Consensus document on acute-on-chronic liver failure (ACLF) established by the Mexican Association of Hepatology.

Acute-on chronic liver failure (ACLF) has been an intensively debated topic mainly due to the lack of a unified definition and diagnostic criteria. The growing number of publications describing the mechanisms of ACLF development, the progression of the disease, outcomes and treatment has contributed to a better understanding of the disease, however, it has also sparked the debate about this condition. As an attempt to provide medical professionals with a more uniform definition that could be applied to our population, the first Mexican consensus was performed by a panel of experts in the area of hepatology in Mexico. We used the most relevant and impactful publications along with the clinical and research experience of the consensus participants. The consensus was led by 4 coordinators who provided the most relevant bibliography by doing an exhaustive search on the topic. The entire bibliography was made available to the members of the consensus for consultation at any time during the process and six working groups were formed to develop the following sections: 1.- Generalities, definitions, and criteria, 2.- Pathophysiology of cirrhosis, 3.- Genetics in ACLF, 4.- Clinical manifestations, 5.- Liver transplantation in ACLF, 6.- Other treatments.

Position statement on the use of albumin in liver cirrhosis.

Cirrhosis is characterised by a prolonged asymptomatic period in which the inflammation persists, increasing as the disease progresses. Characteristic of this is the increase in pro-inflammatory cytokines and pro-oxidant molecules which are determining factors in the development of multiple organ dysfunction. In the early development of cirrhosis, splanchnic arterial vasodilation, activation of vasoconstrictor systems (renin-angiotensin-aldosterone) and the sympathetic nervous system (noradrenaline) bring about bacterial translocation and systemic dissemination via portal circulation of bacterial products, and molecular patterns associated with damage, which exacerbate the systemic inflammation present in the patient with cirrhosis. Albumin is a molecule that undergoes structural and functional changes as liver damage progresses, affecting its antioxidant, immunomodulatory, oncotic and endothelial stabilising properties. Our knowledge of the properties of albumin reveals a molecule with multiple treatment options in patients with cirrhosis, from the compensated then decompensated phases to multiple organ dysfunction. Its recognised uses in spontaneous bacterial peritonitis, post-paracentesis circulatory dysfunction, acute kidney injury and hepatorenal syndrome are fully validated, and a treatment option has opened up in decompensated cirrhosis and in acute-on-chronic liver disease.

NAFLD determined by Dallas Steatosis Index is associated with poor outcomes in COVID-19 pneumonia: a cohort study.

Coronavirus disease 2019 is a worldwide health challenge. Liver steatosis diagnosis based on imaging studies has been implicated in poor outcomes of COVID-19 pneumonia, but results are inconsistent. The Dallas Steatosis Index (DSI) is an available calculator developed to identify patients with non-alcoholic fatty liver disease (NAFLD). We hypothesized that it would be associated with in-hospital mortality, intensive care unit admission (ICU), and invasive mechanical ventilation (IMV). We conducted a retrospective cohort study on inpatients with confirmed COVID-19 pneumonia between February 26 and April 11, 2020. We computed the DSI on admission, and patients with high DSI were considered with NAFLD. We employed logistic regression to study the association between NAFLD, mortality, ICU admission, and IMV. We studied the association between liver steatosis on computed tomography (CT) and these outcomes, and also between Metabolic Associated Fatty Liver Disease (MAFLD) based on CT findings and risk factors and the outcomes. 470 patients were included; 359 had NAFLD according to the DSI. They had a higher frequency of type 2 diabetes (31% vs 14%, p < 0.001), obesity (58% vs 14%, p < 0.001), and arterial hypertension (34% vs 22%, p = 0.02). In univariable analysis, NAFLD was associated with mortality, ICU admission, and IMV. Liver steatosis by CT and MAFLD were not associated with any of these outcomes. In multivariable logistic regression, high DSI remained significantly associated with IMV and death. High DSI, which can be easily computed on admission, was associated with IMV and death, and its use to better stratify the prognosis of these patients should be explored. On the other hand, liver steatosis by CT and MAFLD were not associated with poor outcomes.

Comparison of different prognostic scores for patients with cirrhosis hospitalized with SARS-CoV-2 infection.

INTRODUCTION AND OBJECTIVES: Viral infections have been described to increase the risk of decompensation in patients with cirrhosis. We aimed to determine the effect of SARS-CoV-2 infection on outcome of hospitalized patients with cirrhosis and to compare the performance of different prognostic models for predicting mortality. PATIENTS: We performed a prospective cohort study including 2211 hospitalized patients with confirmed SARS-CoV-2 infection from April 15, 2020 through October 1, 2020 in 38 Hospitals from 11 Latin American countries. We registered clinical and laboratory parameters of patients with and without cirrhosis. All patients were followed until discharge or death. We evaluated the prognostic performance of different scoring systems to predict mortality in patients with cirrhosis using ROC curves. RESULTS: Overall, 4.6% (CI 3.7-5.6) subjects had cirrhosis (n = 96). Baseline Child-Turcotte-Pugh (CTP) class was assessed: CTP-A (23%), CTP-B (45%) and CTP-C (32%); median MELD-Na score was 19 (IQR 14-25). Mortality was 47% in patients with cirrhosis and 16% in patients without cirrhosis (P < .0001). Cirrhosis was independently associated with death [OR 3.1 (CI 1.9-4.8); P < .0001], adjusted by age, gender, and body mass index >30. The areas under the ROC curves for performance evaluation in predicting 28-days mortality for Chronic Liver Failure Consortium (CLIF-C), North American Consortium for the Study of End-Stage Liver Disease (NACSELD), CTP score and MELD-Na were 0.85, 0.75, 0.69, 0.67; respectively (P < .0001). CONCLUSIONS: SARS-CoV-2 infection is associated with elevated mortality in patients with cirrhosis. CLIF-C had better performance in predicting mortality than NACSELD, CTP and MELD-Na in patients with cirrhosis and SARS-CoV-2 infection. Clinicaltrials.gov:NCT04358380.

Low Thoracic Skeletal Muscle Area Is Not Associated With Negative Outcomes in Patients With COVID-19.

OBJECTIVE: Sarcopenia has been related to negative outcomes in different clinical scenarios from critical illness to chronic conditions. The aim of this study was to verify whether there was an association between low skeletal muscle index and in-hospital mortality, intensive care unit admission, and invasive mechanical ventilation need in hospitalized patients with COVID-19. DESIGN: This was a retrospective cohort study of a referral center for COVID-19. We included all consecutive patients admitted to the hospital between February 26 and May 15, 2020, with a confirmed diagnosis of COVID-19. Skeletal muscle index was assessed from a transverse computed tomography image at the level of twelfth thoracic vertebra with National Institutes of Health ImageJ software, and statistical analysis was performed to find an association between skeletal muscle index and in-hospital mortality, need of invasive mechanical ventilation, and intensive care unit admission. RESULTS: We included 519 patients, the median age was 51 (42-61) yrs, and 115 patients (22%) had low skeletal muscle index. On multivariable analysis, skeletal muscle index was not associated with mortality, intensive care unit admission, or invasive mechanical ventilation need nor in a subanalysis of patients 65 yrs or older. CONCLUSIONS: Skeletal muscle index determined by computed tomography at the level of twelfth thoracic vertebra was not associated with negative outcomes in hospitalized patients with COVID-19.

Prospective Latin American cohort evaluating outcomes of patients with COVID-19 and abnormal liver tests on admission.

INTRODUCTION & OBJECTIVES: The independent effect of liver biochemistries as a prognostic factor in patients with COVID-19 has not been completely addressed. We aimed to evaluate the prognostic value of abnormal liver tests on admission of hospitalized patients with COVID-19. MATERIALS & METHODS: We performed a prospective cohort study including 1611 hospitalized patients with confirmed SARS-CoV-2 infection from April 15, 2020 through July 31, 2020 in 38 different Hospitals from 11 Latin American countries. We registered clinical and laboratory parameters, including liver function tests, on admission and during hospitalization. All patients were followed until discharge or death. We fit multivariable logistic regression models, further post-estimation effect through margins and inverse probability weighting. RESULTS: Overall, 57.8% of the patients were male with a mean age of 52.3 years, 8.5% had chronic liver disease and 3.4% had cirrhosis. Abnormal liver tests on admission were present on 45.2% (CI 42.7-47.7) of the cohort (n = 726). Overall, 15.1% (CI 13.4-16.9) of patients died (n = 244). Patients with abnormal liver tests on admission presented higher mortality 18.7% (CI 15.9-21.7), compared to those with normal liver biochemistries 12.2% (CI 10.1-14.6); P < .0001). After excluding patients with history of chronic liver disease, abnormal liver tests on admission were independently associated with death [OR 1.5 (CI 1.1-2.0); P = 0.01], and severe COVID-19 (2.6 [2.0-3.3], P < .0001), both adjusted by age, gender, diabetes, pneumonia and body mass index >30. CONCLUSIONS: The presence of abnormal liver tests on admission is independently associated with mortality and severe COVID-19 in hospitalized patients with COVID-19 infection and may be used as surrogate marker of inflammation. CLINICALTRIALS.GOV: NCT04358380.

Bacterial infections in cirrhosis: Current treatment.

Bacterial infections frequently cause decompensating events in cirrhotic patients and are also the most common factor identified for the development of acute-on-chronic liver failure (ACLF). The increase in the prevalence of infections caused by multidrug-resistant (MDR) microorganisms has resulted in the reduced effectiveness of empiric antimicrobial treatment. We conducted a PubMed search from the last 20 years using the Keywords cirrhosis; multidrug-resistant; infections; diagnosis; treatment; prophylaxis; monitoring; sepsis; nutrition and antibiotic resistant. We made a review about bacterial infections among cirrhotic patients; we mainly focus on the description of diagnostic tools; biomarkers; clinical scores for diagnosis and prognosis also; we made an analysis concerning the monitoring of cirrhotic patients with sepsis and finally made some recommendations about the treatment; prophylaxis and prevention.

The impact of different infectious complications on mortality of hospitalized patients with liver cirrhosis.

INTRODUCTION AND OBJECTIVES: Bacterial infections are common complications in patients with cirrhosis and are associated with poor prognosis. There are no studies that analyze the impact of different infectious complications in the mortality of these patients, so we aimed to perform this evaluation. MATERIALS AND METHODS: We performed a case-control study in adult patients with cirrhosis with a follow-up period of one year. We recorded demographic data, prognostic scales, infectious complications and mortality at 30, 90 and 365 days. For the survival analysis, Kaplan-Meyer survival curve was performed and hazard ratios were calculated with 95% confidence intervals by Cox-regression in univariate and multivariate models. For the comparison between groups the Chi squared test, Fisher's exact test and Mann-Whitney U test were performed. RESULTS: We included 500 patients. Median age was 58 years, predominant sex was woman (52%) and the most common infections were urinary tract infections (35%), pneumonia (28.2%) and spontaneous bacterial peritonitis (SBP) (18%). From the patients, 40.4% were CTP score C and median MELD score was 15. In the univariate analysis, infections in general, SBP, pneumonia and central nervous system (CNS) infections had an increased mortality at the three follow up periods, however in the multivariate analysis with the prognostic scales, only pneumonia (HR 2.03, CI 95%[1.06-3.86]) and CNS infections (HR 4.84, CI 95%[1.38-16.93]) remained with increased mortality. CONCLUSIONS: Some infectious complications, as pneumonia and CNS infections, increase mortality in hospitalized patients with cirrhosis, regardless of the severity of liver disease.