16.8) 0.201 Hyperlipidemia 57 (35.0) 24 (48.0) 33 (29.2) 0.032 Hypertension 61 (37.4) 26 (52.0) 35 (31.0) 0.014 Ischemic heart disease 15 (9.2) 7 (14.0) 8 (7.1) 0.238 Chronic liver disease 4 (2.5) 1 (2.0) 3 (2.7) 1.000 Charlson Comorbidity Index, median (IQR) 0 (0–1) 0 (0–1) 0 (0–1) 0.400 BMI, kg/m2, median (IQR), n=46 24.3 (23.2–27.9) 22.9 (22.1–24.2) 24.6 (23.6–28.7) 0.011 GI symptoms, n (%) Diarrhoea 29 (17.8) 12 (24.0) 17 (15.0) 0.186 Abdominal pain 4 (2.5) 0 (0.0) 4 (3.5) 0.313 Nausea/vomiting 10 (6.1) 0 (0.0) 10 (8.8) 0.032 Abnormal chest radiography on admission 55 (33.7) 22 (44.0) 33 (29.2) 0.074 Laboratory investigations on admission, median (IQR) ALT, U/L 23 (18–31) 29 (22–33) 21 (17–26) <0.0005 ALT/LDH ratio, n=162 0.05 (0.04–0.07) 0.06 (0.04–0.07) 0.05 (0.03–0.06) 0.039 ALP 72 (60–89) 72 (61–90) 72 (60–89) 0.700 R factor 0.94 (0.70–1.26) 1.15 (0.86–1.49) 0.87 (0.63–1.19) <0.0005 WBC, x109/L 4.70 (3.80–5.70) 4.75 (3.80–5.83) 4.70 (3.85–5.70) 0.844 Lymphocyte, x109/L 1.11 (0.84–1.49) 0.99 (0.74–1.23) 1.20 (0.87–1.65) 0.002 PLT, x 109/L 188 (150–225) 177 (142–223) 193 (155–226) 0.306 CRP, mg/L, n=162 10.75 (3.15–39.40) 30.10 (11.28–50.65) 6.85 (1.95–23.88) <0.0005 LDH, U/L, n=162 420 (350–547) 482 (378–572) 408 (342–525) 0.033 Creatinine, μmol/L 72 (61–87) 76 (65–88) 71 (59–87) 0.288 Albumin, g/L, n=156 39 (37–42) 39 (37–41) 40 (37–43) 0.044 BIL, μmol/L, n=152 11 (9–14) 11 (9–14) 12 (9–15) 0.555 Medication used, n (%) NSAIDs 22 (13.5) 4 (8.0) 18 (15.9) 0.218 β-lactam 47 (28.8) 22 (44.0) 25 (22.1) 0.008 Hydroxychloroquine 7 (4.3) 1 (2.0) 6 (5.3) 0.677 Lopinavir/Ritonavir (Kaletra) 25 (15.3) 16 (32.0) 9 (8.0) <0.0005 Remdesivir 12 (7.4) 5 (10.0) 7 (6.2) 0.516 Interferon 9 (5.5) 6(12.0) 3 (2.7) 0.025 Days of symptoms before admission, median (IQR) 4 (3–7) 4 (2–7) 5 (3–7) 0.396 Length of stay in days, median (range) 13(8–17) 16(13–24) 11 (7–16) <0.0005 Clinical severity HDU/ICU, n (%) 29 (17.8) 16 (32.0) 13 (11.5) 0.003 Required supplementary oxygen, n (%) 50 (30.7) 29 (58.0) 21 (18.6) <0.0005 Days on supplementary oxygen, median (IQR), n=50 11 (6–18) 12 (6–21) 8 (5–15) 0.15 Intubated, n (%) 13 (8.0) 10 (20.0) 3 (2.7) <0.0005 Death, n (%) 5 (3.1) 3 (6.0) 2 (1.8) 0.169 Sample size, n=163, except where indicated.¶ P values are from Fisher’s exact test or chi-square test for categorical variables and Mann-Whitney U test for continuous variables. P values< 0.05 are in bold.ALP, alkaline phosphatase;ALT, alanine aminotransferase;AST, aspartate aminotransferase;BIL, bilirubin;BMI, body mass index;CRP, c-reactive protein;GI, gastrointestinal;ICU, intensive care unit;IQR, interquartile range;LDH, lactate dehydrogenase;HDU, high dependency unit;PLT, platelet count;WBC, white blood cell.Results30.7% of patients developed abnormal ALT: they were more likely to be older and had comorbidities of hyperlipidaemia and hypertension. Multivariate logistic regression (IDDF2022-ABS-0170 Table 2) showed that R-factor ≥1 on admission (aOR 3.13, 95%CI 1.41–6.95) and hypoxia (aOR3.54, 95%CI 1.29–9.69) were independent risk factors for developing abnormal ALT, but not medications or comorbidities. The R-factor on admission trended higher for patients who developed abnormal LFT as compared to those who didn’t, regardless of the day of illness (IDDF2022-ABS-0170 Figure 1. R-factor). The patients who developed abnormal ALT also ran a more severe course of illness with a greater proportion needing supplementary oxygen (58%vs18.6%, p <0.0005), admission to Intensive Care/High Dependency Unit (32%vs11.5%, p=0.003) and intubation (20%vs2.7%, p<0.0005). The death rate between the 2 groups was similar. IDDF2022-ABS-0170 Table 2Odds ratio of risk factors for development of abnormal ALTVariable Univariable model Multivariable model ‡ cOR (95% CI) P value aOR (95% CI) P value Age in years <45 1.00 Referent 1.00 Referent 45–64 3.42 (1.28–9.11) 0.014 2.69 (0.84–8.47) 0.096 65+ 4.31 (1.49–12.42) 0.007 2.84 (0.66–12.19) 0.160 Gender Male 1.00 Referent Female 0.57 (0.28–1.15) 0.118 Diabetes 1.74 (0.78–3.87) 0.176 Hyperlipidemia 2.24 (1.13–4.45) 0.022 1.14 (0.43–3.00) 0.796 Hypertension 2.41 (122–4.78) 0.0110.89 (0.31–2.58) 0.835 Ischemic heart disease 2.14 (0.73–6.26) 0.166 Presence of GI symptom(s) on admission 1.17 (0.53–2.58) 0.695 Abnormal chest x-ray on admission 1.90 (0.96–3.80) 0.067 0.91 (0.36–2.25) 0.833 R factor on admission <1 1.00 Referent 1.00 Referent ≥1 3.12 (1.56–6.24) 0.001 3.13 (1.41–6.95) 0.005 Use of acetaminophen No 1.00 Referent Yes, <2 g/day 1.48 (0.39–5.65) 0.567 Yes, ≥2 g/day 2.86 (0.71–11.46) 0.139 Use of β-lactam 2.77 (1.35–5.65) 0.005 1.12 (0.38–3.24) 0.840 Use of Hydroxychloroquine 0.36 (0.04–3.11) 0.355 Use of Lopinavir/Ritonavir (Kaletra) 5.44 (2.20–13.43) <0.0005 2.20 (0.57–8.45) 0.252 Use of Remdesivir 1.68 (0.51–5.58) 0.395 Use of interferon 5.00 (1.20–20.88) 0.027 0.80 (0.12–5.22) 0.813 Hypoxia 6.05 (2.9–12.62) <0.0005 3.54 (1.29–9.69) 0.014 ‡ Variables in the multivariable logistic regression model were age group, hyperlipidemia, hypertension, whether there was abnormal chest x-ray on admission, R factor on admission, use of β-lactam, use of LPV/r, use of interferon, and hypoxia, P values<0.05 are in bold, aOR, adjusted odds ratio, cOR, crude odds ratio IDDF2022-ABS-0170 Figure 1ConclusionsLiver injury is associated with poorer clinical outcomes in COVID-19 patients. R-factor ≥1 on admission and hypoxia are independent risk factors for developing abnormal ALT in COVID-19. More studies are required to see if the incorporation of the R-factor into conventional clinical risk scores can improve the performance in predicting disease progression/discriminating disease severity and applicability in emerging virus variants.

Anicteric hepatitis, a rare extraintestinal manifestation following Campylobacter infection -a case study

AimsIntroductionCampylobacter infection is not uncommon in children, and extraintestinal manifestations following Campylobacter is a recognized entity, although hepatitis is rare. We present a case of anicteric hepatitis associated with Campylobacter infection in a 13-year-old boyMethodsCase StudyA previously healthy 13-year-old boy was admitted to the paediatric department with a 4-day history of fever and crampy abdominal pain which was localized to the right upper quadrant. He reported loss of appetite and nausea.He was not encephalopathic. His clinical examination was unremarkable, except for diffuse tenderness on deep palpation of the abdomen, especially of the right upper quadrant.His stools were normal initially but 48 hours after admission he developed severe diarrhoea.ResultsHe had elevated alanine transaminase (ALT) level (181 IU/L) on admission. The full blood count showed elevated white cell count with neutrophil leukocytosis, and C-reactive protein level was high (196mg/L). His prothrombin time (PT) and activated partial thromboplastin time (APTT) were within normal limits. The faecal molecular assay detected presence of Campylobacter by polymerase chain reaction (PCR). It did not identify any other organism.The viral hepatitis (Hepatitis A IgM, Hepatitis B surface antigen, Hepatitis C IgM, Hepatitis E IgM, and IgG) panel, Epstein-Barr virus (IgG for nuclear antigen, IgM, and IgG for viral capsid antigen), Cytomegalovirus (IgM and IgG) and Parvovirus B19 (IgM and IgG) screening were negative. Pandemic corona virus was not detected on PCR testing. The auto-antibody panel for autoimmune hepatitis (Anti-nuclear antibody, Anti-smooth muscle antibody, Anti-mitochondrial antibody, Liver kidney microsomal antibody) were normal. The ceruloplasmin level and Alpha-1 anti-trypsin levels were not low. The ultrasound scan of the abdomen revealed normal hepatic architecture, making a chronic liver disease less likely. An alternative explanation for high transaminases were not found.He improved clinically within a week and his liver functions continued to improve.ConclusionDiscussionCampylobacter infection has been associated with extra-intestinal manifestations like Guillain-Barre Syndrome, pancreatitis, erythema nodosum, haemolytic uremic syndrome, thrombotic thrombocytopenic purpura, haemolytic anaemia, glomerular nephritis, and reactive arthritis. Hepatitis is a rare complication of Campylobacterinfection and is rarely reported in medical literature.

Post-COVID-19 Cholestasis: A Case Series and Review of Literature.

Background: Coronavirus disease-2019 (COVID-19) cholangiopathy is a recently known entity. There are very few reports of liver transplantation (LT) for COVID-19-induced cholangiopathy. It is well known that vaccines can prevent severe disease and improve outcomes. However, there are no reports on the impact of COVID-19 vaccines on cholestasis. Therefore, we aimed to compare the course and outcome of patients who developed cholestasis following COVID-19 infection among vaccinated and unvaccinated individuals. Methods: Patients diagnosed with post-COVID cholestasis during the pandemic were included in the study after excluding other causes of cholestasis. Results: Eight unvaccinated and seven vaccinated individuals developed cholestasis following COVID-19 infection. Baseline demographics, presentation, severity, and management of COVID-19 were similar in both groups. However, patients in the unvaccinated group had a protracted course. The peak ALP was 312 (239-517) U/L in the vaccinated group and 571.5 (368-1058) U/L in the unvaccinated group (P = 0.02). Similarly, the peak γ-glutamyl transpeptidase values were lower in the vaccinated (325 [237-600] U/L) than in the unvaccinated group (832 [491-1640] U/L; P = 0.004). However, the peak values of total bilirubin, transaminases, and INR were similar in both groups. Five patients developed ascites gradually in the unvaccinated group whereas none in the vaccinated group developed ascites. Plasma exchange was done in five patients, and two were successfully bridged to living donor LT in the unvaccinated group. Only two patients recovered with conservative management in the unvaccinated group, whereas all recovered with conservative management in the vaccinated group. The other four patients in the unvaccinated group were planned for LT. Conclusion: Post-COVID-19 cholestasis is associated with high morbidity and mortality, meriting early identification and appropriate management. Vaccination can modify the course of severe COVID-19 infection and improve outcomes.

Erythema multiforme as a presentation of COVID-19: Case Illustrated format.

COVID-19 is now an established morbidity across races, regions and clinical risks around the world. From its first detection in Wuhan city-China in 2019 to the recent breakthrough of approved vaccines, that are determinants and deterrents and gradually becoming apparent. The phenotype of its presentation however is both variable and challenging especially. For those presenting with unique skin dermatosis such as erythema multiforme. Case report Our case is on a 36 year- old gentleman who presented to the hospital complaining, initially of only urticarial rash (later established to be erythema multiform), which improved with symptomatic treatment. He was discharged, only to be re-admitted a week later with exacerbation of the former cutaneous manifestation, accompanied by fever and gastrointestinal symptoms. He ultimately made complete recovery and was discharged home.

Clinical characteristics of 113 deceased patients with coronavirus disease 2019: retrospective study

ObjectiveTo delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) who died.DesignRetrospective case series.SettingTongji Hospital in Wuhan, China.ParticipantsAmong a cohort of 799 patients, 113 who died and 161 who recovered with a diagnosis of covid-19 were analysed. Data were collected until 28 February 2020.Main outcome measuresClinical characteristics and laboratory findings were obtained from electronic medical records with data collection forms.ResultsThe median age of deceased patients (68 years) was significantly older than recovered patients (51 years). Male sex was more predominant in deceased patients (83;73%) than in recovered patients (88;55%). Chronic hypertension and other cardiovascular comorbidities were more frequent among deceased patients (54 (48%) and 16 (14%)) than recovered patients (39 (24%) and 7 (4%)). Dyspnoea, chest tightness, and disorder of consciousness were more common in deceased patients (70 (62%), 55 (49%), and 25 (22%)) than in recovered patients (50 (31%), 48 (30%), and 1 (1%)). The median time from disease onset to death in deceased patients was 16 (interquartile range 12.0-20.0) days. Leukocytosis was present in 56 (50%) patients who died and 6 (4%) who recovered, and lymphopenia was present in 103 (91%) and 76 (47%) respectively. Concentrations of alanine aminotransferase, aspartate aminotransferase, creatinine, creatine kinase, lactate dehydrogenase, cardiac troponin I, N-terminal pro-brain natriuretic peptide, and D-dimer were markedly higher in deceased patients than in recovered patients. Common complications observed more frequently in deceased patients included acute respiratory distress syndrome (113;100%), type I respiratory failure (18/35;51%), sepsis (113;100%), acute cardiac injury (72/94;77%), heart failure (41/83;49%), alkalosis (14/35;40%), hyperkalaemia (42;37%), acute kidney injury (28;25%), and hypoxic encephalopathy (23;20%). Patients with cardiovascular comorbidity were more likely to develop cardiac complications. Regardless of history of cardiovascular disease, acute cardiac injury and heart failure were more common in deceased patients.ConclusionSevere acute respiratory syndrome coronavirus 2 infection can cause both pulmonary and systemic inflammation, leading to multi-organ dysfunction in patients at high risk. Acute respiratory distress syndrome and respiratory failure, sepsis, acute cardiac injury, and heart failure were the most common critical complications during exacerbation of covid-19.

Patterns of liver profile disturbance in patients with COVID-19.

Fever and cough are the most common clinical symptoms of coronavirus disease 2019 (COVID-19), but complications (such as pneumonia, respiratory distress syndrome, and multiorgan failure) can occur in people with additional comorbidities. COVID-19 may be a new cause of liver disease, as liver profile disturbance is one of the most common findings among patients. The molecular mechanism underlying this phenomenon, however, is still unknown. In this paper, we review the most current research on the patterns of change in liver profile among patients with COVID-19, the possible explanation for these findings, and the relation to pre-existing liver disease in these patients.

Glial fibrillary acidic protein astrocytopathy in a patient with recent mRNA SARS-CoV-2 vaccination: COVERSHEET

Background Literature describing triggers of GFAP astrocytopathy (GFAP-A) is limited. We report a case of GFAP-A in a patient with recent messenger ribonucleic acid (mRNA) severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) vaccination and discuss the possible pathogenesis. Case description A 45-year-old gentleman presented with features of meningoencephalitis 31 days after the first dose and 4 days after the second dose of mRNA SARS-CoV-2 vaccination. He sequentially developed brainstem/cerebellar, autonomic and cord dysfunction. Cerebrospinal fluid was positive for GFAP autoantibody. Clinical improvement occurred after intravenous methylprednisolone and immunoglobulins. Conclusion Although we are uncertain of a causal link of GFAP-A to mRNA vaccine, indirect activation of an underlying dysregulated immune milieu is plausible.

Prognostic Potential of Liver Enzymes in Patients With COVID-19 at the Leishenshan Hospital in Wuhan.

Background: Coronavirus disease 2019 (COVID-19) has evolved into a pandemic. We hypothesized that biochemical indicators of liver function may help determine the prognosis of COVID-19 patients. Methods: Patient information was collected from the Wuhan-Leishenshan hospital. Logistic and Cox regression analyses, Kaplan-Meier curves, and Curve fitting were used to determine the correlation between elevated levels of aspartate transaminase (AST), alanine transaminase (ALT), and AST/ALT and severity of disease/mortality. Results: Logistic and Cox regression analyses and Kaplan-Meier survival curves showed that COVID-19 progression correlated with elevated levels of AST and AST/ALT. The odds ratios for elevated levels of AST and AST/ALT in patients were 0.818 (95% confidence interval [CI]: 0.274-2.441, P = 0.035) and 2.055 (95% CI: 1.269-3.327, P = 0.003), respectively; the hazard ratios were 4.195 (95% CI: 1.219-14.422, P = 0.023) and 3.348 (95% CI: 1.57-7.139, P = 0.002), respectively. The Kaplan-Meier survival curves demonstrated that patients with elevated AST and AST/ALT levels had a higher risk of developing severe COVID-19. Conclusion: Elevated AST and AST/ALT levels correlated with severity of COVID-19 and mortality. Liver function tests may help clinicians in determining the prognosis of patients undergoing treatment for COVID-19.

Herbal Immune Booster-Induced Liver Injury in the COVID-19 Pandemic - A Case Series.

The COVID-19 pandemic has resulted in widespread use of complementary and alternative medicines. Tinospora cordifolia is a widely grown shrub which has been commonly used in India's traditional system of Ayurveda for its immune booster properties and has been extensively used as prophylaxis against COVID-19. Six patients (4 women, 2 men) with a median (IQR) age of 55 years (45-56) and with an history of Tinospora cordifolia consumption presented with symptoms of acute hepatitis during the study period of 4 months in the COVID-19 pandemic. The median (IQR) duration of Tinospora cordifolia consumption was 90 days (21-210). The median (IQR) peak bilirubin and AST were 17.5 mg/dl (12.2-24.9) and 1350 IU/ml (1099-1773), respectively. The patients had either a definite (n = 4) or probable (n = 2) revised autoimmune hepatitis score with an autoimmune pattern of drug-induced liver injury on biopsy. Four of these patients (all women) had underlying silent chronic liver disease of possible autoimmune etiology associated with other autoimmune diseases - hypothyroidism and type 2 diabetes mellitus. One of the three patients treated with steroids decompensated on steroid tapering. The other five patients had resolution of symptoms, liver profile, and autoimmune serological markers on drug withdrawal/continuing steroid treatment. The median (IQR) time to resolution from discontinuing the herb was 86.5 days (53-111). Tinospora cordifolia consumption seems to induce an autoimmune-like hepatitis or unmask an underlying autoimmune chronic liver disease, which may support its immune stimulant mechanism. However, the same mechanism can cause significant liver toxicity, and we recommend that caution be exercised in the use of this herb, especially in those predisposed to autoimmune disorders. Besides, in patients presenting with acute hepatitis, even in the presence of autoimmune markers, a detailed complementary and alternative medicine history needs to be elicited.

Outcomes of COVID-19 in Patients with Cirrhosis or Liver Transplantation.

Coronavirus disease 2019 (COVID-19) is associated with a significant morbidity and mortality in patients with cirrhosis. There is a significantly higher morbidity and mortality due to COVID-19 in patients with decompensated cirrhosis as compared to compensated cirrhosis, and in patients with cirrhosis as compared to noncirrhotic chronic liver disease. The fear of COVID-19 before or after liver transplantation has lead to a significant reduction in liver transplantation numbers, and patients with decompensated cirrhosis remain at risk of wait list mortality. The studies in liver transplantation recipients show that risk of mortality due to COVID-19 is generally driven by higher age and comorbidities. The current review discusses available literature regarding outcomes of COVID-19 in patients with cirrhosis and outcomes in liver transplant recipients.