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1.
Bioengineered ; 12(1): 4054-4069, 2021 12.
Article in English | MEDLINE | ID: covidwho-1348035

ABSTRACT

During the pandemic of the coronavirus disease 2019, there exist quite a few studies on angiotensin-converting enzyme 2 (ACE2) and SARS-CoV-2 infection, while little is known about ACE2 in hepatocellular carcinoma (HCC). The detailed mechanism among ACE2 and HCC still remains unclear, which needs to be further investigated. In the current study with a total of 6,926 samples, ACE2 expression was downregulated in HCC compared with non-HCC samples (standardized mean difference = -0.41). With the area under the curve of summary receiver operating characteristic = 0.82, ACE2 expression showed a better ability to differentiate HCC from non-HCC. The mRNA expression of ACE2 was related to the age, alpha-fetoprotein levels and cirrhosis of HCC patients, and it was identified as a protected factor for HCC patients via Kaplan-Meier survival, Cox regression analyses. The potential molecular mechanism of ACE2 may be relevant to catabolic and cell division. In all, decreasing ACE2 expression can be seen in HCC, and its protective role for HCC patients and underlying mechanisms were explored in the study.


Subject(s)
Angiotensin-Converting Enzyme 2/genetics , Carcinoma, Hepatocellular/genetics , Liver Cirrhosis/genetics , Liver Neoplasms/genetics , Neoplasm Proteins/genetics , Receptors, Virus/genetics , alpha-Fetoproteins/genetics , Age Factors , Aged , Angiotensin-Converting Enzyme 2/metabolism , Area Under Curve , COVID-19/virology , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Databases, Genetic , Datasets as Topic , Female , Gene Expression Regulation, Neoplastic , Humans , Liver Cirrhosis/diagnosis , Liver Cirrhosis/mortality , Liver Cirrhosis/pathology , Liver Neoplasms/diagnosis , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Middle Aged , Neoplasm Proteins/classification , Neoplasm Proteins/metabolism , Protective Factors , Protein Interaction Mapping , ROC Curve , Receptors, Virus/metabolism , SARS-CoV-2/pathogenicity , Survival Analysis , alpha-Fetoproteins/metabolism
2.
J Formos Med Assoc ; 121(2): 454-466, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-1330958

ABSTRACT

This review evaluates the ability of the fibrosis index based on four factors (FIB-4) identifying fibrosis stages, long-time prognosis in chronic liver disease, and short-time outcomes in acute liver injury. FIB-4 was accurate in predicting the absence or presence of advanced fibrosis with cut-offs of 1.0 and 2.65 for viral hepatitis B, 1.45 and 3.25 for viral hepatitis C, 1.30 (<65 years), 2.0 (≥65 years), and 2.67 for non-alcoholic fatty liver disease (NAFLD), respectively, but had a low-to-moderate accuracy in alcoholic liver disease (ALD) and autoimmune hepatitis. It performed better in excluding fibrosis, so we built an algorithm for identifying advanced fibrosis by combined methods and giving work-up and follow-up suggestions. High FIB-4 in viral hepatitis, NAFLD, and ALD was associated with significantly high hepatocellular carcinoma incidence and mortality. Additionally, FIB-4 showed the ability to predict high-risk varices with cut-offs of 2.87 and 3.91 in cirrhosis patients and predict long-term survival in hepatocellular carcinoma patients after hepatectomy. In acute liver injury caused by COVID-19, FIB-4 had a predictive value for mechanical ventilation and 30-day mortality. Finally, FIB-4 may act as a screening tool in the secondary prevention of NAFLD in the high-risk population.


Subject(s)
COVID-19 , Liver Neoplasms , Non-alcoholic Fatty Liver Disease , Fibrosis , Humans , Liver/pathology , Liver Cirrhosis/pathology , Liver Neoplasms/pathology , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/diagnosis , Non-alcoholic Fatty Liver Disease/pathology , SARS-CoV-2 , Severity of Illness Index
3.
J Clin Lab Anal ; 35(8): e23880, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1293190

ABSTRACT

BACKGROUND: There is still little knowledge about the association of liver fibrosis with the clinical outcomes of COVID-19 patients with non-alcoholic fatty liver disease (NAFLD). The aim of the study was to determine the association of NAFLD fibrosis score (NFS)-determined liver fibrosis with clinical outcomes of COVID-19 patients with NAFLD. METHODS: The NAFLD was diagnosed by the Hepatic Steatosis Index (HSI) in the absence of other causes of chronic liver diseases. NFS was used to evaluate the severity of liver fibrosis. RESULTS: A total of 86 COVID-19 patients with NAFLD were included. The median age was 43.5 years, and 58.1% of patients were male. Thirty-eight (44.2%) patients had advanced liver fibrosis according to the NFS. Multivariate analysis indicated that concurrent diabetes (odds ratio [OR] 8.264, 95% confidence interval [CI] 1.202-56.830, p = 0.032) and advanced liver fibrosis (OR 11.057, 95% CI 1.193-102.439, p = 0.034) were independent risk factors of severe illness in COVID-19 patients with NAFLD. CONCLUSION: NAFLD patients with NFS-determined advanced liver fibrosis are at higher risk of severe COVID-19.


Subject(s)
COVID-19/etiology , Liver Cirrhosis/pathology , Non-alcoholic Fatty Liver Disease/complications , Adult , Female , Hospitalization , Humans , Liver Cirrhosis/virology , Logistic Models , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/pathology , Non-alcoholic Fatty Liver Disease/virology , Retrospective Studies , Risk Factors , Severity of Illness Index
4.
Liver Int ; 41 Suppl 1: 1-8, 2021 06.
Article in English | MEDLINE | ID: covidwho-1280355

ABSTRACT

Liver involvement, indicated by elevated liver function test results, is common in hospitalized patients with coronavirus disease 2019 (COVID-19) and has been linked to disease severity and outcome. A dual pattern of elevated liver function tests can be observed especially in patients with severe or critical COVID-19, characterized by an increase in aminotransferases early in the course of this disease, followed by an increase in cholestasis-associated biochemistry markers at later stages. This dual pattern is associated with inflammatory response markers and poor outcome. Current notions on the mechanisms of liver injury in COVID-19 include direct cytopathic effects of the virus on hepatocytes and cholangiocytes, ischemic and hypoxic liver damage, drug-induced liver injury, activation of hepatic immune cells by excess cytokine production and exacerbation of pre-existing liver disease. Patients with obesity-related non-alcoholic fatty liver disease and, in particular, patients with cirrhosis are at high risk of liver injury and a fatal outcome from COVID-19. In contrast, individuals receiving stable immunosuppressive medication for autoimmune liver diseases or during long-term follow-up after liver transplantation do not have a higher case-to-infection ratio and have a fairly favourable outcome. The present review describes the epidemiology, characteristics and potential pathological mechanisms of COVID-19-related liver injury. Moreover, the influence of pre-existing liver disease on the susceptibility and severity of liver injury in COVID-19 are discussed.


Subject(s)
COVID-19 , Liver Diseases , Non-alcoholic Fatty Liver Disease , Humans , Liver/pathology , Liver Cirrhosis/pathology , Liver Diseases/pathology , Non-alcoholic Fatty Liver Disease/pathology , SARS-CoV-2
6.
Eur Rev Med Pharmacol Sci ; 24(23): 12609-12622, 2020 12.
Article in English | MEDLINE | ID: covidwho-995022

ABSTRACT

OBJECTIVE: In human pathology, SARS-CoV-2 utilizes multiple molecular pathways to determine structural and biochemical changes within the different organs and cell types. The clinical picture of patients with COVID-19 is characterized by a very large spectrum. The reason for this variability has not been clarified yet, causing the inability to make a prognosis on the evolution of the disease. MATERIALS AND METHODS: PubMed search was performed focusing on the role of ACE 2 receptors in allowing the viral entry into cells, the role of ACE 2 downregulation in triggering the tissue pathology or in accelerating previous disease states, the role of increased levels of Angiotensin II in determining endothelial dysfunction and the enhanced vascular permeability, the role of the dysregulation of the renin angiotensin system in COVID-19 and the role of cytokine storm. RESULTS: The pathological changes induced by SARS-CoV-2 infection in the different organs, the correlations between the single cell types targeted by the virus in the different human organs and the clinical consequences, COVID-19 chronic pathologies in liver fibrosis, cardiac fibrosis and atrial arrhythmias, glomerulosclerosis and pulmonary fibrosis, due to the systemic fibroblast activation induced by angiotensin II are discussed. CONCLUSIONS: The main pathways involved showed different pathological changes in multiple tissues and the different clinical presentations. Even if ACE2 is the main receptor of SARS-CoV-2 and the main entry point into cells for the virus, ACE2 expression does not always explain the observed marked inter-individual variability in clinical presentation and outcome, evidencing the complexity of this disorder. The proper interpretation of the growing data available might allow to better classifying COVID-19 in human pathology.


Subject(s)
Angiotensin II/metabolism , Angiotensin-Converting Enzyme 2/metabolism , COVID-19/metabolism , Cardiomyopathies/metabolism , Cytokine Release Syndrome/metabolism , Endothelium, Vascular/physiopathology , Liver Cirrhosis/metabolism , Systemic Inflammatory Response Syndrome/metabolism , Thrombosis/metabolism , Angiotensin I/metabolism , Atrial Fibrillation/metabolism , Atrial Fibrillation/physiopathology , Blood Coagulation , COVID-19/pathology , COVID-19/physiopathology , Capillary Permeability , Cardiomyopathies/pathology , Cardiomyopathies/physiopathology , Cytokine Release Syndrome/physiopathology , Cytokines/metabolism , Fibroblasts/metabolism , Fibroblasts/pathology , Fibrosis , Humans , Liver Cirrhosis/pathology , Liver Cirrhosis/physiopathology , Myocarditis/metabolism , Myocarditis/pathology , Myocarditis/physiopathology , Receptors, Coronavirus/metabolism , Renin-Angiotensin System , SARS-CoV-2/metabolism , Systemic Inflammatory Response Syndrome/physiopathology , Thrombosis/physiopathology , Virus Internalization
7.
J Med Virol ; 92(11): 2785-2791, 2020 11.
Article in English | MEDLINE | ID: covidwho-959196

ABSTRACT

Previous studies reported that coronavirus disease 2019 (COVID-19) was likely to result in liver injury. However, few studies reported the impacts of COVID-19 on liver function in patients with chronic liver diseases. We aimed to describe a case series of COVID-19 patients with chronic hepatitis B virus (HBV) infection. Confirmed hospitalized COVID-19 patients from hospitals in 10 cities of Jiangsu province, China, were retrospectively included between 18 January 2020 and 26 February 2020. Demographic information, epidemiologic data, clinical features, and treatment data were extracted from medical records. Seven COVID-19 patients with chronic HBV infection were included. Six (85.7%) patients were male. The patients aged from 33 to 49 years. Two patients had HBV-related cirrhosis. One patient (14.3%) was positive for serum HBV e-antigen. On admission, 1 (14.3%) patient had mildly elevated alanine aminotransferase (ALT) level (>40 U/L) and 1 (14.3%) had elevated aspartate aminotransferase (AST) level (>40 U/L). The serum albumin level and platelet counts were decreased in two patients with HBV-related liver cirrhosis. Three (42.9%) patients had elevated ALT level and 2 (28.6%) patients had elevated AST level in hospitalization. However, the peak ALT and AST level during hospitalization was 51 U/L and 44 U/L, respectively. As of 29 February 2020, all patients were discharged. No patient was admitted to the intensive care units or developed liver failure during hospitalization. The abnormalities of liver function are not uncommon on COVID-19 patients with chronic HBV infection in our case series. However, no patient developed severe liver-related complications during hospitalization.


Subject(s)
COVID-19/virology , Coinfection/virology , Hepatitis B, Chronic/virology , Adult , Alanine Transaminase/blood , Antiviral Agents/therapeutic use , COVID-19/drug therapy , China/epidemiology , DNA, Viral/blood , Female , Hepatitis B e Antigens/blood , Hospitalization/statistics & numerical data , Humans , Liver/pathology , Liver/virology , Liver Cirrhosis/pathology , Liver Cirrhosis/virology , Liver Function Tests , Male , Medical Records , Middle Aged , Retrospective Studies
8.
Clin Mol Hepatol ; 26(4): 562-576, 2020 10.
Article in English | MEDLINE | ID: covidwho-868928

ABSTRACT

BACKGROUND/AIMS: Although coronavirus disease 2019 (COVID-19) has spread rapidly worldwide, the implication of pre-existing liver disease on the outcome of COVID-19 remains unresolved.
. METHODS: A total of 1,005 patients who were admitted to five tertiary hospitals in South Korea with laboratory-confirmed COVID-19 were included in this study. Clinical outcomes in COVID-19 patients with coexisting liver disease as well as the predictors of disease severity and mortality of COVID-19 were assessed.
. RESULTS: Of the 47 patients (4.7%) who had liver-related comorbidities, 14 patients (1.4%) had liver cirrhosis. Liver cirrhosis was more common in COVID-19 patients with severe pneumonia than in those with non-severe pneumonia (4.5% vs. 0.9%, P=0.006). Compared to patients without liver cirrhosis, a higher proportion of patients with liver cirrhosis required oxygen therapy; were admitted to the intensive care unit; had septic shock, acute respiratory distress syndrome, or acute kidney injury; and died (P<0.05). The overall survival rate was significantly lower in patients with liver cirrhosis than in those without liver cirrhosis (log-rank test, P=0.003). Along with old age and diabetes, the presence of liver cirrhosis was found to be an independent predictor of severe disease (odds ratio, 4.52; 95% confidence interval [CI], 1.20-17.02;P=0.026) and death (hazard ratio, 2.86; 95% CI, 1.04-9.30; P=0.042) in COVID-19 patients.
. CONCLUSION: This study suggests liver cirrhosis is a significant risk factor for COVID-19. Stronger personal protection and more intensive treatment for COVID-19 are recommended in these patients.


Subject(s)
Coronavirus Infections/pathology , Liver Diseases/pathology , Pneumonia, Viral/pathology , Age Factors , Aged , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/mortality , Coronavirus Infections/therapy , Coronavirus Infections/virology , Female , Humans , Hyperbaric Oxygenation , Intensive Care Units , Kaplan-Meier Estimate , Liver Cirrhosis/complications , Liver Cirrhosis/mortality , Liver Cirrhosis/pathology , Liver Diseases/complications , Liver Diseases/mortality , Male , Middle Aged , Odds Ratio , Pandemics , Pneumonia, Viral/mortality , Pneumonia, Viral/therapy , Pneumonia, Viral/virology , Prognosis , Republic of Korea , Risk Factors , SARS-CoV-2 , Severity of Illness Index , Survival Rate , Treatment Outcome
9.
Int J Mol Sci ; 21(15)2020 Jul 24.
Article in English | MEDLINE | ID: covidwho-699380

ABSTRACT

Sarcopenia in patients with liver cirrhosis (LC) has been attracting much attention these days because of the close linkage to adverse outcomes. LC can be related to secondary sarcopenia due to protein metabolic disorders and energy metabolic disorders. LC is associated with profound alterations in gut microbiota and injuries at the different levels of defensive mechanisms of the intestinal barrier. Dysbiosis refers to a state in which the diversity of gut microbiota is decreased by decreasing the bacterial species and the number of bacteria that compose the gut microbiota. The severe disturbance of intestinal barrier in LC can result in dysbiosis, several bacterial infections, LC-related complications, and sarcopenia. Here in this review, we will summarize the current knowledge of the relationship between sarcopenia and dysbiosis in patients with LC.


Subject(s)
Bacterial Infections , Dysbiosis , Gastrointestinal Microbiome , Liver Cirrhosis , Sarcopenia , Bacterial Infections/etiology , Bacterial Infections/metabolism , Bacterial Infections/microbiology , Bacterial Infections/pathology , Dysbiosis/etiology , Dysbiosis/metabolism , Dysbiosis/microbiology , Dysbiosis/pathology , Humans , Intestinal Mucosa/metabolism , Intestinal Mucosa/microbiology , Intestinal Mucosa/pathology , Liver Cirrhosis/complications , Liver Cirrhosis/metabolism , Liver Cirrhosis/microbiology , Liver Cirrhosis/pathology , Sarcopenia/etiology , Sarcopenia/metabolism , Sarcopenia/microbiology , Sarcopenia/pathology
10.
J Infect Dis ; 222(5): 726-733, 2020 08 04.
Article in English | MEDLINE | ID: covidwho-607902

ABSTRACT

BACKGROUND: COVID-19 is a potentially severe disease caused by the recently described SARS-CoV-2. Whether liver fibrosis might be a relevant player in the natural history of COVID-19 is currently unknown. We aimed to evaluate the association between FIB-4 and the risk of progression to critical illness in middle-aged patients with COVID-19. METHODS: In this multicenter, retrospective study with prospective follow-up of 160 patients aged 35-65 years with COVID-19, FIB-4, clinical, and biochemical variables were collected at baseline. FIB-4 ≥2.67 defined patients with risk for advanced liver fibrosis. RESULTS: Risk for advanced fibrosis was estimated in 28.1% of patients. Patients with FIB-4 ≥2.67 more frequently required mechanical ventilation (37.8% vs 18.3%; P = .009). In multivariate analysis, FIB-4 ≥2.67 (odds ratio [OR], 3.41; 95% confidence interval [CI], 1.30-8.92), cardiovascular risk factors (OR, 5.05; 95% CI, 1.90-13.39), previous respiratory diseases (OR, 4.54; 95% CI, 1.36-15.10), and C-reactive protein (OR, 1.01; 95% CI, 1.01-1.02) increased significantly the risk of ICU admission. Bootstrap confirmed FIB-4 as an independent risk factor. CONCLUSIONS: In middle-aged patients with COVID-19, FIB-4 may have a prognostic role. The link between liver fibrosis and the natural history of COVID-19 should be evaluated in future studies.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/pathology , Liver Cirrhosis/virology , Pneumonia, Viral/pathology , Adult , Aged , Betacoronavirus/genetics , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Female , Humans , Liver Cirrhosis/diagnosis , Liver Cirrhosis/pathology , Male , Middle Aged , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Prospective Studies , Retrospective Studies , Risk Factors , SARS-CoV-2 , Severity of Illness Index
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