Optimizing nutrition in hepatic cirrhosis: A comprehensive assessment and care approach.

Cirrhosis is considered a growing cause of morbidity and mortality, which represents a significant public health problem. Currently, there is no effective treatment to reverse cirrhosis. Treatment primarily centers on addressing the underlying liver condition, monitoring, and managing portal hypertension-related complications, and evaluating the potential for liver transplantation in cases of decompensated cirrhosis, marked by rapid progression and the emergence of complications like variceal bleeding, hepatic encephalopathy, ascites, malnutrition, and more. Malnutrition, a prevalent complication across all disease stages, is often underdiagnosed in cirrhosis due to the complexities of nutritional assessment in patients with fluid retention and/or obesity, despite its crucial impact on prognosis. Increasing emphasis has been placed on the collaboration of nutritionists within hepatology and Liver transplant teams to deliver comprehensive care, a practice that has shown to improve outcomes. This review covers appropriate screening and assessment methods for evaluating the nutritional status of this population, diagnostic approaches for malnutrition, and context-specific nutrition treatments. It also discusses evidence-based recommendations for supplementation and physical exercise, both essential elements of the standard care provided to cirrhotic patients.

Geographic disparities in access to liver transplant for advanced cirrhosis: Time to ring the alarm!

Decompensated cirrhosis and hepatocellular cancer are major risk factors for mortality worldwide. Liver transplantation (LT), both live-donor LT or deceased-donor LT, are lifesaving, but there are several barriers toward equitable access. These barriers are exacerbated in the setting of critical illness or acute-on-chronic liver failure. Rates of LT vary widely worldwide but are lowest in lower-income countries owing to lack of resources, infrastructure, late disease presentation, and limited donor awareness. A recent experience by the Chronic Liver Disease Evolution and Registry for Events and Decompensation consortium defined these barriers toward LT as critical in determining overall survival in hospitalized cirrhosis patients. A major focus should be on appropriate, affordable, and early cirrhosis and hepatocellular cancer care to prevent the need for LT. Live-donor LT is predominant across Asian countries, whereas deceased-donor LT is more common in Western countries; both approaches have unique challenges that add to the access disparities. There are many challenges toward equitable access but uniform definitions of acute-on-chronic liver failure, improving transplant expertise, enhancing availability of resources and encouraging knowledge between centers, and preventing disease progression are critical to reduce LT disparities.

Rifaximin Alfa and Liver Diseases: More Than a Treatment for Encephalopathy, a Disease Modifier.

RFX, a rifamycin-based antibacterial agent obtained by the culture of the actinomycete Streptomyces mediterranei, has a broad antibacterial spectrum covering gram- positive, gram-negative, aerobic, and anaerobic bacteria. RFX is an antibiotic that elicits its effect by inhibiting bacterial RNA synthesis. When administered orally, its intestinal absorption is extremely low (<0.4%), restricting antibacterial activity mainly in the intestinal tract, with few systemic side effects. RFX has been recommended by the American Association for the Study of Liver Diseases and the European Association for the Study of the Liver guidelines for the treatment of HE. RFX may contribute to restore hepatic function and to decrease the development of liver fibrosis. Its efficacy has been shown in patients with previous hepatic encephalopathy and several complications, such as infections, including spontaneous bacterial peritonitis, ascites and oesophageal variceal bleeding. Thus, RFX has an outstanding role in the therapeutic arsenal in hepatic cirrhosis, under the concept of disease modifier.

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.

Genetic Ancestry, Race, and Severity of Acutely Decompensated Cirrhosis in Latin America.

BACKGROUND & AIMS: Genetic ancestry or racial differences in health outcomes exist in diseases associated with systemic inflammation (eg, COVID-19). This study aimed to investigate the association of genetic ancestry and race with acute-on-chronic liver failure (ACLF), which is characterized by acute systemic inflammation, multi-organ failure, and high risk of short-term death. METHODS: This prospective cohort study analyzed a comprehensive set of data, including genetic ancestry and race among several others, in 1274 patients with acutely decompensated cirrhosis who were nonelectively admitted to 44 hospitals from 7 Latin American countries. RESULTS: Three hundred ninety-five patients (31.0%) had ACLF of any grade at enrollment. Patients with ACLF had a higher median percentage of Native American genetic ancestry and lower median percentage of European ancestry than patients without ACLF (22.6% vs 12.9% and 53.4% vs 59.6%, respectively). The median percentage of African genetic ancestry was low among patients with ACLF and among those without ACLF. In terms of race, a higher percentage of patients with ACLF than patients without ACLF were Native American and a lower percentage of patients with ACLF than patients without ACLF were European American or African American. In multivariable analyses that adjusted for differences in sociodemographic and clinical characteristics, the odds ratio for ACLF at enrollment was 1.08 (95% CI, 1.03-1.13) with Native American genetic ancestry and 2.57 (95% CI, 1.84-3.58) for Native American race vs European American race CONCLUSIONS: In a large cohort of Latin American patients with acutely decompensated cirrhosis, increasing percentages of Native American ancestry and Native American race were factors independently associated with ACLF at enrollment.

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.

Silymarin in the management of liver enzyme activity in steatohepatitis: a case report.

Metabolic-associated fatty liver disease (MAFLD) is the main condition of altered liver enzymes worldwide. With a constant increase in liver hospitalizations, MAFLD is the second cause of cirrhosis and soon will be the first cause of liver transplantation. Early recognition of MAFLD and a personalized approach are essential to its treatment. This case study presents personalized management of a patient with MAFLD with advanced fibrosis and severe steatosis. The impact of silymarin use, concomitant treatment with diet, exercise, insulin sensitizers and antifibrotic agents, was evaluated. This article is part of the Current clinical use of silymarin in the treatment of toxic liver diseases: a case series Special Issue: https://www.drugsincontext.com/special_issues/current-clinical-use-of-silymarin-in-the-treatment-of-toxic-liver-diseases-a-case-series.

Implementation of a re-linkage to care strategy in patients with chronic hepatitis C who were lost to follow-up in Latin America.

To achieve WHO's goal of eliminating hepatitis C virus (HCV), innovative strategies must be designed to diagnose and treat more patients. Therefore, we aimed to describe an implementation strategy to identify patients with HCV who were lost to follow-up (LTFU) and offer them re-linkage to HCV care. We conducted an implementation study utilizing a strategy to contact patients with HCV who were not under regular follow-up in 13 countries from Latin America. Patients with HCV were identified by the international classification of diseases (ICD-9/10) or equivalent. Medical records were then reviewed to confirm the diagnosis of chronic HCV infection defined by anti-HCV+ and detectable HCV-RNA. Identified patients who were not under follow-up by a liver specialist were contacted by telephone or email, and offered a medical reevaluation. A total of 10,364 patients were classified to have HCV. After reviewing their medical charts, 1349 (13%) had undetectable HCV-RNA or were wrongly coded. Overall, 9015 (86.9%) individuals were identified with chronic HCV infection. A total of 5096 (56.5%) patients were under routine HCV care and 3919 (43.5%) had been LTFU. We were able to contact 1617 (41.3%) of the 3919 patients who were LTFU at the primary medical institution, of which 427 (26.4%) were cured at a different institutions or were dead. Of the remaining patients, 906 (76.1%) were candidates for retrieval. In our cohort, about one out of four patients with chronic HCV who were LTFU were candidates to receive treatment. This strategy has the potential to be effective, accessible and significantly impacts on the HCV care cascade.

Liver transplantation is beneficial regardless of cirrhosis stage or acute-on-chronic liver failure grade: A single-center experience.

BACKGROUND: Liver transplantation for the most critically ill remains controversial; however, it is currently the only curative treatment option. AIM: To assess immediate posttransplant outcomes and compare the short (1 year) and long-term (6 years) posttransplant survival among cirrhotic patients stratified by disease severity. METHODS: We included cirrhotic patients undergoing liver transplantation between 2015 and 2019 and categorized them into compensated cirrhosis (CC), decompensated cirrhosis (DC), and acute-on-chronic liver failure (ACLF). ACLF was further divided into severity grades. Our primary outcomes of interest were total days of intensive care unit (ICU) and hospital stay, development of complications and posttransplant survival at 1 and 6 years. RESULTS: 235 patients underwent liver transplantation (CC = 11, DC = 129 and ACLF = 95). Patients with ACLF had a significantly longer hospital stay [8.0 (6.0-13.0) vs CC, 6.0 (3.0-7.0), and DC 7.0 (4.5-10.0); P = 0.01] and developed more infection-related complications [47 (49.5%), vs CC, 1 (9.1%) and DC, 38 (29.5%); P < 0.01]. Posttransplant survival at 1- and 6-years was similar among groups (P = 0.60 and P = 0.90, respectively). ACLF patients stratified according to ACLF grade [ACLF-1 n = 40 (42.1%), ACLF-2 n = 33 (34.7%) and ACLF-3 n = 22 (23.2%)], had similar ICU and hospital stay length (P = 0.68, P = 0.54), as well as comparable frequencies of overall and infectious post-transplant complications (P = 0.58, P = 0.80). There was no survival difference between ACLF grades at 1 year and 6 years (P = 0.40 and P = 0.15). CONCLUSION: Patients may benefit from liver transplantation regardless of the cirrhosis stage. ACLF patients have a longer hospital stay and frequency of infectious complications; however, excellent, and comparable 1 and 6-year survival rates support their enlisting and transplantation including those with ACLF-3.

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.

Stool microbiota show greater linkages with plasma metabolites compared to salivary microbiota in a multinational cirrhosis cohort.

BACKGROUND AND AIMS: Cirrhosis is associated with changes in gut microbiota in both saliva and stool. The relative linkage patterns of stool versus saliva microbiota with systemic metabolomics are unclear and may differ across countries. We hypothesized that stool microbiota have greater linkages with plasma metabolites than saliva microbiota, which may depend on country of origin. METHODS: Age-balanced controls and outpatient patients with cirrhosis, compensated and decompensated, from the USA and Mexico (MX) underwent plasma collection and dietary recall. Plasma metabolomics were analysed using nuclear magnetic resonance spectroscopy. Microbiota in stool and saliva samples were analysed using 16S rRNA analyses. Correlation network differences between both saliva and stool gut microbiota and plasma metabolites were compared between subject groupings and within/between countries. RESULTS: A total of 313 age-balanced subjects-135 USA (47 control, 48 compensated and 40 decompensated) and 178 MX (71 control, 56 compensated and 51 decompensated)-were enrolled. Cirrhosis severity, including lactulose and rifaximin use, were comparable. Plasma metabolites differed with advancing cirrhosis, between countries and according to 90-day hospitalizations. Correlation networks demonstrated more microbiome-metabolite linkages in stool compared to saliva in both populations, although there were no salivary correlation metrics across decompensated subjects in either country. Stool Lactobacillus showed a positive correlation to plasma lactate in decompensated cirrhosis from MX but not USA. CONCLUSIONS: Stool microbiota were more extensively linked with systemic metabolites than were saliva microbiota, irrespective of cirrhosis severity and country. These changes were more prominent in decompensated cirrhosis and were centred around plasma lactate, which might reflect the interaction of diet and lactulose therapy.

Galectin-3 is overexpressed in advanced cirrhosis and predicts post-liver transplant infectious complications.

BACKGROUND & AIMS: Patients with advanced cirrhosis often have immune dysfunction and are more susceptible to infections. Galectin-3 is a ß-galactoside-binding lectin implicated in inflammation, immune regulation and liver fibrosis. We aim to investigate galectin-3 expression in advanced cirrhosis and its ability to predict post-transplant infectious complications. METHODS: We collected sera and liver samples from 129 cirrhotic patients at the time of liver transplantation and from an external cohort of 37 patients with alcoholic liver disease including alcoholic hepatitis (AH) at the time of diagnosis. Galectin-3 was assessed by ELISA, real-time PCR, immunohistochemistry and RNA-seq. Receiver operating characteristic curves and Cox proportional-hazards regression analysis were performed to assess the predictive power of galectin-3 for disease severity and post-transplant infections. RESULTS: Increased galectin-3 levels were found in advanced cirrhosis. Galectin-3 significantly correlated with disease severity parameters and inflammatory markers. Galectin-3 had significant discriminating power for compensated and advanced cirrhosis (AUC = 0.78/0.84, circulating/liver galectin-3; p < .01), and was even higher to discriminate severe AH (AUC = 0.95, p < .0001). Cox Proportional-hazard model showed that galectin-3, MELD-Na and the presence of SIRS predict the development of post-transplant infectious complications. Patients with circulating galectin-3 (>16.58 ng/ml) were at 2.19-fold 95% CI (1.12-4.29) increased risk, but when combined with MELD-Na > 20.0 and SIRS, the risk to develop post-transplant infectious complications, increased to 4.60, 95% CI (2.38-8.90). CONCLUSION: Galectin-3 is a novel biological marker of active inflammation and disease severity that could be clinically useful alone or in combination with other scores to discriminate advanced cirrhosis and predict post-transplant infectious complications.

Epidemiological and Genetic Aspects of NAFLD and NASH in Mexico.

Content available: Author Interview and Audio Recording.

Economic evaluation of long-term albumin use in cirrhosis patients from the Mexican healthcare system perspective.

INTRODUCTION AND OBJECTIVES: Liver cirrhosis is a major public health issue associated with high morbidity and mortality. The ANSWER trial showed that long-term human albumin (LTA) infusions led to significant reduction of complications and mortality in patients with uncomplicated ascites. The present study aimed to assess the incremental cost of cirrhosis patients treated with LTA plus standard medical treatment (SMT) versus those treated with SMT from the perspective of the Mexican Social Security Institute (IMSS). MATERIAL AND METHODS: Cost of illness for patients with cirrhosis and grade 2-3 ascites treated with SMT or with SMT and LTA (following the treatment regimen from ANSWER) over a one-year period was estimated according to the IMSS perspective. Rates of treatments, complications and hospitalizations were based on results from the ANSWER trial. Unit costs from IMSS were gathered from public sources and transformed to 2020 Mexican $ (Mex$). RESULTS: The use of LTA is estimated to require additional annual expenditure derived from the pharmacological cost of human albumin and by the follow up visits required for LTA administration (Mex$28,128). However, this cost may potentially be counterbalanced by the reduction in paracentesis, cirrhosis-related complications and hospitalizations which would lead to cost savings of Mex$33,417 per patient/year. CONCLUSIONS: Based on the ANSWER trial results, our study suggests that LTA may result in improved clinical outcomes and reduced costs for the IMSS when administered to cirrhosis patients with uncomplicated ascites.

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.

Evaluation of cerebral dysfunction in patients with chronic kidney disease using neuropsychometric and neurophysiological tests.

BACKGROUND: Uremic encephalopathy is defined as cerebral dysfunction due to toxin accumulation in patients with chronic kidney disease (CKD). This condition is characterized by subtle to florid symptoms, and its clinical course is always progressive when untreated but partially reversible with renal replacement therapy. While no test exists to measure subclinical uremic encephalopathy, two tests have been validated to measure minimal hepatic encephalopathy: the critical flicker frequency (CFF) test and the psychometric hepatic encephalopathy score (PHES). OBJECTIVE: To use CFF and PHES to measure the prevalence of cerebral dysfunction in individuals with CKD. METHODS: This cross-sectional study included a total of 69 patients with stage-5 CKD. Cutoff points for minimal encephalopathy were established using existing clinical guidelines: ≤39 Hz for CFF and < -4 for PHES. All participants were also screened for cognitive function and depression. RESULTS: Eighteen cases (26.1%) of cerebral dysfunction linked to uremic encephalopathy were detected with CFF, while twelve (17.4%) were detected by PHES; only six cases (8.7%) were diagnosed by both methods. Half of the cases (50%) had diabetes, and 61% were on hemodialysis. Cognitive function scores did not differ significantly between those receiving dialysis, hemodialysis, or no renal replacement therapy. CONCLUSIONS: It is essential to identify cerebral dysfunction when uremic encephalopathy is in early subclinical stages to reduce preventable events as traffic and work accidents.

Hepamet Fibrosis Score in Nonalcoholic Fatty Liver Disease Patients in Mexico: Lower than Expected Positive Predictive Value.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has been associated with different negative outcomes in the presence of advanced fibrosis. The Hepamet Fibrosis Score (HFS), a recently described noninvasive score, has shown excellent performance for the detection of advanced fibrosis. The aim of this study was to assess its performance in a Mexican population with NAFLD. METHODS: This was a retrospective cross-sectional study performed in 222 patients with biopsy-proven NAFLD, of whom 33(14%) had advanced fibrosis. We retrieved clinical data from each patient's medical record to compute the HFS, the NAFLD Fibrosis Score (NFS), and the Fibrosis-4 (FIB-4), and assess their performance. RESULTS: When considering the models as continuous variables, the area under the receiving operating characteristics curve of the HFS(0.758) was not different from that of the NFS(0.669, p = 0.09) or FIB-4(0.796, p = 0.1). The HFS had a sensitivity, specificity, positive and negative predictive values of 76.7% (95% CI 57.7-90.1), 90.1% (95% CI 85-93.9), 36.7% (95% CI 19.9-56.1), and 94.3% (95% CI 88.5-97.7), respectively. Indeterminate results (i.e., gray area) were more common with FIB-4 and HFS when compared with NFS [139(63%) and 122(55%) vs 80(36%), p < 0.001]. The variables that were associated with misclassification using the HFS were diabetes [OR 3.40 (95% CI 1.42-8.10), p = 0.006] and age [OR 1.06 (95% CI 1.01-1.11), p = 0.01]. CONCLUSION: The HFS showed sensitivity and specificity similar to that reported in the original publication; however, the positive predictive value was 36.7% at a pretest probability of 14%. The role of the HFS in prospective studies and in combination with other methods should be further explored.

Renal and brain failure predict mortality of patients with acute-on-chronic liver failure admitted to the intensive care unit.

INTRODUCTION AND OBJECTIVES: Acute on Chronic Liver Failure (ACLF) is characterized by organ failure and high 28-day mortality. Identifying clinical predictors associated with early mortality could have implications for the treatment of patients with ACLF. PATIENTS AND METHODS: Patients diagnosed with chronic liver failure that developed ACLF based on the EASL-CLIF Consortium definition admitted to the Intensive care unit of a tertiary hospital between 2012-2018 were included. Bivariate and multivariate Cox regression analyses were performed to identify factors associated with mortality. RESULTS: 148 patients (55% female) were diagnosed with ACLF of which 55% (n = 82) had ACLF grade 3, 28% (n = 41) grade 2 and 17% (n = 25) grade 1. The median age was 54 years (41-63). Hepatitis C virus (HCV) was the most frequent etiology in 29.8% (n = 44) of the patients with bacterial infection being the most predominant precipitant factor in 58.1% (n = 86). Ninety-day global cumulative survival was only 18%. When divided by grade, mortality reached to 10% in ACLF 3. Moreover, in the multivariate Cox regression analysis, renal failure (HR 3.26, 95% CI (2.13-4.99), brain failure (HR 1.37, 95% CI 1.09-2.04) and male sex (HR 1.62, 95% CI 1.10-2.40) were independent predictors of 28- and 90-day mortality. CONCLUSIONS: ACLF is a frequent syndrome among chronic liver disease patients. Brain and renal failure are significantly associated with higher mortality and are independent predictors of 28 and 90-day mortality.