Comparison of the quality of life of patients with liver cirrhosis before and during the COVID-19 lockdown in Slovakia.

Liver cirrhosis is associated with a poor quality of life (QOL). The COVID-19 pandemic has led to several restriction measures and psychosocial consequences whose impact on QOL has combined with that of cirrhosis in an unknown way. Therefore, we have used our cirrhosis registry to assess the quality of life before the pandemic (on the first admission to the tertiary liver unit) and during the most pronounced phase of the first lockdown. In this cross-sectional study conducted during the first lockdown in Slovakia (from April to May 2020), we have repeated the QOL measurement of QOL in cirrhotic patients previously enrolled in the RH7 registry. Patients who were alive (according to the national registry of deaths) were identified and contacted by phone with a structured and standardized interview led by trained professionals. The tool used for both QOL measurements (at enrolment in RH7 and during lockdown) was a standardized and validated EuroQOL-5D (EQ-5D) questionnaire. The study included 97 patients, of which 37 (38.1%) were women and 60 (61.9%) were men. Responses were achieved from 75 patients (68.18%). In general, patients scored their quality of life significantly higher during the pandemic compared to examination at admission to RH7 (that is, at admission to our tertiary liver unit with cirrhosis) (p = 0.005). In particular, of the domains included in EQ-5D: (1) self-care was better during lockdown compared to the first record on admission to RH7 (p < 0.001). (2) the ability to perform daily activities has also improved during lockdown (p = 0.002). On the other hand, (3) pain and discomfort did not change significantly during the lockdown compared to the previous measurement (p = 0.882). (4) anxiety and depression were lower during lockdown compared to admission to RH7 (p = 0.01). The quality of life in patients with liver cirrhosis was better during the lockdown of SARS-CoV-2 compared to the previous measurement at admission to the tertiary liver unit.

Time-to tertiary care predicts mortality in alcohol-associated hepatitis in patients with cirrhosis

Background: Slovakia ranks first in the world in prevalence of decompensated cirrhosis, with alcohol-associated liver disease (ALD) being the leading etiology. The severe acute phenotype of ALD, alcohol-associated hepatitis (AH) is a distinct clinical syndrome characterized by recent onset of jaundice in the context of heavy alcohol consumption. The majority of patients with AH are admitted to the hospital. In our previous analysis of hospitalized cirrhotics, we found an increased mortality during the COVID-19 lockdown and postulated as main cause a pandemic-associated distortion of time-to tertiary cirrhosis care (TTT). In this proof-of-concept study we aimed to evaluate if the time-to-tertiary care (defined by the time spent in another hospital before referral to a tertiary care center) predicts mortality in patients with acute decompensation of cirrhosis triggered by AH. Methods: Since 2014, our tertiary hospital with liver transplant program has been running the registry RH7 of all the consenting adults admitted for advanced chronic liver disease (ACLD). We included patients from RH7 database between 07/2014 and 5/2020, with AH as the trigger of acute decompensation of cirrhosis who were admitted to the hospital. Severe AH was defined by MDF>31 or MELD>20;acute-on-chronic-liver failure (ACLF) was calculated by EASL-CLIF criteria. We divided the cohort to two groups: 1) patients admitted directly to a tertiary care center (Fig.1 - Central), and 2) patients referred to a tertiary care center after first being hospitalized in a lower-complexity hospital (Fig.1 - Subregional). We recorded demographics, clinical characteristics, time interval between the first and second admission (TTT= days spent in another hospital before admission to a tertiary care), and 30- and 90-day mortality. Results: Of 1,109 patients admitted for decompensated cirrhosis, we included 219 patients with AH decompensating cirrhosis, median age 50 years, 37% females;mean MELD and MDF were 23 and 46, respectively;76 % had severe AH. Subtypes of acute decompensation were pure acute decompensation in 53%, ACLF-1 in 24%, ACLF-2 in 18%, and ACLF -3 in 5%. One hundred and thirteen patients (52%) were admitted primarily to a tertiary care center (Central), 106 patients (48%) were referred from another hospital (Subregional). Median TTT was 15 days (1-95). Thirty- and 90-day mortality was significantly higher in Subregional as compared with Central group at 35.5% vs 11% and 51.4% vs 24.5%, respectively (p<0,0021) (Fig.1) Conclusion: Time-to-tertiary care is an independent predictor of mortality in patients with acute decompensation of cirrhosis triggered by AH. This difference in mortality is sustained for years after discharge.

Hepatokines and covid-19 severity

Introduction: Novel coronavirus disease 2019 (COVID-19) is not only connected with respiratory distress syndrome, but also with gastrointestinal symptoms, hepatic injury and multiorgan and systemic inflammation. Considering the wide range of hepatokines and myokines activities they may influence pathogenesis and infection course. Aims & Methods: Our aim was to assess concentrations of pentraxin 3 (PTX3), fibroblast grow factor 21 (FGF21), irisin and fetuin A among COVID- 19 patients with emphasis on their relationship with COVID-19 severity, concomitant metabolic abnormalities and liver dysfunction. An observational single center cohort study included 70 COVID-19 patients and healthy controls. Hepatokines serum concentrations were measured with enzyme-linked immunosorbent assay in serum collected at the moment of admission to hospital, before any treatment was applied. Results: Serum fetuin A concentrations significantly decreased in COVID- 19 patients compared to healthy volunteers (243.4 [195.0-275.8] vs 333.5 [303.0-371.4] μg/ml;p<0.001). There was no significant difference in serum irisin, FGF21 and PTX3 levels between both groups. Alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) activities, and ferritin levels were significantly higher in COVID-19 patients (34.0 [20.0-52.5] vs 21.0 [16.0-25.7] U/l;p=0.02, 33.5 [20.0-62.5] vs 14.0 [10.7-24.2] U/l;p=0.003 and 210.0 [114.7-487.0] vs 16.5 [13.0-19.6] μg/l;p<0.001, respectively). Fetuin A levels were down-regulated in COVID-19 patients with higher GGT activity and ferritin concentration (258.8 [219.9-310.9] vs 221.9 [182.1- 256.3] μg/ml;p=0.004 and 257.7 [238.3-311.1] vs 220.5 [178.5-264.1] μg/ ml;p=0.001, respectively). HOMA-IR and C-reactive protein were significantly elevated in COVID-19 patients. The presence of gastrointestinal (GI) symptoms did not influence analyzed hepatokines levels. Pneumonia was found in 32.8% of patients. Fetuin A concentration significantly decreased in patients with pneumonia (217.4 [188.3-248.8] vs 256.3 [218.9-285.7] ng/ml;p<0.001), and those requiring admission to intensive care unit (ICU) (194.0 [124.8-229.8] vs 252.4 [209.4- 276.6] ng/ml;p=0.02). Serum PTX3 concentration significantly increased in ITU patients (4769.0 [2896.9-8394.6] vs 2278.2 [1876.9-3106.3] ng/ml;p<0.001). Conclusion: Surprisingly, pointing to proinflammatory and insulin impairing action of fetuin A, its levels were significantly lower in COVID-19 patients despite of higher HOMA-IR, CRP and ferritin levels. Even, more surprising was significant reduction of fetuin A in patients with pneumonia, those requiring ICU and those with higher ferritin levels and HOMA-IR. It suggests that fetuin A deficiency predispose to more serious COVID-19 course, glucose metabolism abnormalities and its measurement may be additional marker of disease severity. Up-regulated PTX3 may also suggest COVID-19 severity. Impaired liver function revealed by GGT activity was associated with serum fetuin A depletion. Predictive factor which could predispose to a more severe course of COVID-19, including the presence of pneumonia and ICU hospitalization, was GGT activity.

Increased mortality and decreased registrations in cirrhosis registry during COVID-19 era

Background: Our HEGITO liver unit provides the in- and out-patient (pt) tertiary referral services including liver transplantation (LT) Since 2014, HEGITO has kept registry (RH7) of patients hospitalized with cirrhosis / advanced chronic liver disease (ACLD) The social distancing policy restrictions were introduced in Slovakia on March 16, 2020 and they have substantially changed the usual provision of HEGITO services: We 1.deferred or diverted to telemedicine most of planned and on-demand outpatient services, 2.deferred planned and delimited to region-proper lower-rank institutions acute hospitalizations and, 3.deferred LT except for urgent indications In this study, we aimed to analyze the registrations to and mortality in RH7 pre- and during the COVID-19 era Methods: Using a sample of pt registered to RH7 anytime from its start in 2014 and passing away before March 16, 2020 (PRE-COVID COHORT), we conducted a survival analysis using a Cox proportional hazard model with following factors: gender, age, BMI, CTP, MELD, LFI, ACLF, TSF, DYNAMO, CRP, LEU We used this model to predict individual median residual lifetime for remaining 563 pt from RH7 who were alive at March 16 (COVID COHORT) We compared actual cumulative number of deaths between March 16 and June 6, with predictions based on the Cox PH model Deaths were ascertained by the weekly reports from the Healthcare Surveillance Authority with the special query for COVID 19 code Results: We identified 1091 pt in PRECOVID COHORT with median age 56 8, MELD 16, 60 8% male, and 563 pt in COVID COHORT with median age 55 7, MELD 14, 57 2% male, respectively Registry data shows a significant drop in weekly new registrations to RH7: four in March 2020 vs 17 8 average in March 2014-2019, followed by a sharp increase after these policies were lifted (Figure) Registered mortality in COVID COHORT was higher than mortality predicted by the Cox PH model using PRE-COVID COHORT (28 vs 22) Of note, there was no death related to COVID 19 in the COVID COHORT Conclusion: Analysis of our cirrhosis registry has revealed significantly decreased regsitrations and increased mortality during COVID 19 era We speculate that they are causally related to the impact of the pandemic on the quality of cirrhosis care (Tapper, J Hep 20;73: 441).