High Child-Pugh and CRUB65 scores predict mortality of decompensated cirrhosis patients with COVID-19: A 23-center, retrospective study.

Background: COVID-19 has rapidly become a major health emergency worldwide. The characteristic, outcome, and risk factor of COVID-19 in patients with decompensated cirrhosis remain unclear.Methods: Medical records were collected from 23 Chinese hospitals. Patients with decompensated cirrhosis and age- and sex-matched non-liver disease patients were enrolled with 1:4 ratio using stratified sampling.Results: There were more comorbidities with higher Chalson Complication Index (p < 0.001), higher proportion of patients having gastrointestinal bleeding, jaundice, ascites, and diarrhea among those patients (p < 0.05) and in decompensated cirrhosis patients. Mortality (p < 0.05) and the proportion of severe ill (p < 0.001) were significantly high among those patients. Patients in severe ill subgroup had higher mortality (p < 0.001), MELD, and CRUB65 score but lower lymphocytes count. Besides, this subgroup had larger proportion of patients with abnormal (PT), activated partial thromboplatin time (APTT), D-Dimer, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBL) and Creatinine (Cr) (p < 0.05). Multivariate logistic regression for severity shown that MELD and CRUB65 score reached significance. Higher Child-Pugh and CRUB65 scores were found among non-survival cases and multivariate logistic regression further inferred risk factors for adverse outcome. Receiver Operating Characteristic (ROC) curves also provided remarkable demonstrations for the predictive ability of Child-Pugh and CRUB65 scores.Conclusions: COVID-19 patients with cirrhosis had larger proportion of more severely disease and higher mortality. MELD and CRUB65 score at hospital admission may predict COVID-19 severity while Child-Pugh and CRUB65 score were highly associated with non-survival among those patients.

Puerarin Exerts the Hepatoprotection from Chronic Alcohol-Induced Liver Injury via Inhibiting the Cyclooxygenase-2 and the 5-Lipoxygenase Pathway in Rats.

BACKGROUND: Puerarin (PR) as one of the main ingredients of the root of the traditional herb Kudzu has been suggested to improve chronic alcohol-induced liver injury. We explore the specific mechanisms of PR on hepatocellular changes after administration of alcohol. METHODS: Sprague-Dawley rats were treated with 55% alcohol for 12 weeks to induce a chronic alcoholic liver damage model. Then the rats in each group were administered by oral gavage with zileuton, celecoxib, and PR for 2 weeks, respectively. RESULTS: In the PR group, the weight loss was markedly improved and the abnormal serum alanine aminotransferase and aspartate aminotransferase were significantly lowered after PR treatment when compared to the alcoholic liver injured model group. Pathological examination indicated that alcohol-induced hepatocellular injury was improved by the PR treatment. The 5-lipoxygenase (5-Lox) and cyclooxygenase-2 (Cox-2) at the protein level and the mRNA level were obviously downregulated accompanied with the PR treatment. Meanwhile, the peroxisome proliferator-activated receptor γ (PPAR-γ) at the protein and mRNA level was notably elevated and the tumor necrosis factor α at the protein and mRNA level was markedly decreased following the PR treatment. CONCLUSION: The possible cytoprotective mechanisms of PR may be involved inhibition of the Cox-2 pathway and the 5-Lox pathway to suppress inflammatory response and regulate the protective factor PPAR-γ expression.

Anti-inflammatory effect of fucoxanthin on dextran sulfate sodium-induced colitis in mice.

The anti-inflammatory activities of fucoxanthin, a marine carotenoid derived from the macroalgae and microalgae, have been demonstrated in the previous studies. However, the effect of fucoxanthin on ulcerative colitis (UC), an inflammatory bowel disease, was still unclear. In this study, we evaluated the in vivo anti-inflammatory effect of fucoxanthin on dextran sulfate sodium(DSS)-induced colitis in mice. Fucoxanthin at the doses of 50 and 100 mg/kg/day significantly protected against DSS-induced gradual loss of body weight, exhibited inhibitory effects on the DSS-induced increase of disease activity index and colon shortening. Moreover, fucoxanthin treatment resulted in a marked amelioration of the histological damage in the colon, and reduced the colonic PGE2 levels in colitic mice. In addition, the DSS-induced overexpressions of inflammation-related molecules including COX-2 and NF-κB were significantly decreased in fucoxanthin-treated mice. These finding suggested that the use of fucoxanthin provides a new and attractive alternative to control UC.

Alcoholic liver disease. Are there any differences between China and Western countries in clinical features?

OBJECTIVE: To investigate the clinical features of alcoholic liver disease (ALD) in hospitalized Chinese patients, and their differences compared with western countries. METHODS: Four hundred and eight hospitalized patients with ALD at First Affiliated Hospital of Zhejiang University College of Medicine, Hangzhou, from January 2008 to December 2010 were studied retrospectively. Clinical data were analyzed and compared with western countries through literature review. RESULTS: The patients with ALD accounted for 7.8% of all hospitalized patients with liver diseases. These patients comprised 400 men and 8 women, aged between 45 and 55 years. Among the patients, there were 318 patients with alcoholic cirrhosis (77.9%), 48 patients with alcoholic hepatitis (11.8%), 9 patients with fatty liver (2.2%), and 33 patients with mild alcoholic injury (8.1%). The abstinence rate in these patients was 37.7%. Logistic-regression analysis showed that daily intake amount, duration of drinking, drinking hard liquors and smoking were the risk factors for alcoholic cirrhosis, but abstinence was the favorable factor for treatment. Compared with western countries, Chinese patients had a lower constituent ratio of ALD among liver diseases, lower proportions of females, and rate of concomitant hepatitis C infection; but the drinking status, clinical manifestations, and abstinence rate were similar between them. CONCLUSION: There are differences as well as similarities between China and western countries in the clinical features of ALD.

Expression and activity of inducible nitric oxide synthase and endothelial nitric oxide synthase correlate with ethanol-induced liver injury.

AIM: To study the expression and activity of inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) in rats with ethanol-induced liver injury and their relation with liver damage, activation of nuclear factor-kappaB (NF-kappaB) and tumor necrosis factor-alpha (TNF-alpha) expression in the liver. METHODS: Female Sprague-Dawley rats were given fish oil (0.5 mL) along with ethanol or isocaloric dextrose daily via gastrogavage for 4 or 6 wk. Liver injury was assessed using serum alanine aminotransferase (ALT) activity and pathological analysis. Liver malondialdehyde (MDA), nitric oxide contents, iNOS and eNOS activity were determined. NF-kappaB p65ìiNOS, eNOS and TNF-alpha protein or mRNA expression in the liver were detected by immunohistochemistry or reverse transcriptase-polymerase chain reaction (RT-PCR). RESULTS: Chronic ethanol gavage for 4 wk caused steatosis, inflammation and necrosis in the liver, and elevated serum ALT activity. Prolonged ethanol administration (6 wk) enhanced the liver damage. These responses were accompanied with increased lipid peroxidation, NO contents, iNOS activity and reduced eNOS activity. NF-kappaB p65, iNOS and TNF-alpha protein or mRNA expression were markedly induced after chronic ethanol gavage, whereas eNOS mRNA expression remained unchanged. The enhanced iNOS activity and expression were positively correlated with the liver damage, especially the necro-inflammation, activation of NF-kappaB, and TNF-alpha mRNA expression. CONCLUSION: iNOS expression and activity are induced in the liver after chronic ethanol exposure in rats, which are correlated with the liver damage, especially the necro-inflammation, activation of NF-kappaB and TNF-alpha expression. eNOS activity is reduced, but its mRNA expression is not affected.

Tea polyphenols inhibit expressions of iNOS and TNF-alpha and prevent lipopolysaccharide-induced liver injury in rats.

BACKGROUND: Tea polyphenols have been shown to protect against carbon tetrachloride (CCl4)-induced liver injury, liver fibrosis, hepatic ischemia-reperfusion injury. In this study, we examined the effect of tea polyphenols on lipopolysaccharide (LPS)-induced liver injury, and explored its mechanisms. METHODS: Sprague-Dawley rats received tea polyphenols (100 mg.kg-1.d-1) or vehicle (water) intragastrically by gavage for 14 days, followed by LPS (5 mg/kg) or saline injection intraperitoneally. Liver injury was assessed by biochemical assay and pathological analysis. Serum tumor necrosis factor-alpha (TNF-alpha) levels and liver malondialdehyde (MDA) contents were determined. Inducible nitric oxide synthase (iNOS) protein and TNF-alpha, iNOS and endothelial nitric oxide synthase (eNOS) mRNA expressions in the liver were detected by immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR), respectively. RESULTS: Administration of LPS resulted in liver injury in rats, evidenced by elevated activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), hepatocellular necrosis, and neutrophil infiltration in the liver. These responses were associated with increased serum TNF-alpha levels, induced iNOS protein, expressions of TNF-alpha, iNOS mRNA in the liver and elevated lipid peroxidation at 90 minutes or 6 hours after LPS injection. Pretreatment with tea polyphenols attenuated LPS-induced liver injury, and blunted the rises of serum TNF-alpha levels and lipid peroxidation and the induction of expressions of TNF-alpha, iNOS in the liver. CONCLUSION: Tea polyphenols prevent LPS-induced liver injury, and the mechanisms may involve the reduction of serum TNF-alpha levels and lipid peroxidation and the suppression of TNF-alpha, iNOS expressions in the liver.

Modulation of liver oxidant-antioxidant system by ischemic preconditioning during ischemia/reperfusion injury in rats.

AIM: To investigate effects of ischemic pre-conditioning on the liver endogenous oxidant-antioxidant system during ischemia/reperfusion injury. METHODS: Twenty-four male Sprague-Dawley rats were randomly divided into sham-operated (Sham), ischemia/reperfusion (I/R), ischemic pre-conditioning plus ischemia/reperfusion (IPC) groups. Serum ALT, AST and hyaluronic acid levels were assayed and pathologic alterations observed. Liver malondialdehyde (MDA) contents, endogenous antioxidant enzymes, superoxidase dismutase (SOD), catalase (CAT), gultathionine peroxidase (GSH-Px) activities, neutrophils accumulation marker, myeloperoxidase (MPO) activities were measured respectively. RESULTS: Compared with I/R group, sinusoidal endothelial cells as well as hepatocytes damages, as assessed biochemically and histochemically, were improved significantly in IPC group; neutrophils infiltration was also markedly reduced. In IPC group, liver peroxidation, as measured by MDA contents, was significantly decreased when compared with I/R group; endogenous antioxidant enzymes, SOD, CAT and GSH-Px activities were markedly higher than that in I/R group. CONCLUSION: Ischemic pre-conditioning exerts protective effects on both hepatic sinusoidal endothelial cells and hepatocytes during liver I/R injury. Its mechanisms may involve dimunition of neutrophils infiltration and modulation of the imbalance of endogenous oxidant-antioxidant system in the organism.