Global disparities in mortality and liver transplantation in hospitalised patients with cirrhosis: a prospective cohort study for the CLEARED Consortium.

BACKGROUND: Cirrhosis, the end result of liver injury, has high mortality globally. The effect of country-level income on mortality from cirrhosis is unclear. We aimed to assess predictors of death in inpatients with cirrhosis using a global consortium focusing on cirrhosis-related and access-related variables. METHODS: In this prospective observational cohort study, the CLEARED Consortium followed up inpatients with cirrhosis at 90 tertiary care hospitals in 25 countries across six continents. Consecutive patients older than 18 years who were admitted non-electively, without COVID-19 or advanced hepatocellular carcinoma, were enrolled. We ensured equitable participation by limiting enrolment to a maximum of 50 patients per site. Data were collected from patients and their medical records, and included demographic characteristics; country; disease severity (MELD-Na score); cirrhosis cause; medications used; reasons for admission; transplantation listing; cirrhosis-related history in the past 6 months; and clinical course and management while hospitalised and for 30 days post discharge. Primary outcomes were death and receipt of liver transplant during index hospitalisation or within 30 days post discharge. Sites were surveyed regarding availability of and access to diagnostic and treatment services. Outcomes were compared by country income level of participating sites, defined according to World Bank income classifications (high-income countries [HICs], upper-middle-income countries [UMICs], and low-income or lower-middle-income countries [LICs or LMICs]). Multivariable models controlling for demographic variables, disease cause, and disease severity were used to analyse the odds of each outcome associated with variables of interest. FINDINGS: Patients were recruited between Nov 5, 2021, and Aug 31, 2022. Complete inpatient data were obtained for 3884 patients (mean age 55·9 years [SD 13·3]; 2493 (64·2%) men and 1391 (35·8%) women; 1413 [36·4%] from HICs, 1757 [45·2%] from UMICs, and 714 [18·4%] from LICs or LMICs), with 410 lost to follow-up within 30 days after hospital discharge. The number of patients who died while hospitalised was 110 (7·8%) of 1413 in HICs, 182 (10·4%) of 1757 in UMICs, and 158 (22·1%) of 714 in LICs and LMICs (p<0·0001), and within 30 days post discharge these values were 179 (14·4%) of 1244 in HICs, 267 (17·2%) of 1556 in UMICs, and 204 (30·3%) of 674 in LICs and LMICs (p<0·0001). Compared with patients from HICs, increased risk of death during hospitalisation was found for patients from UMICs (adjusted odds ratio [aOR] 2·14 [95% CI 1·61-2·84]) and from LICs or LMICs (2·54 [1·82-3·54]), in addition to increased risk of death within 30 days post discharge (1·95 [1·44-2·65] in UMICs and 1·84 [1·24-2·72] in LICs or LMICs). Receipt of a liver transplant was recorded in 59 (4·2%) of 1413 patients from HICs, 28 (1·6%) of 1757 from UMICs (aOR 0·41 [95% CI 0·24-0·69] vs HICs), and 14 (2·0%) of 714 from LICs and LMICs (0·21 [0·10-0·41] vs HICs) during index hospitalisation (p<0·0001), and in 105 (9·2%) of 1137 patients from HICs, 55 (4·0%) of 1372 from UMICs (0·58 [0·39-0·85] vs HICs), and 16 (3·1%) of 509 from LICs or LMICs (0·21 [0·11-0·40] vs HICs) by 30 days post discharge (p<0·0001). Site survey results showed that access to important medications (rifaximin, albumin, and terlipressin) and interventions (emergency endoscopy, liver transplantation, intensive care, and palliative care) varied geographically. INTERPRETATION: Inpatients with cirrhosis in LICs, LMICs, or UMICs have significantly higher mortality than inpatients in HICs independent of medical risk factors, and this might be due to disparities in access to essential diagnostic and treatment services. These results should encourage researchers and policy makers to consider access to services and medications when evaluating cirrhosis-related outcomes. FUNDING: National Institutes of Health and US Department of Veterans Affairs.

Reduction in Nosocomial Infections in Patients With Cirrhosis During the COVID-19 Era Compared to Pre-COVID-19 Era: Impact of Masking and Restricting Visitation?

Data results for pre-COVID era vs COVID-era Pre-COVID-era (n=234) COVID-era (n=296) P value Age 58.6 ± 12.2 55.0±13.7 0.001 Male Gender 103 135 0.72 Latin Ethnicity 7 10 0.92 qSOFA total 1.84 ± 0.60 2.43±0.68 < 0.0001 qSOFA respiration 0.12±0.33 0.81±0.39 <0.0001 qSOFA blood pressure 0.93±0.25 0.87±0.34 0.02 qSOFA brain 0.79±0.41 0.75±0.43 0.33 WBC 10.9±7.6 12.5±8.2 0.02 MELD-Na 23.8±10.1 26.0±10.2 0.01 Reason for ICU: Altered Mental Status 117 141 0.59 Infection 115 138 0.56 CVA 12 13 0.69 Hypotension 134 153 0.20 Renal Support 35 88 <0.0001 Respiratory Failure 115 129 0.20 Post-procedure 16 27 0.34 Type of Infection: Nosocomial infection 24 10 <0.001 UTI 11 27 0.05 Abdominal 31 32 0.39 Bacteremia 32 28 0.13 Respiratory 48 57 0.72 Skin/Soft Tissue 10 7 0.22 Organism details: Gram positive 39 36 0.14 Gram negative 31 25 0.08 Fungus 10 12 0.90 > 1 organism 11 5 0.04 VRE 6 5 0.49 MRSA 7 2 0.04 Fluoro resistance 5 2 0.14 ESBL 11 5 0.04 Outcome: ICU length of stay 4.78±4.34 7.66±8.58 <0.0001 Renal Failure 35 83 <0.0001 Grade 3-4 Hepatic Encephalopathy 55 98 0.02 Shock 78 121 0.08 Ventilation 82 115 0.37 Coagulation failure 144 175 0.57 Death or hospice 82 119 0.22 Liver Transplant 6 31 0.001 Key: quick sepsis-related organ failure assessment (qSOFA);white blood cells (WBC);Model for end-stage liver disease-sodium (MELD-Na);intensive care unit (ICU);cerebrovascular accident (CVA);urinary tract infection (UTI);vancomycin resistant enterococcus (VRE);methicillin resistant staphylococcus aureus (MRSA);fluoro (fluroquinolone);extended spectrum beta-lactamase (ESBL).

Reduction in Nosocomial Infections in Patients With Cirrhosis During the COVID-19 Era Compared with Pre-COVID-19: Impact of Masking and Restricting Visitation.

Nosocomial infections (NIs) in critically ill patients with cirrhosis result in higher death and transplant delisting. NIs are promoted by staff, visitors, and the environment, all of which were altered to reduce pathogen transmission after COVID-19. Two cohorts of intensive care unit patients with cirrhosis from March 2019 to February 2020 (pre-COVID, n = 234) and March 2020 to March 2021 (COVID era, n = 296) were included. We found that despite a higher admission MELD-Na, qSOFA, and WBC count and requiring a longer intensive care unit stay, COVID-era patients developed lower NIs (3% vs 10%, P < 0.001) and had higher liver transplant rates vs pre-COVID patients. COVID-era restrictions could reduce NIs in critically ill patients with cirrhosis.

Liver transplantation for acute liver failure in a SARS-CoV-2 PCR-positive patient.

Current guidelines recommend deferring liver transplantation (LT) in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection until clinical improvement occurs and two PCR tests collected at least 24 hours apart are negative. We report a case of an 18-year-old, previously healthy African-American woman diagnosed with COVID-19, who presents with acute liver failure (ALF) requiring urgent LT in the context of SARS-CoV-2 polymerase chain reaction (PCR) positivity. The patient was thought to have acute Wilsonian crisis on the basis of hemolytic anemia, alkaline phosphatase:bilirubin ratio <4, AST:ALT ratio >2.2, elevated serum copper, and low uric acid, although an unusual presentation of COVID-19 causing ALF could not be excluded. After meeting criteria for status 1a listing, the patient underwent successful LT, despite ongoing SARS-CoV-2 PCR positivity. Remdesivir was given immediately posttransplant, and mycophenolate mofetil was withheld initially and the SARS-CoV-2 PCR test eventually became negative. Three months following transplantation, the patient has made a near-complete recovery. This case highlights that COVID-19 with SARS-CoV-2 PCR positivity may not be an absolute contraindication for transplantation in ALF. Criteria for patient selection and timing of LT amid the COVID-19 pandemic need to be validated in future studies.

Comparison of mortality risk in patients with cirrhosis and COVID-19 compared with patients with cirrhosis alone and COVID-19 alone: multicentre matched cohort.

OBJECTIVE: Comorbid conditions are associated with poor prognosis in COVID-19. Registry data show that patients with cirrhosis may be at high risk. However, outcome comparisons among patients with cirrhosis+COVID-19 versus patients with COVID-19 alone and cirrhosis alone are lacking. The aim of this study was to perform these comparisons. DESIGN: A multicentre study of inpatients with cirrhosis+COVID-19 compared with age/gender-matched patients with COVID-19 alone and cirrhosis alone was performed. COVID-19 and cirrhosis characteristics, development of organ failures and acute-on-chronic liver failure (ACLF) and mortality (inpatient death+hospice) were compared. RESULTS: 37 patients with cirrhosis+COVID-19 were matched with 108 patients with COVID-19 and 127 patients with cirrhosis from seven sites. Race/ethnicity were similar. Patients with cirrhosis+COVID-19 had higher mortality compared with patients with COVID-19 (30% vs 13%, p=0.03) but not between patients with cirrhosis+COVID-19 and patients with cirrhosis (30% vs 20%, p=0.16). Patients with cirrhosis+COVID-19 versus patients with COVID-19 alone had equivalent respiratory symptoms, chest findings and rates of intensive care unit transfer and ventilation. However, patients with cirrhosis+COVID-19 had worse Charlson Comorbidity Index (CCI 6.5±3.1 vs 3.3±2.5, p<0.001), lower presenting GI symptoms and higher lactate. Patients with cirrhosis alone had higher cirrhosis-related complications, maximum model for end-stage liver disease (MELD) score and lower BiPAP/ventilation requirement compared with patients with cirrhosis+COVID-19, but CCI and ACLF rates were similar. In the entire group, CCI (OR 1.23, 95% CI 1.11 to 1.37, p<0.0001) was the only variable predictive of mortality on multivariable regression. CONCLUSIONS: In this multicentre North American contemporaneously enrolled study, age/gender-matched patients with cirrhosis+COVID-19 had similar mortality compared with patients with cirrhosis alone but higher than patients with COVID-19 alone. CCI was the only independent mortality predictor in the entire matched cohort.