Epidemiological data are scarce regarding the association of exposure to mixtures of per-and polyfluoroalkyl substances(PFASs)with liver injury in the general population.In the current study,therefore,we examined data...Epidemiological data are scarce regarding the association of exposure to mixtures of per-and polyfluoroalkyl substances(PFASs)with liver injury in the general population.In the current study,therefore,we examined data from the National Health and Nutrition Examination Survey(2009–2018).The PFAS exposure levels were defined by the serum concentrations of PFASs with over 70%detection in samples,namely perfluorooctanoic acid,perfluorononanoic acid,perfluorohexane sulfonic acid,perfluorodecanoic acid,and perfluorooctane sulfonic acid(PFOS).We evaluated liver injury from two aspects:first,the degree of liver inflammation was determined based on levels of the serum alanine aminotransferase,aspartate aminotransferase,glutamyltransferase,and total bilirubin;second,the degree of liver fibrosis was determined based on the fibrosis-4 index.We assessed the associations of individual or total PFAS exposure with these liver injury outcomes using multivariable linear and logistic regression models,restricted cubic splines,and weighted quantile sum regression.Among the samples of 7484 American adults,the median concentration of PFOS was the highest,followed by perfluorooctanoic acid and perfluorohexane sulfonic acid.Using multivariable linear regression,we observed positive correlations between all PFAS exposure and liver enzyme levels,such as alanine aminotransferase,aspartate aminotransferase,and total bilirubin.Additionally,the weighted quantile sum model indicated an overall positive association between exposure to the five PFASs and liver injury risk.For liver function biomarkers and liver fibrosis,perfluorononanoic acid and PFOS were the most heavily weighted chemicals,respectively.Our findings provide new epidemiological evidence indicating potential associations between PFAS exposure and adverse effects on liver injury biomarkers,highlighting the potentially harmful effects of PFAS exposure on human liver health.展开更多
Objective: To study the value of transient ultrasonic elastography for evaluating the liver fibrosis and liver function in patients with drug-induced liver injury. Methods: A total of 68 patients with drug-induced liv...Objective: To study the value of transient ultrasonic elastography for evaluating the liver fibrosis and liver function in patients with drug-induced liver injury. Methods: A total of 68 patients with drug-induced liver injury who were treated in our hospital between January 2016 and May 2017 were selected as drug-induced liver injury group, and 50 healthy volunteers who received physical examination in our hospital during the same period were selected as normal control group. The liver transient ultrasonic elastography parameter Stiffness levels as well as serum liver fibrosis index and liver function index contents of two groups of subjects were detected. Pearson test was used to evaluate the correlation of Stiffness levels with liver fibrosis and liver function damage degree in patients with drug-induced liver injury. Results:Stiffness level in drug-induced liver injury group was higher than that in normal control group;serum liver fibrosis indexes HA, LN, CⅣ, PⅢNP and CG contents were higher than those of normal control group;serum liver function indexes ALT, AST, ALP, STB and γ-GT contents were higher than those of normal control group. Conclusion: Transient ultrasonic elastography parameter Stiffness levels increase in patients with drug-induced liver injury, and the specific levels are consistent with the liver fibrosis and liver function damage degree, and can be used as the objective means to evaluate the disease severity.展开更多
The outbreak of novel coronavirus disease 2019(COVID-19)has resulted in global emergence.With the expansion of related research,in addition to respiratory symptoms,digestive system involvement such as nausea,vomiting,...The outbreak of novel coronavirus disease 2019(COVID-19)has resulted in global emergence.With the expansion of related research,in addition to respiratory symptoms,digestive system involvement such as nausea,vomiting,and diarrhea have also been reported with COVID-19.Besides,abnormal liver function is also frequent in biochemical tests of COVID-19 patients,which is correlated with the severity and mortality of the disease course.The etiology of liver injury in patients with COVID-19 might include viral immunologic injury,drug-induced liver injury,the systemic inflammatory response,hypoxic hepatitis,and the exacerbation of preexisting liver disease.Although liver injuries in COVID-19 are often transient and reversible,health workers need to pay attention to preexisting liver disease,monitor liver function,strengthen supportive treatment,and reduce the chance of drug-induced liver injury.This article reviews the epidemiological characteristics,etiology,management,and preventive strategies for liver injury in patients with COVID-19.展开更多
Background: Diabetes mellitus has become an increasing global health burden with rapid growing prevalence. Patients with diabetes have higher susceptibility to acute kidney injury(AKI). Liver transplantation(LT) predi...Background: Diabetes mellitus has become an increasing global health burden with rapid growing prevalence. Patients with diabetes have higher susceptibility to acute kidney injury(AKI). Liver transplantation(LT) predisposes the kidney to injury. However, the association between diabetes and AKI in LT patients remains unclear. Methods: We conducted a retrospective cohort study examining risk factors for AKI in patients undergone orthotopic LT. Potential risk factors including baseline estimated glomerular filtration rate(e GFR), the model for end-stage liver disease(MELD) score, diabetes, hypertension and intraoperative blood loss were screened. The primary endpoint was AKI occurrence. Multivariate logistic regression was used to analyze the association between potential risk factors and AKI. Results: A total of 291 patients undergone orthotopic LT were included in the present study. Among them, 102 patients(35.05%) developed AKI within 5 days after LT. Diabetes was identified as an independent risk factor for AKI. Patients who developed AKI had worse graft function recovery and higher mortality within 14 days after LT compared to those who did not develop AKI. AKI patients with diabetes had a significant decline of e GFR within the first postoperative year, compared with patients who did not develop AKI and who developed AKI but without diabetes. Conclusions: Diabetes is an independent risk factor for AKI after orthotopic LT. AKI is associated with delayed graft function recovery and higher mortality in short-term postoperative period. Diabetic patients who developed AKI after LT experience a faster decline of e GFR within the first year after surgery.展开更多
Summary: Evidence-based medicine is advocated by WHO and adopted by developed countries for many years. In China, however, the selection of essential medicine and various medical insurance reimbursement schemes medic...Summary: Evidence-based medicine is advocated by WHO and adopted by developed countries for many years. In China, however, the selection of essential medicine and various medical insurance reimbursement schemes medicine is usually based on experts' experience of prescription practice which is under heavy critics resulting from the lack of related comparative efficacy and evidence-based research. The efficacy of Jian'ganle in prevention of drug-induced liver injury (DILI) caused by antituberculotics was evaluated in this study by comparison with Hugan Pian, glucuronolactone and reduced glutathione. Evidence was provided for relevant sectors such as Ministry for Human Resources and Social Security of the People's Republic of China and National Health and Family Planning Commission of the Peo- ple's Republic of China to select and renew the Essential Medicine List (EML), the new rural cooperative medical scheme in China (NRCMS) list or the reimbursement list of industrial injury insurance. A total of 189 patients with initial pulmonary tuberculosis were divided into four groups who took antituberculotics combined with Jian'ganle, Hugan Pian, glucuronolactone and reduced glutathione respectively. Their liver function profile including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), total protein (TP), albumin (A) and globulin (G) were detected at admission as baseline and after treatment. The Jian'ganle group was compared with the three others by chi-square tests. In an aspect of maintaining bilirubin indexes normal, Jian'ganle was more efficacious than glucuronolactone. And Jian'ganle had a little more efficacy than reduced glutathione to maintain protein indexes normal as well. And the therapeutic regimen of antituberculotics combined with Jian'ganle was the best in treating tuberculosis and preventing DILI at the same time. The study showed that among the four hepatinicas which demonstrated similar prevention of DILI caused by antituberculotics, Jian'ganle has more advantages over the three others to some extent, which provides a reliable basis for health sectors to select and renew the EML, NRCMS List or the reimbursement list of industrial injury insurance.展开更多
AIM: To evaluate the role of the 13C-methacetin breath test(13C-MBT) in the assessment of acute liver injury in a rat model.METHODS: Acute liver injury in rats was induced by a single intraperitoneal injection of D-ga...AIM: To evaluate the role of the 13C-methacetin breath test(13C-MBT) in the assessment of acute liver injury in a rat model.METHODS: Acute liver injury in rats was induced by a single intraperitoneal injection of D-galactosamine(D-GalN). Forty-eight male Sprague-Dawley rats were randomly assigned to a control group(n = 8) and five model groups(each n = 8), and acute liver injury was assessed at different time points(6, 12, 24, 48 and 72 h) after D-GalN injection. The 13C-MBT, biochemical tests, 15-min retention rate of indocyanine green(ICGR15), and liver biopsy were performed and compared between the control and model groups. Correlations between parameters of the 13C-MBT(Tmax, MVmax, CUM120 and DOBmax), biochemical tests, ICGR15 and liver necrosis score were also analyzed using Spearman'scorrelation analysis.RESULTS: Tmax, MVmax, CUM120 and DOBmax, as well as most of the traditional methods, correlated with the liver necrosis score(r = 0.493, P < 0.05; r =-0.731, P < 0.01; r =-0.618, P < 0.01; r =-0.592, P < 0.01, respectively). MVmax, CUM120 and DOBmax rapidly decreased and were lower than those in the controls as early as 6 h after D-GalN injection(3.84 ± 0.84 vs 5.06 ± 0.78, P < 0.01; 3.35 ± 0.72 vs 4.21 ± 1.44, P < 0.05; 52.3 ± 20.58 vs 75.1 ± 9.57, P < 0.05, respectively) and reached the lowest point 24 h after D-GalN injection. MVmax, CUM120 and DOBmax returned to normal levels 72 h after D-GalN injection and preceded most of the traditional methods, including liver biopsy.CONCLUSION: The 13C-MBT is a sensitive tool for the timely detection of acute liver injury and early prediction of recovery in a rat model. Further clinical studies are warranted to validate its role in patients with acute liver injury.展开更多
Coronavirus disease 2019(COVID-19)disease affects multiple organs,including anomalies in liver function.In this review we summarize the knowledge about liver injury found during severe acute respiratory syndrome coron...Coronavirus disease 2019(COVID-19)disease affects multiple organs,including anomalies in liver function.In this review we summarize the knowledge about liver injury found during severe acute respiratory syndrome coronavirus 2(SARSCoV-2)infection with special attention paid to possible mechanisms of liver damage and abnormalities in liver function tests allowing for the evaluation of the severity of liver disease.Abnormalities in liver function observed in COVID-19 disease are associated with the age and sex of patients,severity of liver injury,presence of comorbidity and pre-treatment.The method of antiviral treatment can also impact on liver function,which manifests as increasing values in liver function tests.Therefore,analysis of variations in liver function tests is necessary in evaluating the progression of liver injury to severe disease.展开更多
Coronavirus disease 2019(COVID-19)combined with liver injury has become a very prominent clinical problem.Due to the lack of a clear definition of liver injury in patients with COVID-19,the different selection of eval...Coronavirus disease 2019(COVID-19)combined with liver injury has become a very prominent clinical problem.Due to the lack of a clear definition of liver injury in patients with COVID-19,the different selection of evaluation parameters and statistical time points,there are the conflicting conclusions about the incidence rate in different studies.The mechanism of COVID-19 combined with liver injury is complicated,including the direct injury of liver cells caused by severe acute respiratory syndrome coronavirus 2 replication and liver injury caused by cytokines,ischemia and hypoxia,and drugs.In addition,underlying diseases,especially chronic liver disease,can aggravate COVID-19 liver injury.In the treatment of COVID-19 combined with liver injury,the primary and basic treatment is to treat the etiology and pathogenesis,followed by support,liver protection,and symptomatic treatment according to the clinical classification and severity of liver injury.This article evaluates the incidence,pathogenesis and prevention and treatment of COVID-19 combined with liver injury,and aims to provide countermeasures for the prevention and treatment of COVID-19 combined with liver injury.展开更多
Background/Aims: Antituberculosis drug-induced liver injury (TB DILI) is a frequent medical problem in Pakistan. Critical understanding of various aspects of TB DILI is not only important to manage liver injury but ma...Background/Aims: Antituberculosis drug-induced liver injury (TB DILI) is a frequent medical problem in Pakistan. Critical understanding of various aspects of TB DILI is not only important to manage liver injury but may also prevent unnecessary discontinuation of antituberculosis treatment. The study is aimed to determine the frequency, types, severity and patterns of TB DILI. Study further evaluates various risk factors of TB DILI. Materials and Methods: This is a prospective cohort study of two seventy-eight patients with the diagnosis of tuberculosis, where patients were followed during tuberculosis treatment. TB DILI was defined in accordance to international DILI expert working group. Results: Out of two seventy eight-patients, ninety-five (34.14%) had TB DILI. The most common pattern of TB DILI was hepatocellular (63.15%) followed by mixed (23.15%) and Cholestatic (13.68%). Most of the patients had mild DILI (43.15%) followed by moderate (30.52%), severe (20.01%) and very severe (5.26%). Age > 35 years, concomitant hepatotoxic drugs, extrapulmonary TB and malnutrition are important risk factors for TB DILI. Conclusion: All patterns of TB DILI with varying severity were present. Age > 35 years, malnutrition, extrapulmonary TB and concomitant use of hepatotoxic drugs were risk factors for TB DILI.展开更多
In December 2019,a new strain of coronavirus was discovered in China,and the World Health Organization declared it a pandemic in March 2020.The majority of people with coronavirus disease 19(COVID-19)exhibit no or onl...In December 2019,a new strain of coronavirus was discovered in China,and the World Health Organization declared it a pandemic in March 2020.The majority of people with coronavirus disease 19(COVID-19)exhibit no or only mild symptoms such as fever,cough,anosmia,and headache.Meanwhile,approximately 15%develop a severe lung infection over the course of 10 d,resulting in respiratory failure,which can lead to multi-organ failure,coagulopathy,and death.Since the beginning of the pandemic,it appears that there has been consideration that preexisting chronic liver disease may predispose to deprived consequences in conjunction with COVID-19.Furthermore,extensive liver damage has been linked to immune dysfunction and coagulopathy,which leads to a more severe COVID-19 outcome.Besides that,people with COVID-19 frequently have abnormal liver function,with more significant elevations in alanine aminotransferase and aspartate aminotransferase in patients with severe COVID-19 compared to those with mild/moderate disease.This review focuses on the pathogenesis of severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection in the liver,as well as the use of liver chemistry as a prognostic tool during COVID-19.We also evaluate the findings for viral infection of hepatocytes,and look into the potential mechanisms behind SARS-CoV-2-related liver damage.展开更多
Systemic rheumatic diseases(SRDs)are chronic,inflammatory,autoimmune disorders with the presence of autoantibodies that may affect any organ or system.Liver dysfunction in SRDs can be associated with prescribed drugs,...Systemic rheumatic diseases(SRDs)are chronic,inflammatory,autoimmune disorders with the presence of autoantibodies that may affect any organ or system.Liver dysfunction in SRDs can be associated with prescribed drugs,viral hepatitis,alternative hepatic comorbidities and coexisting autoimmune liver diseases(AILDs),requiring an exclusion of secondary conditions before considering liver involvement.The patterns of overlap diseases depend predominantly on genetic determinants with common susceptible loci widely distributing in both disorders.In AILDs,it is important to identify the overlapping SRDs at an early stage since such a coexistence may influence the disease course and prognosis.Commonly co-occurring SRDs in AILDs are Sjögren syndrome(SS),rheumatoid arthritis(RA)or systemic lupus erythematosus(SLE)in autoimmune hepatitis(AIH),and SS,RA or systemic sclerosis in primary biliary cholangitis.Owing to different disease complications and therapies,it is imperative to differentiate between SLE liver involvement and SLE-AIH overlap disease.Therapeutic options can be personalized to control coexisting conditions of liver autoimmunity and rheumatic manifestations in AILD-SRD overlap diseases.The collaboration between hepatologists and rheumatologists can lead to significant advances in managing such a complex scenario.In this review,we provide a comprehensive overview on coexisting AILDs in different SRDs and the therapeutic approach in managing these overlap diseases.展开更多
BACKGROUND Exposure to high sustained +Gz(head-to-foot inertial load) is known to have harmful effects on pilots' body in flight. Although clinical data have shown that liver dysfunction occurs in pilots, the prec...BACKGROUND Exposure to high sustained +Gz(head-to-foot inertial load) is known to have harmful effects on pilots' body in flight. Although clinical data have shown that liver dysfunction occurs in pilots, the precise cause has not been well defined.AIM To investigate rat liver function changes in response to repeated +Gz exposure.METHODS Ninety male Wistar rats were randomly divided into a blank control group(BC group, n = 30), a +6 Gz/5 min stress group(6 GS group, n = 30), and a +10 Gz/5 min stress group(10 GS group, n = 30). The 6 GS and 10 GS groups were exposed to +6 Gz and +10 Gz, respectively, in an animal centrifuge. The onset rate of +Gz was 0.5 G/s. The sustained time at peak +Gz was 5 min for each exposure(for 5 exposures, and 5-min intervals between exposures for a total exposure and non-exposure time of 50 min). We assessed liver injury bymeasuring the portal venous flow volume, serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST), liver tissue malondialdehyde(MDA), Na+-K+-ATPase, and changes in liver histology. These parameters were recorded at 0 h, 6 h, and 24 h after repeated +Gz exposures.RESULTS After repeated +Gz exposures in the 6 GS and the 10 GS groups, the velocity and flow signal in the portal vein(PV) were significantly decreased as compared to the BC group at 0 h after exposure. Meanwhile, we found that the PV diameter did not change significantly. However, rats in the 6 GS group had a much higher portal venous flow volume than the 10 GS group at 0 h after exposure. The 6 GS group had significantly lower ALT, AST, and MDA values than the 10 GS group 0 h and 6 h post exposure. The Na^+-K^+-ATPase activity in the 6 GS group was significantly higher than that in the 10 GS group 0 h and 6 h post exposure.Hepatocyte injury, determined pathologically, was significantly lower in the 6 GS group than in the 10 GS group.CONCLUSION Repeated +Gz exposures transiently cause hepatocyte injury and affect liver metabolism and morphological structure.展开更多
The last decade saw increased organ donation activity from donors after cardiac death (DCD). This contributed to a signif icant proportion of transplant activity. Despite certain drawbacks, liver transplantation from ...The last decade saw increased organ donation activity from donors after cardiac death (DCD). This contributed to a signif icant proportion of transplant activity. Despite certain drawbacks, liver transplantation from DCD donors continues to supplement the donor pool on the backdrop of a severe organ shortage. Understanding the pathophysiology has provided the basis for modulation of DCD organs that has been proven to be effective outside liver transplantation but remains experimental in liver transplantation models. Research continues on how best to further increase the utility of DCD grafts. Most of the work has been carried out exploring the use of organ preservation using machine assisted perfusion. Both ex-situ and in-situ organ perfusion systems are tested in the liver transplantation setting with promising results. Additional techniques involved pharmacological manipulation of the donor, graft and the recipient. Ethical barriers and end-of-life care pathways are obstacles to widespread clinical application of some of the recent advances to practice. It is likely that some of the DCD offers are in fact probably "prematurely" of-fered without ideal donor management or even prior to brain death being established. The absolute benef its of DCD exist only if this form of donation supplements the existing deceased donor pool; hence, it is worthwhile revisiting organ donation process enabling us to identify counter remedial measures.展开更多
Avocado, Cabbage, and Ginger are a part of a regular human diet and have antioxidant, and antitumor effects. The effect of AVOE (avocado), GE (Ginger) and CE (Cabbage) extracts separately on liver NO (nitric ox...Avocado, Cabbage, and Ginger are a part of a regular human diet and have antioxidant, and antitumor effects. The effect of AVOE (avocado), GE (Ginger) and CE (Cabbage) extracts separately on liver NO (nitric oxide), MDA (malondialdehyde), as well as serum AST (aspartate aminotransferase), ALT (alanine aminotransferase), total bilirubin, TC (total cholesterol), T.G (triglyceride), HDL cholesterol (high-density lipoprotein), LDL cholesterol (low-density lipoprotein), TSH (thyroid-stimulating hormone), T3 (Triiodothyronine), T4 (Thyroxine) in rats treated and untreated with CC14 (carbon tetrachloride) was studied. The levels of NO, MDA, as well as serum AST, ALT, total bilirubin, TC, T.G, LDL, and TSH, showed an elevation while, HDL, T3 and T4 showed the decline in rats treated with CC14 as compared to control. Treatment of rats with AVOE and GE pre, during, and post CC14 administration improve NO, MDA, as well as serum AST, ALT, total bilirubin, TC, T.G, HDL, LDL, TSH, T3, T4 as compared to CC14. Treatment of rats with CE pre, during, and post CC14 administration did not improve in the thyroid hormones and lipid profile levels as compared to CC14. These findings suggest that avocado and ginger treatment exerts a protective effect on metabolic disorders by decreasing oxidative stress.展开更多
AIM: To evaluate the role of leptin in the internal disorders during hepatic ischemia/reperfusion injury. METHODS: A rat model of 70% hepatic ischemia/reperfusion injury was established, with groups of shamoperation (...AIM: To evaluate the role of leptin in the internal disorders during hepatic ischemia/reperfusion injury. METHODS: A rat model of 70% hepatic ischemia/reperfusion injury was established, with groups of shamoperation (Sham), 60 min ischemia/60 min reperfusion (I60'R60'), I60'R150', I60'R240' and I60'R360'. Serum leptin was detected by a self-produced radioimmunoassay; serum glucose, total anti-oxidation capacity, myeloperoxidase, alanine transaminase and diamine oxidase were determined by relevant kits, while histologicalalterations and protein levels of leptin in the lung, liver and duodenum were examined by hematoxylin-eosin staining and immunohistochemistry. Spearman's rank correlation between leptin and other variables or grading of tissue impairment were analyzed simultaneously. RESULTS: Serum leptin in I60'R360' was significantly higher than in Sham and I60'R240' groups (both P < 0.05), serum glucose in I60'R360' was higher than in Sham and I60'R150' (both P < 0.05), and serum total anti-oxidation capacity in I60'R240' and I60'R360' were higher than in Sham (both P < 0.05) and I60'R150' groups (both P < 0.01). Serum myeloperoxidase in groups of I60'R240' and I60'R360' were lower than in I60'R150'group (both P < 0.05), serum alanine transaminase in the four reperfusion groups were higher than in the Sham group (all P < 0.05), while serum DAO in I60'R360' was lower than in I60'R60' (P < 0.05). Histological impairment in the lung, liver and duodenum at the early phase of this injury was more serious, but the impairment at the later phase was lessened gradually. Protein levels of leptin in the lung in the four reperfusion groups were significantly lower than in the Sham group (all P < 0.01), decreasing in the order of I60'R150', I60' R60', I60'R360' and I60'R240'; the levels in the liver in I60'R60' and I60'R240' were higher than in the Sham group (both P < 0.01), while the levels in I60'R240' and I60'R360' were lower than in I60'R60' (both P < 0.01); the levels in duodenum in I60'R240' and I60'R360' were higher than in Sham, I60'R60' and I60'R150' (all P < 0.01), while the level in I60'R150' was lower than in I60' R60' (P < 0.05). There was a significantly positive correlation between serum leptin and alanine transaminase (ρ = 0.344, P = 0.021), a significantly negative correlation between the protein level of leptin in the lung and its damage scores (ρ = -0.313, P = 0.036), and a significantly positive correlation between the protein level of leptin in the liver and its damage scores (ρ = 0.297, P = 0.047). CONCLUSION: Endogenous leptin fluctuates in he-patic ischemia/reperfusion injury, exerts a potency to rehabilitate the internal disorders and represents a potential target for supportive therapy.展开更多
Background and Aims:Anti-tuberculosis(anti-TB)druginduced liver injury(AT-DILI)is the most common side effect in patients who received anti-TB therapy.AT-DILI management includes monitoring liver function until sympto...Background and Aims:Anti-tuberculosis(anti-TB)druginduced liver injury(AT-DILI)is the most common side effect in patients who received anti-TB therapy.AT-DILI management includes monitoring liver function until symptoms arise in patients without high-risk factors for liver damage.The present study aimed to investigate the effect of liver function test(LFT)abnormal identification on the risk of DILI,including liver failure and anti-TB drug resistance in patients without high-risk factors.Methods:A total of 399 patients without high-risk factors for liver damage at baseline and who experienced LFT abnormal during the 6 months of first-line anti-TB treatment were enrolled.The Roussel Uclaf Causal Relationship Assessment Method(RUCAM,2016)was applied in suspected DILI.The correlations between the time of LFT abnormal identification and DILI,liver failure,and anti-TB drug resistance were analyzed by smooth curve fitting and multivariable logistic regression models.Results:Among all study patients,131 met the criteria for DILI with a mean RUCAM causality score of 8.86±0.63.26/131 and 105/131 were in the probable grading and highly probable grading,respectively.The time of abnormal LFT identification was an independent predictor of DILI,liver failure,and anti-TB drug resistance in the crude model and after adjusting for other risk patient factors.The time of abnormal LFT identification was positively correlated with DILI,liver failure,and anti-TB drug resistance.The late identification group(>8 weeks)had the highest risk of DILI,followed by liver failure compared with the other two groups.Conclusions:The time to identification of LFT was positively correlated with DILI,liver failure,and anti-TB drug resistance.The risk of DILI and liver failure was significantly increased in the late identification group with abnormal LFT identified after 8 weeks compared with 4 and 8 weeks.Early monitoring of LFT is recommended for patients without the high-risk factor of DILI after anti-TB treatment is initiated.展开更多
文摘Epidemiological data are scarce regarding the association of exposure to mixtures of per-and polyfluoroalkyl substances(PFASs)with liver injury in the general population.In the current study,therefore,we examined data from the National Health and Nutrition Examination Survey(2009–2018).The PFAS exposure levels were defined by the serum concentrations of PFASs with over 70%detection in samples,namely perfluorooctanoic acid,perfluorononanoic acid,perfluorohexane sulfonic acid,perfluorodecanoic acid,and perfluorooctane sulfonic acid(PFOS).We evaluated liver injury from two aspects:first,the degree of liver inflammation was determined based on levels of the serum alanine aminotransferase,aspartate aminotransferase,glutamyltransferase,and total bilirubin;second,the degree of liver fibrosis was determined based on the fibrosis-4 index.We assessed the associations of individual or total PFAS exposure with these liver injury outcomes using multivariable linear and logistic regression models,restricted cubic splines,and weighted quantile sum regression.Among the samples of 7484 American adults,the median concentration of PFOS was the highest,followed by perfluorooctanoic acid and perfluorohexane sulfonic acid.Using multivariable linear regression,we observed positive correlations between all PFAS exposure and liver enzyme levels,such as alanine aminotransferase,aspartate aminotransferase,and total bilirubin.Additionally,the weighted quantile sum model indicated an overall positive association between exposure to the five PFASs and liver injury risk.For liver function biomarkers and liver fibrosis,perfluorononanoic acid and PFOS were the most heavily weighted chemicals,respectively.Our findings provide new epidemiological evidence indicating potential associations between PFAS exposure and adverse effects on liver injury biomarkers,highlighting the potentially harmful effects of PFAS exposure on human liver health.
基金National Natural Science Foundation of China No:81560497.
文摘Objective: To study the value of transient ultrasonic elastography for evaluating the liver fibrosis and liver function in patients with drug-induced liver injury. Methods: A total of 68 patients with drug-induced liver injury who were treated in our hospital between January 2016 and May 2017 were selected as drug-induced liver injury group, and 50 healthy volunteers who received physical examination in our hospital during the same period were selected as normal control group. The liver transient ultrasonic elastography parameter Stiffness levels as well as serum liver fibrosis index and liver function index contents of two groups of subjects were detected. Pearson test was used to evaluate the correlation of Stiffness levels with liver fibrosis and liver function damage degree in patients with drug-induced liver injury. Results:Stiffness level in drug-induced liver injury group was higher than that in normal control group;serum liver fibrosis indexes HA, LN, CⅣ, PⅢNP and CG contents were higher than those of normal control group;serum liver function indexes ALT, AST, ALP, STB and γ-GT contents were higher than those of normal control group. Conclusion: Transient ultrasonic elastography parameter Stiffness levels increase in patients with drug-induced liver injury, and the specific levels are consistent with the liver fibrosis and liver function damage degree, and can be used as the objective means to evaluate the disease severity.
基金Supported by the National Key Research and Development Program,No.2017YFC0908903National Natural Science Foundation of China,No.81873565 and No.81900507Hospital Funded Clinical Research,Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,No.17CSK04.
文摘The outbreak of novel coronavirus disease 2019(COVID-19)has resulted in global emergence.With the expansion of related research,in addition to respiratory symptoms,digestive system involvement such as nausea,vomiting,and diarrhea have also been reported with COVID-19.Besides,abnormal liver function is also frequent in biochemical tests of COVID-19 patients,which is correlated with the severity and mortality of the disease course.The etiology of liver injury in patients with COVID-19 might include viral immunologic injury,drug-induced liver injury,the systemic inflammatory response,hypoxic hepatitis,and the exacerbation of preexisting liver disease.Although liver injuries in COVID-19 are often transient and reversible,health workers need to pay attention to preexisting liver disease,monitor liver function,strengthen supportive treatment,and reduce the chance of drug-induced liver injury.This article reviews the epidemiological characteristics,etiology,management,and preventive strategies for liver injury in patients with COVID-19.
基金supported by grants from the National Natural Science Foundation of China (81700591, 81520108006, and 81930120)。
文摘Background: Diabetes mellitus has become an increasing global health burden with rapid growing prevalence. Patients with diabetes have higher susceptibility to acute kidney injury(AKI). Liver transplantation(LT) predisposes the kidney to injury. However, the association between diabetes and AKI in LT patients remains unclear. Methods: We conducted a retrospective cohort study examining risk factors for AKI in patients undergone orthotopic LT. Potential risk factors including baseline estimated glomerular filtration rate(e GFR), the model for end-stage liver disease(MELD) score, diabetes, hypertension and intraoperative blood loss were screened. The primary endpoint was AKI occurrence. Multivariate logistic regression was used to analyze the association between potential risk factors and AKI. Results: A total of 291 patients undergone orthotopic LT were included in the present study. Among them, 102 patients(35.05%) developed AKI within 5 days after LT. Diabetes was identified as an independent risk factor for AKI. Patients who developed AKI had worse graft function recovery and higher mortality within 14 days after LT compared to those who did not develop AKI. AKI patients with diabetes had a significant decline of e GFR within the first postoperative year, compared with patients who did not develop AKI and who developed AKI but without diabetes. Conclusions: Diabetes is an independent risk factor for AKI after orthotopic LT. AKI is associated with delayed graft function recovery and higher mortality in short-term postoperative period. Diabetic patients who developed AKI after LT experience a faster decline of e GFR within the first year after surgery.
基金supported by Health and Family Planning Commission of Hubei Province(No.02-16-516052)
文摘Summary: Evidence-based medicine is advocated by WHO and adopted by developed countries for many years. In China, however, the selection of essential medicine and various medical insurance reimbursement schemes medicine is usually based on experts' experience of prescription practice which is under heavy critics resulting from the lack of related comparative efficacy and evidence-based research. The efficacy of Jian'ganle in prevention of drug-induced liver injury (DILI) caused by antituberculotics was evaluated in this study by comparison with Hugan Pian, glucuronolactone and reduced glutathione. Evidence was provided for relevant sectors such as Ministry for Human Resources and Social Security of the People's Republic of China and National Health and Family Planning Commission of the Peo- ple's Republic of China to select and renew the Essential Medicine List (EML), the new rural cooperative medical scheme in China (NRCMS) list or the reimbursement list of industrial injury insurance. A total of 189 patients with initial pulmonary tuberculosis were divided into four groups who took antituberculotics combined with Jian'ganle, Hugan Pian, glucuronolactone and reduced glutathione respectively. Their liver function profile including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), total protein (TP), albumin (A) and globulin (G) were detected at admission as baseline and after treatment. The Jian'ganle group was compared with the three others by chi-square tests. In an aspect of maintaining bilirubin indexes normal, Jian'ganle was more efficacious than glucuronolactone. And Jian'ganle had a little more efficacy than reduced glutathione to maintain protein indexes normal as well. And the therapeutic regimen of antituberculotics combined with Jian'ganle was the best in treating tuberculosis and preventing DILI at the same time. The study showed that among the four hepatinicas which demonstrated similar prevention of DILI caused by antituberculotics, Jian'ganle has more advantages over the three others to some extent, which provides a reliable basis for health sectors to select and renew the EML, NRCMS List or the reimbursement list of industrial injury insurance.
基金Supported by Beijing Health System Advanced Health Technology Talent Cultivation Plan,No.2011-2-08
文摘AIM: To evaluate the role of the 13C-methacetin breath test(13C-MBT) in the assessment of acute liver injury in a rat model.METHODS: Acute liver injury in rats was induced by a single intraperitoneal injection of D-galactosamine(D-GalN). Forty-eight male Sprague-Dawley rats were randomly assigned to a control group(n = 8) and five model groups(each n = 8), and acute liver injury was assessed at different time points(6, 12, 24, 48 and 72 h) after D-GalN injection. The 13C-MBT, biochemical tests, 15-min retention rate of indocyanine green(ICGR15), and liver biopsy were performed and compared between the control and model groups. Correlations between parameters of the 13C-MBT(Tmax, MVmax, CUM120 and DOBmax), biochemical tests, ICGR15 and liver necrosis score were also analyzed using Spearman'scorrelation analysis.RESULTS: Tmax, MVmax, CUM120 and DOBmax, as well as most of the traditional methods, correlated with the liver necrosis score(r = 0.493, P < 0.05; r =-0.731, P < 0.01; r =-0.618, P < 0.01; r =-0.592, P < 0.01, respectively). MVmax, CUM120 and DOBmax rapidly decreased and were lower than those in the controls as early as 6 h after D-GalN injection(3.84 ± 0.84 vs 5.06 ± 0.78, P < 0.01; 3.35 ± 0.72 vs 4.21 ± 1.44, P < 0.05; 52.3 ± 20.58 vs 75.1 ± 9.57, P < 0.05, respectively) and reached the lowest point 24 h after D-GalN injection. MVmax, CUM120 and DOBmax returned to normal levels 72 h after D-GalN injection and preceded most of the traditional methods, including liver biopsy.CONCLUSION: The 13C-MBT is a sensitive tool for the timely detection of acute liver injury and early prediction of recovery in a rat model. Further clinical studies are warranted to validate its role in patients with acute liver injury.
文摘Coronavirus disease 2019(COVID-19)disease affects multiple organs,including anomalies in liver function.In this review we summarize the knowledge about liver injury found during severe acute respiratory syndrome coronavirus 2(SARSCoV-2)infection with special attention paid to possible mechanisms of liver damage and abnormalities in liver function tests allowing for the evaluation of the severity of liver disease.Abnormalities in liver function observed in COVID-19 disease are associated with the age and sex of patients,severity of liver injury,presence of comorbidity and pre-treatment.The method of antiviral treatment can also impact on liver function,which manifests as increasing values in liver function tests.Therefore,analysis of variations in liver function tests is necessary in evaluating the progression of liver injury to severe disease.
基金Novel Coronavirus Pneumonia Emergency Project of University of South China,No.2020-15 and No.2020-25Fund Project of Hengyang City for Prevention and Control of COVID-19,No.202010031577and Key Research and Development Program of Hunan Province,No.2020SK3039 and No.2020SK3040.
文摘Coronavirus disease 2019(COVID-19)combined with liver injury has become a very prominent clinical problem.Due to the lack of a clear definition of liver injury in patients with COVID-19,the different selection of evaluation parameters and statistical time points,there are the conflicting conclusions about the incidence rate in different studies.The mechanism of COVID-19 combined with liver injury is complicated,including the direct injury of liver cells caused by severe acute respiratory syndrome coronavirus 2 replication and liver injury caused by cytokines,ischemia and hypoxia,and drugs.In addition,underlying diseases,especially chronic liver disease,can aggravate COVID-19 liver injury.In the treatment of COVID-19 combined with liver injury,the primary and basic treatment is to treat the etiology and pathogenesis,followed by support,liver protection,and symptomatic treatment according to the clinical classification and severity of liver injury.This article evaluates the incidence,pathogenesis and prevention and treatment of COVID-19 combined with liver injury,and aims to provide countermeasures for the prevention and treatment of COVID-19 combined with liver injury.
文摘Background/Aims: Antituberculosis drug-induced liver injury (TB DILI) is a frequent medical problem in Pakistan. Critical understanding of various aspects of TB DILI is not only important to manage liver injury but may also prevent unnecessary discontinuation of antituberculosis treatment. The study is aimed to determine the frequency, types, severity and patterns of TB DILI. Study further evaluates various risk factors of TB DILI. Materials and Methods: This is a prospective cohort study of two seventy-eight patients with the diagnosis of tuberculosis, where patients were followed during tuberculosis treatment. TB DILI was defined in accordance to international DILI expert working group. Results: Out of two seventy eight-patients, ninety-five (34.14%) had TB DILI. The most common pattern of TB DILI was hepatocellular (63.15%) followed by mixed (23.15%) and Cholestatic (13.68%). Most of the patients had mild DILI (43.15%) followed by moderate (30.52%), severe (20.01%) and very severe (5.26%). Age > 35 years, concomitant hepatotoxic drugs, extrapulmonary TB and malnutrition are important risk factors for TB DILI. Conclusion: All patterns of TB DILI with varying severity were present. Age > 35 years, malnutrition, extrapulmonary TB and concomitant use of hepatotoxic drugs were risk factors for TB DILI.
文摘In December 2019,a new strain of coronavirus was discovered in China,and the World Health Organization declared it a pandemic in March 2020.The majority of people with coronavirus disease 19(COVID-19)exhibit no or only mild symptoms such as fever,cough,anosmia,and headache.Meanwhile,approximately 15%develop a severe lung infection over the course of 10 d,resulting in respiratory failure,which can lead to multi-organ failure,coagulopathy,and death.Since the beginning of the pandemic,it appears that there has been consideration that preexisting chronic liver disease may predispose to deprived consequences in conjunction with COVID-19.Furthermore,extensive liver damage has been linked to immune dysfunction and coagulopathy,which leads to a more severe COVID-19 outcome.Besides that,people with COVID-19 frequently have abnormal liver function,with more significant elevations in alanine aminotransferase and aspartate aminotransferase in patients with severe COVID-19 compared to those with mild/moderate disease.This review focuses on the pathogenesis of severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection in the liver,as well as the use of liver chemistry as a prognostic tool during COVID-19.We also evaluate the findings for viral infection of hepatocytes,and look into the potential mechanisms behind SARS-CoV-2-related liver damage.
文摘Systemic rheumatic diseases(SRDs)are chronic,inflammatory,autoimmune disorders with the presence of autoantibodies that may affect any organ or system.Liver dysfunction in SRDs can be associated with prescribed drugs,viral hepatitis,alternative hepatic comorbidities and coexisting autoimmune liver diseases(AILDs),requiring an exclusion of secondary conditions before considering liver involvement.The patterns of overlap diseases depend predominantly on genetic determinants with common susceptible loci widely distributing in both disorders.In AILDs,it is important to identify the overlapping SRDs at an early stage since such a coexistence may influence the disease course and prognosis.Commonly co-occurring SRDs in AILDs are Sjögren syndrome(SS),rheumatoid arthritis(RA)or systemic lupus erythematosus(SLE)in autoimmune hepatitis(AIH),and SS,RA or systemic sclerosis in primary biliary cholangitis.Owing to different disease complications and therapies,it is imperative to differentiate between SLE liver involvement and SLE-AIH overlap disease.Therapeutic options can be personalized to control coexisting conditions of liver autoimmunity and rheumatic manifestations in AILD-SRD overlap diseases.The collaboration between hepatologists and rheumatologists can lead to significant advances in managing such a complex scenario.In this review,we provide a comprehensive overview on coexisting AILDs in different SRDs and the therapeutic approach in managing these overlap diseases.
文摘BACKGROUND Exposure to high sustained +Gz(head-to-foot inertial load) is known to have harmful effects on pilots' body in flight. Although clinical data have shown that liver dysfunction occurs in pilots, the precise cause has not been well defined.AIM To investigate rat liver function changes in response to repeated +Gz exposure.METHODS Ninety male Wistar rats were randomly divided into a blank control group(BC group, n = 30), a +6 Gz/5 min stress group(6 GS group, n = 30), and a +10 Gz/5 min stress group(10 GS group, n = 30). The 6 GS and 10 GS groups were exposed to +6 Gz and +10 Gz, respectively, in an animal centrifuge. The onset rate of +Gz was 0.5 G/s. The sustained time at peak +Gz was 5 min for each exposure(for 5 exposures, and 5-min intervals between exposures for a total exposure and non-exposure time of 50 min). We assessed liver injury bymeasuring the portal venous flow volume, serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST), liver tissue malondialdehyde(MDA), Na+-K+-ATPase, and changes in liver histology. These parameters were recorded at 0 h, 6 h, and 24 h after repeated +Gz exposures.RESULTS After repeated +Gz exposures in the 6 GS and the 10 GS groups, the velocity and flow signal in the portal vein(PV) were significantly decreased as compared to the BC group at 0 h after exposure. Meanwhile, we found that the PV diameter did not change significantly. However, rats in the 6 GS group had a much higher portal venous flow volume than the 10 GS group at 0 h after exposure. The 6 GS group had significantly lower ALT, AST, and MDA values than the 10 GS group 0 h and 6 h post exposure. The Na^+-K^+-ATPase activity in the 6 GS group was significantly higher than that in the 10 GS group 0 h and 6 h post exposure.Hepatocyte injury, determined pathologically, was significantly lower in the 6 GS group than in the 10 GS group.CONCLUSION Repeated +Gz exposures transiently cause hepatocyte injury and affect liver metabolism and morphological structure.
文摘The last decade saw increased organ donation activity from donors after cardiac death (DCD). This contributed to a signif icant proportion of transplant activity. Despite certain drawbacks, liver transplantation from DCD donors continues to supplement the donor pool on the backdrop of a severe organ shortage. Understanding the pathophysiology has provided the basis for modulation of DCD organs that has been proven to be effective outside liver transplantation but remains experimental in liver transplantation models. Research continues on how best to further increase the utility of DCD grafts. Most of the work has been carried out exploring the use of organ preservation using machine assisted perfusion. Both ex-situ and in-situ organ perfusion systems are tested in the liver transplantation setting with promising results. Additional techniques involved pharmacological manipulation of the donor, graft and the recipient. Ethical barriers and end-of-life care pathways are obstacles to widespread clinical application of some of the recent advances to practice. It is likely that some of the DCD offers are in fact probably "prematurely" of-fered without ideal donor management or even prior to brain death being established. The absolute benef its of DCD exist only if this form of donation supplements the existing deceased donor pool; hence, it is worthwhile revisiting organ donation process enabling us to identify counter remedial measures.
文摘Avocado, Cabbage, and Ginger are a part of a regular human diet and have antioxidant, and antitumor effects. The effect of AVOE (avocado), GE (Ginger) and CE (Cabbage) extracts separately on liver NO (nitric oxide), MDA (malondialdehyde), as well as serum AST (aspartate aminotransferase), ALT (alanine aminotransferase), total bilirubin, TC (total cholesterol), T.G (triglyceride), HDL cholesterol (high-density lipoprotein), LDL cholesterol (low-density lipoprotein), TSH (thyroid-stimulating hormone), T3 (Triiodothyronine), T4 (Thyroxine) in rats treated and untreated with CC14 (carbon tetrachloride) was studied. The levels of NO, MDA, as well as serum AST, ALT, total bilirubin, TC, T.G, LDL, and TSH, showed an elevation while, HDL, T3 and T4 showed the decline in rats treated with CC14 as compared to control. Treatment of rats with AVOE and GE pre, during, and post CC14 administration improve NO, MDA, as well as serum AST, ALT, total bilirubin, TC, T.G, HDL, LDL, TSH, T3, T4 as compared to CC14. Treatment of rats with CE pre, during, and post CC14 administration did not improve in the thyroid hormones and lipid profile levels as compared to CC14. These findings suggest that avocado and ginger treatment exerts a protective effect on metabolic disorders by decreasing oxidative stress.
基金Supported by National Natural Science Foundation of China, No. 30670821National Key Technology R&D Program, No. 2006BAF07B01+1 种基金Special Funds for Key Program of Public Welfare of National Ministry of Science and Technology, No. 2002D1A40019Nursery Fund of Chinese PLA General Hospital, No. 06MP83
文摘AIM: To evaluate the role of leptin in the internal disorders during hepatic ischemia/reperfusion injury. METHODS: A rat model of 70% hepatic ischemia/reperfusion injury was established, with groups of shamoperation (Sham), 60 min ischemia/60 min reperfusion (I60'R60'), I60'R150', I60'R240' and I60'R360'. Serum leptin was detected by a self-produced radioimmunoassay; serum glucose, total anti-oxidation capacity, myeloperoxidase, alanine transaminase and diamine oxidase were determined by relevant kits, while histologicalalterations and protein levels of leptin in the lung, liver and duodenum were examined by hematoxylin-eosin staining and immunohistochemistry. Spearman's rank correlation between leptin and other variables or grading of tissue impairment were analyzed simultaneously. RESULTS: Serum leptin in I60'R360' was significantly higher than in Sham and I60'R240' groups (both P < 0.05), serum glucose in I60'R360' was higher than in Sham and I60'R150' (both P < 0.05), and serum total anti-oxidation capacity in I60'R240' and I60'R360' were higher than in Sham (both P < 0.05) and I60'R150' groups (both P < 0.01). Serum myeloperoxidase in groups of I60'R240' and I60'R360' were lower than in I60'R150'group (both P < 0.05), serum alanine transaminase in the four reperfusion groups were higher than in the Sham group (all P < 0.05), while serum DAO in I60'R360' was lower than in I60'R60' (P < 0.05). Histological impairment in the lung, liver and duodenum at the early phase of this injury was more serious, but the impairment at the later phase was lessened gradually. Protein levels of leptin in the lung in the four reperfusion groups were significantly lower than in the Sham group (all P < 0.01), decreasing in the order of I60'R150', I60' R60', I60'R360' and I60'R240'; the levels in the liver in I60'R60' and I60'R240' were higher than in the Sham group (both P < 0.01), while the levels in I60'R240' and I60'R360' were lower than in I60'R60' (both P < 0.01); the levels in duodenum in I60'R240' and I60'R360' were higher than in Sham, I60'R60' and I60'R150' (all P < 0.01), while the level in I60'R150' was lower than in I60' R60' (P < 0.05). There was a significantly positive correlation between serum leptin and alanine transaminase (ρ = 0.344, P = 0.021), a significantly negative correlation between the protein level of leptin in the lung and its damage scores (ρ = -0.313, P = 0.036), and a significantly positive correlation between the protein level of leptin in the liver and its damage scores (ρ = 0.297, P = 0.047). CONCLUSION: Endogenous leptin fluctuates in he-patic ischemia/reperfusion injury, exerts a potency to rehabilitate the internal disorders and represents a potential target for supportive therapy.
基金supported by the funds for the construction of key medical disciplines in Shenzhen.
文摘Background and Aims:Anti-tuberculosis(anti-TB)druginduced liver injury(AT-DILI)is the most common side effect in patients who received anti-TB therapy.AT-DILI management includes monitoring liver function until symptoms arise in patients without high-risk factors for liver damage.The present study aimed to investigate the effect of liver function test(LFT)abnormal identification on the risk of DILI,including liver failure and anti-TB drug resistance in patients without high-risk factors.Methods:A total of 399 patients without high-risk factors for liver damage at baseline and who experienced LFT abnormal during the 6 months of first-line anti-TB treatment were enrolled.The Roussel Uclaf Causal Relationship Assessment Method(RUCAM,2016)was applied in suspected DILI.The correlations between the time of LFT abnormal identification and DILI,liver failure,and anti-TB drug resistance were analyzed by smooth curve fitting and multivariable logistic regression models.Results:Among all study patients,131 met the criteria for DILI with a mean RUCAM causality score of 8.86±0.63.26/131 and 105/131 were in the probable grading and highly probable grading,respectively.The time of abnormal LFT identification was an independent predictor of DILI,liver failure,and anti-TB drug resistance in the crude model and after adjusting for other risk patient factors.The time of abnormal LFT identification was positively correlated with DILI,liver failure,and anti-TB drug resistance.The late identification group(>8 weeks)had the highest risk of DILI,followed by liver failure compared with the other two groups.Conclusions:The time to identification of LFT was positively correlated with DILI,liver failure,and anti-TB drug resistance.The risk of DILI and liver failure was significantly increased in the late identification group with abnormal LFT identified after 8 weeks compared with 4 and 8 weeks.Early monitoring of LFT is recommended for patients without the high-risk factor of DILI after anti-TB treatment is initiated.