Effects of elafibranor on liver fibrosis and gut barrier function in a mouse model of alcohol-associated liver disease

BACKGROUND Alcohol-associated liver disease(ALD)is a leading cause of liver-related morbidity and mortality,but there are no therapeutic targets and modalities to prevent ALD-related liver fibrosis.Peroxisome proliferator activated receptor(PPAR)α and δ play a key role in lipid metabolism and intestinal barrier homeostasis,which are major contributors to the pathological progression of ALD.Meanwhile,elafibranor(EFN),which is a dual PPARαand PPARδagonist,has reached a phase III clinical trial for the treatment of metabolic dysfunctionassociated steatotic liver disease and primary biliary cholangitis.However,the benefits of EFN for ALD treatment is unknown.AIM To evaluate the inhibitory effects of EFN on liver fibrosis and gut-intestinal barrier dysfunction in an ALD mouse model.METHODS ALD-related liver fibrosis was induced in female C57BL/6J mice by feeding a 2.5% ethanol(EtOH)-containing Lieber-DeCarli liquid diet and intraperitoneally injecting carbon tetrachloride thrice weekly(1 mL/kg)for 8 weeks.EFN(3 and 10 mg/kg/day)was orally administered during the experimental period.Histological and molecular analyses were performed to assess the effect of EFN on steatohepatitis,fibrosis,and intestinal barrier integrity.The EFN effects on HepG2 lipotoxicity and Caco-2 barrier function were evaluated by cell-based assays.RESULTS The hepatic steatosis,apoptosis,and fibrosis in the ALD mice model were significantly attenuated by EFN treatment.EFN promoted lipolysis and β-oxidation and enhanced autophagic and antioxidant capacities in EtOH-stimulated HepG2 cells,primarily through PPARαactivation.Moreover,EFN inhibited the Kupffer cell-mediated inflammatory response,with blunted hepatic exposure to lipopolysaccharide(LPS)and toll like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)signaling.EFN improved intestinal hyperpermeability by restoring tight junction proteins and autophagy and by inhibiting apoptosis and proinflammatory responses.The protective effect on intestinal barrier function in the EtOH-stimulated Caco-2 cells was predominantly mediated by PPARδ activation.CONCLUSION EFN reduced ALD-related fibrosis by inhibiting lipid accumulation and apoptosis,enhancing hepatocyte autophagic and antioxidant capacities,and suppressing LPS/TLR4/NF-κB-mediated inflammatory responses by restoring intestinal barrier function.

Short-term efficacy of microwave ablation in the treatment of liver cancer and its effect on immune function

BACKGROUND Hepatectomy is the first choice for treating liver cancer.However,inflammatory factors,released in response to pain stimulation,may suppress perioperative immune function and affect the prognosis of patients undergoing hepatectomies.AIM To determine the short-term efficacy of microwave ablation in the treatment of liver cancer and its effect on immune function.METHODS Clinical data from patients with liver cancer admitted to Suzhou Ninth People’s Hospital from January 2020 to December 2023 were retrospectively analyzed.Thirty-five patients underwent laparoscopic hepatectomy for liver cancer(liver cancer resection group)and 35 patients underwent medical image-guided microwave ablation(liver cancer ablation group).The short-term efficacy,complications,liver function,and immune function indices before and after treatment were compared between the two groups.RESULTS One month after treatment,19 patients experienced complete remission(CR),8 patients experienced partial remission(PR),6 patients experienced stable disease(SD),and 2 patients experienced disease progression(PD)in the liver cancer resection group.In the liver cancer ablation group,21 patients experienced CR,9 patients experienced PR,3 patients experienced SD,and 2 patients experienced PD.No significant differences in efficacy and complications were detected between the liver cancer ablation and liver cancer resection groups(P>0.05).After treatment,total bilirubin(41.24±7.35 vs 49.18±8.64μmol/L,P<0.001),alanine aminotransferase(30.85±6.23 vs 42.32±7.56 U/L,P<0.001),CD4+(43.95±5.72 vs 35.27±5.56,P<0.001),CD8+(20.38±3.91 vs 22.75±4.62,P<0.001),and CD4+/CD8+(2.16±0.39 vs 1.55±0.32,P<0.001)were significantly different between the liver cancer ablation and liver cancer resection groups.CONCLUSION The short-term efficacy and safety of microwave ablation and laparoscopic surgery for the treatment of liver cancer are similar,but liver function recovers quickly after microwave ablation,and microwave ablation may enhance immune function.

Elafibranor alleviates alcohol-related liver fibrosis by restoring intestinal barrier function

We discuss the article by Koizumi et al published in the World Journal of Gastroenterology.Our focus is on the therapeutic targets for fibrosis associated with alcohol-related liver disease(ALD)and the mechanism of action of elafibranor(EFN),a dual agonist of peroxisome proliferator-activated receptorα(PPARα)and peroxisome PPARδ(PPARδ).EFN is currently in phase III clinical trials for the treatment of metabolic dysfunction-associated fatty liver disease and primary biliary cholangitis.ALD progresses from alcoholic fatty liver to alcoholic steatohepatitis(ASH),with chronic ASH eventually leading to fibrosis,cirrhosis,and,in some cases,hepatocellular carcinoma.The pathogenesis of ALD is driven by hepatic steatosis,oxidative stress,and acetaldehyde toxicity.Alcohol consumption disrupts lipid metabolism by inactivating PPARα,exacerbating the progression of ALD.EFN primarily activates PPARα,promoting lipolysis andβ-oxidation in ethanol-stimulated HepG2 cells,which significantly reduces hepatic steatosis,apoptosis,and fibrosis in an ALD mouse model.Additionally,alcohol disrupts the gut-liver axis at several interconnected levels,contributing to a proinflammatory environment in the liver.EFN helps alleviate intestinal hyperpermeability by restoring tight junction protein expression and autophagy,inhibiting apoptosis and inflammatory responses,and enhancing intestinal barrier function through PPARδactivation.

Prevalence and risk factors for impaired renal function among Asian patients with nonalcoholic fatty liver disease

Background:Nonalcoholic fatty liver disease(NAFLD)is associated with impaired renal function,and both diseases often occur alongside other metabolic disorders.However,the prevalence and risk factors for impaired renal function in patients with NAFLD remain unclear.The objective of this study was to identify the prevalence and risk factors for renal impairment in NAFLD patients.Methods:All adults aged 18-70 years with ultrasound-diagnosed NAFLD and transient elastography examination from eight Asian centers were enrolled in this prospective study.Liver fibrosis and cirrhosis were assessed by FibroScan-aspartate aminotransferase(FAST),Agile 3+and Agile 4 scores.Impaired renal function and chronic kidney disease(CKD)were defined by an estimated glomerular filtration rate(eGFR)with value of<90 mL/min/1.73 m^(2) and<60 mL/min/1.73 m^(2),respectively,as estimated by the CKD-Epidemiology Collaboration(CKD-EPI)equation.Results:Among 529 included NAFLD patients,the prevalence rates of impaired renal function and CKD were 37.4%and 4.9%,respectively.In multivariate analysis,a moderate-high risk of advanced liver fibrosis and cirrhosis according to Agile 3+and Agile 4 scores were independent risk factors for CKD(P<0.05).Furthermore,increased fasting plasma glucose(FPG)and blood pressure were significantly associated with impaired renal function after controlling for the other components of metabolic syndrome(P<0.05).Compared with patients with normoglycemia,those with prediabetes[FPG≥5.6 mmol/L or hemoglobin A1c(HbA1c)≥5.7%]were more likely to have impaired renal function(P<0.05).Conclusions:Agile 3+and Agile 4 are reliable for identifying NAFLD patients with high risk of CKD.Early glycemic control in the prediabetic stage might have a potential renoprotective role in these patients.

Interplay between metabolic dysfunction-associated fatty liver disease and renal function: An intriguing pediatric perspective

Over recent years,the nomenclature of non-alcoholic fatty liver disease has undergone significant changes.Indeed,in 2020,an expert consensus panel proposed the term“Metabolic(dysfunction)associated fatty liver disease”(MAFLD)to underscore the close association of fatty liver with metabolic abnormalities,thereby highlighting the cardiometabolic risks(such as metabolic syndrome,type 2 diabetes,insulin resistance,and cardiovascular disease)faced by these patients since childhood.More recently,this term has been further replaced with metabolic associated steatotic liver disease.It is worth noting that emerging evidence not only supports a close and independent association of MAFLD with chronic kidney disease in adults but also indicates its interplay with metabolic impairments.However,comparable pediatric data remain limited.Given the progressive and chronic nature of both diseases and their prognostic cardiometabolic implications,this editorial aims to provide a pediatric perspective on the intriguing relationship between MAFLD and renal function in childhood.

Clinical effect of spleen aminopeptide on improving liver function damage and immune function in children with infant hepatitis syndrome

BACKGROUND Infant hepatitis syndrome(IHS)is a clinical syndrome in infants less than one year of age with generalized skin jaundice,abnormal liver function,and hepato-megaly due to various etiologies such as infection.AIM To investigate the effect of IHS patients,after treatment with arsphenamine-based peptides,on patients'liver function damage and immune function.METHODS Of 110 patients with IHS treated in our hospital from January 2019 to January 2021 were grouped according to the randomized residual grouping method,with 5 cases in each group shed due to transfer,etc.Ultimately,50 cases remained in each group.The control group was treated with reduced glutathione,and the treat-ment group was treated with sesquiterpene peptide based on the control group.Observe and compare the differences in indicators after treatment.RESULTS The comparison of serum total bilirubin,direct bilirubin,and serum alanine transferase after treatment was significantly different and lower in the treatment group than in the control group(P<0.05).The comparison of CD4+,CD3+,CD4+/CD8+after treatment was significantly different and higher in the treatment group than in the control group,and the comparison was statist-ically significant(P<0.05).The complication of the two groups showed that the rash,cough and sputum,elevated platelets,and gastrointestinal reactions in the treatment group were significantly lower than those in the control group,and the differences were statistically significant by test(P<0.05).CONCLUSION The comparative study of IHS treated with arsphenamine combined with reduced glutathione is more effective.

Effects of Lactobacillus paracasei N1115 on gut microbial imbalance and liver function in patients with hepatitis B-related cirrhosis

BACKGROUND Hepatitis B cirrhosis(HBC)is a chronic disease characterized by irreversible diffuse liver damage and aggravated by intestinal microbial imbalance and metabolic dysfunction.Although the relationship between certain single probiotics and HBC has been explored,the impact of the complex ready-to-eat Lactobacillus paracasei N1115(LP N1115)supplement on patients with HBC has not been determined.AIM To compare the changes in the microbiota,inflammatory factor levels,and liver function before and after probiotic treatment in HBC patients.METHODS This study included 160 HBC patients diagnosed at the General Hospital of Ningxia Medical University between October 2018 and December 2020.Patients were randomly divided into an intervention group that received LP N1115 supplementation and routine treatment and a control group that received routine treatment only.Fecal samples were collected at the onset and conclusion of the 12-wk intervention period.The structure of the intestinal microbiota and the levels of serological indicators,such as liver function and inflammatory factors,were assessed.RESULTS Following LP N1115 intervention,the intestinal microbial diversity significantly increased in the intervention group(P<0.05),and the structure of the intestinal microbiota was characterized by an increase in the proportions of probiotic microbes and a reduction in harmful bacteria.Additionally,the intervention group demonstrated notable improvements in liver function indices and significantly lower levels of inflammatory factors(P<0.05).CONCLUSION LP N1115 is a promising treatment for ameliorating intestinal microbial imbalance in HBC patients by modulating the structure of the intestinal microbiota,improving liver function,and reducing inflammatory factor levels.

Biochemical Liver Functions and Molecular Identification of Fasciola hepatica from Experimentally Infected Rat Model

The current study was performed to evaluate the liver function status as well as molecular characterization of the recovered worms in rats experimentally infected with F. hepatica. Sixteen male Wister rats aged 30 days were randomly allocated into two groups (n = 8). The first group was infected orally with 15 viable encysted metacercaria of F. hepatica per animal. The other group was kept non-infected (control group). At zero time (before infection), the 2nd, 4th, 6th, 8th, 10th, 12th and 14th weeks post-infection (WPI), blood and serum samples were collected via puncture of retro-orbital plexus of veins from each rat. Serum enzyme level (AST and ALT) and total protein were measured, and the serum protein profile was carried out using agarose gel electrophoresis. During the period of the experiment, serum ALT and AST activities and serum total globulins significantly increased while serum total proteins and albumin markedly decreased in the infected group. On the 14th WPI, the data of the electropherogram showed that globulin fractions (α1-, β- and γ-globulin) levels were significantly increased while α2-globulin was markedly decreased in the infected group. The molecular analysis confirmed the amplification of the ITS1, ITS2 and NDI genes of F. hepatica recovered from the infected liver of rats with amplicon sizes of 630, 510 and 560 bp, respectively. Sequencing of the amplified ITS gene resulted in the determination of 3 strains (PP108836, PP108837, and PP108838). Also, analysis of the ITS2 gene resulted in obtaining 3 isolates under the accession numbers (PP109065, PP109066, and PP109067). In conclusion, fasciolosis in the rat model is suitable for routine experimental infections and caused a pronounced liver dysfunction with discharging of the Fasciola eggs in the faeces and the development of adult stages in the bile ducts. Furthermore, molecular techniques are a sensitive tool for the identification and characterisation of the Fasciola parasite.

Effect of Shuanghuanglian Oral Solution on Liver Function in a Mouse Model of Non-alcoholic Steatohepatitis

[Objectives]To observe the effect of Shuanghuanglian oral solution on liver function in BABL/cJ mice in non-alcoholic steatohepatitis(NASH)model.[Methods]The BABL/cJ mice were randomly divided into three groups:a control group,a model group,and an experimental group.The experimental group was administered with 10%Shuanghuanglian oral solution at a dose of 0.1 mL/(10 g·d),while the control group and experimental group received an equivalent dosage of normal saline.All three groups were treated for a period of 28 d.The liver function of the mice in each group was examined after the treatment.[Results]The body mass,liver index,triacylglycerol(TG),total cholesterol(TC),aspartate aminotransferase(AST),and alanine aminotransferase(ALT)levels were all significantly reduced compared to the model group(P<0.05).[Conclusions]Shuanghuanglian oral solution has a beneficial effect on liver function in BABL/cJ mice.

Effect of CT-Guided Microwave Ablation Combined with TACE on Liver Function and Survival of Patients with Primary Liver Cancer

Objective:To explore the effect of transarterial chemoembolization(TACE)+CT-guided microwave ablation(MWA)on treating patients with primary liver cancer.Methods:78 primary liver cancer cases were enrolled and divided into groups according to their assigned surgical plans.The control group was treated with TACE alone,and the observation group was treated with TACE+CT-guided MWA.The efficacy of the treatment and the liver function indicators and follow-up results of the patients of the two groups were compared.Results:The efficacy of the treatment received by the observation group was higher than that of the control group.Besides,the patients in the observation group exhibited better improvement in liver function indicators after 3 months of treatment.Furthermore,the survival rates of 1 and 2 years after surgery of the observation group were all higher than those of the control group(P<0.05).Conclusion:TACE combined with CT-guided MWA is more effective in treating primary liver cancer compared to TACE alone.Besides,it resulted in better improvement of liver function and long-term survival rate.Therefore,this treatment regime should be popularized.

Study on the Application Value of Liver Function and Serological Index Levels in the Diagnosis of Fatty Liver

Objective:To explore the application value of liver function and serological index detection in diagnosing fatty liver.Methods:Ninety patients with fatty liver disease(disease group)and ninety healthy subjects(healthy group)were selected as the subjects of this study.They all underwent liver function index testing and serological index testing.Test results were compared,and the diagnostic accuracy of single and combined tests was evaluated.Results:Liver function indicators of patients in the disease group were higher than those in the healthy group,with severe patients exhibiting higher levels than moderate patients and mild patients(P<0.05).Serological indicators in patients in the disease group were higher than those in the healthy group,with severe patients showing higher levels than moderate patients and mild patients(P<0.05).The diagnostic accuracy of liver function index testing was higher than that of serological index testing,and the accuracy of combined testing was higher than that of single testing(P<0.05).Conclusion:In diagnosing fatty liver,combining liver function testing and serological testing enables the initial diagnosis of the disease and facilitates the accurate assessment of its severity.

hucMSC-derived exosomes protect ovarian reserve and restore ovarian function in cisplatin treated mice

Anti-cancer therapy often causes premature ovarian insufficiency and infertility as the ovarian follicle reserve is extremely sensitive to chemotherapy drugs,such as cisplatin.Various fertility preservation methods have been explored for women,especially prepubertal girls undergoing radiotherapy and chemotherapy due to cancer.In recent years,mesenchymal stem cell-derived exosomes(MSC-exos)have been reported to play an important role in tissue repair and the treatment of various diseases.In the current study,we observed that human umbilical cord-derived MSC-exos(hucMSC-exos)after short-term culture improved follicular survival and development while receiving cisplatin treatment.Moreover,intravenous injection of hucMSC-exos improved ovarian function and ameliorated inflammatory environment within the ovary.The underlying mechanism of hucMSC-exos on fertility preservation was associated with the down-regulation of p53-related apoptosis and their anti-inflammatory function.Based on these findings,we propose that hucMSC-exos may be a potential approach to improve fertility in women diagnosed with cancer.

Indocyanine green clearance in evaluating the recovery of liver reserve function after superselective transarterial chemoembolization

Transarterial chemoembolization(TACE)may ravage normal liver tissues apart from the neoplastic nodules which offset the anti-tumor effect.This study aimed to evaluate the recovery of liver reserve function(LRF)after TACE by indocyanine green(ICG)clearance test and other routine liver function tests.Forty-six newly diagnosed HCC patients who had undergone TACE as the initial treatment from January 2011 to January 2012 were enrolled in this study.The effects of age,basic ICG clearance rate and interval time between two assessments on the recovery of LRF were analyzed.We found that ICG retention rate at the 15 minutes(ICGR15)was significantly increased after TACE(12.3±8.1%vs 16.8±12.1%,P【0.01)in all the 46 patients.In particular,the ICGR15 value was increased in older patients(age】55 years,20.3±12.5%vs 13.7±7.2%,P【0.01).The interval of ICG test also affected the ICGR15 value(≤47days,17.8±11.4%after vs 12.1±7.1%before TACE,P【0.01).Our data suggested that TACE decreased LRF,especially in older patients.ICG test was more sensitive to evaluate the recovery of LRF after TACE than the Child-Pugh grade and routine liver function tests.

Use of magnetic resonance elastography for assessing liver functional reserve:A clinical study

AIM: To investigate the value of magnetic resonance elastography(MRE) with regard to assessing liver functional reserve.METHODS: Data from inpatients diagnosed with a liver tumor at an interventional radiology department from July 2013 to June 2014 were analyzed. A 3.0 Tesla magnetic resonance unit was used to scan 32 patients with confirmed diagnoses of hepatocellular carcinoma(HCC); an MRE sequence was added to the protocol, and the data were reconstructed and analyzed by two attending radiologists. Regions of interest were identified in different slices of the non-tumor liver parenchyma to measure average stiffness. In addition, the indocyanine green(ICG) test was performed no more than 1 wk before or after the magnetic resonance examination for all 32 patients; the ICG retention rate at 15 min(ICGR-15) and the ICG plasma clearance rate(ICG-K) were recorded. Correlational analyses were performed between the liver stiffness values and the ICGR-15 as well as between the liver stiffness values and the ICG-K.RESULTS: Magnetic resonance imaging, including an MRE sequence and the ICG test, was performed successfully in all 32 enrolled patients. None of the patients developed complications. The mean ± SD of the elasticity values measured by the two attending radiologists were 4.7 ± 2.2 k Pa and 4.7 ± 2.1 k Pa, respectively. The average liver stiffness value of the non-tumor parenchyma measured using MRE in HCC patients was 4.7 ± 2.2 k Pa. The average ICGR-15 was 0.089 ± 0.077, and the average ICG-K was 0.19 ± 0.07. We found that the liver stiffness value of the non-tumor parenchyma was significantly and positively related to the ICGR-15(r = 0.746, P < 0.01) as well as significantly and negatively related to the ICG-K(r =-0.599, P < 0.01). The ICGR-15 was significantly and negatively related to the ICG-K(r =-0.852, P < 0.01).CONCLUSION: MRE is accurate and non-invasive; furthermore, it can be used to effectively assess the liver functional reserve of HCC patients.

Assessment of hepatic functional reserve by cirrhosis grading and liver volume measurement using CT

AIM： To explore a method for quantitative assessment of hepatic functional reserve by combining computed tomography （CT） volumetry with CT grading of liver cirrhosis before liver resection in patients with hepatocellular carcinoma. METHODS： CT images of 55 patients undergoing liver resection were studied prospectively. The degree of liver cirrhosis was referred as ＂CT grade＂ and the percentage of remnant liver volume （PRLV） [PRLV = predicted RLV/predicted total liver volume （PTLV） × 100%; PTLV （mL） = 121.75 ＋ 16.49 × body mass （kg）] were calculated by adding slice by slice of CT liver images. The postoperative RLV, pathologic stages of liver fibrosis in non-tumor area and survival time in these cases were analyzed. RESULTS： There was a significant difference in survival time between the group with PRLV ≤ 50% and the group with PRLV 〉 50% （X^2= 4.988, P = 0.026）, and between the group with CT grade 0/1 and the group with CT grade 2/3 （X^2= 5.429, P = 0.026）. With combination of the both parameters, an oblique line was identified according to the distribution of 32 survivors versus 23 deceased subjects. The mortality rate above the line was 7.1% （1/14）, and that below the line was 53.7% （22/41）, indicating a significant difference between the two rates （X^2 = 9.281, P = 0.002, P 〈 0.05）. CONCLUSION： PRLV and CT grades are significantly correlated with hepatic functional reserve. The predicted line using these two parameters is useful in candidates undergoing liver resection for judging hepatic functional reserve.

Liver reserve function assessment by acoustic radiation force impulse imaging

AIM: To evaluate the utility of liver reserve function by acoustic radiation force impulse(ARFI) imaging in patients with liver tumors. METHODS: Seventy-six patients with liver tumors were enrolled in this study. Serum biochemical indexes, such as aminotransferase(ALT), aspartate aminotransferase(AST), serum albumin(ALB), total bilirubin(T-Bil), and other indicators were observed. Liver stiffness(LS) was measured by ARFI imaging, measurements were repeated 10 times, and the average value of the results was taken as the final LS value. Indocyanine green(ICG) retention was performed, and ICG-K and ICG-R15 were recorded. Child-Pugh(CP) scores were carried out based on patient's preoperative biochemical tests and physical condition. Correlations among CP scores,ICG-R15, ICG-K and LS values were observed and analyzed using either the Pearson correlation coefficient or the Spearman rank correlation coefficient. KruskalWallis test was used to compare LS values of CP scores, and the receiver-operator characteristic(ROC) curve was used to analyze liver reserve function assessment accuracy. RESULTS: LS in the ICG-R15 10%-20% group was significantly higher than in the ICG-R15 < 10% group; and the difference was statistically significant(2.19 ± 0.27 vs 1.59 ± 0.32, P < 0.01). LS in the ICG-R15 > 20% group was significantly higher than in the ICG-R15 < 10% group; and the difference was statistically significant(2.92 ± 0.29 vs 1.59 ± 0.32, P < 0.01). The LS value in patients with CP class A was lower than in patients with CP class B(1.57 ± 0.34 vs 1.86 ± 0.27, P < 0.05), while the LS value in patients with CP class B was lower than in patients with CP class C(1.86 ± 0.27 vs 2.47 ± 0.33, P < 0.01). LS was positively correlated with ICG-R15(r = 0.617, P < 0.01) and CP score(r = 0.772, P < 0.01). Meanwhile, LS was negatively correlated with ICG-K(r =-0.673, P < 0.01). AST, ALT and T-Bil were positively correlated with LS, while ALB was negatively correlated with LS(P < 0.05). The ROC curve revealed that the when the LS value was 2.34 m/s, the Youden index was at its highest point, sensitivity was 69.2% and specificity was 92.1%. CONCLUSION: For patients with liver tumors, ARFI imaging is a useful tool for assessing liver reserve function.

Clinical value of predictive models based on liver stiffness measurement in predicting liver reserve function of compensated chronic liver disease

BACKGROUND Assessment of liver reserve function(LRF)is essential for predicting the prognosis of patients with chronic liver disease(CLD)and determines the extent of liver resection in patients with hepatocellular carcinoma.AIM To establish noninvasive models for LRF assessment based on liver stiffness measurement(LSM)and to evaluate their clinical performance.METHODS A total of 360 patients with compensated CLD were retrospectively analyzed as the training cohort.The new predictive models were established through logistic regression analysis and were validated internally in a prospective cohort(132 patients).RESULTS Our study defined indocyanine green retention rate at 15 min(ICGR15)≥10%as mildly impaired LRF and ICGR15≥20%as severely impaired LRF.We constructed predictive models of LRF,named the mLPaM and sLPaM,which involved only LSM,prothrombin time international normalized ratio to albumin ratio(PTAR),age and model for end-stage liver disease(MELD).The area under the curve of the mLPaM model(0.855,0.872,respectively)and sLPaM model(0.869,0.876,respectively)were higher than that of the methods for MELD,albumin bilirubin grade and PTAR in the two cohorts,and their sensitivity and negative predictive value were the highest among these methods in the training cohort.In addition,the new models showed good sensitivity and accuracy for the diagnosis of LRF impairment in the validation cohort.CONCLUSION The new models had a good predictive performance for LRF and could replace the indocyanine green(ICG)clearance test,especially in patients who are unable to undergo ICG testing.

Status of Renal and Liver Function in Rheumatoid Arthritis (RA) Patients of Chattogram, Bangladesh Treated with Methotrexate (MTX)

Rheumatoid Arthritis (RA) is a chronic autoimmune disorder that is usually manifested as inflammation in multiple joints and several extra-articular symptoms, involving the liver, kidney, eye, skin, blood, blood vessels, heart, lungs, nervous system, and other organs. Methotrexate (MTX) is the anchor drug that treats RA. As renal and liver abnormalities are more common during disease conditions as well as during the treatment period, we tried to find out if there is any impact of MTX in these organs during the treatment of RA patients. Once the disease complications are developed, it is quite difficult to reverse the disease, and treatment in this situation is not very effective. Consequently, patients suffer a lot. So, early evaluation of renal and liver function is essential for the treatment of RA patients and it might also help prevent different complications which are usually very frequently observed. This was a cross-sectional study. A total of 150 RA patients treated with MTX were evaluated for the study where female and male respondents were 115 and 35 respectively. In this study, we found that 82% of RA patients had creatinine levels ≤ 1.1 mg/dL although the normal range of serum creatinine is below 1.4 mg/dL. Usually, a 15% increase in Serum creatinine level from the baseline is considered renal impairment. We found 4% of such cases. Moreover, 2% of RA patients had creatinine levels above the normal range of 1.4 mg/dL and those patients were hypertensive as well. So, a total (4 + 2 = 6)% had renal impairments. Among them, 5% had diabetes mellitus. On the other hand, the ultrasonogram (USG) of RA patients with kidney disease showed signs of renal parenchymal disease and 3% of RA patients having renal problems whose serum creatinine level was within the normal range showed signs of chronic kidney disease (CKD). On the other hand, 2% of RA patients showed signs of hepatic parenchymal disease. In this study, 69% of RA patients had ALT levels ≤ 50 mg/dL, 23% had 50 - 100 mg/dL, and 5% had 101 - 150 mg/dL. The remaining 3% of RA patients had ALT levels above 150 mg/dL. All those patients with ALT levels above 100 mg/dL used Nonsteroidal anti-inflammatory drugs (NSAIDs) concomitantly. Different parameters of liver and renal function should be monitored strongly in RA patients treated with MTX and NSAIDs. MTX should not be given for a prolonged period without monitoring renal and liver function. As MTX, Diabetes Mellitus, Hypertension, etc., may cause renal complications, we could not concretely conclude which one is the actual causative agent.

Application of DDG-3300K Liver Reserve Function Analyzer and Relevant Nursing Procedures at the Department of Infectious Diseases

Objective: To discuss some key points about nursing in the use of DDG-3300K liver reserve function analyzer in patients at the department of infectious diseases. Method: DDG-3300K liver reserve function analyzer was applied to 5464 patients at the department of infectious diseases. The reasons for failed detection and complications related to the detection were analyzed, and the measures for improving the nursing procedures were proposed. Result: Among the 5464 patients, the detections were successful at the first attempt in 5458 patients;2 patients had leakage of liquid;2 patients were poorly prepared, and 1 case failed because of mistaken selection of CO mode, which led to adverse drug reactions;1 case did not finish the detection due to anaphylactic shock;8 patients had nausea and 6 patients had skin rash on the four limbs and torso during the detection. Conclusion: It is necessary to formulate the nursing procedures for the use of DDG-3300K liver reserve function analyzer. Moreover, preparatory work, health education, refined nursing procedures and skillful operations are closely related to the success rate and accuracy of the detection.

Function of macrophage-derived exosomes in chronic liver disease:From pathogenesis to treatment

Chronic liver disease(CLD)imposes a heavy burden on millions of people worldwide.Despite substantial research on the pathogenesis of CLD disorders,no optimal treatment is currently available for some diseases,such as liver cancer.Exosomes,which are extracellular vesicles,are composed of various cellular components.Exosomes have unique functions in maintaining cellular homeostasis and regulating cell communication,which are associated with the occurrence of disease.Furthermore,they have application potential in diagnosis and treatment by carrying diverse curative payloads.Hepatic macrophages,which are key innate immune cells,show extraordinary heterogeneity and polarization.Hence,macrophage-derived exosomes may play a pivotal role in the initiation and progression of various liver diseases.This review focuses on the effects of macrophage-derived exosomes on liver disease etiology and their therapeutic potential,which will provide new insights into alleviating the global pressure of CLD.