Project description:With the aging of the population, sarcopenia has become more common. Studies have shown a broad association between liver disease and sarcopenia. However, this link remains unclear. Our study explored the link between NAFLD and sarcopenia and predicting the pathogenesis. To begin, we investigated the causal relationship and genetic correlation between them using MR and LDSC. Second, each GWAS was annotated by MAGMA. The annotated genes were analyzed for pleiotropy using the PLACO approach. Finally, functional analysis was conducted on the identified pleiotropic genes. We observed a significant genetic correlation between NAFLD and sarcopenia. Subsequently, we conducted gene-level pleiotropy analysis using PLACO and identified a total of 153 genes with pleiotropic effects. Functional analysis revealed enrichment of these genes in various tissues, including pancreas, liver, heart, blood, brain, and muscle, with involvement in cellular regulation, intracellular function, and antigen response. Moreover, our MR analysis provided evidence of a causal relationship between NAFLD and sarcopenia. Our study has discovered the genetic and causal relationships between NAFLD and sarcopenia, providing further insights into their pathophysiological mechanisms. The identification of pleiotropic genes also offers potential targets for future drug therapies aimed at controlling or treating NAFLD and sarcopenia.
Project description: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.
Project description:Non-alcoholic fatty liver disease (NAFLD) is identified as a risk factor for developing severe COVID-19. While NAFLD is associated with chronic low-grade inflammation, mechanisms leading to immune system hyperactivation remain unclear. The aim of this prospective observational study is to analyze cytokine profiles in patients with severe COVID-19 and NAFLD. A total of 94 patients with severe COVID-19 were included. Upon admission, clinical and laboratory data were collected, a liver ultrasound was performed to determine the presence of steatosis, and subsequently, 51 were diagnosed with NAFLD according to the current guidelines. There were no differences in age, sex, comorbidities, and baseline disease severity between the groups. Serum cytokine concentrations were analyzed using a multiplex bead-based assay by flow cytometry. Upon admission, the NAFLD group had higher C-reactive protein, procalcitonin, alanine aminotransferase, lactate dehydrogenase, and fibrinogen. Interleukins-6, -8, and -10 and CXCL10 were significantly higher, while IFN-γ was lower in NAFLD patients. Patients with NAFLD who progressed to critical illness had higher concentrations of IL-6, -8, -10, and IFN-β, and IL-8 and IL-10 appear to be effective prognostic biomarkers associated with time to recovery. In conclusion, NAFLD is associated with distinct cytokine profiles in COVID-19, possibly associated with disease severity and adverse outcomes.
Project description:People across the world are affected by the "coronavirus disease 2019 (COVID-19)", brought on by the "SARS-CoV type-2 coronavirus". Due to its high incidence in individuals with diabetes, metabolic syndrome, and metabolic-associated fatty liver disease (MAFLD), COVID-19 has gained much attention. The metabolic syndrome's hepatic manifestation, MAFLD, carries a significant risk of type-2-diabetes. The link between the above two conditions has also drawn increasing consideration since MAFLD is intricately linked to the obesity epidemic. Independent of the metabolic syndrome, MAFLD may impact the severity of the viral infections, including COVID-19 or may even be a risk factor. An important question is whether the present COVID-19 pandemic has been fueled by the obesity and MAFLD epidemics. Many liver markers are seen elevated in COVID-19. MAFLD patients with associated comorbid conditions like obesity, cardiovascular disease, renal disease, malignancy, hypertension, and old age are prone to develop severe disease. There is an urgent need for more studies to determine the link between the two conditions and whether it might account for racial differences in the mortality and morbidity rates linked to COVID-19. The role of innate and adaptive immunity alterations in MAFLD patients may influence the severity of COVID-19. This review investigates the implications of COVID-19 on liver injury and disease severity and vice-versa. We also addressed the severity of COVID-19 in patients with prior MAFLD and its potential implications and therapeutic administration in the clinical setting.
Project description:Covid-19 disease causes significant morbidity and mortality through increase inflammation and thrombosis. Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are states of chronic inflammation and indicate advanced metabolic disease. We sought to understand the risk of hospitalization for Covid-19 associated with NAFLD/NASH. Retrospective analysis of electronic medical record data of 6,700 adults with a positive SARS-CoV-2 PCR from March 1, 2020 to Aug 25, 2020. Logistic regression and competing risk were used to assess odds of being hospitalized. Additional adjustment was added to assess risk of hospitalization among patients with a prescription for metformin use within the 3 months prior to the SARS-CoV-2 PCR result, history of home glucagon-like-peptide 1 receptor agonist (GLP-1 RA) use, and history of metabolic and bariatric surgery (MBS). Interactions were assessed by gender and race. A history of NAFLD/NASH was associated with increased odds of admission for Covid-19: logistic regression OR 2.04 (1.55, 2.96, p<0.01), competing risks OR 1.43 (1.09-1.88, p<0.01); and each additional year of having NAFLD/NASH was associated with a significant increased risk of being hospitalized for Covid-19, OR 1.86 (1.43-2.42, p<0.01). After controlling for NAFLD/NASH, persons with obesity had decreased odds of hospitalization for Covid-19, OR 0.41 (0.34-0.49, p<0.01). NAFLD/NASH increased risk of hospitalization in men and women, and in all racial/ethnic subgroups. Mediation treatments for metabolic syndrome were associated with non-significant reduced risk of admission: OR 0.42 (0.18-1.01, p=0.05) for home metformin use and OR 0.40 (0.14-1.17, p=0.10) for home GLP-1RA use. MBS was associated with a significant decreased risk of admission: OR 0.22 (0.05-0.98, p<0.05). NAFLD/NASH is a significant risk factor for hospitalization for Covid-19, and appears to account for risk attributed to obesity. Treatments for metabolic disease mitigated risks from NAFLD/NASH. More research is needed to confirm risk associated with visceral adiposity, and patients should be screened for and informed of treatments for metabolic syndrome.
Project description:Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease whose prevalence has reached global epidemic proportions. Although the disease is relatively benign in the early stages, when severe clinical forms, including nonalcoholic steatohepatitis (NASH), cirrhosis and even hepatocellular carcinoma, occur, they result in worsening the long-term prognosis. A growing body of evidence indicates that NAFLD develops from a complex process in which many factors, including genetic susceptibility and environmental insults, are involved. In this review, we focused on the genetic component of NAFLD, with special emphasis on the role of genetics in the disease pathogenesis and natural history. Insights into the topic of the genetic susceptibility in lean individuals with NAFLD and the potential use of genetic tests in identifying individuals at risk are also discussed.
Project description:Background & aimsSeries studies have associated increased serum levels of ferritin with liver fibrosis in patients with nonalcoholic fatty liver disease. We aimed to determine the accuracy with which measurements of serum ferritin determine the presence and severity of liver fibrosis, and whether combining noninvasive scoring systems with serum ferritin analysis increases the accuracy of diagnosis of advanced liver fibrosis.MethodsWe performed a retrospective analysis of data from 1014 patients with liver biopsy-confirmed nonalcoholic fatty liver disease. Three cut points of serum ferritin level, adjusted for sex, were established based on receiver operating characteristic curve analysis: 1.0-, 1.5-, and 2.0-fold the upper limit of normal. Three multiple logistic regression models were created to determine the association of these cutoff values with liver fibrosis, adjusting for age, sex, race, diabetes, body mass index, and level of alanine aminotransferase.ResultsA greater proportion of patients with increased serum levels of ferritin had definitive nonalcoholic steatohepatitis and more-advanced fibrosis than patients without increased levels. In all models, serum level of ferritin was significantly associated with the presence and severity of liver fibrosis. However, for all 3 cutoff values, area under the receiver operating characteristic curve values were low (less than 0.60) for the presence of fibrosis or any stage of liver fibrosis; ferritin level identified patients with fibrosis with 16%-41% sensitivity and 70%-92% specificity. The accuracy with which noninvasive scoring systems identified patients with advanced fibrosis did not change with inclusion of serum ferritin values.ConclusionsAlthough serum levels of ferritin correlate with more-severe liver fibrosis, based on adjusted multiple logistic regression analysis, serum ferritin levels alone have a low level of diagnostic accuracy for the presence or severity of liver fibrosis in patients with nonalcoholic fatty liver disease.
Project description:BackgroundThe association between metabolic-associated fatty liver disease (MAFLD) and disease progression in patients with the coronavirus disease 2019 (COVID-19) are unclear.AimsTo explore the association between MAFLD and the severity of COVID-19 by meta-analysis.MethodsWe 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.ResultsA 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).ConclusionIn 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.