ABSTRACT
Background and aim: Infections in cirrhotic patients are associated with an increased risk of liver-related complications (LRC) and mortality. Limited data regarding the prevalence of Coronavirus disease (COVID-19) in cirrhotic patients’ awaiting liver transplantation (LT) are available. The aim of this study was to evaluate the prevalence of SARS-CoV2 in a cohort of cirrhotic patients and its impact on LRC rate and on LT.Materials and methods: We retrospectively included 187 waitlist patients for LT from 24-January-2020 (2020-cohort) and 123 patients from 24-January-2019 (2019-cohort). All 2020-cohort patients were screened for COVID-19 symptoms with a survey. COVID-19 infection was defined by a positive PCR assay for SARS-CoV-2 on nasopharyngeal swab or the positivity for specific antibodies or typical lung lesions on CT scan. We also assessed the indirect impact of SARSCoV2 infection on LRC and LT rate, estimated by competitive risk survival analyses in 2020-cohort vs. 2019-cohort (Fine and Gray method).Results: In 2020-cohort, 72.7% (n=136) of patients were male with mean age of 55.5±12, 47.2% (n=85) patients have alcohol and/or NASH related cirrhosis, with a median MELD score of 14.1±7.4. 45.5% (n=71), 38.5% (n=60) and 14.8% (n=23) of patients were A, B and C for Child-Pugh-score, respectively. 172 patients responded to survey and 22% (n= 38) had symptoms. 20/38 patients were tested for SARS-CoV2 and 4 patients were positive. 3/4 patients with COVID-19 disease needed hospitalization and 1 intensive care support. No death was reported and 1 patient was LT. The 2020-cohort and 2019-cohort were comparable for sex (p=0,6), age (p=0.7), comorbidities (p=0.2) and Child-Pugh-score (p=0.2). The cumulative incidence of LRC was not significantly higher in the 2020-cohort vs. 2019-cohort (SHR 0.65, 95% CI 0.36-1.15, p=0.138). The cumulative incidence of LT was significantly lower in the 2020-cohort than in the 2019-cohort (SHR0.21, 95% CI 0.13-0.33, p<0.001). Conclusions: Our study reported a low prevalence rate of SARSCoV2 infection in a cohort of cirrhotic patients waiting for LT. No SARS-CoV2 infection direct or indirect impact on mortality and LRC rate was reported. However, a significant shortage of LT was found in 2020 cohort.
ABSTRACT
Background: A1 and HP serum levels are associated with, spread, severity and recovery of SI.1 Low A1 level measured 10 years prior to SI exposure, is also a clinical risk factor (fragility) for SI.2 In patients (Pts) it is difficult to assess the real number of days post infection (Dpi). The aim of this pilot study was to compare the A1 and HP dynamic changes during the first 4 weeks after SI in a nonhuman primate model, the macaque (NHP), that recapitulates mild COVID- 19 symptoms, in 2 ancillary experimental SI,3 vs Pts of an updated prospective observational study.1 Methods: NHP had 3-5 years of age, 2 female rhesus and 2 cynomolgus, and originating from Mauritian and Chinese AAALAC certified breeding centers, respectively, infected intranasally and intratracheally with 2×107 plaque-forming units of the clinical isolate hCoV-19/France/lDF0372/2020. Viral loads in nasopharyngeal, tracheal and rectal fluids were analyzed using an RT-qPCR assay, (Roche). Pts were those included in the observational study of SI in the GHPS hospital (intermediate severity 3to5 WHO grades), the Dpi being defined since the first symptom. A1 and HP were measured in all 283 Pts and in a subset of 58 with at least 3 repeated samples, a population (n=7482) representative of French population was used as Controls. Results: (Figure): In NHP, A1 had no significant changes from Dpi7 to Dpi26 (Panel A), contrarily to Pts who had lower values than Controls (blue box) (Repeated ANOVA Dunnets test) P<.001) before, during SI, and after recovery in all or repeated samples (Panel B). In NHP, HP was peaking at 7Dpi, close to the peak of nasal viral loads, still elevated at 20Dpi (Panel C);CRP in the same HP was peaking later at 13Dpi, and still high at 20Dpi.3 In Pts, HP changes were similar with a peak at 14Dpi and returned to normal values at 60Dpi (Panel D). Conclusion: These results validate in NHP the HP changes observed in hospitalized patients with intermediate severity SI. HP is an earlier marker of SI than CRP, and ApoA1 changes should be evaluated in NHP with shorter Dpi.
ABSTRACT
Purpose: Infections in cirrhotic patients are associated with an increased risk of liverrelated complications (LRC) and mortality. Limited data regarding the prevalence of Coronavirus disease (COVID-19) in cirrhotic patients' awaiting liver transplantation (LT) are available. The aim of this study was to evaluate the prevalence of Sars-cov2 in a cohort of cirrhotic patients and its impact on LRC rate and on LT. Methods: We retrospectively included 187 waitlist patients for LT from 24-January-2020 (2020-cohort) and 123 patients from 24-January-2019 (2019-cohort). All 2020-cohort patients were screened for COVID-19 symptoms with a survey. COVID-19 infection was defined by a positive PCR assay for SARS-CoV-2 on nasopharyngeal swab or the positivity for specific antibodies or typical lung lesions on CT scan. We also assessed the indirect impact of Sars-Cov2 infection on LRC and LT rate, estimated by competitive risk survival analyses in 2020-cohort vs. 2019-cohort (Fine and Gray method). Results: In 2020-cohort, 72.7% (n=136) of patients were male with mean age of 55.5±12, 47.2% (n=85) patients have alcohol and/or NASH related cirrhosis, with a median MELD score of 14.1±7.4. 45.5% (n=71), 38.5% (n=60) and 14.8% (n=23) of patients were A, B and C for Child-Pugh-score, respectively. 172 patients responded to survey and 22% (n= 38) had symptoms. 20/38 patients were tested for Sars-Cov2 and 4 patients were positive. 3/4 patients with COVID-19 disease needed hospitalization and 1 intensive care support. No death was reported and 1 patient was LT. The 2020-cohort and 2019-cohort were comparable for sex (p=0,6), age (p=0.7), comorbidities (p=0.2) and Child-Pugh-score (p=0.2). The cumulative incidence of LRC was not significantly higher in the 2020-cohort vs. 2019-cohort (SHR 0.65, 95% CI 0.36-1.15, p=0.138). The cumulative incidence of LT was significantly lower in the 2020-cohort than in the 2019-cohort (SHR0.21, 95% CI 0.13-0.33, p<0.001). Conclusions: Our study reported a low prevalence rate of Sars-Cov2 infection in a cohort of cirrhotic patients waiting for LT. No Sars-Cov2 infection direct or indirect impact on mortality and LRC rate was reported. However, a significant shortage of LT was found in 2020 cohort.
ABSTRACT
Background: Since 1920, a decrease in serum cholesterol has been identified as a marker of severe pneumonia. We have assessed the performance of serum apolipoprotein-A1 (A1), the main transporter of HDL-cholesterol, to identify the early spread of coronavirus disease 2019 (Covid-19) in the general population and its diagnostic performance for the Covid-19 Methods: We compared the daily mean A1 during the first 26 weeks of 2020 in a population that is routinely followed for a risk of liver fibrosis risk in France (18,239 sera) and in the USA (161,655 sera) in relation to a local increase in confirmed cases, and in comparison to the same period in 2019 (respectively 26,513 and 211,419 sera) Linear regression curves with 95% confidence intervals between the mean daily serum levels of A1 were compared by the F-test, and a significant difference was defined as P <0.001. We prospectively assessed the sensitivity of this marker in an observational study of 136 consecutive hospitalized cases and retrospectively evaluated its specificity in 7,481 controls representing the general population Results: The mean A1 levels in these populations began decreasing in January 2020, compared to the same 26 weeks in 2019 This decrease was highly correlated to and in parallel with the daily increase in confirmed Covid-19 cases in the following 26 weeks, in both France (national and hospital cohort APHP-PSL) and USA, including the June recovery period in France Figure 1 shows the proportion of low A1 (<1 24 g/L) during the 26 weeks Same differences were observed after stratifications on the following confounding factors: previous years 2017-2018, age, gender, hepatitis C or non-alcoholic fatty liver disease, BMI, fasting glucose and triglycerides No similar changes were observed for ALT, AST, GGT, and haptoglobin A1 at the 1 25 g/L cutoff had a sensitivity of 90 6% (95%CI84 2-95 1) and a specificity of 96.1% (95.7-96.6%) for the diagnosis of Covid-19 The area under the characteristics curve was 0 978 (0 957-0 988), and outperformed haptoglobin and liver function tests For a prevalence of 1 8% (136/7617;95%CI 1 5-2 1) of Covid-19 cases, the positive predictive value (PPV) was 30 0% (95%CI 25 6-34 7) and the negative predictive value (NPV) was 99 8% (95%CI 99 7-99 9) When adjusted on the range of Covid-19 prevalence predicted in the French population, the PPV was 40 5% and NPV was 99 7% for the 2 8% lower limit, and PPV was 56 0% and NPV was 99 3% for the 7 2% higher limit In the prospective recovery subset repeated measurements showed an increase of A1 from 0 89 to 1 04 g/L in a median of 11 days (n=305;ANOVA P<0 01) Conclusion: Apolipoprotein-A1 could be both a sentinel of the pandemic in existing routine surveillance of the general population, as well as a candidate predictor of suspected Covid-19 in multivariate analysis in cases with a negative virological test.