Fibrosis-4 (FIB-4) score and D-dimer (DD) have emerged as prognostic markers in coronavirus disease 2019 (COVID-19). However, precise cutoff points remain undefined, and their combined use has been scarcely studied. We aimed to analyze FIB-4 and DD performance, individually and combined, to predict outcomes among COVID-19 patients.

From March to December 2020, hospitalized COVID-19 patients were evaluated based on clinical and laboratory tests from their first day of hospitalization. Primary outcome was inhospital mortality, and secondary outcomes included hospital stay length, ICU admission and duration, need for hemodialysis, ventilatory support, and extent of lung involvement. Optimal FIB-4 and DD cutoff points to predict mortality were established to maximize sensitivity and specificity. A sequential diagnostic strategy using both markers was subsequently evaluated.

Among 518 patients (61 ± 16 years, 64% men), the inhospital mortality rate was 18%. FIB-4 outperformed DD in predicting mortality (area under the receiver operating characteristic curve: 0.76 vs. 0.65, P = 0.003) and was chosen as the first step in sequential analysis. Mortality was higher in patients with FIB-4 ≥1.76 vs. FIB-4 <1.76 (26 vs. 5%, P < 0.001) and DD ≥2000 ng/ml vs. DD <2000 ng/ml (38 vs. 16%, P < 0.001). Using FIB-4 as a screening test (cutoff = 1.76, 90% sensitivity) followed by DD (cutoff = 2000 ng/ml; 90% specificity) identified a subgroup with higher mortality when compared with FIB-4 alone (48 vs. 26%, P < 0.001), missing the identification of only 2% of deaths.

Sequential use of FIB-4 and DD represents a comprehensive strategy to identify high-risk COVID-19 patients at hospital admission, potentially minimizing unnecessary DD tests in those deemed low-risk by FIB-4.

to determine the impact of liver fibrosis on the prognosis of COVID and liver injury associated with the infection.

retrospective multicenter study including 575 patients requiring admission for COVID-19 between January and June 2020. Fibrosis index-4 (FIB-4) was calculated within six months prior to infection and at six months post-infection.

baseline FIB-4 was elevated in patients who died (1.91 ± 0.95 vs 1.43 ± 0.85; p < 0.001). In addition, 17.1 % (32/187) of patients with baseline FIB-4 < 1.45 died vs 52.9 % (9/17) with FIB-4 > 3.25 (p < 0.001). In the adjusted multivariate analysis, baseline FIB-4 (OR 1.61 [95 % CI: 1.19-2.18]; p = 0.002) was independently associated with mortality. Parameters associated with liver injury, including aspartate aminotransferase (AST) (28 ± 10 vs 45 ± 56 IU/l; p < 0.001) and alanine aminotransferase (ALT) (20 ± 12 vs 38 ± 48 IU/l; p < 0.001) were significantly higher at admission compared to baseline. Furthermore, FIB-4 increased from baseline to the time of admission (1.53 ± 0.88 vs 2.55 ± 1.91; p < 0.001), and up to 6.9 % (10/145) of patients with FIB-4 < 1.45 on admission died vs 47.5 % if FIB-4 > 3.25 (58/122) (p < 0.001). In the adjusted multivariate analysis, FIB-4 on admission (OR 1.14 [95 % CI: 1.03-1.27]; p = 0.015) was independently associated with mortality. In addition, AST (42 ± 38 vs 22 ± 17 IU/l; p < 0.001) and ALT (40 ± 50 vs 20 ± 19 IU/l; p < 0.001) were significantly reduced at six months after the resolution of infection. Accordingly, FIB-4 decreased significantly (2.12 ± 1.25 vs 1.32 ± 0.57; p < 0.001) six months after the infection.

increased FIB-4, either at baseline or at the time of admission, was associated with severity and mortality related to respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, the liver damage expressed by elevated transaminases and FIB-4 levels was reversible in most of patients.

Abnormal liver biochemistry (ALB) is common among patients with COVID-19 infection due to various factors. It is uncertain if it persists after the acute infection. We aimed to investigate this.

A multicenter study of adult patients hospitalized for COVID-19 infection, with at least a single abnormal liver function test, was conducted. Detailed laboratory and imaging tests, including transabdominal ultrasound and FibroScan, were performed at assessment and at 6-month follow-up after hospital discharge.

From an initial cohort of 1246 patients who were hospitalized, 731 (58.7%) had ALB. A total of 174/731 patients fulfilled the inclusion criteria with the following characteristics: 48.9% patients had severe COVID-19; 62.1% had chronic liver disease (CLD); and 56.9% had metabolic-associated fatty liver disease (MAFLD). ALB was predominantly of a mixed pattern (67.8%). Among those (55.2%) who had liver injury (aspartate aminotransferase/alanine aminotransferase >3 times the upper limit of normal, or alkaline phosphatase/γ-glutamyl transferase/bilirubin >2 times the upper limit of normal), a mixed pattern was similarly predominant. Approximately 52.3% had normalization of the liver lunction test in the 6-month period post discharge. Patients with persistent ALB had significantly higher mean body mass index (BMI) and serum low-density lipoprotein (LDL), higher rates of MAFLD and CLD, higher mean liver stiffness measurement and continuous attenuated parameter score on FibroScan, and higher rates of liver injury on univariate analysis. Multivariate analysis was not statistically significant.

Approximately 47.7% of COVID-19 patients were found to have persistent ALB up to 6 months following the acute infection, and it was associated with raised BMI, elevated serum LDL, increased rates of MAFLD and CLD, and higher rates of liver injury on univariate analysis, but not on multivariate analysis.

SARS-Cov-2 infection manifests as a wide spectrum of clinical presentation and even now, despite the global spread of the vaccine, contagiousness is still elevated. The aim of the study was the evaluation of the impact of liver fibrosis assessed by FIB-4 and liver impairment, assessed by cytolysis indices, on intrahospital mortality in COVID-19 subjects.

This is a retrospective observational cohort study, which involved 23 COVID Hospital Units in Campania Region, Italy. Exposure variables were collected during hospital admission and at discharge. According to FIB-4 values, we subdivided the overall population in three groups (FIB-4<1.45; 1.453.25), respectively group 1,2,3.

At the end of the study, 938 individuals had complete discharged/dead data. At admission, 428 patients were in group 1 (45.6%), 387 in group 2 (41.3%) and 123 in group 3 (13.1%). Among them, 758 (81%) subjects were discharged, while the remaining 180 (19%) individuals died. Multivariable Cox's regression model showed a significant association between mortality risk and severity of FIB-4 stages (group 3 vs group 1, HR 2.12, 95%CI 1.38-3.28, p<0.001). Moreover, Kaplan-Meier analysis described a progressive and statistically significant difference (p<0.001 Log-rank test) in mortality according to FIB-4 groups. Among discharged subjects, 507 showed a FIB-4<1.45 (66.9%, group 1), 182 a value 1.453.25 (9.0%, group 3). Among dead subjects, 42 showed a FIB-4<1.45 (23.3%, group 1), 62 a value 1.453.25 (42.3%, group 3).

FIB-4 value is significantly associated with intrahospital mortality of COVID-19 patients. During hospitalization, particularly in patients with worse outcomes, COVID-19 seems to increase the risk of acute progression of liver damage.

We aimed to determine the reliability of using the Fibrosis-4 (FIB-4) index in COVID-19 patients without underlying liver illness.

We employed multivariate logistic regression to identify variables that exhibited statistically significant influence on the ultimate outcome. Multilayer perceptron analysis was employed to develop a prediction model for the FIB-4 index concerning ICU admission and intubation rates. However, the scarcity of cases rendered the assessment of the mortality rate unfeasible. We plotted ROC curves to analyze the predictive strength of the FIB-4 index across various age groups.

In univariate logistic regression, only the FIB-4 index and respiratory rate demonstrated statistical significance on all poor outcomes. The FIB-4 index for mortality prediction had an ROC and AUC of 0.863 (95% CI: 0.781-0.9444). It demonstrates predictive power across age groups, particularly for age ≥65 (AUC: 0.812, 95% CI: 0.6571-0.9673) and age <65 (AUC: 0.878, 95% CI: 0.8012-0.9558). Its sensitivity for intubation and ICU admission prediction is suboptimal.

FIB-4 index had promising power in prediction of mortality rate in all age groups.

The aim of this study was to ascertain patient characteristics, outcomes, and liver injuries in patients infected with different SARS-CoV-2 variants. Data from consecutive adult patients with severe/critical COVID-19 admitted to our hospital during the peak month of the Delta wave were compared to the ancestral, Alpha, and Omicron waves. The dataset of 551 hospitalized patients was similar in the Delta/non-Delta waves. At admission and discharge, the median aminotransferase levels were normal or slightly increased. During the Delta wave (172 vs. 379 non-Delta patients), more patients died (OR 1.69, 95%CI 1.09-2.56) or had liver injury at discharge (alanine aminotransferase, ALT ≥ 2 ULN) (OR 1.97, 95%CI 1.08-3.54). In-hospital mortality was associated with age, lung injury, intensive care unit admission, number of and cardiovascular comorbidities, diabetes, chronic kidney disease, and all inflammatory biomarkers. Serious liver injury at admission (ALT ≥ 5 × ULN) was significantly associated with in-hospital mortality (OR = 7.9, 95%CI 2-28.9). At discharge, drug-induced liver injury (DILI) was found in patients treated with remdesivir, ALT ≥ 2 ULN (OR = 2.62, 95%CI 1.22-5.75). Treatment with dexamethasone, remdesivir, and immunomodulators showed improved survival, OR = 0.50 (95%CI 0.33-0.77). Regardless of the variant and treatment options, less than 2% of patients displayed serious liver injury, which was not found to be a death predictor in multivariable analysis.

Patients with chronic liver disease (CLD) have a higher risk of mortality when infected with severe acute respiratory syndrome coronavirus 2. Although the fibrosis-4 (FIB-4) index, aspartate aminotransferase-to-platelet ratio index (APRI), and albumin-bilirubin grade (ALBI) score can predict mortality in CLD, their correlation with the clinical outcomes of CLD patients with coronavirus disease 2019 (COVID-19) is unclear. This study aimed to investigate the association between the liver severity and the mortality in hospitalized patients with non-cirrhotic CLD and COVID-19.

This retrospective study analyzed 231 patients with non-cirrhotic CLD and COVID-19. Clinical characteristics, laboratory data, including liver status indices, and clinical outcomes were assessed to determine the correlation between liver status indices and the mortality among patients with non-cirrhotic CLD and COVID-19.

Non-survivors had higher levels of prothrombin time-international normalized ratio (PT-INR), alanine aminotransferase, aspartate aminotransferase, and high-sensitivity C-reactive protein (hs-CRP) and lower albumin levels. Multivariable analysis showed that ALBI grade 3 (odds ratio (OR): 22.80, 95% confidence interval (CI) [1.70-305.38], p = 0.018), FIB-4 index ≥ 3.25 (OR: 10.62, 95% CI [1.12-100.31], p = 0.039), PT-INR (OR: 19.81, 95% CI [1.31-299.49], p = 0.031), hs-CRP (OR: 1.02, 95% CI [1.01-1.02], p = 0.001), albumin level (OR: 0.08, 95% CI [0.02-0.39], p = 0.002), and use of vasopressors (OR: 4.98, 95% CI [1.27-19.46], p = 0.021) were associated with the mortality.

The ALBI grade 3 and FIB-4 index ≥ 3.25, higher PT-INR, hsCRP levels and lower albumin levels could be associated with mortality in non-cirrhotic CLD patients with COVID-19. Clinicians could assess the ALBI grade, FIB-4 index, PT-INR, hs-CRP, and albumin levels of patients with non-cirrhotic CLD upon admission.

Patients with Coronavirus disease 2019 (COVID-19) often have elevations in markers of liver injury, particularly serum aspartate transaminase (AST) and alanine transaminase (ALT). Such alterations may affect the AST/ALT ratio (De Ritis ratio) and, potentially, clinical outcomes. We conducted an updated systematic review and meta-analysis of the association between the De Ritis ratio and COVID-19 severity and mortality in hospitalized patients. PubMed, Web of Science, and Scopus were searched between 1 December 2019 and 15 February 2023. The Joanna Briggs Institute Critical Appraisal Checklist and the Grading of Recommendations, Assessment, Development, and Evaluation were used to assess the risk of bias and the certainty of the evidence, respectively. Twenty-four studies were identified. The De Ritis ratio on admission was significantly higher in patients with severe disease and non-survivors vs. patients with non-severe disease and survivors (15 studies, weighted mean difference = 0.36, 95% CI 0.24 to 0.49, p < 0.001). The De Ritis ratio was also associated with severe disease and/or mortality using odds ratios (1.83, 95% CI 1.40 to 2.39, p ˂ 0.001; nine studies). Similar results were observed using hazard ratios (2.36, 95% CI 1.17 to 4.79, p = 0.017; five studies). In six studies, the pooled area under the receiver operating characteristic curve was 0.677 (95% CI 0.612 to 0.743). In our systematic review and meta-analysis, higher De Ritis ratios were significantly associated with severe disease and mortality in COVID-19 patients. Therefore, the De Ritis ratio can be useful for early risk stratification and management in this patient group (PROSPERO registration number: CRD42023406916).

Predictors of mortality that indicate disease severity plays an important role in COVID-19 management and treatment decisions. This study aimed to investigate the association between fibrosis-4 (FIB-4) score, aspartate aminotransferase-to-platelet ratio index (APRI), and novel biomarker-based score (SAD-60) with mortality in COVID-19 patients treated in a tertiary hospital.

In this single-center retrospective study, patients ≥18 years of age who were admitted to our hospital for COVID-19 between December 1 and 31, 2021, were included. Patients were divided into two groups as deceased and survived. A comparative analysis was applied. Predictive abilities of the FIB-4, APRI, and SAD-60 scores for in-hospital mortality were evaluated.

Of the 453 patients enrolled in the study, 248 (54.6%) were male, and the mean age was 52.2±14.7 years. Mortality was recorded in 39 (8.5%) of the patients. The median values of APRI (0.43 and 0.58; p=0.001), FIB-4 score (1.66 and 2.91; p<0.001), and SAD-60 (2 and 8.25; p<0.001) were higher in deceased patients than in survivors. The optimal cut-off value for predicting mortality in the receiver operating characteristic (ROC) curve analysis was 0.58 for APRI (sensitivity=56.4%, specificity=63.6%); 2.14 for FIB-4 score (sensitivity=79.5%, specificity=68.2%); 4.25 for SAD-60 (sensitivity=90%, specificity=73.8%). In Cox regression analysis with a model that included gender, chronic obstructive pulmonary disease (COPD), and coronary artery disease (CAD), FIB-4 (hazard ratio [HR]=4.013, 95% confidence interval [CI]=1.643-9.803; p=0.002), and SAD-60 (HR=8.850, 95% CI=1.035-75.696; p=0.046) were independent risk factors for mortality.

SAD-60 and FIB-4 scores are easily applicable and may be used to predict mortality in COVID-19 patients.

There has been an increasing number of reported cases of acute hepatitis of unknown origin in previously healthy children since first reported on March 31, 2022. This clinical syndrome is identified by jaundice and markedly elevated liver enzymes with increased aspartate transaminase and/or alanine aminotransaminase (greater than 500 IU/L). We conducted an inclusive literature review with respect to acute hepatitis outbreaks in children using the search terms acute hepatitis, outbreak, children, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coronavirus disease 2019 (COVID-19), and adenovirus. According to the cumulative data presented in four main studies, the median age is 4 years, with a male predominance (1.3:1). Jaundice was the most common clinical manifestation (69%), followed by vomiting (63%), anorexia (52.9%), diarrhea (47.2%), abdominal pain (39%), pyrexia (33.3%), pale stool (30%), and dark urine (30%). Coryza and lethargy were reported in 16.6%, while pruritus was reported in 2% of cases. Acute liver failure was observed in 25% of cases. The exact mechanism of this acute hepatitis outbreak is still not entirely clear. Adenoviruses and SARS-CoV-2 were detected in a significant number of patients. Coinfection with adenovirus and SARS-CoV-2 could be a possible underlying mechanism. However, other possible infections and mechanisms must be considered in the pathogenesis of this condition. Acute hepatitis of unknown origin in children has been a serious problem since the start of the COVID-19 pandemic but has not yet been sufficiently addressed. Many questions remain regarding the underlying mechanisms leading to acute liver failure in children, and it is likely that extensive future research is needed.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, broke out in December 2019 in Wuhan city of China and spread rapidly worldwide. Therefore, by March 2020, the World Health Organization declared the disease a global pandemic. Apart from the respiratory system, various other organs of the human body are also seriously affected by the virus. Liver injury in patients with a severe form of COVID-19 is estimated to be 14.8%-53.0%. Elevated levels of total bilirubin, aspartate aminotransferase and alanine aminotransferase and low levels of serum albumin and prealbumin are the main laboratory findings. Patients with pre-existing chronic liver disease and cirrhosis are much more prone to develop severe liver injury. This literature review presented the recent scientific findings regarding the pathophysiological mechanisms responsible for liver injury in critically ill patients with COVID-19, the various interactions between drugs used to treat the disease and the function of the liver and the specific tests providing the possibility of early diagnosis of severe liver injury in these patients. Moreover, it highlighted the burden that COVID-19 put on health systems worldwide and its effect on transplant programs and the care provided to critically ill patients in general and particularly to those with chronic liver disease.

Although several liver- and inflammation-based scores to predict the clinical course of patients with coronavirus disease 2019 (COVID-19) have been evaluated, no direct comparison regarding their predictive ability has been performed.

1038 patients (608 males, age 63.5 ± 17 years) hospitalized with documented COVID-19 infection to the non-ICU ward, were included retrospectively. Clinical and laboratory characteristics on admission including evaluation of Fibrosis-4 (FIB-4) score and C-Reactive Protein (CRP) to albumin ratio (CAR) were recorded.

One hundred and twenty-four patients (11.9%) died during hospitalization after 8 (3-72) days. In multivariate analysis, FIB-4 (hazard ratio, 1.11; 95% confidence interval (CI), 1.034-1.19; P = 0.004), was independently associated with mortality, with very good discriminative ability (area under the receiver operating characteristic curve curve, 0.76). The patients with FIB-4 &amp;gt;2.67 (n = 377), compared to those with ≤2.67 (n = 661), had worse survival (log-rank 32.6; P &amp;lt; 0.001). Twenty-four (6.8%) of 352 patients with possible nonalcoholic fatty liver disease (NAFLD) (defined as Hepatic Steatosis Index &amp;gt;36) died during hospitalization. In multivariate analysis, CAR was an independent risk factor (1) for mortality (hazard ratio, 1.014; 95% CI, 1.002-1.025; P = 0.021), (2) the need for high-flow nasal cannula with or without intubation (hazard ratio, 1.016; 95% CI, 1.004-1.027; P = 0.007) and (3) development of acute kidney injury (hazard ratio, 1.017; 95% CI, 1.006-1.028; P = 0.002). In addition, the patients with possible NAFLD and CAR &amp;gt;12 (n = 154), compared to those with CAR ≤12 (n = 198), had worse survival (log-rank 5.1; P = 0.024).

FIB-4 was an independent factor for mortality with better performance compared to other liver function test- and inflammation-based scores in patients with COVID-19, while CAR was the only score independently associated with the clinical course in COVID-19 patients with possible NAFLD.

Discovering novel risk and prognostic factors for COVID-19 may help not only in reducing severity and mortality but also in creating targeted therapies considering patients’ individual features. Liver fibrosis is considered a complication in Non-alcoholic Fatty Liver Disease (NAFLD), it is a feature of steatohepatitis (NASH), and it has already been related to an increased risk for a wide range of diseases. Here, we aimed to define if any parameter assessing metabolic status has predictive power in identifying inpatients at risk for poorer prognosis and an increased mortality from COVID-19. This retrospective study was conducted at the Sub-Intensive Medicine Care Unit of the Presidio Maxi-Emergenze Fiera del Levante, Azienda Ospedaliero-Universitaria Policlinico di Bari, Italy. We evaluated 271 inpatients with moderate-to-severe SARS-CoV-2-related respiratory failure by comparing biochemical features and non-invasive liver fibrosis scores among discharged, transferred to Intensive Care Units (ICU) and non-survivor patients. Moreover, by performing ROC curves, we defined cut-off values to predict mortality and disease severity for each score. We found that non-invasive scores of liver fibrosis, obtained at day of admission, such as AAR (p < 0.001), FIB-4 and mFIB-4, FORNS, and AARPRI (p < 0.05) strongly predict not only in-hospital mortality but also the length of hospitalization and eventual admission to ICU. FIB-4 was the best score to identify non-survivor patients (sensitivity of 80% and specificity of 63%) and predict the need for ICU or mortality (71% of sensitivity and 65% of specificity), with a cut-off value of 1.94. Therefore, we present the predictive power and the cut-off values of several liver fibrosis scores here for disease severity and mortality in SARS-CoV-2 in-patients and we proposed the use of the present scores to identify ab initio the clinical therapeutic and diagnostic protocols for high-risk patients.

Liver damage worsens the prognosis of coronavirus 19 disease (COVID-19). However, the best strategy to stratify mortality risk according to liver damage has not been established. The aim of this study is to test the predictive value of the validated Fibrosis-4 (FIB-4) Index and compared it to liver transaminases and to the AST-to-Platelet ratio index (APRI). Multicenter cohort study including 992 consecutive COVID-19 patients admitted to the Emergency Department. FIB-4 > 3.25 and APRI > 0.7 were used to define liver damage. Multivariable Cox regression and ROC curve analysis for mortality were performed. Secondary endpoints were (1) need for high-flow oxygen and (2) mechanical ventilation. 240 (24.2%) patients had a FIB-4 > 3.25. FIB-4 > 3.25 associated with an increased mortality (n = 119, log-rank test p < 0.001 and adjusted hazard ratio (HR) 1.72 (95% confidence interval [95%CI] 1.14-2.59, p = 0.010). ROC analysis for mortality showed that FIB-4 (AUC 0.734, 95% CI 0.705-0.761) had a higher predictive value than AST (p = 0.0018) and ALT (p < 0.0001). FIB-4 > 3.25 was also superior to APRI > 0.7 (AUC 0.58, 95% CI 0.553-0.615, p = 0.0008). Using an optimized cut-off > 2.76 (AUC 0.689, 95% CI 0.659-0.718, p < 0.0001), FIB-4 was superior to FIB-4 > 3.25 (p = 0.0302), APRI > 0.7 (p < 0.0001), AST > 51 (p = 0.0119) and ALT > 42 (p < 0.0001). FIB-4 was also associated with high-flow oxygen use (n = 255, HR 1.69, 95% CI 1.25-2.28, p = 0.001) and mechanical ventilation (n = 39, HR 2.07, 95% CI 1.03-4.19, p = 0.043). FIB-4 score predicts mortality better than liver transaminases and APRI score. FIB-4 score may be an easy tool to identify COVID-19 patients at worse prognosis in the emergency department.

Despite vaccination programs, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains a public health problem. Identifying key prognostic determinants of severity of the disease may help better focus health resources. The negative prognostic role for metabolic and hepatic alterations is established; however, the interplay among different metabolic comorbidities and their interconnections with the liver have never been explored.The objective of this study is to evaluate the impact of liver alterations in addition to metabolic comorbidities as a predictor of SARS-CoV-2 severity. 382 SARS-CoV-2 patients were enrolled. Severe SARS-CoV-2 was diagnosed according to international consensus. Transaminases > 2 times the upper limit of normality (2ULN), hepatic steatosis (by ultrasound and/or computed tomography in 133 patients), and FIB-4 defined liver alterations. All data were collected on admission. The results are severe SARS-CoV-2 infection in 156 (41%) patients (mean age 65 ± 17; 60%males). Prevalence of obesity was 25%; diabetes, 17%; hypertension, 44%; dyslipidaemia, 29%; with 13% of the cohort with ≥ 3 metabolic alterations. Seventy patients (18%) had transaminases > 2ULN, 82 (62%) steatosis; 199 (54%) had FIB-4 < 1.45 and 45 (12%) > 3.25. At multivariable analysis, ≥ 3 metabolic comorbidities (OR 4.1, CI 95% 1.8-9.1) and transaminases > 2ULN (OR 2.6, CI 95% 1.3-6.7) were independently associated with severe SARS-CoV-2. FIB-4 < 1.45 was a protective factor (OR 0.42, CI 95% 0.23-0.76). Hepatic steatosis had no impact on disease course. The presence of metabolic alterations is associated with severe SARS-CoV-2 infection, and the higher the number of coexisting comorbidities, the higher the risk of severe disease. Normal FIB-4 values are inversely associated with advanced SARS-CoV-2 regardless of metabolic comorbidities, speculating on use of these values to stratify the risk of severe infection.

Acute liver failure (ALF) and acute-on-chronic liver failure (ACLF), respectively, occur in patients with normal liver and patients with chronic liver diseases, including cirrhosis [...].

The fibrosis 4 (FIB-4) index was developed to predict advanced fibrosis in patients with liver disease. We aimed to evaluate the association of FIB-4 with risk factors for progression to critical illness in middle-aged patients hospitalized for coronavirus disease 2019 (COVID-19).

We included patients aged 35-65 years who were hospitalized following a positive RT-PCR SARS-Cov-2 test in a tertiary hospital. All data were obtained from the medical records of the patients during the first admission to the hospital. The FIB-4 index was calculated according to the equation (age (years) x AST (IU/L)/platelet count (10⁹/L)/√ALT (IU/L)). The FIB-4 index was divided into three categories according to the score categorisation: <1.3 = low risk, 1.3-2.67 = moderate risk, and >2.67 = high risk.

A total of 619 confirmed COVID-19 patients (mean age = 52 yrs.) were included in this study; 37 (6.0%) were admitted to the intensive care unit (ICU), of which 44% were intubated and eight (1.3%) patients died during follow-up. The results of patients with high FIB-4 scores were compared with those with low FIB-4 scores. In patients with high FIB-4 scores, male gender, and advanced age, decreased neutrophil, lymphocyte, thrombocyte, and albumin counts, elevated AST, LDH, CK, ferritin, CRP, and D-dimer, and low GFR were the high-risk factors for critical illness. Additionally, the number of patients referred to ICU with high FIB-4 who died had higher scores than from those with low scores.

The FIB-4 index derived from baseline data obtained during hospitalisation can be used as a simple, inexpensive, and straightforward indicator to predict ICU requirement and/or death in middle-aged hospitalized COVID-19 patients.