Role of fecal microbiota transplant in management of hepatic encephalopathy: Current trends and future directions

Fecal microbiota transplantation(FMT)offers a potential treatment avenue for hepatic encephalopathy(HE)by leveraging beneficial bacterial displacement to restore a balanced gut microbiome.The prevalence of HE varies with liver disease severity and comorbidities.HE pathogenesis involves ammonia toxicity,gut-brain communication disruption,and inflammation.FMT aims to restore gut microbiota balance,addressing these factors.FMT's efficacy has been explored in various conditions,including HE.Studies suggest that FMT can modulate gut microbiota,reduce ammonia levels,and alleviate inflammation.FMT has shown promise in alcohol-associated,hepatitis B and C-associated,and non-alcoholic fatty liver disease.Benefits include improved liver function,cognitive function,and the slowing of disease progression.However,larger,controlled studies are needed to validate its effectiveness in these contexts.Studies have shown cognitive improvements through FMT,with potential benefits in cirrhotic patients.Notably,trials have demonstrated reduced serious adverse events and cognitive enhancements in FMT arms compared to the standard of care.Although evidence is promising,challenges remain:Limited patient numbers,varied dosages,administration routes,and donor profiles.Further large-scale,controlled trials are essential to establish standardized guidelines and ensure FMT's clinical applications and efficacy.While FMT holds potential for HE management,ongoing research is needed to address these challenges,optimize protocols,and expand its availability as a therapeutic option for diverse hepatic conditions.

Fecal microbiota transplantation in the treatment of hepatic encephalopathy:A perspective

Due to its complex pathogenesis,treatment of hepatic encephalopathy(HE)continues to be a therapeutic challenge.Of late,gut microbiome has garnered much attention for its role in the pathogenesis of various gastrointestinal and liver diseases and its potential therapeutic use.New evidence suggests that gut micro-biota plays a significant role in cerebral homeostasis.Alteration in the gut microbiota has been documented in patients with HE in a number of clinical and experimental studies.Research on gut dysbiosis in patients with HE has opened newer therapeutic avenues in the form of probiotics,prebiotics and the latest fecal microbiota transplantation(FMT).Recent studies have shown that FMT is safe and could be effective in improving outcomes in advanced liver disease patients presenting with HE.However,questions over the appropriate dose,duration and route of administration for best treatment outcome remains unsettled.

Spleen volume is associated with overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunt in patients with portal hypertension

BACKGROUND Portal shunt and immune status related to the spleen are related to the occurrence of hepatic encephalopathy(HE).It is unknown whether spleen volume before transjugular intrahepatic portosystemic shunt(TIPS)is related to postoperative HE.AIM To investigate the relationship between spleen volume and the occurrence of HE.METHODS This study included 135 patients with liver cirrhosis who underwent TIPS,and liver and spleen volumes were elevated upon computed tomography imaging.The Kaplan-Meier curve was used to compare the difference in the incidence rate of HE among patients with different spleen volumes.Univariate and multivariate Cox regression analyses were performed to identify the factors affecting overt HE(OHE).Restricted cubic spline was used to examine the shapes of the dose-response association between spleen volumes and OHE risk.RESULTS The results showed that 37(27.2%)of 135 patients experienced OHE during a 1-year follow-up period.Compared with preoperative spleen volume(901.30±471.90 cm3),there was a significant decrease in spleen volume after TIPS(697.60±281.0 cm^(3))in OHE patients.As the severity of OHE increased,the spleen volume significantly decreased(P<0.05).Compared with patients with a spleen volume≥782.4 cm^(3),those with a spleen volume<782.4 cm^(3) had a higher incidence of HE(P<0.05).Cox regression analysis showed that spleen volume was an independent risk factor for post-TIPS OHE(hazard ratio=0.494,P<0.05).Restricted cubic spline model showed that with an increasing spleen volume,OHE risk showed an initial increase and then decrease(P<0.05).CONCLUSION Spleen volume is related to the occurrence of OHE after TIPS.Preoperative spleen volume is an independent risk factor for post-TIPS OHE.

Can rifaximin for hepatic encephalopathy be discontinued during broad-spectrum antibiotic treatment?

Hepatic encephalopathy(HE)is a formidable complication in patients with decompensated cirrhosis,often necessitating the administration of rifaximin(RFX)for effective management.RFX,is a gut-restricted,poorly-absorbable oral rifamycin derived antibiotic that can be used in addition to lactulose for the secondary prophylaxis of HE.It has shown notable reductions in infection,hospital readmission,duration of hospital stay,and mortality.However,limited data exist about the concurrent use of RFX with broad-spectrum antibiotics,because the patients are typically excluded from studies assessing RFX efficacy in HE.A pharmacist-driven quasi-experimental pilot study was done to address this gap.They argue against the necessity of RFX in HE during broad-spectrum antibiotic treatment,particularly in critically ill patients in intensive care unit(ICU).The potential for safe RFX discontinuation without adverse effects is clearly illuminated and valuable insight into the optimization of therapeutic strategies is offered.The findings also indicate that RFX discontinuation during broadspectrum antibiotic therapy was not associated with higher rates of delirium or coma,and this result remained robust after adjustment in multivariate analysis.Furthermore,rates of other secondary clinical and safety outcomes,including ICU mortality and 48-hour changes in vasopressor requirements,were comparable.However,since the activity of RFX is mainly confined to the modulation of gut microbiota,its potential utility in patients undergoing extensive systemic antibiotic therapy is debatable,given the overlapping antibiotic activity.Further,this suggests that the action of RFX on HE is class-specific(related to its activity on gut microbiota),rather than drug-specific.A recent double-blind randomized controlled(ARiE)trial provided further evidence-based support for RFX withdrawal in critically ill cirrhotic ICU patients receiving broad-spectrum antibiotics.Both studies prompt further discussion about optimal therapeutic strategy for patients facing the dual challenge of HE and systemic infections.Despite these compelling results,both studies have limitations.A prospective,multi-center evaluation of a larger sample,with placebo control,and comprehensive neurologic evaluation of HE is warranted.It should include an exploration of longer-term outcome and the impact of this protocol in non-critically ill liver disease patients.

Liver transplantation for hepatitis B virus-related cirrhosis with acute-on-chronic liver failure and grade 3-4 hepatic encephalopathy:Survival and quality of life

To the Editor:Twenty-eight-day mortality rates in patients with acute-on-chronic liver failure(ACLF)grades 1,2,and 3,as per the European Association for the Study of the Liver-Chronic Liver Failure(EASL-CLIF)classification,are 22%,32%,and 73%,respectively.[1]The 30-day mortality rates in cirrhosis with grade 3-4 hepatic encephalopathy(HE)and≥2 extra-hepatic organ failures(OFs),and one OF are 70%and 44%,respectively.[2]It suggests that the prognosis in cirrhotic patients with ACLF and grades 3-4 HE is usually poor,which can be effectively treated by liver transplantation(LT)with good post-LT survival rates.[3,4]Hepatitis B virus(HBV)is the main cirrhotic etiology in China.[5]Currently,there is limited data available regarding LT for HBV-related ACLF patients with grade 3-4 HE(hereinafter referred to as ACLF with grade 3-4 HE).This study aimed to investigate the peri-LT complications,pre-LT prognostic scorings,survival,and quality of life assessed by the Karnofsky performance status(KPS)scores at post-LT 1 year in ACLF with grade 3-4 HE,when compared with other three transplanted groups(ACLF with grade 1-2 HE,ACLF with no HE,and cirrhosis with no ACLF and HE).

Progress in pathogenesis and treatment of type A hepatic encephalopathy in acute liver failure:a comprehensive review

Hepatic encephalopathy is a serious neuropsychiatric complication caused by liver failure,which is characterized by the development of cognitive and motor disorders into coma.Typically,hepatic encephalopathy can be divided into three types(A,B,and C)according to the etiology.Type A hepatic encephalopathy(AHE)caused by acute liver failure seriously affects the prognosis of patients,ranging from mild neuropsychological changes to coma,brain edema,and even death.So far,the research on the pathogenesis of AHE has focused on the toxic effects of ammonia on the central nervous system,metabolic disorders(glutamine and lactate accumulation),neurotransmission alteration,systemic inflammation,especially neuro-inflammation.All these mechanisms are not independent,but mutually have synergistic effects.In clinic,treatment of AHE based on only one mechanism is often ineffective.To clarify the pathogenesis and the interaction among the mechanisms will be beneficial to the effective treatment of AHE and reduce the mortality.The aim of this review is to provide comprehensive scientific evidence for the clinical treatment of AHE via collecting and analyzing the latest mechanism of AHE,and clarifying the relationship among these mechanisms combing the investigation of the latest research progress of drug treatment of acute liver failure.Consequently,we find that the pathogenesis of AHE is a complex neurocognitive disorder shaped by interactions among hyperammonemia,inflammation,and changes in neurotransmission,the signaling pathways thereby integrating the inflammatory and neurological inputs to impact pathophysiological or neurobehavioral outcomes.

Alterations in the gut microbiome after transjugular intrahepatic portosystemic shunt in patients with hepatitis B virus-related portal hypertension

BACKGROUND Gut microbiota(GM)affects the progression and response to treatment in liver diseases.The GM composition is diverse and associated with different etiologies of liver diseases.Notably,alterations in GM alterations are observed in patients with portal hypertension(PH)secondary to cirrhosis,with hepatitis B virus(HBV)infection being a major cause of cirrhosis in China.Thus,understanding the role of GM alterations in patients with HBV infection-related PH is essential.AIM To evaluate GM alterations in patients with HBV-related PH after transjugular intrahepatic portosystemic shunt(TIPS)placement.METHODS This was a prospective,observational clinical study.There were 30 patients(with a 100%technical success rate)recruited in the present study.Patients with esophagogastric variceal bleeding due to HBV infection-associated PH who underwent TIPS were enrolled.Stool samples were obtained before and one month after TIPS treatment,and GM was analyzed using 16S ribosomal RNA amplicon sequencing.RESULTS One month after TIPS placement,8 patients developed hepatic encephalopathy(HE)and were assigned to the HE group;the other 22 patients were assigned to the non-HE group.There was no substantial disparity in the abundance of GM at the phylum level between the two groups,regardless of TIPS treatment(all,P>0.05).However,following TIPS placement,the following results were observed:(1)The abundance of Haemophilus and Eggerthella increased,whereas that of Anaerostipes,Dialister,Butyricicoccus,and Oscillospira declined in the HE group;(2)The richness of Eggerthella,Streptococcus,and Bilophila increased,whereas that of Roseburia and Ruminococcus decreased in the non-HE group;and(3)Members from the pathogenic genus Morganella appeared in the HE group but not in the non-HE group.CONCLUSION Intestinal microbiota-related synergism may predict the risk of HE following TIPS placement in patients with HBVrelated PH.Prophylactic microbiome therapies may be useful for preventing and treating HE after TIPS placement.

Hepatic recompensation according to Baveno VII criteria via transjugular intrahepatic portosystemic shunt

Transjugular intrahepatic portosystemic shunt is a therapeutic modality done through interventional radiology.It is aimed to decrease portal pressure in special situations for patients with decompensated liver disease with portal hypertension.It represents a potential addition to the therapeutic modalities that could achieve hepatic recompensation in those patients based on Baveno VII criteria.

Hepatic arterial infusion chemotherapy with anti-angiogenesis agents and immune checkpoint inhibitors for unresectable hepatocellular carcinoma and meta-analysis

BACKGROUND Hepatic arterial infusion chemotherapy(HAIC)has been proven to be an ideal choice for treating unresectable hepatocellular carcinoma(uHCC).HAIC-based treatment showed great potential for treating uHCC.However,large-scale studies on HAIC-based treatments and meta-analyses of first-line treatments for uHCC are lacking.AIM To investigate better first-line treatment options for uHCC and to assess the safety and efficacy of HAIC combined with angiogenesis inhibitors,programmed cell death of protein 1(PD-1)and its ligand(PD-L1)blockers(triple therapy)under real-world conditions.METHODS Several electronic databases were searched to identify eligible randomized controlled trials for this meta-analysis.Study-level pooled analyses of hazard ratios(HRs)and odds ratios(ORs)were performed.This was a retrospective single-center study involving 442 patients with uHCC who received triple therapy or angiogenesis inhibitors plus PD-1/PD-L1 blockades(AIPB)at Sun Yat-sen University Cancer Center from January 2018 to April 2023.Propensity score matching(PSM)was performed to balance the bias between the groups.The Kaplan-Meier method and cox regression were used to analyse the survival data,and the log-rank test was used to compare the suvival time between the groups.RESULTS A total of 13 randomized controlled trials were included.HAIC alone and in combination with sorafenib were found to be effective treatments(P values for ORs:HAIC,0.95;for HRs:HAIC+sorafenib,0.04).After PSM,176 HCC patients were included in the analysis.The triple therapy group(n=88)had a longer median overall survival than the AIPB group(n=88)(31.6 months vs 14.6 months,P<0.001)and a greater incidence of adverse events(94.3%vs 75.4%,P<0.001).CONCLUSION This meta-analysis suggests that HAIC-based treatments are likely to be the best choice for uHCC.Our findings confirm that triple therapy is more effective for uHCC patients than AIPB.

Role of gut microbiota in the pathogenesis and therapeutics of minimal hepatic encephalopathy via the gut-liver-brain axis

Minimal hepatic encephalopathy(MHE) is a frequent neurological and psychiatric complication of liver cirrhosis. The precise pathogenesis of MHE is complicated and has yet to be fully elucidated. Studies in cirrhotic patients and experimental animals with MHE have indicated that gut microbiota dysbiosis induces systemic inflammation, hyperammonemia, and endotoxemia, subsequently leading to neuroinflammation in the brain via the gut-liver-brain axis. Related mechanisms initiated by gut microbiota dysbiosis have significant roles in MHE pathogenesis. The currently available therapeutic strategies for MHE in clinical practice, including lactulose, rifaximin, probiotics, synbiotics, and fecal microbiota transplantation, exert their effects mainly by modulating gut microbiota dysbiosis. Microbiome therapies for MHE have shown promised efficacy and safety;however, several controversies and challenges regarding their clinical use deserve to be intensively discussed. We have summarized the latest research findings concerning the roles of gut microbiota dysbiosis in the pathogenesis of MHE via the gut-liver-brain axis as well as the potential mechanisms by which microbiome therapies regulate gut microbiota dysbiosis in MHE patients.

Hepatoprotective effects of Xiaoyao San formula on hepatic steatosis and inflammation via regulating the sex hormones metabolism

BACKGROUND The modified Xiaoyao San(MXS)formula is an adjuvant drug recommended by the National Health Commission of China for the treatment of liver cancer,which has the effect of preventing postoperative recurrence and metastasis of hepatocellular carcinoma and prolonging patient survival.However,the molecular mechanisms underlying that remain unclear.AIM To investigate the role and mechanisms of MXS in ameliorating hepatic injury,steatosis and inflammation.METHODS A choline-deficient/high-fat diet-induced rat nonalcoholic steatohepatitis(NASH)model was used to examine the effects of MXS on lipid accumulation in primary hepatocytes.Liver tissues were collected for western blotting and immunohisto chemistry(IHC)assays.Lipid accumulation and hepatic fibrosis were detected using oil red staining and Sirius red staining.The serum samples were collected for biochemical assays and NMR-based metabonomics analysis.The inflammation/lipid metabolism-related signaling and regulators in liver tissues were also detected to reveal the molecular mechanisms of MXS against NASH.RESULTS MXS showed a significant decrease in lipid accumulation and inflammatory response in hepatocytes under metabolic stress.The western blotting and IHC results indicated that MXS activated AMPK pathway but inhibited the expression of key regulators related to lipid accumulation,inflammation and hepatic fibrosis in the pathogenesis of NASH.The metabonomics analysis systemically indicated that the arachidonic acid metabolism and steroid hormone synthesis are the two main target metabolic pathways for MXS to ameliorate liver inflammation and hepatic steatosis.Mechanistically,we found that MXS protected against NASH by attenuating the sex hormone-related metabolism,especially the metabolism of male hormones.CONCLUSION MXS ameliorates inflammation and hepatic steatosis of NASH by inhibiting the metabolism of male hormones.Targeting male hormone related metabolic pathways may be the potential therapeutic approach for NASH.

Branched chain amino acids in hepatic encephalopathy and sarcopenia in liver cirrhosis:Evidence and uncertainties

Liver cirrhosis is commonly associated with nutritional alterations,reported in 20% of patients with compensated disease and over 60% of patients with decompensated cirrhosis.Nutritional disturbances are associated with a worse prognosis and increased risk of complication.Serum levels of branched-chain amino acids(BCAAs)are decreased in patients with liver cirrhosis.The imbalance of amino acids levels has been suggested to be associated with the development of complications,such as hepatic encephalopathy and sarcopenia,and to affect the clinical presentation and prognosis of these patients.Several studies investigated the efficacy of BCAAs supplementation as a therapeutic option in liver cirrhosis,but uncertainties remain about the real efficacy,the best route of administration,and dosage.

Contributory roles of sarcopenia and myosteatosis in development of overt hepatic encephalopathy and mortality after transjugular intrahepatic portosystemic shunt

BACKGROUND Skeletal muscle abnormalities,such as muscle mass depletion(sarcopenia)and fatty infiltration of the muscle(myosteatosis),are frequent complications in cirrhotic patients scheduled for transjugular intrahepatic portosystemic shunt(TIPS).AIM To investigate the association and predictive value of sarcopenia and myosteatosis for overt hepatic encephalopathy(HE)and mortality after TIPS.METHODS The records of cirrhotic patients who underwent the TIPS procedure at our hospital between January 2020 and June 2021 were retrospectively retrieved.The transversal psoas muscle thickness(TPMT)and psoas muscle attenuation(PMA)measured from the unenhanced abdominal computed tomography(CT)at the level of the third lumbar vertebrae were used to analyze the sarcopenia and myosteatosis,respectively.The area under curve(AUC)was used to evaluate the discriminative power of TPMT,PMA,and relevant clinical parameters.Furthermore,log-rank test was performed to compare the incidence of overt HE and survival between the different groups,and the association of risk factors with overt HE and mortality was analyzed using Cox proportional hazards regression models.RESULTS A total of 108 patients were collected.Among these patients,45.4%of patients developed overt HE after TIPS treatment.Furthermore,32.4%and 28.7%of these patients were identified to have myosteatosis and sarcopenia,respectively.Myosteatosis(51.0%vs 16.9%,P<0.001)and sarcopenia(40.8 vs 18.6%,P=0.011)were found to be more frequent in patients with overt HE,when compared to patients without overt HE.The receiver operating characteristics analysis indicated that the predictive power of TPMT and PMA in overt HE(AUC=0.713 and 0.778,respectively)was higher when compared to the neutrophil lymphocyte ratio(AUC=0.636).The cumulative incidence of overt HE was the highest in patients with concomitant sarcopenia and myosteatosis,followed by patients with myosteatosis or sarcopenia,while this was the lowest in patients without sarcopenia and myosteatosis.In addition,sarcopenia and myosteatosis were independently associated with overt HE and mortality after adjusting for confounding factors in post-TIPS patients.CONCLUSION CT-based estimations for sarcopenia and myosteatosis can be used as reliable predictors for the risk of developing overt HE and mortality in cirrhotic patients after TIPS.

"Five steps four quadrants" modularized en bloc dissection technique for accessing hepatic hilum lymph nodes in laparoscopic pancreaticoduodenectomy

BACKGROUND Although en bloc dissection of hepatic hilum lymph nodes has many advantages in radical tumor treatment,the feasibility and safety of this approach for laparo-scopic pancreaticoduodenectomy(LPD)require further clinical evaluation and investigation.AIM To explore the application value of the"five steps four quadrants"modularized en bloc dissection technique for accessing hepatic hilum lymph nodes in LPD patients.METHODS A total of 52 patients who underwent LPD via the"five steps four quadrants"modularized en bloc dissection technique for hepatic hilum lymph nodes from April 2021 to July 2023 in our department were analyzed retrospectively.The patients'body mass index(BMI),preoperative laboratory indices,intraoperative variables and postoperative complications were recorded.The relationships between preoperative data and intraoperative lymph node dissection time and blood loss were also analyzed.RESULTS Among the 52 patients,36 were males and 16 were females,and the average age was 62.2±11.0 years.There were 26 patients with pancreatic head cancer,16 patients with periampullary cancer,and 10 patients with distal bile duct cancer.The BMI was 22.3±3.3 kg/m²,and the median total bilirubin(TBIL)concentration was 57.7(16.0-155.7)µmol/L.All patients successfully underwent the"five steps four quadrants"modularized en bloc dissection technique without lymph node clearance-related complications such as postoperative bleeding or lymphatic leakage.Correlation analysis revealed significant associations between preoperative BMI(r=0.3581,P=0.0091),TBIL level(r=0.2988,P=0.0341),prothrombin time(r=0.3018,P=0.0297)and lymph node dissection time.Moreover,dissection time was significantly correlated with intraoperative blood loss(r=0.7744,P<0.0001).Further stratified analysis demonstrated that patients with a preoperative BMI≥21.9 kg/m²and a TIBL concentration≥57.7μmol/L had significantly longer lymph node dissection times(both P<0.05).CONCLUSION The"five steps four quadrants"modularized en bloc dissection technique for accessing the hepatic hilum lymph node is safe and feasible for LPD.This technique is expected to improve the efficiency of hepatic hilum lymph node dissection and shorten the learning curve;thus,it is worthy of further clinical promotion and application.

Prevention and treatment of hepatic encephalopathy during the perioperative period of transjugular intrahepatic portosystemic shunt

Transjugular intrahepatic portosystemic shunt(TIPS)is an established procedure for treating the complications of portal hypertension in liver cirrhosis.While the pathogenesis of postoperative TIPS-related hepatic encephalopathy(HE)has yet to be fully understood,intraoperative portosystemic shunts may provide a pathological basis for the occurrence of postope-rative HE in patients with liver cirrhosis.Studies at home and abroad have expressed mixed opinions about TIPSrelated HE.This study presents a literature review on the risk factors for and prevention and treatment of perioperative TIPS-related HE in patients with liver cirrhosis,aiming to optimize the procedure and reduce the incidence of postoperative HE.

Hepatic Elastometry in the Management of Hepatitis B at National Hospital of Niamey

Introduction: Viral hepatitis B is a public health problem in Niger which is classified as a high endemicity area with a prevalence ranging from 8 to 17% depending on the studies [1] and that of HBV-related cirrhosis is about 40.26% in 2024. The decision to treat is based on a combination of three parameters: viral load, ALT values and the degree of hepatic fibrosis [2]. The latter is assessed by hepatic elastography (Fibroscan), which is a decisive factor in treatment. In Niger, until 2024, the decision to treat or not to treat a patient with HBV was based on the determination of viral load B and transaminases, and no work evaluating the contribution of this third element, liver elasticity, has been done, hence the interest of our study. Objective: To study the contribution of Fibroscan in measuring hepatic elasticity in the management of patients with HBV. Methodology: This was a prospective descriptive study conducted from January 05 to November 30, i.e. a period of 11 months, on clinically asymptomatic HBsAg-positive patients who had undergone FibroScan liver elasticity measurement. The examination was carried out by a hepatogastroenterologist who had received training in the Fibroscan. The median of ten measures of liver elasticity at the same point with an IQR of less than 30% was considered the valid measure and no or minimal fibrosis was defined as a value ˂7 Kpa, moderate fibrosis as a value between 7 and 10 kpa, severe fibrosis as a value greater than 10 Kpa, and the existence of cirrhosis as a value greater than 14 Kpa were analyzed using SPSS version 20 software. Results: Out of 398 patients monitored for HBV, 60 cases met the inclusion criteria, i.e., a frequency of 15.07%. The mean age of the patients was 35.63 years, with extremes of 18 and 70 years. They were predominantly male, with a sex ratio of 3.2. Married patients accounted for 61.67% (n = 37). Jaundice was absent in 91.67% (n = 55). The circumstances of discovery of HBV were the routine health check-up, followed by blood donation with 50% and 46.67%, respectively. The viral load was >2000 UI/ml in 32.7% (n = 17). HBeAg was negative in 93.33% of cases (n = 56). ALT levels were normal in 47 patients (78.33%). Mean liver elasticity was 6.7 KPa. Fibrosis was classified as F0 - F1 in 75% (n = 45), F1 - F2 in 18.33% (n = 11) and F3 - F4 in 6.67% (n = 4) of patients. There was no significant relationship between viremia value, liver activity, degree of fibrosis and quantitative HBsAg. Conclusion: Measurement of hepatic elasticity has made it possible to diagnose cases of compensated cirrhosis and significant fibrosis in patients considered to be inactive carriers (viral load ˂2000 IU/ml and normal transaminases) in asymptomatic HBV+ patients. This made it possible to put these patients on Tenofovir in order to avoid decompensation for the first group and for the second the progression to cirrhosis. It is an excellent tool to aid in the decision to start treatment.

Diagnosis and treatment experience of atypical hepatic cystic echinococcosis type 1 at a tertiary center in China

BACKGROUND Some hydatid cysts of cystic echinococcosis type 1(CE1)lack well-defined cyst walls or distinctive endocysts,making them difficult to differentiate from simple hepatic cysts.AIM To investigate the diagnostic methods for atypical hepatic CE1 and the clinical efficacy of laparoscopic surgeries.METHODS The clinical data of 93 patients who had a history of visiting endemic areas of CE and were diagnosed with cystic liver lesions for the first time at the People's Hospital of Xinjiang Uygur Autonomous Region(China)from January 2018 to September 2023 were retrospectively analyzed.Clinical diagnoses were made based on findings from serum immunoglobulin tests for echinococcosis,routine abdominal ultrasound,high-frequency ultrasound,abdominal computed tomography(CT)scan,and laparoscopy.Subsequent to the treatments,these patients underwent reexaminations at the outpatient clinic until October 2023.The evaluations included the diagnostic precision of diverse examinations,the efficacy of surgical approaches,and the incidence of CE recurrence.RESULTS All 93 patients were diagnosed with simple hepatic cysts by conventional abdominal ultrasound and abdominal CT scan.Among them,16 patients were preoperatively diagnosed with atypical CE1,and 77 were diagnosed with simple hepatic cysts by high-frequency ultrasound.All the 16 patients preoperatively diagnosed with atypical CE1 underwent laparoscopy,of whom 14 patients were intraoperatively confirmed to have CE1,which was consistent with the postoperative pathological diagnosis,one patient was diagnosed with a mesothelial cyst of the liver,and the other was diagnosed with a hepatic cyst combined with local infection.Among the 77 patients who were preoperatively diagnosed with simple hepatic cysts,4 received aspiration sclerotherapy of hepatic cysts,and 19 received laparoscopic fenestration.These patients were intraoperatively diagnosed with simple hepatic cysts.During the followup period,none of the 14 patients with CE1 experienced recurrence or implantation of hydatid scolices.One of the 77 patients was finally confirmed to have CE complicated with implantation to the right intercostal space.CONCLUSION Abdominal high-frequency ultrasound can detect CE1 hydatid cysts.The laparoscopic technique serves as a more effective diagnostic and therapeutic tool for CE.

Treatment of portosystemic shunt-borne hepatic encephalopathy in a 97-year-old woman using balloon-occluded retrograde transvenous obliteration:A case report

BACKGROUND Hyperammonemia and hepatic encephalopathy are common in patients with portosystemic shunts.Surgical shunt occlusion has been standard treatment,although recently the less invasive balloon-occluded retrograde transvenous obliteration(B-RTO)has gained increasing attention.Thus far,there have been no reports on the treatment of portosystemic shunts with B-RTO in patients aged over 90 years.In this study,we present a case of hepatic encephalopathy caused by shunting of the left common iliac and inferior mesenteric veins,successfully treated with B-RTO.CASE SUMMARY A 97-year-old woman with no history of liver disease was admitted to our hospital because of disturbance of consciousness.She had no jaundice,spider angioma,palmar erythema,hepatosplenomegaly,or asterixis.Her blood tests showed hyperammonemia,and abdominal contrast-enhanced computed tomography revealed a portosystemic shunt running between the left common iliac vein and the inferior mesenteric vein.She was diagnosed with hepatic encephalopathy secondary to a portosystemic shunt.The patient did not improve with conservative treatment:Lactulose,rifaximin,and a low-protein diet.B-RTO was performed,which resulted in shunt closure and improvement in hyperammonemia and disturbance of consciousness.Moreover,there was no abdominal pain or elevated levels of liver enzymes due to complications.The patient was discharged without further consciousness disturbance.CONCLUSION Portosystemic shunt-borne hepatic encephalopathy must be considered in the differential diagnosis for consciousness disturbance,including abnormal behavior and speech.

Risk of hepatic decompensation from hepatitis B virus reactivation in hematological malignancy treatments

In this editorial,we discussed the apparent discrepancy between the findings described by Colapietro et al,in their case report and data found in the literature.Colapietro et al reported a case of hepatitis B virus(HBV)-related hepatic decompensation in a patient with chronic myeloid leukemia and a previously resolved HBV infection who was receiving Bruton’s tyrosine kinase(BTK)inhibitor therapy.First of all,we recapitulated the main aspects of the immune system involved in the response to HBV infection in order to underline the role of the innate and adaptive response,focusing our attention on the protective role of anti-HBs.We then carefully analyzed literature data on the risk of HBV reactivation(HBVr)in patients with previous HBV infection who were treated with either tyrosine kinase inhibitors or BTK inhibitors for their hematologic malignancies.Based on literature data,we suggested that several factors may contribute to the different risks of HBVr:The type of hematologic malignancy;the type of therapy(BTK inhibitors,especially second-generation,seem to be at a higher risk of HBVr than those with tyrosine kinase inhibitors);previous exposure to an anti-CD20 as first-line therapy;and ethnicity and HBV genotype.Therefore,the warning regarding HBVr in the specific setting of patients with hematologic malignancies requires further investigation.

Targeting GPR65 alleviates hepatic inflammation and fibrosis by suppressing the JNK and NF-κB pathways

Background:G-protein coupled receptors(GPCRs)are recognized as attractive targets for drug therapy.However,it remains poorly understood how GPCRs,except for a few chemokine receptors,regulate the progression of liver fibrosis.Here,we aimed to reveal the role of GPR65,a proton-sensing receptor,in liver fibrosis and to elucidate the underlying mechanism.Methods:The expression level of GPR65 was evaluated in both human and mouse fibrotic livers.Furthermore,Gpr65-deficient mice were treated with either bile duct ligation(BDL)for 21 d or carbon tetrachloride(CCl4)for 8 weeks to investigate the role of GPR65 in liver fibrosis.A combination of experimental approaches,including Western blotting,quantitative real-time reverse transcription-polymerase chain reaction(qRT-PCR),and enzyme-linked immunosorbent assay(ELISA),confocal microscopy and rescue studies,were used to explore the underlying mechanisms of GPR65’s action in liver fibrosis.Additionally,the therapeutic potential of GPR65 inhibitor in the development of liver fibrosis was investigated.Results:We found that hepatic macrophage(HM)-enriched GPR65 was upregulated in both human and mouse fibrotic livers.Moreover,knockout of Gpr65 significantly alleviated BDL-and CCl4-induced liver inflammation,injury and fibrosis in vivo,and mouse bone marrow transplantation(BMT)experiments further demonstrated that the protective effect of Gpr65knockout is primarily mediated by bone marrow-derived macrophages(BMMs).Additionally,in vitro data demonstrated that Gpr65 silencing and GPR65 antagonist inhibited,while GPR65 overexpression and application of GPR65 endogenous and exogenous agonists enhanced the expression and release of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and transforming growth factor-β(TGF-β),all of which subsequently promoted the activation of hepatic stellate cells(HSCs)and the damage of hepatocytes(HCs).Mechanistically,GPR65 overexpression,the acidic pH and GPR65 exogenous agonist induced up-regulation of TNF-αand IL-6 via the Gαq-Ca^(2+)-JNK/NF-κB pathways,while promoted the expression of TGF-βthrough the Gαq-Ca^(2+)-MLK3-MKK7-JNK pathway.Notably,pharmacological GPR65 inhibition retarded the development of inflammation,HCs injury and fibrosis invivo.Conclusions:GPR65 is a major regulator that modulates the progression of liver fibrosis.Thus,targeting GPR65 could be an effective therapeutic strategy for the prevention of liver fibrosis.