An artificial intelligence-generated model predicts 90-day survival in alcohol-associated hepatitis: A global cohort study.

BACKGROUND AIMS: Alcohol-associated hepatitis (AH) poses significant short-term mortality. Existing prognostic models lack precision for 90-day mortality. Utilizing artificial intelligence (AI) in a global cohort, we sought to derive and validate an enhanced prognostic model. APPROACH AND RESULTS: The Global AlcHep initiative, a retrospective study across 23 centers in 12 countries, enrolled AH patients per NIAAA criteria. Centers were partitioned into derivation (11 centers, 860 patients) and validation cohorts (12 centers, 859 patients). Focusing on 30 and 90-day post-admission mortality, three AI algorithms (Random Forest, Gradient Boosting Machines, and eXtreme Gradient Boosting) informed an ensemble model, subsequently refined via Bayesian updating, integrating the derivation cohort's average 90-day mortality with each center's approximate mortality rate to produce post-test probabilities. The ALCoholic Hepatitis Artificial INtelligence (ALCHAIN) Ensemble score integrated age, gender, cirrhosis, and 9 laboratory values, with center-specific mortality rates. Mortality was 18.7% (30-day) and 27.9% (90-day) in the derivation cohort, versus 21.7% and 32.5% in the validation cohort. Validation cohort 30 and 90-day AUCs were 0.811 (0.779 - 0.844) and 0.799 (0.769 - 0.830), significantly surpassing legacy models like Maddrey's Discriminant Function, MELD variations, ABIC, Glasgow, and modified Glasgow Scores (p<0.001). ALCHAIN Ensemble score also showcased superior calibration against MELD and its variants. Steroid use improved 30-day survival for those with an ALCHAIN Ensemble score>0.20 in both derivation and validation cohorts. CONCLUSIONS: Harnessing AI within a global consortium, we pioneered a scoring system excelling over traditional models for 30 and 90-day AH mortality predictions. Beneficial for clinical trials, steroid therapy, and transplant indications, it's accessible at: https://aihepatology.shinyapps.io/ALCHAIN/.

MELD 3.0 adequately predicts mortality and renal replacement therapy requirements in patients with alcohol-associated hepatitis.

Background & Aims: Model for End-Stage Liver Disease (MELD) score better predicts mortality in alcohol-associated hepatitis (AH) but could underestimate severity in women and malnourished patients. Using a global cohort, we assessed the ability of the MELD 3.0 score to predict short-term mortality in AH. Methods: This was a retrospective cohort study of patients admitted to hospital with AH from 2009 to 2019. The main outcome was all-cause 30-day mortality. We compared the AUC using DeLong's method and also performed a time-dependent AUC with competing risks analysis. Results: A total of 2,124 patients were included from 28 centres from 10 countries on three continents (median age 47.2 ± 11.2 years, 29.9% women, 71.3% with underlying cirrhosis). The median MELD 3.0 score at admission was 25 (20-33), with an estimated survival of 73.7% at 30 days. The MELD 3.0 score had a better performance in predicting 30-day mortality (AUC:0.761, 95%CI:0.732-0.791) compared with MELD sodium (MELD-Na; AUC: 0.744, 95% CI: 0.713-0.775; p = 0.042) and Maddrey's discriminant function (mDF) (AUC: 0.724, 95% CI: 0.691-0.757; p = 0.013). However, MELD 3.0 did not perform better than traditional MELD (AUC: 0.753, 95% CI: 0.723-0.783; p = 0.300) and Age-Bilirubin-International Normalised Ratio-Creatinine (ABIC) (AUC:0.757, 95% CI: 0.727-0.788; p = 0.765). These results were consistent in competing-risk analysis, where MELD 3.0 (AUC: 0.757, 95% CI: 0.724-0.790) predicted better 30-day mortality compared with MELD-Na (AUC: 0.739, 95% CI: 0.708-0.770; p = 0.028) and mDF (AUC:0.717, 95% CI: 0.687-0.748; p = 0.042). The MELD 3.0 score was significantly better in predicting renal replacement therapy requirements during admission compared with the other scores (AUC: 0.844, 95% CI: 0.805-0.883). Conclusions: MELD 3.0 demonstrated better performance compared with MELD-Na and mDF in predicting 30-day and 90-day mortality, and was the best predictor of renal replacement therapy requirements during admission for AH. However, further prospective studies are needed to validate its extensive use in AH. Impact and implications: Severe AH has high short-term mortality. The establishment of treatments and liver transplantation depends on mortality prediction. We evaluated the performance of the new MELD 3.0 score to predict short-term mortality in AH in a large global cohort. MELD 3.0 performed better in predicting 30- and 90-day mortality compared with MELD-Na and mDF, but was similar to MELD and ABIC scores. MELD 3.0 was the best predictor of renal replacement therapy requirements. Thus, further prospective studies are needed to support the wide use of MELD 3.0 in AH.

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.

Procedural-Related Bleeding in Hospitalized Patients With Liver Disease (PROC-BLeeD): An International, Prospective, Multicenter Observational Study.

BACKGROUND & AIMS: Hospitalized patients with cirrhosis frequently undergo multiple procedures. The risk of procedural-related bleeding remains unclear, and management is not standardized. We conducted an international, prospective, multicenter study of hospitalized patients with cirrhosis undergoing nonsurgical procedures to establish the incidence of procedural-related bleeding and to identify bleeding risk factors. METHODS: Hospitalized patients were prospectively enrolled and monitored until surgery, transplantation, death, or 28 days from admission. The study enrolled 1187 patients undergoing 3006 nonsurgical procedures from 20 centers. RESULTS: A total of 93 procedural-related bleeding events were identified. Bleeding was reported in 6.9% of patient admissions and in 3.0% of the procedures. Major bleeding was reported in 2.3% of patient admissions and in 0.9% of the procedures. Patients with bleeding were more likely to have nonalcoholic steatohepatitis (43.9% vs 30%) and higher body mass index (BMI; 31.2 vs 29.5). Patients with bleeding had a higher Model for End-Stage Liver Disease score at admission (24.5 vs 18.5). A multivariable analysis controlling for center variation found that high-risk procedures (odds ratio [OR], 4.64; 95% confidence interval [CI], 2.44-8.84), Model for End-Stage Liver Disease score (OR, 2.37; 95% CI, 1.46-3.86), and higher BMI (OR, 1.40; 95% CI, 1.10-1.80) independently predicted bleeding. Preprocedure international normalized ratio, platelet level, and antithrombotic use were not predictive of bleeding. Bleeding prophylaxis was used more routinely in patients with bleeding (19.4% vs 7.4%). Patients with bleeding had a significantly higher 28-day risk of death (hazard ratio, 6.91; 95% CI, 4.22-11.31). CONCLUSIONS: Procedural-related bleeding occurs rarely in hospitalized patients with cirrhosis. Patients with elevated BMI and decompensated liver disease who undergo high-risk procedures may be at risk to bleed. Bleeding is not associated with conventional hemostasis tests, preprocedure prophylaxis, or recent antithrombotic therapy.

Hepatitis C screening and detection program in a large population: Epidemiological transition and characterization of the disease.

INTRODUCTION: Chronic hepatitis C (CHC) is considered an important public health challenge. Traditionally identified risk factors have undergone an epidemiological transition where other risk factors have become the main cause of new infections. OBJECTIVE: To describe risk factors associated to hepatitis C positivity through the evaluation of the epidemiological profile in hepatitis-C high-risk populations. METHODS: Cross-sectional study was conducted as part of an HCV screening program in Mexican population. All participants answered an HCV risk-factor questionnaire and took a rapid test (RT). All patients reactive to the test were subject to HCV PCR (polymerase chain reaction) confirmation. A logistic regression model was used to examine associations between HCV infection and risk factors. RESULTS: The study included 297 631 participants that completed a risk factor questionnaire and underwent an HCV rapid test (RT). In total, 12 840 (4.5%) were reactive to RT and 9257 (3.2% of participants) were confirmed as positives by PCR test. Of these, 72.9% had at least one risk factor and 10.8% were in prison. Most common risk factors were history of acupuncture/tattooing/piercing (21%), intravenous drug use (15%) and high-risk sexual practices (12%). Logistic regressions found that having at least one risk factor increased the probability of having an HCV-positive result by 20% (OR = 1.20, 95% CI: 1.15-1.26), compared to the population without risk factors. CONCLUSIONS: We identified 3.2% of HCV-viremic subjects, all associated with risk factors and older age. Screening and diagnosis of HCV in high-risk populations (including underserved populations) should be more efficient.

Exploration of the Severity of Hepatic Encephalopathy Deterioration Process Through Dynamics of the EEG Band Power time series.

Cirrhosis is a liver disease that could impair the functionality of the neural system, limiting cognitive processes and reduce mobility, possibly because alterations on dynamics of neural communications. In this study the dynamics of band power fluctuations on ß and γ bands were studied on three groups: control, patients with cirrhosis and patients diagnosed with minimal hepatic encephalopathy. EEG signals were recorded on an oddball paradigm and analyzed to obtain the latency and amplitude of the P300 wave and Detrended Fluctuation Analysis (DFA) exponent values over ß and γ band power time series for each channel. As expected, the latency of the P300 wave was significantly different for control subjects ( ). Amplitudes were not as different, but they tend to decrease for cirrhosis and minimal hepatic encephalopathy groups. DFA exponent values also tends to describe a more regular process and seems to be related with presence of symptoms of hepatic encephalopathy. These subtle changes could be produced by the mechanisms of a mild neurological impairment and be used, if it is confirmed, as an index to evaluate such deterioration.

Alcoholic Liver Disease.

Content available: Author Interview and Audio Recording.

Auditory and visual P300 event-related potentials to detect minimal hepatic encephalopathy.

INTRODUCTION: the diagnosis of minimal hepatic encephalopathy (MHE) requires psychometric tests, although new methods are needed since their sensitivity, specificity, and accuracy are low. The P300 event-related potential (ERP) is obtained by auditory and visual stimuli, although only the auditory P300 has been used to detect MHE. This study aimed to compare the diagnostic features of auditory and visual P300 to detect MHE. MATERIALS AND METHODS: sixty patients with liver cirrhosis and thirty-five healthy controls completed the Psychometric Hepatic Encephalopathy Score (PHES), the critical flicker frequency (CFF), and auditory and visual P300 tests. MHE was diagnosed if PHES and CFF scores were abnormal. RESULTS: fifty-three cirrhotic patients (aged 54.5 ± 8.6 years) completed all tests. Abnormal scores were obtained for PHES (49.1 %) and CFF (67.9 %). The proportion of MHE was 21.4 %. The area under the receiver operating (ROC) curves (AUROC) for auditory P300 was better than for visual P300 for distinguishing MHE from controls (AUROC: 0.792 vs 0.725; p < 0.005 for both; accuracy: 73.8 % vs 70.2 %; sensitivity: 72.2 % for both; specificity: 74.2 vs 69.7, respectively). Among cirrhotic patients, only auditory P300 was useful to detect MHE (AUROC: 0.723; p < 0.05; 77.4 % accuracy; 61.1 % sensitivity, and 81.8 % specificity). CONCLUSIONS: auditory P300 sensitivity, specificity, and accuracy were similar to those of CFF. Our results showed that only auditory P300 is useful to differentiate patients with MHE, although both modalities, auditory and visual, differentiated patients with cirrhosis from controls. Thus, we consider that visual P300 is not suitable for detecting MHE.

Effects of immunosuppressive drugs on COVID-19 severity in patients with autoimmune hepatitis.

BACKGROUND: We investigated associations between baseline use of immunosuppressive drugs and severity of Coronavirus Disease 2019 (COVID-19) in autoimmune hepatitis (AIH). PATIENTS AND METHODS: Data of AIH patients with laboratory confirmed COVID-19 were retrospectively collected from 15 countries. The outcomes of AIH patients who were on immunosuppression at the time of COVID-19 were compared to patients who were not on AIH medication. The clinical courses of COVID-19 were classified as (i)-no hospitalization, (ii)-hospitalization without oxygen supplementation, (iii)-hospitalization with oxygen supplementation by nasal cannula or mask, (iv)-intensive care unit (ICU) admission with non-invasive mechanical ventilation, (v)-ICU admission with invasive mechanical ventilation or (vi)-death and analysed using ordinal logistic regression. RESULTS: We included 254 AIH patients (79.5%, female) with a median age of 50 (range, 17-85) years. At the onset of COVID-19, 234 patients (92.1%) were on treatment with glucocorticoids (n = 156), thiopurines (n = 151), mycophenolate mofetil (n = 22) or tacrolimus (n = 16), alone or in combinations. Overall, 94 (37%) patients were hospitalized and 18 (7.1%) patients died. Use of systemic glucocorticoids (adjusted odds ratio [aOR] 4.73, 95% CI 1.12-25.89) and thiopurines (aOR 4.78, 95% CI 1.33-23.50) for AIH was associated with worse COVID-19 severity, after adjusting for age-sex, comorbidities and presence of cirrhosis. Baseline treatment with mycophenolate mofetil (aOR 3.56, 95% CI 0.76-20.56) and tacrolimus (aOR 4.09, 95% CI 0.69-27.00) were also associated with more severe COVID-19 courses in a smaller subset of treated patients. CONCLUSION: Baseline treatment with systemic glucocorticoids or thiopurines prior to the onset of COVID-19 was significantly associated with COVID-19 severity in patients with AIH.

Long-standing effect of cholecystectomy in patients with metabolic-associated fatty liver disease.

OBJECTIVE: The role of cholecystectomy as a risk factor in patients with metabolic-associated fatty liver disease (MAFLD) remains unclear. This study aimed to investigate if long-standing cholecystectomy is associated with advanced liver fibrosis and cirrhosis in patients with recently diagnosed MAFLD. METHODS: A retrospective observational study was performed in four hospitals in Mexico including patients with recently diagnosed MAFLD and a history of cholecystectomy. Subjects were divided into those with cholecystectomy ≥6 months before MAFLD diagnosis (ChBM), and those with cholecystectomy at the time of MAFLD diagnosis (ChAM). Odds ratios (OR) for the association of advanced liver fibrosis and cirrhosis with the timing of cholecystectomy were calculated. RESULTS: Mean age of 211 participants was 49.06 ± 15.12 years and the majority were female (72.5%). Patients from the ChBM (n = 70) group were significantly older (53.14 vs. 47.03 years; P = 0.003), had higher BMI (30.54 vs. 28.52 kg/m2; P = 0.011) and lower platelet count (236.23 vs. 266.72 × 103/µL; P = 0.046) compared with patients from ChAM group (n = 141). In multivariable-adjusted analysis, age (OR = 2.37; P = 0.024), dyslipidemia (OR = 4.28; P = 0.005) and severe liver fibrosis (OR = 4.68; P = 0.0) were independent risk factors associated with long-standing cholecystectomy. CONCLUSION: Patients with long-standing cholecystectomy (≥6 months) are at increased risk of severe liver fibrosis and cirrhosis at the time of MAFLD diagnosis compared to those with recently done cholecystectomy. Advanced age (>50 years) and dyslipidemia are also commonly found in these subjects.

Progress and challenges in the comprehensive management of chronic viral hepatitis: Key ways to achieve the elimination.

Chronic viral hepatitis is a significant health problem throughout the world, which already represents high annual mortality. By 2040, chronic viral hepatitis due to virus B and virus C and their complications cirrhosis and hepatocellular carcinoma will be more deadly than malaria, vitellogenesis-inhibiting hormone, and tuberculosis altogether. In this review, we analyze the global impact of chronic viral hepatitis with a focus on the most vulnerable groups, the goals set by the World Health Organization for the year 2030, and the key points to achieve them, such as timely access to antiviral treatment of direct-acting antiviral, which represents the key to achieving hepatitis C virus elimination. Likewise, we review the strategies to prevent transmission and achieve control of hepatitis B virus. Finally, we address the impact that the coronavirus disease 2019 pandemic has had on implementing elimination strategies and the advantages of implementing telemedicine programs.

Impact of Public Health Policies on Alcohol-Associated Liver Disease in Latin America: An Ecological Multinational Study.

BACKGROUND AND AIMS: Alcohol-associated liver disease (ALD) is the leading cause of liver-related mortality in Latin America, yet the impact of public health policies (PHP) on liver disease is unknown. We aimed to assess the association between alcohol PHP and deaths due to ALD in Latin American countries. APPROACH AND RESULTS: We performed an ecological multinational study including 20 countries in Latin America (628,466,088 inhabitants). We obtained country-level sociodemographic information from the World Bank Open Data source. Alcohol-related PHP data for countries were obtained from the World Health Organization Global Information System of Alcohol and Health. We constructed generalized linear models to assess the association between the number of PHP (in 2010) and health outcomes (in 2016). In Latin America, the prevalence of obesity was 27% and 26.1% among male and female populations, respectively. The estimated alcohol per capita consumption among the population at 15 years old or older was 6.8 L of pure alcohol (5.6 recorded and 1.2 unrecorded). The overall prevalence of alcohol use disorders (AUD) was 4.9%. ALD was the main cause of cirrhosis in 64.7% of male and 40.0% of female populations. A total of 19 (95%) countries have at least one alcohol-related PHP on alcohol. The most frequent PHP were limiting drinking age (95%), tax regulations (90%), drunk-driving policies and countermeasures (90%), and government monitoring systems and community support (90%). A higher number of PHP was associated with a lower ALD mortality (PR, 0.76; 95% CI, 0.61-0.93; P = 0.009), lower AUD prevalence (PR, 0.80; 95% CI, 0.65-0.99; P = 0.045), and lower alcohol-attributable road traffic deaths (PR, 0.81; 95% CI, 0.65-1.00; P = 0.051). CONCLUSIONS: Our study indicates that in Latin America, countries with higher number of PHP have lower mortality due to ALD, lower prevalence of AUD, and lower alcohol-attributable road traffic mortality.

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.

The Age-AST-D Dimer (AAD) Regression Model Predicts Severe COVID-19 Disease.

AIM: Coronavirus disease (COVID-19) ranges from mild clinical phenotypes to life-threatening conditions like severe acute respiratory syndrome (SARS). It has been suggested that early liver injury in these patients could be a risk factor for poor outcome. We aimed to identify early biochemical predictive factors related to severe disease development with intensive care requirements in patients with COVID-19. METHODS: Data from COVID-19 patients were collected at admission time to our hospital. Differential biochemical factors were identified between seriously ill patients requiring intensive care unit (ICU) admission (ICU patients) versus stable patients without the need for ICU admission (non-ICU patients). Multiple linear regression was applied, then a predictive model of severity called Age-AST-D dimer (AAD) was constructed (n = 166) and validated (n = 170). RESULTS: Derivation cohort: from 166 patients included, there were 27 (16.3%) ICU patients that showed higher levels of liver injury markers (P < 0.01) compared with non-ICU patients: alanine aminotrasnferase (ALT) 225.4 ± 341.2 vs. 41.3 ± 41.1, aspartate aminotransferase (AST) 325.3 ± 382.4 vs. 52.8 ± 47.1, lactic dehydrogenase (LDH) 764.6 ± 401.9 vs. 461.0 ± 185.6, D-dimer (DD) 7765 ± 9109 vs. 1871 ± 4146, and age 58.6 ± 12.7 vs. 49.1 ± 12.8. With these finding, a model called Age-AST-DD (AAD), with a cut-point of <2.75 (sensitivity = 0.797 and specificity = 0.391, c - statistic = 0.74; 95%IC: 0.62-0.86, P < 0.001), to predict the risk of need admission to ICU (OR = 5.8; 95% CI: 2.2-15.4, P = 0.001), was constructed. Validation cohort: in 170 different patients, the AAD model < 2.75 (c - statistic = 0.80 (95% CI: 0.70-0.91, P < 0.001) adequately predicted the risk (OR = 8.8, 95% CI: 3.4-22.6, P < 0.001) to be admitted in the ICU (27 patients, 15.95%). CONCLUSIONS: The elevation of AST (a possible marker of early liver injury) along with DD and age efficiently predict early (at admission time) probability of ICU admission during the clinical course of COVID-19. The AAD model can improve the comprehensive management of COVID-19 patients, and it could be useful as a triage tool to early classify patients with a high risk of developing a severe clinical course of the disease.

Outcome of COVID-19 in Patients With Autoimmune Hepatitis: An International Multicenter Study.

BACKGROUND AND AIMS: Data regarding outcome of COVID-19 in patients with autoimmune hepatitis (AIH) are lacking. APPROACH AND RESULTS: We performed a retrospective study on patients with AIH and COVID-19 from 34 centers in Europe and the Americas. We analyzed factors associated with severe COVID-19 outcomes, defined as the need for mechanical ventilation, intensive care admission, and/or death. The outcomes of patients with AIH were compared to a propensity score-matched cohort of patients without AIH but with chronic liver diseases (CLD) and COVID-19. The frequency and clinical significance of new-onset liver injury (alanine aminotransferase > 2 × the upper limit of normal) during COVID-19 was also evaluated. We included 110 patients with AIH (80% female) with a median age of 49 (range, 18-85) years at COVID-19 diagnosis. New-onset liver injury was observed in 37.1% (33/89) of the patients. Use of antivirals was associated with liver injury (P = 0.041; OR, 3.36; 95% CI, 1.05-10.78), while continued immunosuppression during COVID-19 was associated with a lower rate of liver injury (P = 0.009; OR, 0.26; 95% CI, 0.09-0.71). The rates of severe COVID-19 (15.5% versus 20.2%, P = 0.231) and all-cause mortality (10% versus 11.5%, P = 0.852) were not different between AIH and non-AIH CLD. Cirrhosis was an independent predictor of severe COVID-19 in patients with AIH (P < 0.001; OR, 17.46; 95% CI, 4.22-72.13). Continuation of immunosuppression or presence of liver injury during COVID-19 was not associated with severe COVID-19. CONCLUSIONS: This international, multicenter study reveals that patients with AIH were not at risk for worse outcomes with COVID-19 than other causes of CLD. Cirrhosis was the strongest predictor for severe COVID-19 in patients with AIH. Maintenance of immunosuppression during COVID-19 was not associated with increased risk for severe COVID-19 but did lower the risk for new-onset liver injury during COVID-19.

Lactate-dehydrogenase associated with mortality in hospitalized patients with COVID-19 in Mexico: a multi-centre retrospective cohort study.

INTRODUCTION AND OBJECTIVES: As of January 2021, over 88 million people have been infected with COVID-19. Almost two million people have died of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A high SOFA score and a D-Dimer >1 µg/mL identifies patients with high risk of mortality. High lactate dehydrogenase (LDH) levels on admission are associated with severity and mortality. Different degrees of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) abnormalities have been reported in these patients, its association with a mortality risk remains controversial. The aim of this study was to explore the correlation between LDH and in-hospital mortality in Mexican patients admitted with COVID-19. MATERIALS & METHODS: We performed a retrospective multi-centre cohort study with 377 hospitalized patients with confirmed SARS-CoV-2 in three centres in Mexico City, Mexico, who were ≥18 years old and died or were discharged between April 1 and May 31, 2020. RESULTS: A total of 377 patients were evaluated, 298 (79.1%) patients were discharged, and 79 (20.9%) patients died during hospitalization. Non-survivors were older, with a median age of 46.7 ± 25.7 years old, most patients were male. An ALT > 61 U/l (OR 3.45, 95% CI 1.27-9.37; p = 0.015), C-reactive protein (CRP) > 231 mg/l (OR 4.71, 95% CI 2.35-9.46; p = 0.000), LDH > 561 U/l (OR 3.03, 95% CI 1.40-6.55; p = 0.005) were associated with higher odds for in-hospital death. CONCLUSIONS: Our results indicate that higher levels of LDH, CRP, and ALT are associated with higher in-hospital mortality risk in Mexican patients admitted with COVID-19.

Production and activity of matrix metalloproteinases during liver fibrosis progression of chronic hepatitis C patients.

BACKGROUND: Matrix metalloproteinases (MMPs) participate in the degradation of extracellular matrix compounds, maintaining the homeostasis between fibrogenesis and fibrolytic processes in the liver. However, there are few studies on the regulation of liver MMPs in fibrosis progression in humans. AIM: To assess the production activity and regulation of matrix metalloproteinases in liver fibrosis stages in chronic hepatitis C (CHC). METHODS: A prospective, cross-sectional, multicenter study was conducted. CHC patients were categorized in fibrosis grades through FibroTest ® and/or FibroScan ® . Serum MMP-2, -7, and -9 were determined by western blot and multiplex suspension array assays. Differences were validated by the Kruskal-Wallis and Mann-Whitney U tests. The Spearman correlation coefficient and area under the receiver operating characteristic curve were calculated. Collagenolytic and gelatinase activity was determined through the Azocoll substrate and zymogram test, whereas tissue inhibitor of metalloproteinase-1 production was determined by dot blot assays. RESULTS: Serum concentrations of the MMPs evaluated were higher in CHC patients than in healthy subjects. MMP-7 distinguished early and advanced stages, with a correlation of 0.32 (P < 0.001), and the area under the receiver operating characteristic displayed moderate sensitivity and specificity for MMP-7 in F4 (area under the receiver operating characteristic, 0.705; 95% confidence interval: 0.605-0.805; P < 0.001). Collagenolytic activity was detected at F0 and F1, whereas gelatinase activity was not detected at any fibrosis stage. Tissue inhibitor of metalloproteinase-1 determination showed upregulation in F0 and F1 but downregulation in F2 (P < 0.001). CONCLUSION: High concentrations of inactive MMPs were present in the serum of CHC patients, reflecting the impossibility to restrain liver fibrosis progression. MMPs could be good diagnostic candidates and therapeutic targets for improving novel strategies to reverse liver fibrosis in CHC.

Impact of liver enzymes on SARS-CoV-2 infection and the severity of clinical course of COVID-19.

BACKGROUND AND AIM: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the current pandemic, can have multi-organ impact. Recent studies show that liver injury could be a manifestation of the disease, and that liver disease could also be related to a worse prognosis. Our aim was to compare the characteristics of patients with severe coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 who required intubation versus stable hospitalized patients to identify the early biochemical predictive factors of a severe course of COVID-19 and subsequent requirement for intubation, specifically in Mexican. METHODS: This was an observational case-control study nested in a cohort study. Complete medical records of patients admitted for confirmed COVID-19 at a tertiary level center in Mexico City were reviewed. Clinical and biochemical data were collected, and the characteristics of patients who required invasive mechanical ventilation (IMV) (cases) were compared with stable hospitalized patients without ventilation (controls). RESULTS: We evaluated 166 patients with COVID-19 due to SARS-CoV-2 infection; 114 (68.7%) were men, the mean age was 50.6 ± 13.3 years, and 27 (16.3%) required IMV. The comparative analysis between cases and controls showed (respectively) significantly lower blood oxygen saturation (SpO2) (73.5 ± 12.0% vs. 83.0 ± 6.8%, P < 0.0001) and elevated alanine aminotransferase (ALT) (128 (14-1123) IU/L vs. 33 (8-453) IU/L, P = 0.003), aspartate aminotransferase (AST) (214 (17-1247) vs. 44 (12-498) IU/L, P = 0.001), lactic dehydrogenase (LDH) (764.6 ± 401.9 IU/L vs. 461.0 ± 185.6 IU/L, P = 0.001), and D-dimer (3463 (524-34,227) ng/mL vs. 829 (152-41,923) ng/mL, P = 0.003) concentrations. Patients in the cases group were older (58.6 ± 12.7 years vs. 49.1 ± 12.8 years, P=0.001). Multivariate analysis showed that important factors at admission predicting the requirement for IMV during hospitalization for COVID-19 were AST ≥250 IU/L (odds ratio (OR) = 64.8, 95% confidence interval (CI) 7.5-560.3, P < 0.0001) and D-dimer ≥ 3500 ng/mL (OR = 4.1, 95% CI 1.2-13.7, P=0.02). CONCLUSIONS: Our study confirms the importance of monitoring liver enzymes in hospitalized patients with COVID-19; seriously ill patients have significantly elevated AST and D-dimer concentrations, which have prognostic implications in the SARS-CoV-2 disease course.