Hepatic ischemia/reperfusion injury (IRI) remains a critical complication contributing to graft dysfunction following liver surgery. As part of an ongoing search for hepatoprotective natural products, five previously unreported homoadamantane-type polycyclic polyprenylated acylphloroglucinols (PPAPs), named hyperhomanoons A-E (1-5), and one known analog, hypersampsone O (6), were isolated from Hypericum patulum. Among these, compound 6 demonstrated potent protective effects against CoCl₂-induced hypoxic injury in hepatocytes. Furthermore, in a murine model of hepatic IRI induced by vascular occlusion, pretreatment with 6 markedly alleviated liver damage and reduced hepatocyte apoptosis. This study is the first to identify PPAPs as promising scaffolds for the development of therapeutic agents targeting hepatic IRI, underscoring their potential as lead compounds in drug discovery efforts for ischemic liver diseases.
Reperfusion Injury/prevention & control* ; Animals ; Hypericum/chemistry* ; Phloroglucinol/administration & dosage* ; Mice ; Humans ; Male ; Liver/blood supply* ; Apoptosis/drug effects* ; Molecular Structure ; Protective Agents/pharmacology* ; Hepatocytes/drug effects* ; Mice, Inbred C57BL ; Liver Diseases/drug therapy*

Liver disease-associated thrombocytopenia syndrome refers to thrombocytopenia caused by liver disease or the treatment of liver disease, and its incidence rate is related to the duration and severity of liver disease. The direct effect of thrombocytopenia on clinical outcomes is an increased risk of bleeding in patients with liver disease, whereas the indirect effect involves delay or termination of treatment due to the potential risk of bleeding. Liver disease-associated thrombocytopenia pathophysiological mechanisms involve decreased platelet production, abnormal distribution, destruction, or increased consumption. Presently, treatment strategies targeting different mechanisms include platelet-stimulating drugs, surgery, immunosuppressive drugs, and platelet transfusion, but the clinical application needs to be standardized further. The National Clinical Research Center for Infectious Diseases organized experts to discuss and formulate consensus with reference to the latest evidence-based medical evidence in the field so as to improve the clinical management level of liver disease-associated thrombocytopenia syndrome in China in terms of diagnosis, typing, and reasonable selection of treatment schemes.
Humans ; Consensus ; Thrombocytopenia/complications* ; Liver Diseases/complications* ; Hemorrhage/etiology* ; Blood Platelets

OBJECTIVES: To analyze the clinical characteristics in patients of coronavirus disease 2019 (COVID-19) complicated with liver injury, to explore the relationship between COVID-19 clinical classification and liver injury, and to elucidate whether COVID-19 complicated with hepatitis B virus can aggravate liver injury. METHODS: The abnormal liver function in 110 patients in the First Hospital of Changsha, who were confirmed COVID-19 and admitted to the designated hospital from January 17, 2020 to February 20, 2020, wereretrospectively analyzed. The detection indexes included serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (ALB), and total bilirubin (TBIL). RESULTS: A total of 49.1% of the COVID-19 patients had liver injury. There were significant difference in the ALT, AST, ALB (all <0.05), but there was no significant difference in the TBIL (>0.05) between the severe (critical) patients and the general (light) patients. There was also no significant difference in the liver function injury between the HBsAg-positive COVID-19 patients and HBsAg-negative COVID-19 patients (>0.05). Acute liver injury was not found to be a direct cause of death in the patients. CONCLUSIONS In the COVID-19 patients, the incidence of liver injury is high with the increase of ALT and AST and the decrease of ALB. Severe and critical patients have obvious liver injury, and those patients complicated with hepatitis B virus infection don't show aggravated liver injury.
Alanine Transaminase ; blood ; Aspartate Aminotransferases ; blood ; Betacoronavirus ; Bilirubin ; blood ; Coronavirus Infections ; diagnosis ; Humans ; Liver ; physiopathology ; virology ; Liver Diseases ; virology ; Pandemics ; Pneumonia, Viral ; diagnosis ; Serum Albumin, Human ; analysis

liver disease (NAFLD) is the most common liver disease which has become a public health concern. Since oxidative stress plays a crucial role in the pathogenesis of NAFLD, subsequent hematological disorders are expected. Therefore, antioxidant compounds such as quercetin could ameliorate the related side-effect of oxidative stress. The aim of the current study was to assess the effect of quercetin on hematological parameters in NAFLD patients. A randomized, double-blind, placebo-controlled trial was conducted as a pilot study. In this study 90 patients with NAFLD were supplemented with either a quercetin or a placebo capsule twice daily (500 mg) for 12 weeks. Blood sample was obtained for laboratory parameters at baseline and the end of week 12. End of trial values for red blood cell (RBC; p = 0.002), mean corpuscular hemoglobin concentration (p = 0.029), and mean platelet volume (p = 0.017), significantly increased and the levels of mean corpuscular volume (MCV; p = 0.023), RBC distribution width-coefficient of variation (p = 0.005), platelet distribution width (p = 0.015), and ferritin (p = 0.002) significantly decreased compared to the baseline in group receiving quercetin. Between group analysis revealed that RBC significantly increased (p = 0.025) but, mean corpuscular volume (p = 0.004), mean corpuscular hemoglobin (MCH; p = 0.002), and ferritin (p = 0.013) significantly decreased compared to placebo group. In this work quercetin showed significant effect on RBC, ferritin, MCV, and MCH in intervention group.TRIAL REGISTRATION: Iranian Center for Clinical Trials Identifier: IRCT2016060628299N1]]>
Anemia ; Blood Platelets ; Erythrocyte Indices ; Erythrocytes ; Ferritins ; Hematology ; Humans ; Inflammation ; Liver Diseases ; Mean Platelet Volume ; Non-alcoholic Fatty Liver Disease ; Oxidative Stress ; Pilot Projects ; Public Health ; Quercetin

BACKGROUND: Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by specific autoantibodies. We evaluated the prevalence of autoantibodies against nucleoporin p62 (anti-p62) in PBC patients' sera to determine whether it can be a marker for PBC, in comparison with other immunological and biochemical parameters. We validated the performance of our in-house ELISA technique. METHODS: Serum samples were collected from 135 PBC patients. Thirty patients with primary sclerosing cholangitis (PSC) and 30 with autoimmune hepatitis (AIH) were included as pathological controls, and 40 healthy blood donors served as healthy controls. The presence of anti-p62 was determined by an in-house ELISA using a recombinant protein. We calculated the sensitivity, specificity, positive and negative predictive values (PPV and NPV), and positive and negative likelihood ratio (LR+ and LR−) of our in-house ELISA for diagnosing PBC based on anti-p62. Findings were correlated with biochemical data and survival. RESULTS: Anti-p62 was detected in 32 PBC patients (23.7%). Specificity and PPV of anti-p62 for PBC were 99% and 97%, respectively. The difference between proportions of anti-p62-positive patients and controls was 0.23 (95% confidence interval [CI]: 0.03–0.40; P < 0.0001); LR+ and LR− were 23.7 and 0.77, respectively. The presence of anti-p62 was associated with higher levels of bilirubin and alkaline phosphatase (P < 0.001). The odds ratio for survival was 2.44 (95% CI: 0.87–6.87; P=0.091). CONCLUSIONS: Anti-p62 may be regarded as a significant serological marker of PBC.
Alkaline Phosphatase ; Autoantibodies ; Bilirubin ; Blood Donors ; Cholangitis ; Cholangitis, Sclerosing ; Enzyme-Linked Immunosorbent Assay ; Hepatitis, Autoimmune ; Humans ; Liver ; Liver Diseases ; Nuclear Pore Complex Proteins ; Odds Ratio ; Prevalence ; Sensitivity and Specificity

In the present study,non-targeted metabolomics technique was used to screen potentially susceptibility biomarkers in patients with mild liver function abnormalities during long-term use of Chinese herbal compound. According to the inclusion and exclusion criteria,we collected 7 cases of patients with abnormal liver function during the period of complete taking Chinese herbal medicine( 60 days),and 18 cases of patients with normal liver function in re-examination from the reproductive medicine center in our hospital. Ultra performance liquid chromatography coupled with time-of-flight mass spectrometry( UPLC-Q-TOF/MS~E) technique combined with Progenesis QI software was used to analyze the differential biomarkers in serum of patients with wild liver function abnormalities and normal liver function. 11 potential biomarkers such as bilirubin,pantothenic acid,hippuric acid,sphingomyelin,palmitic acid,and oleic acid were tentatively identified. Metabolic disorders in patients with herbal-induced mild liver abnormality were mainly related to two pathways: pantothenic acid and coenzyme A biosynthesis and linoleic acid metabolism. It could provide a reference for the early warning of mild liver function abnormalities of patients that may be caused by long-term use of Chinese medicine compound in clinical application,and will lay a foundation for further understanding the endogenous substance changes in different levels of liver injury.
Biomarkers ; blood ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Humans ; Liver Diseases ; blood ; Mass Spectrometry ; Metabolomics

A girl, aged 8 years, developed jaundice and liver dysfunction in the neonatal period, with congenital glaucoma diagnosed on day 5 after birth, hypertension and unusual facies (broad forehead, hypertelorism and deep-set eyes). Cholestasis was the main type of liver dysfunction. Cardiac macrovascular CTA showed stenosis at the abdominal aorta and the beginning of the bilateral renal arteries. Whole exon sequencing revealed a heterozygous frameshift mutation, c.1485delC (absence of cytosine), in exon 12 of the JAG1gene. The girl was diagnosed with Alagille syndrome and was given transaminase-lowering, cholagogic and antihypertensive treatment with multiple drugs. There were significant reductions in serum levels of alanine aminotransferase, aspartate aminotransferase and total bile acid, but blood pressure fluctuated between 102-140 mm Hg/53-89 mm Hg. After renal artery angiography and balloon dilatation angioplasty, the girl was given oral administration of antihypertensive drugs, and blood pressure was controlled at a level of 110-120 mm Hg/60-80 mm Hg. The rare disease Alagille syndrome should be considered when a child has refractory hypertension with the involvement of multiple systems, especially liver dysfunction with cholestasis as the main manifestation. Genetic causes should be analyzed for a early diagnosis.
Alagille Syndrome ; Blood Pressure ; Child ; Female ; Humans ; Hypertension ; etiology ; Liver Diseases ; etiology ; Renal Artery

Antrodia camphorata, a well-known and highly valued edible medicinal mushroom with intriguing activities like liver protection, has been traditionally used for the treatment of alcoholic liver disease. A. camphorata shows highly medicinal and commercial values with the demand far exceeds the available supply. Thus, the petri-dish cultured A. camphorata (PDCA) is expected to develope as a substitute. In this paper, nineteen triterpenes were isolated from PDCA, and thirteen of them were the unique anthroic acids in A. camphorata, including the main content antcin K, which suggested that PDCA produced a large array of the same anthroic acids as the wild one. Furthermore, no obvious acute toxicity was found suggesting the edible safety of PDCA. In mice alcohol-induced liver injury model, triglyceride (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and malondialdehyde (MDA) had been reduced by the PDCA powder as well as the main content antcin K, which indicated that the PDCA could protect alcoholic liver injury in mice model and antcin K could be the effective component responsible for the hepatoprotective activities of PDCA against alcoholic liver diseases.
Alanine Transaminase ; blood ; Aldehyde Dehydrogenase ; blood ; Animals ; Antrodia ; chemistry ; Aspartate Aminotransferases ; blood ; Biological Products ; chemistry ; pharmacology ; therapeutic use ; Chemical and Drug Induced Liver Injury ; etiology ; prevention & control ; Cholestenes ; chemistry ; pharmacology ; therapeutic use ; Cholesterol, VLDL ; blood ; Disease Models, Animal ; Ethanol ; toxicity ; Female ; Fruiting Bodies, Fungal ; chemistry ; Liver ; drug effects ; metabolism ; pathology ; Liver Diseases, Alcoholic ; prevention & control ; Male ; Malondialdehyde ; blood ; Mice ; Molecular Structure ; Triglycerides ; blood ; Triterpenes ; chemistry ; pharmacology ; therapeutic use

BACKGROUND: Liver fibrosis evaluation is an important issue in chronic liver disease patients. We aimed to develop noninvasive liver fibrosis biomarkers based on transient elastography (TE, FibroScan®) through retrospective review of clinicopathological data. METHODS: We recruited 278 chronic hepatitis B patients who underwent Fibroscan and HBV DNA testing. A total of 115 HBeAg-positive and 159 HBeAg-negative chronic hepatitis B patients were analyzed. A total of 100 hepatitis C patients were analyzed. Successful fibroscan data, gamma-glutamyl transferase (GGT) to platelet ratio (GPR), platelet count, AST, ALT, international normalized ratio of prothrombin time, total cholesterol, triglycerides, bilirubin, mean platelet volume, AST to platelet ratio index, fibrosis index based on four factors (FIB-4), neutrophil to lymphocyte ratio (NLR), and NLR to platelet ratio were analyzed to determine the new noninvasive markers for assessing liver fibrosis. RESULTS: Elevated GPR (OR=9.1, P=0.011) and FIB-4 (OR=2.3, P=0.01) were associated with greater risk of liver fibrosis in chronic hepatitis B patients. FIB-4 (OR=6.04, P=0.005) was a risk factor for liver fibrosis in HBeAg-positive patients. FIB-4 (OR=2.371, P=0.015) and GPR (OR=33.78, P=0.003) were liver fibrosis risk factor in HBeAg-negative patients. In chronic hepatitis C patients, GGT (OR=1.033, P=0.002), triglyceride (OR=−0.990, P=0.038) and FIB-4 (OR=3.499, P=0.006) showed statistical significances. The AUCs were 0.816 in FIB-4 (P<0.001) and 0.849 in GPR (P<0.001). CONCLUSIONS: FIB-4 and GPR may be useful blood markers for assessing liver fibrosis in chronic hepatitis B and hepatitis C patients. Further well-designed prospective study is required to validate these noninvasive blood markers in clinical practice.
Area Under Curve ; Bilirubin ; Biomarkers ; Blood Platelets ; Cholesterol ; DNA ; Elasticity Imaging Techniques ; Fibrosis ; Hepatitis B ; Hepatitis B, Chronic ; Hepatitis C ; Hepatitis C, Chronic ; Hepatitis ; Hepatitis, Chronic ; Humans ; International Normalized Ratio ; Liver Cirrhosis ; Liver Diseases ; Liver ; Lymphocytes ; Mean Platelet Volume ; Neutrophils ; Platelet Count ; Prospective Studies ; Prothrombin Time ; Retrospective Studies ; Risk Factors ; Transferases ; Triglycerides

BACKGROUND/AIMS: Advanced hepatic fibrosis is associated with cardiovascular disease (CVD) in patients with nonalcoholic fatty liver disease (NAFLD). We investigated the association between noninvasive serum fibrosis markers and the coronary artery calcium score (CACS) in subjects with NAFLD. METHODS: We analyzed 665 NAFLD subjects without chronic liver disease or heart disease between 2011 and 2015. The noninvasive fibrosis markers that were used to evaluate the severity of hepatic fibrosis included the NAFLD fibrosis score (NFS), fibrosis-4 (FIB-4) score, Forn's index, and the aspartate aminotransferase to platelet ratio index (APRI). RESULTS: The areas under the receiver operating characteristics curves for the NFS, FIB-4 score, Forn's index and APRI for predicting CACS >100 were 0.689, 0.683, 0.659, and 0.595, respectively. According to the multivariate analysis, older age, increased body mass index (BMI), and decreased estimated glomerular filtration rate (eGFR) were significant factors associated with CACS >100. The NFS, FIB-4 score and APRI were significantly associated with CACS >100 after adjusting for age and gender (p=0.006, p=0.012, and p=0.012, respectively) and after adjusting for age, gender, BMI and eGFR (p=0.013, p=0.022, and p=0.027, respectively). Scores integrating noninvasive fibrosis markers and other risk factors improved the predictive accuracy. CONCLUSIONS: The NFS and FIB-4 score were associated with coronary atherosclerosis in subjects with NAFLD. Furthermore, scores integrating these noninvasive scores and risk factors for CVD showed good discriminatory power in predicting CACS >100. Therefore, noninvasive serum fibrosis markers may be useful tools for identifying NAFLD subjects at a high risk for CVD.
Aspartate Aminotransferases ; Blood Platelets ; Body Mass Index ; Calcium ; Cardiovascular Diseases ; Coronary Artery Disease ; Coronary Vessels ; Fibrosis ; Glomerular Filtration Rate ; Heart Diseases ; Humans ; Liver Diseases ; Multivariate Analysis ; Non-alcoholic Fatty Liver Disease ; Risk Factors ; ROC Curve