Lactiplantibacillus plantarum FRT4 attenuates high-energy low-protein dietinduced fatty liver hemorrhage syndrome in laying hens through regulating gut-liver axis

Background Fatty liver hemorrhage syndrome(FLHS)becomes one of the most major factors resulting in the laying hen death for caged egg production.This study aimed to investigate the therapeutic effects of Lactiplantibacillus plan-tarum(Lp.plantarum)FRT4 on FLHS model in laying hen with a focus on liver lipid metabolism,and gut microbiota.Results The FLHS model of laying hens was established by feeding a high-energy low-protein(HELP)diet,and the treatment groups were fed a HELP diet supplemented with differential proportions of Lp.plantarum FRT4.The results indicated that Lp.plantarum FRT4 increased laying rate,and reduced the liver lipid accumulation by regulating lipid metabolism(lipid synthesis and transport)and improving the gut microbiota composition.Moreover,Lp.plan-tarum FRT4 regulated the liver glycerophospholipid metabolism.Meanwhile,“gut-liver”axis analysis showed that there was a correlation between gut microbiota and lipid metabolites.Conclusions The results indicated that Lp.plantarum FRT4 improved the laying performance and alleviated FLHS in HELP diet-induced laying hens through regulating“gut-liver”axis.Our findings reveal that glycerophospholipid metabolism could be the underlying mechanism for the anti-FLHS effect of Lp.plantarum FRT4 and for future use of Lp.plantarum FRT4 as an excellent additive for the prevention and mitigation of FLHS in laying hens.

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.

Leukopenia-a rare complication secondary to invasive liver abscess syndrome in a patient with diabetes mellitus:A case report

BACKGROUND Thrombocytopenia is a common complication of invasive liver abscess syndrome(ILAS)by Klebsiella pneumoniae(K.pneumoniae)infection,which indicates severe infection and a poor prognosis.However,the presence of leukopenia is rare.There are rare reports on leukopenia and its clinical significance for ILAS,and there is currently no recognized treatment plan.Early and broad-spectrum antimi-crobial therapy may be an effective therapy for treating ILAS and improving its prognosis.CASE SUMMARY A 55-year-old male patient who developed fever,chills,and abdominal distension without an obvious cause presented to the hospital for treatment.Laboratory tests revealed thrombocytopenia,leukopenia,and multiple organ dysfunction.Imaging examinations revealed an abscess in the right lobe of the liver and thromboph-lebitis,and K.pneumoniae was detected in the blood cultures.Since the patient was diabetic and had multi-system involvement,he was diagnosed with ILAS accom-panied by leukopenia and thrombocytopenia.After antibiotic treatment and sys-temic supportive therapy,the symptoms disappeared,and the patient’s condition almost completely resolved.CONCLUSION Leukopenia is a rare complication of ILAS,which serves as an indicator of adverse prognostic outcomes and the severity of infection.

Predictors of survival in autoimmune liver disease overlap syndromes

BACKGROUND Survival in patients with autoimmune liver disease overlap syndromes(AILDOS)compared to those with single autoimmune liver disease is unclear.AIM To investigate the survival of patients with AILDOS and assess the accuracy of non-invasive serum models for predicting liver-related death.METHODS Patients with AILDOS were defined as either autoimmune hepatitis and primary biliary cholangitis overlap(AIH-PBC)or autoimmune hepatitis and primary sclerosing cholangitis overlap(AIH-PSC)and were identified from three tertiary centres for this cohort study.Liver-related death or transplantation(liver-related mortality)was determined using a population-based data linkage system.Prognostic scores for liver-related death were compared for accuracy[including liver outcome score(LOS),Hepascore,Mayo Score,model for end-stage liver disease(MELD)score and MELD incorporated with serum sodium(MELD-Na)score].RESULTS Twenty-two AILDOS patients were followed for a median of 3.1 years(range,0.35-7.7).Fourteen were female,the median age was 46.7 years(range,17.8 to 82.1)and median Hepascore was 1(range,0.07-1).At five years post enrolment,57%of patients remained free from liver-related mortality(74%AIH-PBC,27%AIH-PSC).There was no significant difference in survival between AIH-PBC and AIH-PSC.LOS was a significant predictor of liver-related mortality(P<0.05)in patients with AIH-PBC(n=14)but not AIH-PSC(n=8).A LOS cut-point of 6 discriminated liver-related mortality in AIH-PBC patients(P=0.012,log-rank test,100%sensitivity,77.8%specificity)(Harrell's C-statistic 0.867).The MELD score,MELD-Na score and Mayo Score were not predictive of liver-related mortality in any group.CONCLUSION Survival in the rare,AILDOS is unclear.The current study supports the LOS as a predictor of liver-related mortality in AIH-PBC patients.Further trials investigating predictors of survival in AILDOS are required.

Calcineurin inhibitors-related posterior reversible encephalopathy syndrome in liver transplant recipients: Three case reports and review of literature

BACKGROUND Posterior reversible encephalopathy syndrome(PRES),characterized by acute neurological deterioration and extensive white matter lesions on T2-fluid attenuated inversion recovery magnetic resonance imaging(MRI),is increasingly associated with calcineurin inhibitors(CNI)-related neurotoxicity.Prompt diagnosis is crucial,as early intervention,including the modification or discontinuation of CNI therapy,strict blood pressure management,corticosteroid treatment,and supportive care can significantly improve patient outcomes and prognosis.The growing clinical recognition of CNI-related PRES underscores the importance of identifying and managing this condition in patients presenting with acute neurological symptoms.CASE SUMMARY This report describes three cases of liver transplant recipients who developed PRES.The first case involves a 60-year-old woman who experienced seizures,aphasia,and hemiplegia on postoperative day(POD)9,with MRI revealing ischemic foci followed by extensive white matter lesions.After replacing tacrolimus,her symptoms improved,and no significant MRI abnormalities were observed after three years of follow-up.The second case concerns a 54-year-old woman with autoimmune hepatitis who developed headaches,seizures,and extensive white matter demyelination on MRI on POD24.Following the switch to rapamycin and the initiation of corticosteroids,her symptoms resolved,and she was discharged on POD95.The third case details a 60-year-old woman with hepatocellular carcinoma who developed PRES,evidenced by brain MRI abnormal-ities on POD11.Transitioning to rapamycin and corticosteroid therapy led to her full recovery,and she was discharged on POD22.These cases highlight the critical importance of early diagnosis,CNI modification,and stringent management in improving outcomes for liver transplant recipients with CNI related PRES.CONCLUSION Clinical manifestations,combined with characteristic MRI findings,are crucial in diagnosing PRES among organ transplant recipients.However,when standard treatments are ineffective or MRI results are atypical,alternative diagnoses should be taken into considered.

Pituitary stalk interruption syndrome complicated with liver cirrhosis:A case report

BACKGROUND Pituitary stalk interruption syndrome(PSIS)is a rare disorder,often characterized by delayed growth and development,short stature,and hypogonadism as the main clinical manifestations.It is not clear whether PSIS can lead to liver cirrhosis.CASE SUMMARY This paper reported a case of liver cirrhosis of unknown origin.The patient was admitted to Beijing Ditan Hospital Affiliated to Capital Medical University in November 2023.The diagnosis of PSIS complicated with liver cirrhosis was established after a series of blood tests and pituitary magnetic resonance imaging examination.CONCLUSION We also reviewed the literature from both domestic and international sources to deepen the clinical understanding of PSIS in conjunction with liver cirrhosis among medical practitioners.

New therapeutic strategy with extracorporeal membrane oxygenation for refractory hepatopulmonary syndrome after liver transplant: A case report

BACKGROUND Due to the lack of published literature about treatment of refractory hepatopulmonary syndrome(HPS)after liver transplant(LT),this case adds information and experience on this issue along with a treatment with positive outcomes.HPS is a complication of end-stage liver disease,with a 10%-30%incidence in cirrhotic patients.LT can reverse the physiopathology of this process and restore normal oxygenation.However,in some cases,refractory hypoxemia persists,and extracorporeal membrane oxygenation(ECMO)can be used as a rescue therapy with good results.CASE SUMMARY A 59-year-old patient with alcohol-related liver cirrhosis and portal hypertension was included in the LT waiting list for HPS.He had good liver function(Model for End-Stage Liver Disease score 12,Child-Pugh class B7).He had pulmonary fibrosis and a mild restrictive respiratory pattern with a basal oxygen saturation of 82%.The macroaggregated albumin test result was>30.Spirometry demonstrated a forced expiratory volume in one second(FEV1)of 78%,forced vital capacity(FVC)of 74%,FEV1/FVC ratio of 81%,diffusion capacity for carbon monoxide of 42%,and carbon monoxide transfer coefficient of 57%.He required domiciliary oxygen at 2 L/min(16 h/d).The patient was admitted to the intensive care unit(ICU)and extubated in the first 24 h,needing high-flow therapy and non-invasive ventilation and inhaled nitric oxide afterwards.Reintubation was needed after 72 h.Due to the non-response to supportive therapies,installation of ECMO was decided with progressive recovery after 9 d.Extubation was possible on the tenth day,maintaining a high-flow nasal cannula and de-escalating to conventional oxygen therapy after 48 h.He was discharged from ICU on postoperative day(POD)20 with a 90%-92%oxygen saturation.Steroid recycling was needed twice for acute rejection.The patient was discharged from hospital on POD 27 with no symptoms,with an 89%-90%oxygen saturation.CONCLUSION Due to the favorable results observed,ECMO could become the central axis of treatment of HPS and refractory hypoxemia after LT.

Tacrolimus-induced posterior reversible encephalopathy syndrome following liver transplantation

In this editorial,we talk about a compelling case focusing on posterior reversible encephalopathy syndrome(PRES)as a complication in patients undergoing liver transplantation and treated with Tacrolimus.Tacrolimus(FK 506),derived from Streptomyces tsukubaensis,is a potent immunosuppressive macrolide.It inhibits Tcell transcription by binding to FK-binding protein,and is able to amplify glucocorticoid and progesterone effects.Tacrolimus effectively prevents allograft rejection in transplant patients but has adverse effects such as Tacrolimus-related PRES.PRES presents with various neurological symptoms alongside elevated blood pressure,and is primarily characterized by vasogenic edema on neuroimaging.While computed tomography detects initial lesions,magnetic resonance imaging,especially the Fluid-Attenuated Inversion Recovery sequence,is superior for diagnosing cortical and subcortical edema.Our discussion centers on the incidence of PRES in solid organ transplant recipients,which ranges between 0.5 to 5+ACU-,with varying presentations,from seizures to visual disturbances.The case of a 66-year-old male status post liver transplantation highlights the diagnostic and management challenges associated with Tacrolimus-related PRES.Radiographically evident in the parietal and occipital lobes,PRES underlines the need for heightened vigilance among healthcare providers.This editorial emphasizes the importance of early recognition,accurate diagnosis,and effective management of PRES to optimize outcomes in liver transplant patients.The case further explores the balance between the efficacy of immunosuppression with Tacrolimus and its potential neurological risks,underlining the necessity for careful monitoring and intervention strategies in this patient population.

Metabolic syndrome’s new therapy:Supplement the gut microbiome

This letter to the editor discusses the publication on gut microbiome supple-mentation as therapy for metabolic syndrome.Gut microbiome dysbiosis disrupts intestinal bacterial homeostasis and is related to chronic inflammation,insulin resistance,cardiovascular diseases,type 2 diabetes mellitus,and obesity.Previous research has found that increasing the abundance of beneficial microbiota in the gut modulates metabolic syndrome by reducing chronic inflammation and insulin resistance.Prebiotics,probiotics,synbiotics,and postbiotics are often used as supplements to increase the number of beneficial microbes and thus the produc-tion of short-chain fatty acids,which have positive effects on the gut microbiome and metabolic syndrome.In this review article,the author summarizes the available supplements to increase the abundance of beneficial gut microbiota and reduce the abundance of harmful microbiota in patients with metabolic disorders.Our group is also researching the role of the gut microbiota in chronic liver disease.This article will be of great help to our research.At the end of the letter,the mechanism of the gut microbiota in chronic liver disease is discussed.

A Budd-Chiari Syndrome Due to C Protein Deficiency: A Case Report at YaoundéGeneral Hospital (Cameroon)

Primary Budd-Chiari syndrome (BCS) is a spontaneously fatal disease characterized by an obstruction of the hepatic venous outflow tract due to thrombosis or a primary disease of the venous wall. The primary form of BCS is extremely rare. This is a disease mainly affecting young adults of both sexes. Clinical manifestations are variable;they can be asymptomatic, acute, or subacute but mostly chronic. Several causes have been identified, such as myeloproliferative syndrome, antiphospholipid syndrome, paroxysmal nocturnal hemoglobinuria, and inherited thrombotic disorders. Data on primary BCS in Sub-Saharan Africa is rare as most publications available are case reports. In these reports, the causes are unknown with poor prognosis in most cases often leading to patient death. We herein present a case report of a male patient diagnosed with a primary BCS at Yaoundé General Hospital (Cameroon) caused by a Protein C deficiency who presented with ascites decompensating liver cirrhosis. Treatment was based on anticoagulants, diuretics and laxatives administration. Two years after the diagnosis, the patient is alive with clinical and paraclinical improvement.

Clinical profile and outcomes of hepatocellular carcinoma in primary Budd-Chiari syndrome

BACKGROUND There is scant literature on hepatocellular carcinoma(HCC)in patients with Budd-Chiari syndrome(BCS).AIM To assess the magnitude,clinical characteristics,feasibility,and outcomes of treatment in BCS-HCC.METHODS A total of 904 BCS patients from New Delhi,India and 1140 from Mumbai,India were included.The prevalence and incidence of HCC were determined,and among patients with BCS-HCC,the viability and outcomes of interventional therapy were evaluated.RESULTS In the New Delhi cohort of 35 BCS-HCC patients,18 had HCC at index presentation(prevalence 1.99%),and 17 developed HCC over a follow-up of 4601 person-years,[incidence 0.36(0.22-0.57)per 100 person-years].BCS-HCC patients were older when compared to patients with BCS alone(P=0.001)and had a higher proportion of inferior vena cava block,cirrhosis,and long-segment vascular obstruction.The median alpha-fetoprotein level was higher in patients with BCS-HCC at first presentation than those who developed HCC at follow-up(13029 ng/mL vs 500 ng/mL,P=0.01).Of the 35 BCS-HCC,26(74.3%)underwent radiological interventions for BCS,and 22(62.8%)patients underwent treatment for HCC[transarterial chemoembolization in 18(81.8%),oral tyrosine kinase inhibitor in 3(13.6%),and transarterial radioembolization in 1(4.5%)].The median survival among patients who underwent interventions for HCC compared with those who did not was 3.5 years vs 3.1 mo(P=0.0001).In contrast to the New Delhi cohort,the Mumbai cohort of BCS-HCC patients were predominantly males,presented with a more advanced HCC[Barcelona Clinic Liver Cancer C and D],and 2 patients underwent liver transplantation.CONCLUSION HCC is not uncommon in patients with BCS.Radiological interventions and liver transplantation are feasible in select primary BCS-HCC patients and may improve outcomes.

Associations between irritable bowel syndrome and non-alcoholic fatty liver disease:A systematic review

BACKGROUND Irritable bowel syndrome(IBS)is associated with obesity and metabolic syndrome.IBS and non-alcoholic fatty liver disease(NAFLD)are highly prevalent entities worldwide and may share similar mechanisms including gut dysbiosis,impaired intestinal mucosal barrier and immune system activation.AIM To systematically review their association according to the Preferred Reporting Items for Systemic Review and Meta-analyses guidelines.METHODS PubMed,EMBASE and Cochrane Database of Systematic Reviews were searched for relevant papers.Manual searches were also performed.RESULTS Six studies were included.Both IBS and NAFLD subjects had significantly more metabolic risk factors like hypertension,obesity,dyslipidaemia and diabetes.Our review showed that 23.2%to 29.4%of NAFLD patients had IBS.IBS was significantly higher in NAFLD patients compared with patients without NAFLD(23.2%vs 12.5%,P<0.01).A higher proportion of IBS patients had NAFLD(65.8%to 74.0%).IBS patients were three times more likely to have NAFLD compared with non-IBS patients(P<0.001).Two studies showed a significant correlation between the severity of IBS and NAFLD.The proportion of NAFLD subjects with IBS increased with NAFLD severity.CONCLUSION Further prospective studies are warranted to evaluate the relationship and shared pathways between IBS and NAFLD,potentially leading to the development of future therapeutics.

Successful treatment of invasive liver abscess syndrome caused by Klebsiella variicola with intracranial infection and septic shock:A case report

BACKGROUND Klebsiella variicola(K.variicola)is a member of the Klebsiella genus and is often misidentied as Klebsiella pneumoniae.In this report,we present a rare case of invasive liver abscess caused by K.variicola.CASE SUMMARY We report a rare case of liver abscess due to K.variicola.A 57-year-old female patient presented with back pain for a month.She developed a high-grade fever associated with chills,and went into a coma and developed shock.The clinical examinations and tests after admission confirmed a diagnosis of primary liver abscess caused by K.variicola complicated by intracranial infection and septic shock.The patient successfully recovered following early percutaneous drainage of the abscess,prompt appropriate antibiotic administration,and timely open surgical drainage.CONCLUSION This is a case of successful treatment of invasive liver abscess syndrome caused by K.variicola,which has rarely been reported.The findings of this report point to the need for further study of this disease.

Protective effect of long-chain polyunsaturated fatty acids on hepatorenal syndrome in rats

BACKGROUND Hepatorenal syndrome(HRS)is the most prevalent form of acute kidney injury in cirrhotic patients.It is characterized by reduced renal blood flow and represents the most severe complication in cirrhotic patients with advanced disease.Previous research has indicated that antioxidants can delay the onset of a hyperdynamic circulatory state in cirrhosis and improve renal function in HRS patients.Regular omega-3 supplementation has significantly reduced the risk of liver disease.This supplementation could represent an additional therapy for individuals with HRS.AIM To evaluated the antioxidant effect of omega-3 polyunsaturated fatty acid supplementation on the kidneys of cirrhotic rats.METHODS Secondary biliary cirrhosis was induced in rats by biliary duct ligation(BDL)for 28 d.We used 24 male Wistar rats divided into the following groups:I(control);II(treated with omega-3,1 g/kg of body weight);III(BDL treated with omega-3,1 g/kg of body weight);and IV(BDL without treatment).The animals were killed by overdose of anesthetic;the kidneys were dissected,removed,frozen in liquid nitrogen,and stored in a freezer at-80℃for later analysis.We evaluated oxidative stress,nitric oxide(NO)metabolites,DNA damage by the comet assay,cell viability test,and apoptosis in the kidneys.Data were analyzed by one-way analysis of variance,and means were compared using the Tukey test,with P≤0.05.RESULTS Omega-3 significantly decreased the production of reactive oxygen species(P<0.001)and lipoperoxidation in the kidneys of cirrhotic rats treated with omega-3(P<0.001).The activity of the antioxidant enzymes superoxide dismutase and catalase increased in the BDL+omega-3 group compared to the BDL group(P<0.01).NO production,DNA damage,and caspase-9 cleavage decreased significantly in the omega-3-treated BDL group.There was an increase in mitochondrial electrochemical potential(P<0.001)in BDL treated with omega-3 compared to BDL.No changes in the cell survival index in HRS with omega-3 compared to the control group(P>0.05)were observed.CONCLUSION The study demonstrates that omega-3 can protect cellular integrity and function by increasing antioxidant enzymes,inhibiting the formation of free radicals,and reducing apoptosis.

Assessing the impact of concurrent high-fructose and highsaturated fat diets on pediatric metabolic syndrome:A review

High-saturated fat(HF)or high-fructose(HFr)consumption in children predispose them to metabolic syndrome(MetS).In rodent models of MetS,diets containing individually HF or HFr lead to a variable degree of MetS.Nevertheless,simultaneous intake of HF plus HFr have synergistic effects,worsening MetS outcomes.In children,the effects of HF or HFr intake usually have been addressed individually.Therefore,we have reviewed the outcomes of HF or HFr diets in children,and we compare them with the effects reported in rodents.In humans,HFr intake causes increased lipogenesis,hypertriglyceridemia,obesity and insulin resistance.On the other hand,HF diets promote low grade-inflammation,obesity,insulin resistance.Despite the deleterious effects of simultaneous HF plus HFr intake on MetS development in rodents,there is little information about the combined effects of HF plus HFr intake in children.The aim of this review is to warn about this issue,as individually addressing the effects produced by HF or HFr may underestimate the severity of the outcomes of Western diet intake in the pediatric population.We consider that this is an alarming issue that needs to be assessed,as the simultaneous intake of HF plus HFr is common on fast food menus.

Prevalence of non-alcoholic fatty liver disease in patients with nephrotic syndrome:A population-based study

BACKGROUND Non-alcoholic fatty liver disease(NAFLD) is a global health concern with a prevalence of about 25% amongst United States adults. Its increased prevalence is attributed to increase in patients with obesity and metabolic syndrome, partly due to similar mechanisms of injury. Nephrotic syndrome(NS) is a clinical entity resulting from extensive proteinuria leading to hypoalbuminemia, hyperlipidemia, edema, and other complications. Given its association with hyperlipidemia, there is concern that patients with NS may be at increased risk of NAFLD.AIM To perform a cross-sectional population-based study to investigate the prevalence and risk factors of NAFLD in patients with NS.METHODS A large multicenter database(Explorys Inc., Cleveland, OH, United States) was utilized for this retrospective cohort study. A cohort of 49700 patients with a diagnosis of “Non-Alcoholic fatty liver disease” using the Systematized Nomenclature of Medicine-Clinical Terms(SNOMED-CT) between 1999-2022 was identified. Inclusion criteria were age ≥ 18 years, presence of NAFLD, presence of NS. There were no specific exclusion criteria. Univariate and multivariate analysis were performed to adjust for multiple risk factors including age, gender, Caucasian race, NS, type Ⅱ diabetes mellitus, hypothyroidism, dyslipidemia, obesity, metabolic syndrome and chronic kidney disease. Statistical analysis was conducted using R, and for all analyses, a 2-sided P value of < 0.05 was considered statistically significant.RESULTS Among the 78734750 individuals screened in this database, there were a total of 49700 subjects with NAFLD. In univariate analysis, the odds of having NAFLD in patients with NS, type 2 diabetes mellitus, hypothyroidism, dyslipidemia, obesity, metabolic syndrome and chronic kidney disease were 14.84 [95% confidence interval(95%CI) 13.67-16.10], 17.05(95%CI 16.78-17.32), 6.99(95%CI 6.87-7.11), 13.61(95%CI 13.38-13.84), 19.19(95%CI 18.89-19.50), 29.09(95%CI 28.26--29.95), and 9.05(95%CI 8.88-9.22), respectively. In multivariate analysis, the odds of having NAFLD amongst patients with NS were increased to 1.85(95%Cl 1.70-2.02), while the odds were also remained high in patients that have type 2 diabetes mellitus [odds ratio(OR) 3.84], hypothyroidism(OR 1.57), obesity(OR 5.10), hyperlipidemia(OR 3.09), metabolic syndrome(OR 3.42) and chronic kidney disease(OR 1.33).CONCLUSION Patients with NS are frequently found to have NAFLD, even when adjusting for common risk factors. Hence, clinicians should maintain a high index of suspicion regarding presence of NAFLD in patients with NS.

Severe acute respiratory syndrome coronavirus 2 may cause liver injury via Na^(+)/H^(+) exchanger

The liver has many significant functions,such as detoxification,the urea cycle,gluconeogenesis,and protein synthesis.Systemic diseases,hypoxia,infections,drugs,and toxins can easily affect the liver,which is extremely sensitive to injury.Systemic infection of severe acute respiratory syndrome coronavirus 2 can cause liver damage.The primary regulator of intracellular pH in the liver is the Na+/H+exchanger(NHE).Physiologically,NHE protects hepatocytes from apoptosis by making the intracellular pH alkaline.Severe acute respiratory syndrome coronavirus 2 increases local angiotensin II levels by binding to angiotensinconverting enzyme 2.In severe cases of coronavirus disease 2019,high angiotensin II levels may cause NHE overstimulation and lipid accumulation in the liver.NHE overstimulation can lead to hepatocyte death.NHE overstimulation may trigger a cytokine storm by increasing proinflammatory cytokines in the liver.Since the release of proinflammatory cytokines such as interleukin-6 increases with NHE activation,the virus may indirectly cause an increase in fibrinogen and D-dimer levels.NHE overstimulation may cause thrombotic events and systemic damage by increasing fibrinogen levels and cytokine release.Also,NHE overstimulation causes an increase in the urea cycle while inhibiting vitamin D synthesis and gluconeogenesis in the liver.Increasing NHE3 activity leads to Na+loading,which impairs the containment and fluidity of bile acid.NHE overstimulation can change the gut microbiota composition by disrupting the structure and fluidity of bile acid,thus triggering systemic damage.Unlike other tissues,tumor necrosis factor-alpha and angiotensin II decrease NHE3 activity in the intestine.Thus,increased luminal Na+leads to diarrhea and cytokine release.Severe acute respiratory syndrome coronavirus 2-induced local and systemic damage can be improved by preventing virus-induced NHE overstimulation in the liver.

Polycystic Ovary Syndrome-Related Infertility Based on the Theory of“Liver and Kidney Homology”

Polycystic ovary syndrome(PCOS)is an endocrine disorder caused by hypothalamic-pituitary-ovarian(HPO)axis dysfunction.In the field of gynecology and reproduction,PCOS has emerged as both a research hot spot and a challenging area of study.According to Chinese medicine,this disease is related to kidney deficiency,phlegm and dampness obstruction,blood stasis and interconnection,Chong pulse impassability,the lack of Ren pulse,and the loss of uterine nourishment,all of which affect the normal development and maturation of eggs as well as the duration at which menstrual blood stores.In this paper,based on the theoretical basis of“liver collects blood,regulates the flow of qi,and is the master of drainage,”we explore the rationality of the treatment of this disease from the perspective of“liver and kidney have the same origin”and the development of PCOS-related infertility in relation to dysfunctional internal organs.We also explore the feasibility of treatment from the perspective of“liver and kidney homology,”expand the ideas for treatment,as well as develop and innovate the application of organ identification in PCOS in relation to infertility.

Efficacy of dexamethasone and N-acetylcysteine combination in preventing post-embolization syndrome after transarterial chemoembolization in hepatocellular carcinoma

BACKGROUND Conventional transarterial chemoembolization(cTACE)is the current standard treatment for intermediate-stage hepatocellular carcinoma(HCC).Postembolization syndrome(PES)is complex clinical syndrome that presents as fever,abdominal pain,nausea,and vomiting.Either dexamethasone(DEXA)or Nacetylcysteine(NAC)is used to prevent PES;however,the synergistic effect of their combined therapy for preventing PES and liver decompensation has not been determined.AIM To evaluate the efficacy of DEXA and NAC combination in preventing PES and liver decompensation after cTACE.METHODS Patients with Barcelona Clinic Liver Cancer stage A or B HCC who were scheduled for TACE were prospectively enrolled.All patients were randomly stratified to receive NAC and DEXA or placebo.The dual therapy(NAC+DEXA)group received intravenous administration of 10 mg DEXA every 12 h,NAC 24 h prior to cTACE(150 mg/kg/h for 1 h followed by 12.5 mg/kg/h for 4 h),and a continuous infusion of 6.25 mg/h NAC plus 4 mg DEXA every 12 h for 48 h after cTACE.The placebo group received an infusion of 5%glucose solution until 48 h after procedure.PES was defined by South West Oncology Group toxicity code grading of more than 2 that was calculated using incidence of fever,nausea,vomiting,and pain.RESULTS One-hundred patients were enrolled with 50 patients in each group.Incidence of PES was significantly lower in the NAC+DEXA group compared with in the placebo group(6%vs 80%;P<0.001).Multivariate analysis showed that the dual treatment is a protective strategic therapy against PES development[odds ratio(OR)=0.04;95%confidence interval(CI):0.01-0.20;P<0.001).Seven(14%)patients in the placebo group,but none in the NAC+DEXA group,developed post-TACE liver decompensation.A dynamic change in Albumin-Bilirubin score of more than 0.5 point was found to be a risk factor for post-TACE liver decompensation(OR=42.77;95%CI:1.01-1810;P=0.049).CONCLUSION Intravenous NAC+DEXA administration ameliorated the occurrence of PES event after cTACE in patients with intermediate-stage HCC.

Clinical and pathophysiological understanding of the hepatorenal syndrome:Still wrong or still not exactly right?

The hepatorenal syndrome(HRS)is one major extrahepatic complication of endstage liver diseases.While circulatory dysregulation is considered as primary etiology for HRS,cirrhosis-related(systemic)inflammation and/or cardial dysfunction may also play a key pathogenic role in HRS development.Exclusion of other causes of acute kidney injury(AKI)is required for diagnosis of HRS-AKI by the definition of the International Club of Ascites.However,the pathophysiology of HRS is not understood completely and there are still limited therapeutic options.Reversibility of renal dysfunction after liver transplantation indicates that HRS-AKI is a functional disorder caused by altered cellular function.The interplay between systemic inflammation and the onset of kidneyrelated hypometabolism may have a key role and needs to be studied in depth.This minireview challenges simplified views of the HRS in the context of diagnostics and therapy stressing the need for further evidence to advance the knowledge on this syndrome.