Prognostic performance of an index based on lactic dehydrogenase and transaminases for patients with liver steatosis and COVID-19.

BACKGROUND: Metabolic associated fatty liver disease (MAFLD) is associated with complications and mortality in patients with coronavirus disease 2019 (COVID-19). However, there are no prognostic scores aimed to evaluate the risk of severe disease specifically in patients with MAFLD, despite its high prevalence. Lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase have been used as markers of liver damage. Therefore, we propose an index based on lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase for the prediction of complications and mortality in patients with MAFLD and COVID-19. AIM: To evaluate the prognostic performance of an index based on lactate dehydrogenase and transaminases (aspartate aminotransferase/alanine aminotransferase) in patients with COVID-19 and MAFLD [liver fibrosis and nutrition (LNF)-COVID-19 index]. METHODS: In this retrospective cohort study, two cohorts from two different tertiary centers were included. The first was the derivation cohort to obtain the score cutoffs, and the second was the validation cohort. We included hospitalized patients with severe COVID-19 and MAFLD. Liver steatosis was evaluated by computed tomography scan. Area under the receiver operating characteristic (ROC) curve analysis and survival analysis were used. RESULTS: In the derivation cohort, 44.6% had MAFLD; ROC curve analysis yielded a LFN-COVID-19 index > 1.67 as the best cutoff, with a sensitivity of 78%, specificity of 63%, negative predictive value of 91% and an area under the ROC curve of 0.77. In the multivariate analysis, the LFN-COVID-19 index > 1.67 was independently associated with the development of acute kidney injury (odds ratio: 1.8, 95% confidence interval: 1.3-2.5, P < 0.001), orotracheal intubation (odds ratio: 1.9, 95% confidence interval: 1.4-2.4, P < 0.001), and death (odds ratio: 2.86, 95% confidence interval: 1.6-4.5, P < 0.001) in both cohorts. CONCLUSION: LFN-COVID-19 index has a good performance to predict prognosis in patients with MAFLD and COVID-19, which could be useful for the MAFLD population.

Impact of the new definition of metabolic dysfunction-associated fatty liver disease on detection of significant liver fibrosis in US adolescents.

Recently, an expert panel proposed diagnostic criteria for metabolic dysfunction-associated fatty liver disease (MAFLD) in the pediatric population. The aim of this study was to evaluate the prevalence of MAFLD among US adolescents and to investigate whether the new MAFLD definition is able to identify individuals with more advanced liver disease. We analyzed data from participants 12-18 years old included in the 2017-2020 cycles of the National Health and Nutrition Examination Survey, a large survey aimed at including individuals representative of the non-institutionalized general US population. Participants with a complete vibration-controlled transient elastography exam were included. Steatosis was evaluated through the median controlled attenuation parameter (CAP) and fibrosis through median liver stiffness measurement (LSM). Recently proposed criteria for the diagnosis of MAFLD were applied. Multivariable logistic regression analysis was performed to evaluate the impact of the new MAFLD definition on the odds of significant liver fibrosis. We included a total of 1446 adolescents (mean age: 14.9 years; 52.0% male; 47.3% overweight or obese). No participant reported a previous history of viral hepatitis. Steatosis (CAP ≥ 248 dB/m) was present in 25.9% (95% confidence interval [CI] 23.3-28.9) of individuals, and among these, 87.7% met the MAFLD criteria. Only 22.9% of patients with steatosis had elevated alanine aminotransferase levels. Among participants with steatosis, prevalence of significant liver fibrosis (LSM ≥ 7.4 kPa) did not differ significantly according to whether they met MAFLD criteria (9.7% vs. 15.2%, p = 0.276). In the multivariable model, odds of significant fibrosis did not differ significantly between these two groups. MAFLD criteria are met by most US adolescents with elastographic evidence of steatosis. Nonetheless, these criteria do not appear to improve detection of subjects with more advanced liver disease. Further longitudinal studies are needed to evaluate whether metabolic dysfunction is associated with faster progression toward inflammation, fibrosis, and liver-related events.

Four-week omega-3 polyunsaturated fatty acids supplementation for liver left lateral section volume reduction in individuals with morbid obesity undergoing bariatric surgery: A double blind, multicenter, randomized placebo-controlled trial.

BACKGROUND: Liver steatosis in morbidly obese individuals undergoing bariatric surgery increases liver volume and may complicate the surgical procedure. This study aimed to assess whether a 4-week supplementation with omega-3 polyunsaturated fatty acids (PUFA) is effective in reducing liver left lateral section (LLLS) volume. PATIENTS AND METHODS: This randomized controlled trial included morbidly obese individuals with metabolic syndrome undergoing bariatric surgery at 3 French bariatric centers between 2017 and 2020. The experimental group had a 4-week preoperative supplementation with omega-3 PUFA, whereas the control group had only placebo. The primary outcome was the reduction of the LLLS volume measured with Magnetic Resonance Imaging (MRI). RESULTS: 42 patients were randomized and 37 completed the study (19 in the experimental group and 18 in the placebo group). The mean LLLS volume decreased of 3.3% (±9.6) in the experimental group vs 1.0% (±18.3) in the placebo group, indicating that omega-3 PUFA were not effective in reducing the LLLS volume compared to the placebo (p = 0.3741). Omega-3 PUFA supplementation was not effective in reducing total liver volume, liver steatosis, rate of liver injuries during surgery and operative time. CONCLUSION: A 4-week preoperative supplementation with omega-3 PUFA was not effective in reducing LLLS volume in morbidly obese individuals undergoing bariatric surgery.

Molecular Networking for Drug Toxicities Studies: The Case of Hydroxychloroquine in COVID-19 Patients.

Using drugs to treat COVID-19 symptoms may induce adverse effects and modify patient outcomes. These adverse events may be further aggravated in obese patients, who often present different illnesses such as metabolic-associated fatty liver disease. In Rennes University Hospital, several drug such as hydroxychloroquine (HCQ) have been used in the clinical trial HARMONICOV to treat COVID-19 patients, including obese patients. The aim of this study is to determine whether HCQ metabolism and hepatotoxicity are worsened in obese patients using an in vivo/in vitro approach. Liquid chromatography high resolution mass spectrometry in combination with untargeted screening and molecular networking were employed to study drug metabolism in vivo (patient's plasma) and in vitro (HepaRG cells and RPTEC cells). In addition, HepaRG cells model were used to reproduce pathophysiological features of obese patient metabolism, i.e., in the condition of hepatic steatosis. The metabolic signature of HCQ was modified in HepaRG cells cultured under a steatosis condition and a new metabolite was detected (carboxychloroquine). The RPTEC model was found to produce only one metabolite. A higher cytotoxicity of HCQ was observed in HepaRG cells exposed to exogenous fatty acids, while neutral lipid accumulation (steatosis) was further enhanced in these cells. These in vitro data were compared with the biological parameters of 17 COVID-19 patients treated with HCQ included in the HARMONICOV cohort. Overall, our data suggest that steatosis may be a risk factor for altered drug metabolism and possibly toxicity of HCQ.

Hepatic Steatosis Is Associated with Increased Disease Severity and Liver Injury in Coronavirus Disease-19.

BACKGROUND: Coronavirus disease-2019 (COVID-19) is a global pandemic. Obesity has been associated with increased disease severity in COVID-19, and obesity is strongly associated with hepatic steatosis (HS). However, how HS alters the natural history of COVID-19 is not well characterized, especially in Western populations. AIMS: To characterize the impact of HS on disease severity and liver injury in COVID-19. METHODS: We examined the association between HS and disease severity in a single-center cohort study of hospitalized COVID-19 patients at Michigan Medicine. HS was defined by either hepatic steatosis index > 36 (for Asians) or > 39 (for non-Asians) or liver imaging demonstrating steatosis > 30 days before onset of COVID-19. The primary predictor was HS. The primary outcomes were severity of cardiopulmonary disease, transaminitis, jaundice, and portal hypertensive complications. RESULTS: In a cohort of 342 patients, metabolic disease was highly prevalent including nearly 90% overweight. HS was associated with increased transaminitis and need for intubation, dialysis, and vasopressors. There was no association between HS and jaundice or portal hypertensive complications. In a sensitivity analysis including only patients with liver imaging > 30 days before onset of COVID-19, imaging evidence of hepatic steatosis remained associated with disease severity and risk of transaminitis. CONCLUSIONS: HS was associated with increased disease severity and transaminitis in COVID-19. HS may be relevant in predicting risk of complications related to COVID-19.

Metabolic associated fatty liver disease increases the severity of COVID-19: A meta-analysis.

BACKGROUND: The association between metabolic-associated fatty liver disease (MAFLD) and disease progression in patients with the coronavirus disease 2019 (COVID-19) are unclear. AIMS: To explore the association between MAFLD and the severity of COVID-19 by meta-analysis. METHODS: We conducted a literature search using PubMed, EMBASE, Medline (OVID), and MedRxiv from inception to July 6, 2020. Newcastle-Ottawa Scale (NOS) and Stata 14.0 were used for quality assessment of included studies as well as for performing a pooled analysis. RESULTS: A total of 6 studies with 1,293 participants were included after screening. Four studies reported the prevalence of MAFLD patients with COVID-19, with a pooled prevalence of 0.31 for MAFLD (95CI 0.28, 0.35, I2 = 38.8%, P = 0.179). MAFLD increased the risk of COVID-19 disease severity, with a pooled OR of 2.93 (95CI 1.87, 4.60, I2 = 34.3%, P = 0.166). CONCLUSION: In this meta-analysis, we found that a high percentage of patients with COVID-19 had MAFLD. Meanwhile, MAFLD increased the risk of disease progression among patients with COVID-19. Thus, better intensive care and monitoring are needed for MAFLD patients infected by SARS-COV-2.

Severe pre-eclampsia complicated by acute fatty liver disease of pregnancy, HELLP syndrome and acute kidney injury following SARS-CoV-2 infection.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has presented many diagnostic challenges and uncertainties. Little is known about common pathologies complicating pregnancy and how their behaviour is modified by the presence of SARS-CoV-2. Pregnancy itself can alter the body's response to viral infection, which can cause more severe symptoms. We report the first case of a patient affected with sudden-onset severe pre-eclampsia complicated by acute fatty liver disease of pregnancy, HELLP (haemolysis, elevated liver enzymes and low platelet) syndrome and acute kidney injury following SARS-CoV-2 infection. Although an initial diagnostic dilemma, a multidisciplinary team approach was required to ensure a favourable outcome for both the mother and the baby. Our case report highlights the need for health professionals caring for pregnant women to be aware of the complex interplay between SARS-CoV-2 infection and hypertensive disorders of pregnancy.

Higher frequency of hepatic steatosis at CT among COVID-19-positive patients.

PURPOSE: Recent studies have demonstrated that obesity is significantly associated with increased disease severity, hospitalizations and mortality in COVID-19, with a potential role in the pathogenesis and prevalence in the new pandemic. The association with hepatic steatosis, however, a condition closely related to obesity within the spectrum of systemic metabolic dysfunctions, remains to be elucidated. We aimed to evaluate the frequency of hepatic steatosis as incidentally detected in chest CT examinations of COVID-19 positive patients in comparison to non-infected controls. METHODS: A retrospective study was performed with 316 patients (204 RT-PCR positive; 112 RT-PCR negative and chest CT negative). Steatosis was measured with placement of a single ROI in the right lobe of the liver (segments VI-VII) and defined as a liver attenuation value ≤ 40 HU. RESULTS: The frequency of hepatic steatosis was higher in the RT-PCR positive group in comparison to controls (31.9% vs. 7.1%, p < 0.001). Logistic linear regression analysis showed a 4.7 times odds of steatosis in the COVID-19 positive group as compared to controls after adjusting for age and sex (OR 4.698; 95% IC 2.12-10.41, p < 0.001). CONCLUSION: A significantly higher prevalence of steatosis was found among COVID-19 positive individuals. These findings are in accordance with other recent studies linking obesity and COVID-19 infection, as there is an intricate relationship between liver steatosis, metabolic syndrome and obesity. Further studies are required to confirm if such association remains after accounting for multiple variables, as well as possible relationships with disease severity and worst clinical outcomes.

Metabolic-associated fatty liver disease is associated with severity of COVID-19.

The Corona Virus Disease 2019 (COVID-19) pandemic has attracted increasing worldwide attention. While metabolic-associated fatty liver disease (MAFLD) affects a quarter of world population, its impact on COVID-19 severity has not been characterized. We identified 55 MAFLD patients with COVID-19, who were 1:1 matched by age, sex and obesity status to non-aged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients without MAFLD. Our results demonstrate that in patients aged less than 60 years with COVID-19, MAFLD is associated with an approximately fourfold increase (adjusted odds ratio 4.07, 95% confidence interval 1.20-13.79, P = .02) in the probability for severe disease, after adjusting for confounders. Healthcare professionals caring for patients with COVID-19 need to be aware that there is a positive association between MAFLD and severe illness with COVID-19.

Metabolic dysfunction associated fatty liver disease increases risk of severe Covid-19.

BACKGROUND AND AIMS: Liver involvement is common in COVID-19. Elevated aspartate and alanine amino transaminase (AST/ALT) and borderline increase in serum bilirubin and serum alkaline phosphatase (ALP) are the commonest findings. Patients with associated co morbid conditions like obesity, cardiovascular disease, renal disease, malignancy, hypertension and old age are prone to develop severe disease. Limited data is available in patients with COVID-19 and metabolic dysfunction associated fatty liver disease (MAFLD).The aim of this review is to analyse the effect of MAFLD on severity of COVID-19. METHODS: We systematically searched the PubMed database till May 20, 2020 and retrieved all the articles published on COVID-19 and fatty liver/MAFLD/NAFLD. RESULTS: Limited studies done had shown four to six fold high risk of severe COVID-19 in patients with MAFLD. Patients with MAFLD and associated obesity, severe fibrosis and age <60 yrs are more prone to develop severe COVID-19. CONCLUSION: MAFLD is associated with 4-6 fold increase in severity of COVID-19 compared to non MAFLD patients. Physician and hepatologist should follow these patients cautiously and preventive measures to be taken strictly in these high risk patients.